Influence of the COVID-19 pandemic on births and induced abortions in Southern Sweden: a register-based study.

BACKGROUND: Pandemics are linked with declining birth rates, but little is known about how the COVID-19 pandemic has influenced childbearing decisions. We aimed to investigate the associations between the COVID-19 pandemic and reproductive decisions, specifically to identify potential changes in the frequency of deliveries and induced abortions in Skåne, Sweden. METHODS: Using the Skåne Healthcare Register, we identified women aged 15-45 years who had at least one pregnancy-related care visit registered between 1 January 2013 and 11 November 11 2021. Deliveries and induced abortions were identified, and changes in weekly delivery and abortion counts were assessed using an interrupted time series design. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated from a Poisson regression model. RESULTS: During the study period we identified 129 131 deliveries and 38 591 abortions. Compared with the counterfactual (exposed interval assuming COVID-19 had not occurred), pandemic exposure was associated with fewer deliveries (RR 0.93; 95% CI 0.89 to 0.98). For abortions, pandemic exposure appeared to be associated with fewer abortions (RR 0.95; 95% CI 0.90 to 1.00); however, age-related differences were found. Among women aged 25 years and over, pandemic exposure was more strongly associated with fewer abortions. Contrastingly, among women aged under 25 years, abortions appeared to increase. CONCLUSIONS: The COVID-19 pandemic seemed to have contributed to a decline in births in Southern Sweden. During the same period, abortions declined in women in the older age range, but contrastingly increased among younger women.

Gating small conductance calcium-activated potassium channels in the thalamic reticular nucleus.

Small conductance calcium-activated potassium (SK) channels are well-known regulators of neuronal excitability. In the thalamic hub, SK2 channels act as pacemakers of thalamic reticular neurons, which play a key role in the thalamocortical circuit. Several disease-linked genes are highly enriched in these neurons, including genes known to be associated with schizophrenia and attentional disorders, which could affect neuronal firing. The present study assessed the effect of pharmacological modulation of SK channels in the firing pattern and intrinsic properties of thalamic reticular neurons by performing whole cell patch clamp recordings in brain slices. Two SK positive allosteric modulators and one negative allosteric modulator were used: CyPPA, NS309, and NS8593, respectively. By acting on the burst afterhyperpolarization (AHP), negative modulation of SK channels resulted in increased action potential (AP) firing, increased burst duration, and decreased intervals between bursts. Conversely, both CyPPA and NS309 increased the afterburst AHP, prolonging the interburst interval, which additionally resulted in reduced AP firing in the case of NS309. Alterations in SK channel activity would be expected to alter functioning of thalamocortical circuits. Targeting SK channels could be promising in treating disorders involving thalamic reticular dysfunction such as psychiatric and neurodevelopmental disorders.

Relationship between cumulative exposure to occupational lifting throughout working life and risk of ischemic heart disease in men and women. The Copenhagen Aging and Midlife Biobank.

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.

Performing up to Nordic principles? Geographic and socioeconomic equity in ambulatory care sensitive conditions among older adults in capital areas of Denmark, Finland and Sweden in 2000-2015.

BACKGROUND: Denmark, Finland and Sweden pursue equity in health for their citizens through universal health care. However, it is unclear if these services reach the older adult population equally across different socioeconomic positions or living areas. Thus, we assessed geographic and socioeconomic equity in primary health care (PHC) performance among the older adults in the capital areas of Denmark (Copenhagen), Finland (Helsinki) and Sweden (Stockholm) in 2000-2015. Hospitalisations for ambulatory care sensitive conditions (ACSC) were applied as a proxy for PHC performance. METHODS: We acquired individual level ACSCs for those aged ≥ 45 in 2000-2015 from national hospitalisation registers. To identify whether the disparities varied by age, we applied three age groups (those aged 45-64, 65-75 and ≥ 75). Socioeconomic disparities in ACSCs were described with incidence rate ratios (IRR) and annual rates by education, income and living-alone; and then analysed with biennial concentration indices by income. Geographic disparities were described with biennial ACSC rates by small areas and analysed with two-level Poisson multilevel models. These models provided small area estimates of IRRs of ACSCs in 2000 and their slopes for development over time, between which Pearson correlations were calculated within each capital area. Finally, these models were adjusted for income to distinguish between geographic and socioeconomic disparities. RESULTS: Copenhagen had the highest IRR of ACSCs among those aged 45-64, and Helsinki among those aged ≥ 75. Over time IRRs decreased among those aged ≥ 45, but only in Helsinki among those aged ≥ 75. All concentration indices slightly favoured the affluent population but in Stockholm were mainly non-significant. Among those aged ≥ 75, Pearson correlations were low in Copenhagen (-0.14; p = 0.424) but high in both Helsinki (-0.74; < 0.001) and Stockholm (-0.62; < 0.001) - with only little change when adjusted for income. Among those aged ≥ 45 the respective correlations were rather similar, except for a strong correlation in Copenhagen (-0.51, 0.001) after income adjustment. CONCLUSIONS: While socioeconomic disparities in PHC performance persisted among older adults in the three Nordic capital areas, geographic disparities narrowed in both Helsinki and Stockholm but persisted in Copenhagen. Our findings suggest that the Danish PHC incorporated the negative effects of socio-economic segregation to a lesser degree.

Infertility-related stress and the risk of antidepressants prescription in women: a 10-year register study.

STUDY QUESTION: Is the first-time redeemed prescription of antidepressants predicted by the level of infertility-related stress in women seeking ART treatment? SUMMARY ANSWER: Infertility-related stress in the personal and marital domains and general physical stress reactions were significant predictors of a first redeemed prescription of antidepressants after ART treatment in this 10-year follow-up cohort study. WHAT IS KNOWN ALREADY: The literature has found inconsistent findings regarding the association between infertility-related stress and later psychological adjustment in fertility patients. The association between infertility-related stress and later prescription of antidepressants had never been explored in long-term cohort studies. STUDY DESIGN, SIZE, DURATION: All women (n = 1169) who participated in the Copenhagen Cohort Multi-centre Psychosocial Infertility (COMPI) cohort study in the year 2000 (questionnaire data) were linked with the register-based Danish National ART-Couple (DANAC) I cohort, which includes women and their partners having received ART treatment from 1 January 1994 to 30 September 2009. The study population were among other national health and sociodemographic registers further linked with the Danish National Prescription Registry. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women initiating ART treatment were followed until they had redeemed the first prescription of antidepressants or until 31 December 2009. Logistic regression analyses were conducted to test the association between general physical stress reactions and infertility-related stress in the personal, marital and social domains, respectively, and a future redeemed prescription of antidepressants. Age, education level, marital status, number of fertility treatments prior to study inclusion and female infertility diagnosis were included as covariates in the adjusted analyses. Further, the analysis was stratified according to childbirth or no childbirth during follow-up. MAIN RESULTS AND THE ROLE OF CHANCE: The final sample consisted of 1009 women with a mean age of 31.8 years. At study inclusion, women had tried to conceive for an average of 3.45 years. At 10-year follow-up, a total of 13.7% of women had a first redeemed prescription of antidepressant medication. The adjusted odds ratio (OR) showed that high general physical stress predicted the later prescription of antidepressants (adjusted (adj) OR = 2.85, 95% confidence interval (CI) 1.96-4.16). Regarding infertility-related stress domains, high personal stress (adj OR = 2.14, 95% CI 1.46-3.13) and high marital stress (adj OR = 1.80, 95% CI 1.23-2.64) were significantly associated with the later prescription of antidepressants. Social stress was not significantly associated with the future redeemed prescription of antidepressants (adj OR = 1.10, 95% CI 0.76-1.61). Among women not having achieved childbirth during follow-up, the risk of a first-time prescription of antidepressants associated with infertility-specific stress was higher compared to the risk among women having childbirth during follow-up. LIMITATIONS, REASONS FOR CAUTION: This study did not account for potential mediating factors, such as negative life events, which could be associated with the prescription of antidepressants. Second, we are not able to know if these women had sought psychological support during follow-up. Additionally, antidepressants might be prescribed for other health conditions than depressive disorders. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that women presenting high infertility-related stress in the personal and marital domains were at higher risk of redeemed first-time prescription of antidepressants after ART, independently of having delivered a child or not after initiation of ART treatment. Women would benefit from an initial screening specifically for high infertility-related stress. The COMPI Fertility Problem Stress Scales can be used by clinical staff in order to identify women in need of psychological support before starting ART treatments. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Portuguese Foundation for Science and Technology (FCT) under an individual doctoral grant attributed to the first author (SFRH/BD/103234/2014). The establishment of the DANAC I cohort was funded by Rosa Ebba Hansen's Fund. The COMPI Infertility Cohort project was supported by The Danish Health Insurance Fund (J.nr. 11/097-97), the Else and Mogens Wedell-Wedellsborgs Fund, the manager E. Danielsens and Wife's Fund, the merchant L.F. Foghts Fund, the Jacob Madsen and Wife Olga Madsens Fund. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: NA.

Life course analysis on income and incident AMI: a Danish register-based cohort study.

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.

Phosphodiesterase 1 Bridges Glutamate Inputs with NO- and Dopamine-Induced Cyclic Nucleotide Signals in the Striatum.

The calcium-regulated phosphodiesterase 1 (PDE1) family is highly expressed in the brain, but its functional role in neurones is poorly understood. Using the selective PDE1 inhibitor Lu AF64196 and biosensors for cyclic nucleotides including a novel biosensor for cGMP, we analyzed the effect of PDE1 on cAMP and cGMP in individual neurones in brain slices from male newborn mice. Release of caged NMDA triggered a transient increase of intracellular calcium, which was associated with a decrease in cAMP and cGMP in medium spiny neurones in the striatum. Lu AF64196 alone did not increase neuronal cyclic nucleotide levels, but blocked the NMDA-induced reduction in cyclic nucleotides indicating that this was mediated by calcium-activated PDE1. Similar effects were observed in the prefrontal cortex and the hippocampus. Upon corelease of dopamine and NMDA, PDE1 was shown to down-regulate the D1-receptor mediated increase in cAMP. PDE1 inhibition increased long-term potentiation in rat ventral striatum, showing that PDE1 is implicated in the regulation of synaptic plasticity. Overall, our results show that PDE1 reduces cyclic nucleotide signaling in the context of glutamate and dopamine coincidence. This effect could have a therapeutic value for treating brain disorders related to dysfunctions in dopamine neuromodulation.

Pharmacological rescue of mutated Kv3.1 ion-channel linked to progressive myoclonus epilepsies.

Progressive myoclonus epilepsies (PMEs) constitute a cluster of inherent, genetically diverse, rare seizure disorders characterized by ataxia, tonic-clonic seizures, and action myoclonus. Recently, a mutation in the KCNC1 gene (Arg320His) was described in a group of PME patients. The KCNC1 gene encodes the Kv3.1 potassium ion channel responsible for the rapid repolarization of the membrane potential following action potential firing in fast spiking GABAergic interneurons (FSI), thereby enabling high firing frequency. In the present study, we demonstrate that the Arg320His mutation cause a reduction in the Kv3.1 current amplitude and acts in a dominantly negative fashion. The mutation profoundly affects channel activation and deactivation kinetics, and we further find that it impairs recruitment of the Kv3.1 channel to the plasma membrane. The Kv3 activating compound, RE01, partly rescues the electrophysiological deficit, suggesting that pharmacological activation of Kv3.1 activity might be a feasible approach for treatment of this cohort of PME patients.

The impact of ART on union dissolution: a register-based study in Denmark 1994-2010.

STUDY QUESTION: Are couples initiating ART treatment at higher risk for future union dissolution compared to other couples? SUMMARY ANSWER: There is no effect of ART treatments in future marital dissolution over a period of 16 years when adjusting for all confounders. WHAT IS KNOWN ALREADY: Findings regarding marital stability and infertility treatments have been sparse and controversial. While there is data showing higher divorce rates among women who go through infertility treatments, there is also some evidence of this experience bringing couples closer by forcing them to communicate more and to deal with the surrounding stigma. Using a population-based study and couple-level data, we investigated the extent to which ART treatment increases the risk for divorce/marital dissolution during up to 16 years of follow-up. STUDY DESIGN SIZE, DURATION: Register-based national cohort study including all women registered with ART treatment in Denmark between 1 January 1994 and 30 September 2009 (n = 42 845). Marital/cohabiting status was confirmed by matching these women to partners who they were married to or shared an address with. To account for having a significant relationship at baseline (2 years), marital/cohabiting status was confirmed by accessing this variable before the establishment of the cohort back to 1 January 1992. PARTICIPANTS/MATERIALS, SETTING, METHODS: A comparison group from the background population including five controls per case and matched to female age at baseline was prospectively sampled. Participants could change status during follow-up if they entered ART. The final sample had 148 972 couples, followed until marital dissolution, death of self/spouse, migration or until 31 December 2010. We used Cox regression models adjusting for female and male age, education, marriage, common child at baseline and live-born child during follow-up. MAIN RESULTS AND THE ROLE OF CHANCE: At baseline, the majority of couples were married (69%). More non-ART couples opted for marriage (70% versus 64%; P < 0.0001) and already had common children at study entry (43% versus 9%; P < 0.0001). During the 16 years of follow-up the majority of couples had children with their baseline partners (56% non-ART versus 65% ART), and 22% ended up separated or divorced (20% ART versus 22% non-ART). Findings revealed a lower risk of break-up among ART couples (crude HR 0.84, 95% CI 0.82-0.86), even after adjusting for both partners' age, education, partnership status and having a common child at baseline (adj HR 0.83, 95% CI 0.80-0.86). However, when subsequent common children (time-dependent) was added to the model, no difference in the risk of dissolution was found (adj HR 1.00, 95% CI 0.99-1.01). A significant interaction between ART status and common children showed that the risk of break-up was attributed to childlessness regardless of having gone through ART treatment. LIMITATIONS REASON FOR CAUTION: This study did not control for involuntary childlessness, non-ART fertility care (ovulation induction, IUI) and biological parenthood. Additionally, there are important predictors of divorce that were not considered. We were unable to adjust for religion, existence of previous marital relationships, income, employment, health status of parents and child(ren), and quality of relationship. WIDER IMPLICATION OF FINDINGS: The finding that going through ART does not increase the risk of break up per se is reassuring for couples who underwent ART and have children or are contemplating to start ART. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by FCT (Portuguese Foundation for Science and Technology), grant ref. SFRH/BPD/85789/2012. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

A small molecule activator of Nav 1.1 channels increases fast-spiking interneuron excitability and GABAergic transmission in vitro and has anti-convulsive effects in vivo.

Nav 1.1 (SCN1A) channels primarily located in gamma-aminobutyric acid (GABA)ergic fast-spiking interneurons are pivotal for action potential generation and propagation in these neurons. Inappropriate function of fast-spiking interneurons, leading to disinhibition of pyramidal cells and network desynchronization, correlates with decreased cognitive capability. Further, reduced functionality of Nav 1.1 channels is linked to various diseases in the central nervous system. There is, at present, however no subtype selective pharmacological activators of Nav 1.1 channels available for studying pharmacological modulation of interneuron function. In the current study, we identified a small molecule Nav 1.1 activator, 3-amino-5-(4-methoxyphenyl)thiophene-2-carboxamide, named AA43279, and provided an in vitro to in vivo characterization of the compound. In HEK-293 cells expressing human Nav 1.1 channels, AA43279 increased the Nav 1.1-mediated current in a concentration-dependent manner mainly by impairing the fast inactivation kinetics of the channels. In rat hippocampal brain slices, AA43279 increased the firing activity of parvalbumin-expressing, fast-spiking GABAergic interneurons and increased the spontaneous inhibitory post-synaptic currents (sIPSCs) recorded from pyramidal neurons. When tested in vivo, AA43279 had anti-convulsive properties in the maximal electroshock seizure threshold test. AA43279 was tested for off-target effects on 72 different proteins, including Nav 1.2, Nav 1.4, Nav 1.5, Nav 1.6 and Nav 1.7 and exhibited reasonable selectivity. Taken together, AA43279 might constitute a valuable tool compound for revealing biological functions of Nav 1.1 channels.

Kv3.1/Kv3.2 channel positive modulators enable faster activating kinetics and increase firing frequency in fast-spiking GABAergic interneurons.

Due to their fast kinetic properties, Kv3.1 voltage gated potassium channels are important in setting and controlling firing frequency in neurons and pivotal in generating high frequency firing of interneurons. Pharmacological activation of Kv3.1 channels may possess therapeutic potential for treatment of epilepsy, hearing disorders, schizophrenia and cognitive impairments. Here we thoroughly investigate the selectivity and positive modulation of the two small molecules, EX15 and RE01, on Kv3 channels. Selectivity studies, conducted in Xenopus laevis oocytes confirmed a positive modulatory effect of the two compounds on Kv3.1 and to a minor extent on Kv3.2 channels. RE01 had no effect on the Kv3.3 and Kv3.4 channels, whereas EX15 had an inhibitory impact on the Kv3.4 mediated current. Voltage-clamp experiments in monoclonal hKv3.1b/HEK293 cells (34 °C) revealed that the two compounds indeed induced larger currents and faster activation kinetics. They also decrease the speed of deactivation and shifted the voltage dependence of activation, to a more negative activation threshold. Application of action potential clamping and repetitive stimulation protocols of hKv3.1b expressing HEK293 cells revealed that EX15 and RE01 significantly increased peak amplitude, half width and decay time of Kv3.1 mediated currents, even during high-frequency action potential clamping (250 Hz). In rat hippocampal slices, EX15 and RE01 increased neuronal excitability in fast-spiking interneurons in dentate gyrus. Action potential frequency was prominently increased at minor depolarizing steps, whereas more marginal effects of EX15 and RE01 were observed after stronger depolarizations. In conclusion, our results suggest that EX15 and RE01 positive modulation of Kv3.1 and Kv3.2 currents facilitate increased firing frequency in fast-spiking GABAergic interneurons.

Job mobility and health in the Danish workforce.

AIMS: The globalized economy has stimulated mobility in the labour market in many countries and Denmark has one of the highest rates of mobility between workplaces among the OECD countries. This raises the question of the potential health effects of mobility and the effect of disease on mobility. METHODS: This study was register-based with a longitudinal design using data on the entire Danish population in 1992-2006. The data included mobility between employers and workplaces and seven different diseases based on admissions to hospital and drug prescriptions. RESULTS: After adjusting for relevant confounders, an exposure-response relationship was seen between mobility and the incidence of ischaemic heart disease, stroke, duodenal ulcer, anxiety/depression and, most strongly, with alcohol-related disorders. The effects were not very strong, however, with odds ratios varying from 1.2 to 1.6. As expected, no effect was seen for colorectal cancer. We also found an effect of both somatic and mental disorders on mobility, but not for the two cancer types. Mobility did not seem to prevent being out of the labour force after diagnosis. CONCLUSIONS: Frequent mobility in the labour market increases the risk of cardiovascular disease, common mental disorders and alcohol-related disorders and these diagnoses also seem to increase the risk of subsequent mobility.

Quantification of the functional expression of the Ca2+ -activated K+ channel KCa 3.1 on microglia from adult human neocortical tissue.

The KCa 3.1 channel (KCNN4) is an important modulator of microglia responses in rodents, but no information exists on functional expression on microglia from human adults. We isolated and cultured microglia (max 1% astrocytes, no neurons or oligodendrocytes) from neocortex surgically removed from epilepsy patients and employed electrophysiological whole-cell measurements and selective pharmacological tools to elucidate functional expression of KCa 3.1. The channel expression was demonstrated as a significant increase in the voltage-independent current by NS309, a KCa 3.1/KCa 2 activator, followed by full inhibition upon co-application with NS6180, a highly selective KCa 3.1 inhibitor. A major fraction (79%) of unstimulated human microglia expressed KCa 3.1, and the difference in current between full activation and inhibition (ΔKCa 3.1) was estimated at 292 ± 48 pA at -40 mV (n = 75), which equals at least 585 channels per cell. Serial KCa 3.1 activation/inhibition significantly hyperpolarized/depolarized the membrane potential. The isolated human microglia were potently activated by lipopolysaccharide (LPS) shown as a prominent increase in TNF-α production. However, incubation with LPS neither changed the KCa 3.1 current nor the fraction of KCa 3.1 expressing cells. In contrast, the anti-inflammatory cytokine IL-4 slightly increased the KCa 3.1 current per cell, but as the membrane area also increased, there was no significant change in channel density. A large fraction of the microglia also expressed a voltage-dependent current sensitive to the KCa 1.1 modulators NS1619 and Paxilline and an inward-rectifying current with the characteristics of a Kir channel. The high functional expression of KCa 3.1 in microglia from epilepsy patients accentuates the need for further investigations of its role in neuropathological processes. GLIA 2016;64:2065-2078.

Increasing illness among people out of labor market - A Danish register-based study.

In spite of decades of very active labor market policies, 25% of Denmark's population in the working ages are still out-of-work. The aim of this study was to investigate whether that is due to consistent or even increasing prevalence of ill health. For the period of 2002-2011, we investigated if i) the prevalence of four chronic diseases (cardiovascular disease, diabetes, cancer and mental disorders) among those out-of-work had changed, ii) the occurrence of new cases of those diseases were higher among those who were already out-of-work, or iii) if non-health-related benefits were disproportionately given to individuals recently diagnosed with a disease compared to those without disease. The study was register-based and comprised all Danish residents aged 20-60. During the study period, the prevalence of cardiovascular diseases and mental disorders increased among both employed and non-employed people. The increased prevalence for mental disorder was particularly high among people receiving means-tested benefits. Disease incidence was higher among people outside rather than inside the labor market, especially for mental disorders. Employed people with incident diseases had an unsurprisingly increased risk of leaving the labor market. However, a high proportion of people with incident mental disorders received low level means-tested benefits in the three years following this diagnosis, which is concerning. Men treated for mental disorders in 2006 had high excess probability of receiving a cash-benefit, OR = 4.83 (4.53-5.14) for the period 2007-2010. The estimates were similar for women.

Are repeated assisted reproductive technology treatments and an unsuccessful outcome risk factors for unipolar depression in infertile women?

INTRODUCTION: Previous studies have shown conflicting results as to whether unsuccessful medically assisted reproduction is a risk factor for depression among women. This study therefore investigated if women with no live birth after assisted reproductive technology (ART) treatment had a higher risk of unipolar depression compared with women with a live birth after ART treatment. MATERIAL AND METHODS: The Danish National ART-Couple (DANAC) Cohort is a national register-based cohort study that consists of women who received ART treatment from 1 January 1994 to 30 September 2009, in Denmark (n = 41 050). Information on unipolar depression was obtained from the Danish Psychiatric Central Research Register. The analyses were conducted in Cox regression analysis. RESULTS: During the 308 494 person-years of follow up, 552 women were diagnosed with unipolar depression. A Cox proportional hazards model showed that women in ART treatment, with no live birth yet, had a lower risk of unipolar depression compared with women with a live birth. Women had the highest risk of unipolar depression 0-42 days after a live birth (adjusted hazard ratio 5.08, 95% CI 3.11-8.29) compared with women with no live birth. A lower, but still increased, risk of unipolar depression, was found in women 43 days to 1 year and >1 year after a live birth compared with women with no live birth yet. CONCLUSIONS: Motherhood is an important trigger of unipolar depression in women conceiving after ART treatment.

Assisted reproductive technology treatment in women with severe eating disorders: a national cohort study.

INTRODUCTION: This national retrospective cohort study investigates the prevalence of women with severe eating disorders in assisted reproductive technology (ART) treatment compared with an age-matched background population without ART treatment. It assesses the frequency distribution of the first and last eating disorder diagnosis before, during, and after ART treatment, and evaluates differences in obstetric outcomes between women with and without a severe eating disorder. MATERIAL AND METHODS: Hospital-diagnosed eating disorders among 42,915 women in the Danish National ART cohort (DANAC), registered during 1994-2009 in the mandatory Psychiatric Central Research Register, were compared with a non-eating disorder ART cohort of 42,644 women and an age-matched background population of 215,290 women without a history of ART treatment for the main outcome measures prevalence of eating disorders, frequency distribution of diagnoses before/during/after ART treatment, as well as ART treatment and obstetric outcomes. RESULTS: In the ART cohort, 271 women (0.63%) had an eating disorder diagnosis compared with 0.73% in the background population (p = 0.025). The prevalence of ovulatory disorder was significantly higher in women with a severe eating disorder compared with the ART cohort without eating disorders. Obstetric outcomes were similar in ART-treated women with and without an eating disorder. CONCLUSION: Women with severe eating disorders were identified in the ART cohort, although significantly less often than in the age-matched background population. Women with severe eating disorders suffered more often from anovulatory infertility than the ART comparison cohort without this disease. Obstetric outcomes appeared reassuring in the ART cohort with eating disorders.

NS19504: a novel BK channel activator with relaxing effect on bladder smooth muscle spontaneous phasic contractions.

Large-conductance Ca(2+)-activated K(+) channels (BK, KCa1.1, MaxiK) are important regulators of urinary bladder function and may be an attractive therapeutic target in bladder disorders. In this study, we established a high-throughput fluorometric imaging plate reader-based screening assay for BK channel activators and identified a small-molecule positive modulator, NS19504 (5-[(4-bromophenyl)methyl]-1,3-thiazol-2-amine), which activated the BK channel with an EC50 value of 11.0 ± 1.4 µM. Hit validation was performed using high-throughput electrophysiology (QPatch), and further characterization was achieved in manual whole-cell and inside-out patch-clamp studies in human embryonic kidney 293 cells expressing hBK channels: NS19504 caused distinct activation from a concentration of 0.3 and 10 µM NS19504 left-shifted the voltage activation curve by 60 mV. Furthermore, whole-cell recording showed that NS19504 activated BK channels in native smooth muscle cells from guinea pig urinary bladder. In guinea pig urinary bladder strips, NS19504 (1 µM) reduced spontaneous phasic contractions, an effect that was significantly inhibited by the specific BK channel blocker iberiotoxin. In contrast, NS19504 (1 µM) only modestly inhibited nerve-evoked contractions and had no effect on contractions induced by a high K(+) concentration consistent with a K(+) channel-mediated action. Collectively, these results show that NS19504 is a positive modulator of BK channels and provide support for the role of BK channels in urinary bladder function. The pharmacologic profile of NS19504 indicates that this compound may have the potential to reduce nonvoiding contractions associated with spontaneous bladder overactivity while having a minimal effect on normal voiding.

Assisted reproductive technology (ART) treatment in women with schizophrenia or related psychotic disorder: a national cohort study.

OBJECTIVES: To determine the prevalence rate of women with a diagnosis of schizophrenia or related psychotic disorder in assisted reproductive technology (ART) treatment and to study these women's fertility treatment outcome in comparison to women with no psychotic disorders. STUDY DESIGN: We used a national register-based cohort of 42,915 Danish women in ART treatment from 1.1.1994 to 30.9.2009. All women with a diagnosis of schizophrenia or related psychotic disorders before, during or after their ART treatment were identified by individual-level linkage of nationwide registers of ART treatment, psychiatric admission, birth and socio-demographic status. The comparison group (N=42,671) consisted of all women in the study cohort never diagnosed with psychotic disorders. Conventional descriptive methods were used for the statistical analyses. RESULTS: Two hundred and forty-four (0.6%) women in the study cohort received a diagnosis of psychotic disorder before (N=135-55.3%), during (N=7-2.9%) or after (N=102-41.8%) ART treatment. The mean time from last diagnosis of psychotic disorder to their first ART treatment in the 135 women with a psychiatric diagnosis prior to their first ART treatment was 7.1 ± 5.6 years (25-75% percentile: ±2.8-10.4 years). The most frequent diagnoses were acute and transient psychotic disorder. Women with a diagnosis of schizophrenia or related psychotic disorder before their first ART treatment had a lower ART treatment success rate as significantly fewer women obtained a live birth (40.0% vs. 51.9%, P<0.01). However, we found no statistical differences in perinatal outcomes for the children born by women in the study population and comparison group. CONCLUSIONS: The prevalence of women with a psychotic diagnosis in fertility treatment is lower than the prevalence in the general population. Women with a psychotic disorder prior to ART treatment have a lower fertility treatment success rate compared to women without psychotic disorder. Women with a psychotic disorder achieving delivery show similar obstetric outcomes to women with no psychotic disorder.

Addressing social inequality in aging by the Danish occupational social class measurement.

OBJECTIVE: To present the Danish Occupational Social Class (DOSC) measurement as a measure of socioeconomic position (SEP) applicable in a late midlife population, and to analyze associations of this measure with three aging-related outcomes in midlife, adjusting for education. METHOD: Systematic coding procedures of the DOSC measurement were applied to 7,084 participants from the Copenhagen Aging and Midlife Biobank (CAMB) survey. We examined the association of this measure of SEP with chronic conditions, self-rated health, and mobility in logistic regression analyses, adjusting for school education in the final analysis. RESULTS: The measure of SEP showed a strong social gradient along the social classes in terms of prevalence of chronic conditions, poor self-rated health, and mobility limitations. Adjusting for school education attenuated the association only to a minor degree. DISCUSSION: The DOSC measure was associated with aging-related outcomes in a midlife Danish population, and is, thus, well suited for future epidemiological research on social inequalities in health and aging.