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Pauline Warselius,1 Sven Cnattingius,1 Jiong Li,2 Dang Wei,3 Unnur Anna Valdimarsdottir,4,5 Kyriaki Kosidou,3,6 Johan Reutfors,1 Jørn Olsen,2,7 Mogens Vestergaard,8,9 Carsten Obel,8,9 Krisztina D László31Department of Medicine Solna, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden; 2Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark; 3Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden; 4Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; 5Faculty of Medicine, University of Iceland, Reykjavik, Iceland; 6Centre for Epidemiology and Community Medicine, Stockholm County’s Health Care District, Stockholm, Sweden; 7Department of Epidemiology, School of Public Health, University of California, Los Angeles, CA, USA; 8Department of Public Health, Aarhus University, Aarhus, Denmark; 9Research Unit and Section for General Practice, Department of Public Health, University of Aarhus, Aarhus, DenmarkPurpose: Postpartum psychosis is a rare but severe complication following childbirth, with unknown etiology. This study investigated whether the death of a close family member — a source of severe stress — the year before or during pregnancy was associated with an increased risk of psychotic illness in the postpartum period among women without and with a history of psychiatric disorder.Methods: We studied live births in Denmark during 1978–2008 and births in Sweden during 1973–2006 (n=5,246,978). Information on death of women’s relatives and partners and sociodemographic, health-, and pregnancy-related factors was obtained through linkage with nationwide registries.Results: The death of a close relative the year before or during pregnancy was not associated with psychotic illness during the first 90 days postpartum among women without (adjusted HR 1.02, 95% CI 0.76–1.37) or with a history of psychiatric disorder (HR 0.96, 95% CI 0.74–1.25). Similarly, there was no association between bereavement and risk of postpartum psychosis according to the timing of the loss (the year before or during pregnancy), the relative’s cause of death (natural or unnatural), or the woman’s relationship to the deceased (parent/sibling or partner/older child).Conclusions: Death of a close relative, one of the most severe sources of stress, before or during pregnancy was not associated with postpartum psychosis. Therefore, these data do not support the hypothesis that severely stressful life events, such as bereavement around the time of pregnancy, are associated with postpartum psychosis.Keywords: postpartum, psychosis, bereavement, stress, pregnancy, cohort study

Morten Fenger-Grøn,1,* Maiken Ina Siegismund Kjaersgaard,1,2,* Erik Thorlund Parner,2 Mai-Britt Guldin,1 Peter Vedsted,1 Mogens Vestergaard1 1Research Unit for General Practice and Section for General Medical Practice, Department of Public Health, Aarhus University, Aarhus, Denmark; 2Section for Biostatistics, Department of Public Health, Aarhus University, Aarhus, Denmark *These authors contributed equally to the work Purpose: Losing a loved one to death is a common and natural life-course experience. Still, bereavement has been associated with an increased risk of suicidal behavior and psychiatric hospitalization and little is known of how to counter these adverse events. We aimed to study the effect of early treatment in primary care with talk therapy (TT) or antidepressants (AD) in severely bereaved people.Methods: We conducted a population-based cohort study including 207,435 adult Danes who experienced a severe loss in 1996–2013. We compared treatment and no treatment with either of the two treatment regimens within 6 months after the loss. The main outcome was a serious mental health condition (defined as suicide, deliberate self-harm, or psychiatric hospitalization) occurring >6 months after bereavement. Adjusted risk differences (RDs) 2 years after bereavement were calculated using both standard regression analysis and instrumental variable analysis (IVA) in which estimated physician preferences for treatment served as instruments.Results: The standard adjusted regression analysis showed a higher risk of developing a serious mental health condition associated with both TT (RD, 7.1; 95% CI, 5.0 to 9.1 per 1000 people) and AD (RD, 30.1; 95% CI, 25.7 to 34.6 per 1000 people). The IVA, which was used to control for unmeasured confounding, showed that TT was associated with a lower risk of a serious mental health condition (RD, -17.1; 95% CI, -30.7 to -3.5 per 1000 people), whereas the results were inconclusive for AD (RD, -8.6; 95% CI, -62.6 to 45.4 per 1000 people).Conclusion: This study suggests that early treatment with TT is associated with reduced long-term risk of serious mental health conditions in severely bereaved people. No clear benefit or harm of treatment with AD after bereavement was ascertained since the statistical precision was low. Keywords: bereavement, loss, suicide, self-harm, practice variation

Anne Mette Lund Würtz,1,2 Claus Høstrup Vestergaard,1 Dorte Rytter,2 Merete Juul Sørensen,3 Jakob Christensen,4 Mogens Vestergaard,1,5 Bodil Hammer Bech1,2 1Research Unit for General Practice, 2Section for Epidemiology, Department of Public Health, Aarhus University, 3Regional Centre for Child and Adolescent Psychiatry, 4Department of Neurology, Aarhus University Hospital, 5Section for General Practice, Department of Public Health, Aarhus University, Aarhus, Denmark Background: Antipsychotic (AP) medication is increasingly used for many health conditions. Prenatal exposure to AP medication has been associated with several adverse outcomes, but the findings remain inconsistent.Purpose: We aimed to investigate prenatal exposure to AP medication and the use of primary health care system in childhood.Subjects and methods: All live-born singletons in Denmark during 1997–2012 were identified in the nationwide Danish National Patient Register and followed until December 31, 2013 (n = 963,010). Information on prenatal exposure to AP medication was obtained from the Danish Register of Medicinal Product Statistics. Contacts to the general practitioner (GP) were used as a proxy for the overall health of the children. Negative binomial regression was used to calculate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the association between prenatal exposure to AP medication and number and type of GP contacts, excluding routine well-child visits and vaccinations. The models were adjusted for sex and birth date of the child, maternal age, parity, cohabitation status, income, education, smoking status, diagnosis of substance abuse, severe psychiatric disorder, depression and epilepsy as well as the use of antiepileptic drugs, antidepressants, benzodiazepines and insulin.Results: The prenatally AP-exposed children had 7% more GP contacts than unexposed children, IRR: 1.07 (95% CI: 1.03, 1.11). The association was slightly stronger among children of mothers with no diagnosis of severe psychiatric disorder (IRR: 1.08, 95% CI: 1.04–1.13) than among children of mothers with severe psychiatric disorder (IRR: 1.03, 95% CI: 0.96–1.11), but the difference was not statistically significant. We found no difference between prenatally AP-exposed children and their unexposed siblings, IRR: 1.00 (95% CI: 0.97–1.04) for total contacts.Conclusion: Children of women using AP medication in pregnancy had more GP contacts in childhood than children of mothers not using AP medication. However, this might be explained by confounding from maternal behavior and mental illness. Keywords: antipsychotic medication, prenatal drug exposure, primary health care, general practitioner

Tina Hovgaard Lützen,1 Bodil Hammer Bech,2 Jesper Mehlsen,3 Claus Høstrup Vestergaard,1 Lene Wulff Krogsgaard,1 Jørn Olsen,4 Mogens Vestergaard,1 Oleguer Plana-Ripoll,5 Dorte Rytter2 1Research Unit for General Practice, Department of Public Health, Aarhus University, Aarhus C, Denmark; 2Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus C, Denmark; 3Coordinating Research Centre, Frederiksberg Hospital, Frederiksberg, Denmark, 4Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark; 5National Center for Register-based Research, Aarhus University, Aarhus V, Denmark Aim: No association between human papilloma virus (HPV) vaccination and numerous diseases has been found. Still, a large number of Danish women are reporting suspected adverse events. Other factors may play a role, and the aim of this study is to examine the association between psychiatric conditions, general practitioner (GP) attendance and indicators of psychological symptoms prior to HPV vaccination and the risk of referral to an HPV center following vaccination. Study design and setting: Register-based, matched case–control study. Cases were identified from five Danish, regional HPV centers, and health data for cases and controls were obtained from national registries. Participants: Cases were defined as women referred to an HPV center between January 1, 2015 and December 31, 2015 (n=1,496). Each case was matched with five controls on age, region and time of first vaccine registration. The total study population consisted of 8,976 women. Results: Overall, women above 18 years who had been referred to an HPV center were more likely to have used psychiatric medication (odds ratio [OR]: 1.88 [95% CI 1.48–2.40]) or to have been hospitalized because of a psychiatric disorder within 5 years prior to the first vaccine registration (OR: 2.13 [95% CI 1.59–2.86]). Specifically, referred women were more likely to have used antipsychotics, antidepressants, attention deficit hyperactivity disorder (ADHD) medication or anxiolytics, and to have been hospitalized for affective disorders or anxiety, but not to have been hospitalized for schizoid, ADHD or eating disorders. In addition, they were more likely to have had talk therapy or psychometric test performed prior to vaccination (OR: 1.72 [95% CI 0.1.35–2.18] and OR: 1.67 [95% CI 1.30–2.13], respectively). Referred women of all ages had higher use of GP before vaccination. Population attributable fraction analyses indicated that psychiatric medication, hospitalization due to a psychiatric disorder and use of talk therapy, or psychometric test “explained” 13%, 10%, 12% and 11% of the referrals, respectively. Results did not change substantially when adjusted for potential confounders. Conclusion: Women referred to HPV centers because of suspected adverse events after vaccination more often had preexisting psychiatric conditions, psychological symptoms or frequent GP attendance prior to HPV vaccination. Keywords: papillomavirus vaccines, adverse drug events, psychoactive drugs, general practice

Marie Germund Nielsen,1 Eva Ørnbøl,2 Per Bech,3 Mogens Vestergaard,1,4 Kaj Sparle Christensen1 1Research Unit for General Practice, Department of Public Health, Aarhus University, 2Research Clinic for Functional Disorders and Psychosomatics, Aarhus University Hospital, Aarhus, 3Psychiatric Research Unit, Psychiatric Centre North Zealand, University Hospital of Copenhagen, Hillerød, 4Section for General Medical Practice, Department of Public Health, Aarhus University, Aarhus, Denmark Background: The Major Depression Inventory (MDI) is widely used in Danish general practice as a screening tool to assess depression in symptomatic patients. Nevertheless, no validation studies of the MDI have been performed. The aim of this study was to validate the web-based version of the MDI against a fully structured telephone interview in a population selected on clinical suspicion of depression (ie, presence of two or three core symptoms of depression) in general practice.Materials and methods: General practitioners (GPs) invited consecutive persons suspected of depression to complete the web-based MDI in a primary care setting. The validation was based on the Munich-Composite International Diagnostic Interview (M-CIDI) by phone. GPs in the 22 practices in our study included 132 persons suspected of depression. Depression was rated as yes/no according to the MDI and M-CIDI. Sensitivity, specificity, and positive predictive value of the International Classification of Diseases, Tenth Revision (ICD-10) algorithms of the MDI were examined.Results: According to the M-CIDI interview, 87.9% of the included population was depressed and 64.4% was severely depressed. According to the MDI scale, 59.1% of the population was depressed and 31.8% was severely depressed. The sensitivity of the MDI for depression was 62.1% (95% confidence interval [95% CI]: 52.6–70.9) and the specificity was 62.5% (95% CI: 35.4–84.8). The sensitivity for severe depression was 42.2% (95% CI: 30.6–52.4) and the specificity was 85.1% (95% CI: 71.7–93.8). The receiver operating curve showed an area under the curve of 0.66 (95% CI: 0.52–0.81) for any depression and of 0.72 (95% CI: 0.63–0.81) for severe depression.Conclusion: The MDI is a conservative instrument for diagnosing ICD-10 depression in a clinical setting compared to the M-CIDI interview. Only a few false-positive diagnoses were identified when the MDI was used on clinical suspicion of depression. Keywords: Major Depression Inventory, depression, criterion validity, M-CIDI interview, diagnosing

Nikoline Lund Jensen,1,2 Henrik Søndergaard Pedersen,1 Mogens Vestergaard,1,2 Stewart W Mercer,3 Charlotte Glümer,4 Anders Prior,1,2 1Research Unit for General Practice, 2Section for General Medical Practice, Department of Public Health, Aarhus University, Aarhus, Denmark; 3General Practice and Primary Care, Institute of Health and Wellbeing, University of Glasgow, Glasgow, Scotland; 4Research Centre for Prevention and Health, The Capital Region of Denmark, Glostrup, Denmark Objective: Multimorbidity (MM) is more prevalent among people of lower socioeconomic status (SES), and both MM and SES are associated with higher mortality rates. However, little is known about the relationship between SES, MM, and mortality. This study investigates the association between educational level and mortality, and to what extent MM modifies this association. Methods: We followed 239,547 individuals invited to participate in the Danish National Health Survey 2010 (mean follow-up time: 3.8 years). MM was assessed by using information on drug prescriptions and diagnoses for 39 long-term conditions. Data on educational level were provided by Statistics Denmark. Date of death was obtained from the Civil Registration System. Information on lifestyle factors and quality of life was collected from the survey. The main outcomes were overall and premature mortality (death before the age of 75). Results: Of a total of 12,480 deaths, 6,607 (9.5%) were of people with low educational level (LEL) and 1,272 (2.3%) were of people with high educational level (HEL). The mortality rate was higher among people with LEL compared with HEL in groups of people with 0–1 disease (hazard ratio: 2.26, 95% confidence interval: 2.00–2.55) and ≥4 diseases (hazard ratio: 1.14, 95% confidence interval: 1.04–1.24), respectively (adjusted model). The absolute number of deaths was six times higher among people with LEL than those with HEL in those with ≥4 diseases. The 1-year cumulative mortality proportions for overall death in those with ≥4 diseases was 5.59% for people with HEL versus 7.27% for people with LEL, and 1-year cumulative mortality proportions for premature death was 2.93% for people with HEL versus 4.04% for people with LEL. Adjusting for potential mediating factors such as lifestyle and quality of life eliminated the statistical association between educational level and mortality in people with MM. Conclusion: Our study suggests that LEL is associated with higher overall and premature mortality and that the association is affected by MM, lifestyle factors, and quality of life. Keywords: multimorbidity, socioeconomic status, social epidemiology, inequality in health, mortality, population-based cohort study

Maiken Ina Siegismund Kjaersgaard,1 Peter Vedsted,2 Erik Thorlund Parner,1 Bodil Hammer Bech,3 Mogens Vestergaard,2,4 Kaare Rud Flarup,2 Morten Fenger-Grøn,2 1Section for Biostatistics, 2Research Unit for General Practice, 3Section for Epidemiology, 4Section for General Medical Practice, Department of Public Health, Aarhus University, Aarhus, Denmark Background: The patient list system in Denmark assigns virtually all residents to a general practice. Nevertheless, historical information on this link between patient and general practice is not readily available for research purposes. Objectives: To develop, implement, and evaluate the performance of an algorithm linking individual patients to their general practice by using information from the Danish National Health Service Register and the Danish Civil Registration System. Materials and methods: The National Health Service Register contains information on all services provided by general practitioners from 1990 and onward. On the basis of these data and information on migration history and death obtained from the Civil Registration System, we developed an algorithm that allocated patients to a general practice on a monthly basis. We evaluated the performance of the algorithm between 2002 and 2007. During this time period, we had access to information on the link between patients and general practices. Agreement was assessed by the proportion of months for which the algorithm allocated patients to the correct general practice. We also assessed the proportion of all patients in the patient list system for which the algorithm was able to suggest an allocation. Results: The overall agreement between algorithm and patient lists was 98.6%. We found slightly higher agreement for women (98.8%) than for men (98.4%) and lower agreement in the age group 18–34 years (97.1%) compared to all other age groups (≥98.6%). The algorithm had assigned 83% of all patients in the patient list system after 1 year of follow-up, 91% after 2 years of follow-up, and peaked at 94% during the fourth year. Conclusion: We developed an algorithm that enables valid and nearly complete linkage between patients and general practices. The algorithm performs better in subgroups of patients with high health care needs. The algorithm constitutes a valuable tool for primary health care research. Keywords: general practice, medical record linkage, patient list, primary care, registers

Søren Pauli Bro,1 Maiken Ina Siegismund Kjaersgaard,2 Erik Thorlund Parner,2 Merete Juul Sørensen,3 Jørn Olsen,4 Bodil Hammer Bech,4 Lars Henning Pedersen,4,5 Jakob Christensen,6,7 Mogens Vestergaard11Research Unit and Section for General Practice, Department of Public Health, 2Section for Biostatistics, Department of Public Health, Aarhus University, 3Regional Center for Child and Adolescent Psychiatry, Aarhus University Hospital, 4Section for Epidemiology, Department of Public Health, 5Department of Clinical Medicine – Obstetrics and Gynecology, Aarhus University, 6Department of Clinical Pharmacology, 7Department of Neurology, Aarhus University Hospital, Aarhus, DenmarkObjective: To determine if prenatal exposure to methylphenidate (MPH) or atomoxetine (ATX) increases the risk of adverse pregnancy outcomes in women with attention deficit/hyperactivity disorder (ADHD).Materials and methods: This was a population-based cohort study of all pregnancies in Denmark from 1997 to 2008. Information on use of ADHD medication, ADHD diagnosis, and pregnancy outcomes was obtained from nationwide registers.Results: We identified 989,932 pregnancies, in which 186 (0.02%) women used MPH/ATX and 275 (0.03%) women had been diagnosed with ADHD but who did not take MPH/ATX. Our reference pregnancies had no exposure to MPH/ATX and no ADHD diagnosis. Exposure to MPH/ATX was associated with an increased risk of spontaneous abortion (SA; ie, death of an embryo or fetus in the first 22 weeks of gestation) (adjusted relative risk [aRR] 1.55, 95% confidence interval [CI] 1.03–2.36). The risk of SA was also increased in pregnancies where the mother had ADHD but did not use MPH/ATX (aRR 1.56, 95% CI 1.11–2.20). The aRR of Apgar scores

Merete Juul Sørensen,1 Therese Koops Grønborg,2 Jakob Christensen,3,4 Erik Thorlund Parner,2 Mogens Vestergaard,5,6 Diana Schendel,7 Lars Henning Pedersen8,9 1Regional Centre of Child and Adolescent Psychiatry, Aarhus University Hospital, Risskov, Denmark; 2Department of Public Health, Section of Biostatistics, Aarhus University, Aarhus, Denmark; 3Department of Neurology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Clinical Pharmacology, 5Department of Public Health, Section of General Practice, 6Research unit for General Practice, Aarhus University, Aarhus, Denmark; 7Centers for Disease Control and Prevention, Atlanta, GA, USA; 8Danish Epidemiological Science Centre, Institute of Public Health, 9Department of Obstetrics and Gynecology, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark Background: Both the use of antidepressant medication during pregnancy and the prevalence of autism spectrum disorder have increased during recent years. A causal link has recently been suggested, but the association may be confounded by the underlying indication for antidepressant use. We investigated the association between maternal use of antidepressant medication in pregnancy and autism, controlling for potential confounding factors. Methods: We identified all children born alive in Denmark 1996–2006 (n=668,468) and their parents in the Danish Civil Registration System. We obtained information on the mother's prescriptions filled during pregnancy from the Danish National Prescription Registry, and on diagnoses of autism spectrum disorders in the children and diagnoses of psychiatric disorders in the parents from the Danish Psychiatric Central Register. In a cohort analysis, we estimated hazard ratios of autism spectrum disorders in children exposed to antidepressant medication during pregnancy compared with children who were not exposed, using Cox proportional hazards regression analysis. Furthermore, we estimated the risk for autism spectrum disorder in a sibling design. Results: Children exposed prenatally to antidepressants had an adjusted hazard ratio of 1.5 (95% confidence interval [CI] 1.2–1.9) for autism spectrum disorder compared with unexposed children. Restricting the analysis to children of women with a diagnosis of affective disorder, the adjusted hazard ratio was 1.2 (95% CI 0.7–2.1), and the risk was further reduced when exposed children were compared with their unexposed siblings (adjusted hazard ratio 1.1; 95% CI 0.5–2.3). Conclusion: After controlling for important confounding factors, there was no significant association between prenatal exposure to antidepressant medication and autism spectrum disorders in the offspring. Keywords: antidepressants, depression; autism, autism spectrum disorder, childhood autism, pregnancy

Mrk 590 is a known changing-look active galactic nuclei (AGNs) which almost turned off in 2012, and then in 2017 partially re-ignited into a repeat flaring state, unusual for an AGN. Our Swift observations since 2013 allow us to characterize the accretion-generated emission and its reprocessing in the central engine of a changing-look AGN. The X-ray and UV variability amplitudes are higher than those typically observed in 'steady-state' AGN at similar moderate accretion rates; instead, the variability is similar to that of highly accreting AGN. The unusually strong X-ray to UV correlation suggests that the UV-emitting region is directly illuminated by X-ray outbursts. We find evidence that the X-rays are reprocessed by two UV components, with the dominant one at ∼3 d and a faint additional reprocessor at near-zero lag. However, we exclude a significant contribution from diffuse broad line region continuum, known to contribute for bonafide AGN. A near-zero lag is expected for a standard 'lamp-post' disc reprocessing model with a driving continuum source near the black hole. That the overall UV response is dominated by the ∼3-d lagged component suggests a complicated reprocessing geometry, with most of the UV continuum not produced in a compact disc, as also found in recent studies of NGC 5548 and NGC 4151. None the less, the observed flares display characteristic time-scales of ∼100 rest-frame days, consistent with the expected thermal time-scale in an accretion disc. [ABSTRACT FROM AUTHOR]

Prepubertal Friesian heifer calves (n = 24, initial BW = 195[+ or -]5 kg) were assigned to a 2 x 2 factorial block design and used to evaluate the effects of daily GH treatment (0 or 15 mg/d) at either a low or a high feeding level in a 5-wk treatment period on endocrine measurements, hormone receptors, muscle growth, and overall performance. In the pretreatment period, a low feeding level was employed for all calves. During the treatment period, animals at the low feeding level had free access to a roughage-based mixture, whereas animals at the high feeding level had free access to a concentrate mixture and were offered 2 kg/ d of the roughage-based mixture. Blood samples were collected weekly starting 3 wk before treatment. Longissimus (LM) and supraspinatus (SS) muscles were obtained at slaughter. Metabolizable energy intake was 81% higher, digestible CP intake was 140% higher, and ADG was 115% higher (all P < 0.001) at the high vs. low feeding level. Feed (DMI, ME, and protein) intake was not affected by GH treatment, but ADG was 18% higher (P < 0.13) in GH-treated than in control heifers at both feeding levels. Although of different magnitudes, the muscle anabolic effects of GH treatment and high vs. low feeding level were additive, and both treatments increased carcass weights (P Key Words: Binding Proteins, Biochemical Receptors, Heifers, Insulin-Like Growth Factor, Plane of Nutrition, Somatotropin

We present a dynamical study of the narrow-line regions in two nearby type 2 quasars (QSO2s). We construct dynamical models based on detailed photoionization models of the emission-line gas, including the effects of internal dust, to apply to observations of large-scale outflows from these active galactic nuclei (AGNs). We use Mrk 477 and Mrk 34 in order to test our models against recent Hubble Space Telescope (HST) Space Telescope Imaging Spectrograph (STIS) observations of [O  iii ] emission-line kinematics, since these AGNs possess more energetic outflows than found in Seyfert galaxies. We find that the outflows within 500 pc are consistent with radiative acceleration of dusty gas, however the outflows in Mrk 34 are significantly more extended and may not be directly accelerated by radiation. We characterize the properties of X-ray winds found from the expansion of [O  iii ]-emitting gas close to the black hole. We show that such winds possess the kinetic energy density to disturb [O  iii ] gas at ∼1.8 kpc, and have sufficient energy to entrain the [O  iii ] clouds at ∼1.2 kpc. Assuming that the X-ray wind possesses the same radial mass distribution as the [O  iii ] gas, we find that the peak kinetic luminosity for this wind is 2 per cent of Mrk 34's bolometric luminosity, which is in the 0.5–5 per cent range required by some models for efficient feedback. Our work shows that, although the kinetic luminosity as measured from [O  iii ]-emitting gas is frequently low, X-ray winds may provide more than one order of magnitude higher kinetic power. [ABSTRACT FROM AUTHOR]

Summary: Background: Psychological stress may reduce cellular immunity, but its role in triggering latent infections, including herpes zoster (HZ), is controversial. Objectives: To examine the association between perceived psychological stress and risk of HZ. Methods: In a linked registry‐based cohort study, we followed 77 310 persons aged 40 years or older who participated in the 2010 Danish National Health Survey from 1 May 2010 until HZ diagnosis, death, emigration or 1 July 2014, whichever occurred first. We computed hazard ratios (HRs) of HZ associated with Cohen's Perceived Stress Scale (PSS) score (range 0–40) using Cox regression with age as the timescale, adjusted for sex, immunosuppressive and selected chronic conditions, immunosuppressive drugs, and sociodemographic, lifestyle and anthropometric factors. The PSS measures chronic stress perceived by an individual in response to various demands of daily life. We modelled the PSS score using quintiles and a restricted cubic spline function. Results: The unadjusted rate of HZ varied from 5·53 to 7·20 per 1000 person‐years from the lowest to the highest PSS score quintile. Compared with the lowest PSS score quintile, the adjusted HR for HZ was 1·00 [95% confidence interval (CI) 0·86–1·16], 1·08 (95% CI 0·92–1·26), 1·05 (95% CI 0·90–1·23) and 1·14 (95% CI 0·97–1·34) for the second to the fifth quintile, respectively. In cubic spline analyses, PSS scores < 20 were not associated with increased HR of HZ, but thereafter the HR increased linearly from 1·10 (95% CI 0·85–1·41) to 2·22 (95% CI 1·32–3·75). Conclusions: Our study indicated that high levels of psychological stress are associated with increased risk of HZ. What is already known about this topic? Psychological stress may reduce cellular immunity, but its role in triggering latent infections, such as herpes zoster (HZ), is controversial.Previous epidemiological studies have mainly focused on the effects of negative life events (e.g. bereavement) on HZ risk, and dose–response analyses are lacking.It is possible that the allostatic load (the cumulative 'wear and tear' on the body associated with stress) depends on the type of stress and coping mechanisms. What does this study add? In this large population‐based cohort study, we found that persons reporting the highest levels of perceived psychological stress in daily life had an increased risk of HZ.Perceived psychological stress may be a modifiable risk factor for HZ.Our study adds HZ to the growing list of potential negative health consequences of psychological stress and underscores the importance of supporting mental wellbeing and resilience in the general population. Linked Comment: A.W.M. Evers and S. van Beugen. Br J Dermatol 2021; 185:12–13. [ABSTRACT FROM AUTHOR]

We derive a distance of D = 16.6 ± 0.3 Mpc (μ = 31.10 ± 0.04 mag) to the archetypal narrow-line Seyfert 1 galaxy NGC 4051 based on Cepheid period–luminosity relations and new Hubble Space Telescope multiband imaging. We identify 419 Cepheid candidates and estimate the distance at both optical and near-infrared wavelengths using subsamples of precisely photometered variables (123 and 47 in the optical and near-infrared subsamples, respectively). We compare our independent photometric procedures and distance-estimation methods to those used by the Supernovae, H0, for the Equation of State team and find agreement to 0.01 mag. The distance we obtain suggests an Eddington ratio of for NGC 4051, typical of narrow-line Seyfert 1 galaxies, unlike the seemingly odd value implied by previous distance estimates. We derive a peculiar velocity of −490 ± 34 km s−1 for NGC 4051, consistent with the overall motion of the Ursa Major Cluster in which it resides. We also revisit the energetics of the NGC 4051 nucleus, including its outflow and mass accretion rates. [ABSTRACT FROM AUTHOR]