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Vera Ehrenstein,1 Rohini K Hernandez,2 Merete Lund Maegbaek,1 Johnny Kahlert,1 Mary Nguyen-Nielsen,1 Mette Nørgaard,1 Alexander Liede2 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Center for Observational Research, Amgen, Thousand Oaks, CA, USA Objective: Among patients with prostate cancer, diagnostic codes for bone metastases in the Danish National Registry of Patients have a sensitivity of 44%. In an attempt to improve the sensitivity of registry-based identification of metastases from prostate cancer, we tested a series of algorithms, combining elevated prostate-specific antigen (PSA) levels, use of antiresorptive therapy, and performed bone scintigraphy. Patients and methods: We randomly selected 212 men diagnosed with prostate cancer in 2005–2010 in the Central Denmark Region with prespecified PSA values, antiresorptive therapy, and bone scintigraphy who did not have a registry-based diagnostic code indicating presence of distant metastases. We defined three candidate algorithms for bone metastases: 1) PSA >50 µg/L and bone scintigraphy, 2) PSA >50 µg/L and antiresorptive therapy, and 3) PSA ≤50 µg/L with antiresorptive therapy or bone scintigraphy. An algorithm for distant metastasis site other than bone was defined as PSA >50 µg/L alone. Medical chart review was used as the reference standard to establish the presence or absence of metastases. Validity was expressed as a positive predictive value (PPV) or a negative predictive value, based on whether the algorithms correctly classified metastases compared with the reference standard. Results: We identified 113 men with evidence of metastases according to the candidate algorithms, and 99 men without evidence of metastases according to the candidate algorithm. The PPVs of PSA >50 µg/L were 0.10 (95% confidence interval [CI] 0.04–0.19) for bone metastases and 0.14 (95% CI 0.07–0.24) for nonbone metastases, regardless of receipt of antiresorptive therapy or presence of bone scintigraphy. The PPVs for any metastases were 0.16 (95% CI 0.06–0.32) for PSA >50 µg/L and 0.28 (95% CI 0.14–0.47) for PSA >50 µg/L with bone scintigraphy. Adding antiresorptive treatment to the algorithm did not improve PPV. All negative predictive values approached 1.00. Conclusion: Algorithms based on elevated PSA, antiresorptive therapy, or bone scintigraphy are not suitable for supplementing diagnostic codes to identify additional cases of distant metastases among men with prostate cancer. However, it is possible that in this setting, medical chart review is not a gold standard to identify metastases. Keywords: algorithm, bone metastases, prostate-specific antigen, validation, Danish databases

Sigrun Alba Johannesdottir, Merete Lund Mægbæk, Jens Georg Hansen, Timothy L Lash, Lars Pedersen, Vera EhrensteinDepartment of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, DenmarkAbstract: Epidemiologic studies often rely on drug dispensation records to measure medication intake. We aimed to estimate correspondence between general practitioner (GP)-reported treatment and timing of prescription dispensation. From seven GPs in northern Denmark, we obtained 317 prescription records for 286 patients treated with ten commonly prescribed medication types for chronic diseases. We linked the GP-reported information to the regional prescription database to retrieve patients’ prescription records both prospectively and retrospectively in relation to the GP-reported date of treatment (index date, August 20, 2008 for all patients). We computed overall and medication-specific correspondence between GP-reported treatment and the timing of dispensation. We computed correspondence based on both exact medication and therapeutic subgroup agreement. The correspondence for dispensation within ±90 days of GP-reported treatment was 0.81 (95% confidence interval = 0.76–0.85) with variation by medication type, ranging from 0.55 for ACE-inhibitors to 1.00 for oral glucose-lowering agents. The correspondence was greater when analyzed within therapeutic groups than when analyzed for exact medications within these groups.Keywords: pharmacoepidemiology, predictive value, drug prescriptions, primary health care

Background: We quantified relative and absolute risks of postpartum psychiatric episodes (PPE) following risk factors: Young age, past personal or family history of psychiatric disorders, and genetic liability., Methods: We conducted a register-based study using the iPSYCH2012 case-cohort sample. Exposures were personal history of psychiatric episodes prior to childbirth, being a young mother (giving birth before the age of 21.5 years), having a family history of psychiatric disorders, and a high (highest quartile) polygenic score (PGS) for major depression. PPE was defined within 12 months postpartum by prescription of psychotropic medication or in- and outpatient contact to a psychiatric facility. We included primiparous women born 1981-1999, giving birth before January 1st, 2016. We conducted Cox regression to calculate hazard ratios (HRs) of PPE, absolute risks were calculated using cumulative incidence functions., Results: We included 8174 primiparous women, and the estimated baseline PPE risk was 6.9% (95% CI 6.0%-7.8%, number of PPE cases: 2169). For young mothers with a personal and family history of psychiatric disorders, the absolute risk of PPE was 21.6% (95% CI 15.9%-27.8%). Adding information on high genetic liability to depression, the risk increased to 29.2% (95% CI 21.3%-38.4%) for PPE., Conclusions: Information on prior personal and family psychiatric episodes as well as age may assist in estimating a personalized risk of PPE. Furthermore, additional information on genetic liability could add even further to this risk assessment., (© 2023 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Background: Personal and family history of psychiatric disorders are key risk factors for postpartum depression (PPD), yet their combined contribution has been understudied., Objective: To examine personal and family psychiatric history, alone and combined, and their effect on absolute risk and relative risk (RR) of mild/moderate or severe PPD., Methods: In this cohort study, we used data from 142 064 childbirths with PPD screenings from 2015 to 2021 merged with population registers. Exposures were personal and family psychiatric history defined as a psychiatric hospital contact or psychotropic prescription fills by index mothers and their parents prior to delivery. Outcomes were mild/moderate PPD (Edinburgh Postnatal Depression Scale, cut-off: ≥11 within 12 weeks post partum) and severe PPD (antidepressant fill or depression diagnosis within 6 months post partum). We calculated absolute risks and RRs using Poisson regression models adjusted for parity, education, maternal age, and calendar year., Findings: Of the 142 064 participants, 23.4% had no psychiatric history, 47.4% had only family history, 6.0% had only personal history, and 23.2% had both. The latter group had the highest risk of PPD: absolute risk of mild/moderate PPD was 11.7% (95% CI 11.5%; 11.8%), and adjusted RR: 2.35 (95% CI 2.22; 2.49). Alone, personal psychiatric history was the most potent risk factor. Dose-response relationship based on severity of personal and family psychiatric history was found., Discussion: Our study documents a substantial association between personal and family psychiatric history and PPD risk., Clinical Implications: Evaluating combinations of risk factors is important to improve risk assessment., Competing Interests: Competing interests: KBM has received a speaker fee from Medice Nordic within the last 3 years. TM-O has received a speaker fee from Lundbeck within the last 3 years., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. Published by BMJ.)

Background: Little is known about the time trends of postpartum depression (PPD) and whether they differ from time trends of depression among women in general., Methods: Using Danish health registers, we identified a postpartum population from all women who had a liveborn child from 2000-2022. We sampled a background population by matching five women for each delivery on age and date of childbirth. Depression and PPD were measured as incident depression diagnosis or redeemed antidepressant prescription within 180 days from childbirth/matching. We described incidence rates from 2000-2022 using Poisson regression with a restricted cubic spline., Results: The study population included 1,133,947 postpartum women (669,101 unique), matched to 5,669,735 women (1,165,505 unique). Overall IR per 10,000 person-years of diagnoses was 34.3 (95% CI: 32.8-35.9) for PPD and 18.9 (95% CI: 18.3-19.4) for depression. Both IRs increased similarly over time in the main analyses, but more pronounced for PPD in primiparous and older mothers. Correspondingly, IR for prescriptions was 135.7 (95% CI: 132.7-138.8) for PPD and 209.8 (95% CI: 208.1-211.5) for depression, and both groups had fluctuating time trends., Limitations: Depression measures were based on women who actively sought and received treatment, expectedly underestimating true disease incidence., Conclusions: Incidence rates of PPD and depression diagnoses increased over time, especially for PPD among primiparous and older mothers. These findings could suggest either increased vulnerability or increased awareness and detection over time in these groups. Fluctuating trends overserved from prescriptions could likely be driven by external factors and not a reflection of disease trends., Competing Interests: Declaration of competing interest Trine Munk-Olsen has received honorarium as a speaker for Lundbeck Pharma A/S. Remaining authors: Nothing to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The HOPE cohort is a Danish nationwide cohort with ongoing follow-up, holding information on postpartum depression (PPD) symptoms and diagnoses on 170,218 childbirths (142,795 unique mothers). These data have been linked with extensive register data on health and socioeconomic information on the mothers, their partners, parents, and children. This cohort profile aimed to provide an overview of the data collection and content, describe characteristics, and evaluate potential selection bias. PPD screenings, using the Edinburgh Postnatal Depression Scale, were collected from 67 of the 98 Danish municipalities, covering the period January 2015 to December 2021. This data was linked with register data on PPD diagnoses (identified through medication prescriptions and hospital contacts) as well as background information. Cohort characteristics were compared to the source population, defined as all childbirths by women residing in Denmark during the same period (452,207 childbirths). Potential selection bias was evaluated by comparing odds ratios of five well-established associations between the cohort and the source population. The HOPE cohort holds information on 170,218 childbirths (38% of the source population) involving 142,795 unique mothers. The HOPE cohort only differed slightly from the source population on most characteristics examined, but larger differences were observed on specific characteristics with an underrepresentation of the youngest and oldest age groups, women with more than three children or twins/triplets, and women born outside Denmark. Similar associations were identified across the two populations within the five well-established associations. There was no indication of selection bias on the five examined associations, and the HOPE cohort is representative of the source population on important perinatal characteristics., (© 2024. The Author(s).)

Objective: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD., Method: Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)-based heritability ([Formula: see text]), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system., Results: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The [Formula: see text] of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD., Conclusions: While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone)., Competing Interests: Dr. Choi has received an honorarium from Depression and Anxiety for service as Deputy Editor. Dr. Raffield has served as a consultant for the TOPMed Administrative Coordinating Center (through Westat). Dr. Andreassen has received speaking honoraria from Janssen, Lundbeck, and Sunovion, and he has served as a consultant for Cortechs.ai and HealthLytix. Dr. Frey has received research support from MediPharm and Janssen. Dr. Grigoriadis has received royalties from the Canadian Pharmacists Association, Norton, and UpToDate. Dr. Jones has received grant funding from Takeda and Akrivia health. Dr. Kennedy has served as a scientific advisory board member for Myriad Neuroscience. Dr. McIntosh has served as a speaker for Illumina and Janssen. Dr. Munk-Olsen has served as a speaker for Lundbeck. Dr. Rubinow has received research funding from the Buszucki Foundation, NIH, and Sage Therapeutics; he serves on scientific advisory boards for the Foundation of Hope, Sage Therapeutics, and Sensorium Therapeutics and on clinical advisory boards for EmbarkNeuro and Felicity Pharma; he has served as a consultant for Aldeyra Therapeutics, Arrivo Bioventures, Brii Biosciences, and GH Research–Ireland; and he has stock options from Sage Therapeutics and Sensorium Therapeutics. Dr. Skalkidou has served as a consultant for Biogen; she receives compensation for lectures and organization of courses in reproductive endocrinology; and she is a shareholder and serves on the board of Svensk Telepsykiatri. Dr. Smoller has served on a scientific advisory board for Sensorium Therapeutics; he has received grant support from Biogen; and he is principal investigator of a collaborative study of the genetics of depression and bipolar disorder sponsored by 23andMe, for which 23andMe provides analysis time as in-kind support but no payments. Dr. Stein has received personal fees from Discovery Vitality, Johnson & Johnson, Kanna, L'Oreal, Lundbeck, Orion, Sanofi, Servier, Takeda, and Vistagen. Dr. Stowe has served on scientific advisory boards for Sage Therapeutics and Reunion Neuroscience. Dr. Taylor has given a lecture for AbbVie. Dr. Vigod has received royalties from UpToDate. Dr. Zar has received funding from the Bill and Melinda Gates Foundation. Dr. Meltzer-Brody has received sponsored research grant funding from Sage Therapeutics; she has served as a consultant for EmbarkNeuro and the Neuroscience Education Institute; and she serves as a professional corporation owner for Modern Health. Dr. Sullivan has served as an adviser for, and is a shareholder in, Neumora Therapeutics. The other authors report no financial relationships with commercial interests.

It remains inconclusive whether postpartum depression (PPD) and depression with onset outside the postpartum period (MDD) are genetically distinct disorders. We aimed to investigate whether polygenic risk scores (PGSs) for major mental disorders differ between PPD cases and MDD cases in a nested case-control study of 50,057 women born from 1981 to 1997 in the iPSYCH2015 sample in Demark. We identified 333 women with first-onset postpartum depression (PPD group), who were matched with 993 women with first-onset depression diagnosed outside of postpartum (MDD group), and 999 female population controls. Data on genetics and depressive disorders were retrieved from neonatal biobanks and the Psychiatric Central Research Register. PGSs were calculated from both individual-level genetic data and meta-analysis summary statistics from the Psychiatric Genomics Consortium. Conditional logistic regression was used to calculate the odds ratio (OR), accounting for the selection-related reproductive behavior. After adjustment for covariates, higher PGSs for severe mental disorders were associated with increased ORs of both PPD and MDD. Compared with MDD cases, MDD PGS and attention-deficit/hyperactivity disorder PGS were marginally but not statistically higher for PPD cases, with the OR of PPD versus MDD being 1.12 (95% CI: 0 .97-1.29) and 1.11 (0.97-1.27) per-standard deviation increase, respectively. The ORs of PPD versus MDD did not statistically differ by PGSs of bipolar disorder, schizophrenia, or autism spectrum disorder. Our findings suggest that relying on PGS data, there was no clear evidence of distinct genetic make-up of women with depression occurring during or outside postpartum, after taking the selection-related reproductive behavior into account., (© 2023. The Author(s).)

Background: Depressive episodes during pregnancy are widely investigated but it is still unknown whether pregnancy is a high-risk period compared to the pre-pregnancy period. Therefore, we aimed to investigate the incidence and recurrence of depressive episodes before, during, and after pregnancy., Methods: In the current population-based registry study, we calculated monthly incidence and recurrence of psychiatric inpatient admissions and outpatient psychiatric contact for depressive episodes. We identified a population consisting of all first childbirths in Denmark from 1999 through 2015 (N = 392,287)., Results: Incidence of inpatient admission during pregnancy was lower than before pregnancy. After childbirth, a significant increase in first-time and recurrent psychiatric inpatient admissions was observed, especially in the first months. In contrast, outpatient psychiatric treatment incidence and recurrence were increased both during pregnancy as well as in the postpartum period, as compared to pre-pregnancy., Limitations: Analyses were performed on depressive episodes representing the severe end of the spectrum, questioning generalizability to milder forms of depression treated outside psychiatric specialist treatment facilities., Conclusion: We found a different pattern of severe episodes of depression compared to moderate episodes before, during, and after pregnancy. In light of our findings and those of others, we suggest distinguishing between timing of onset in the classification of depression in the perinatal period: Depression with pregnancy onset OR with postpartum onset (instead of the current DSM classifier "with perinatal onset"), as well as severity of depression, which is important for both clinical and future research endeavors., Competing Interests: Conflict of Interest The authors state there is no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Postpartum depression (PPD) is a serious condition associated with potentially tragic outcomes, and in an ideal world PPDs should be prevented. Risk prediction models have been developed in psychiatry estimating an individual's probability of developing a specific condition, and recently a few models have also emerged within the field of PPD research, although none are implemented in clinical care. For the present study we aimed to develop and validate a prediction model to assess individualized risk of PPD and provide a tentative template for individualized risk calculation offering opportunities for additional external validation of this tool. Danish population registers served as our data sources and PPD was defined as recorded contact to a psychiatric treatment facility (ICD-10 code DF32-33) or redeemed antidepressant prescriptions (ATC code N06A), resulting in a sample of 6,402 PPD cases (development sample) and 2,379 (validation sample). Candidate predictors covered background information including cohabitating status, age, education, and previous psychiatric episodes in index mother (Core model), additional variables related to pregnancy and childbirth (Extended model), and further health information about the mother and her family (Extended+ model). Results indicated our recalibrated Extended model with 14 variables achieved highest performance with satisfying calibration and discrimination. Previous psychiatric history, maternal age, low education, and hyperemesis gravidarum were the most important predictors. Moving forward, external validation of the model represents the next step, while considering who will benefit from preventive PPD interventions, as well as considering potential consequences from false positive and negative test results, defined through different threshold values., (© 2022. The Author(s).)

Background: For women, the perinatal period confers an increased risk of severe psychiatric disorders, but similar evidence for fathers is lacking. We examined rates of first-time and recurrent psychiatric disorders in men before and after becoming fathers., Methods: A descriptive prospective study design was applied using information from the Danish National registers. Perinatal psychiatric episodes were assessed as incidence of first-time and prevalence (including recurrence) of recorded in- or outpatient admissions for any mental disorder and redeemed prescriptions for psychotropic medication in fathers to children born from January 1, 1998 until December 31, 2015., Results: We identified 929,415 births and 543,555 unique fathers. Incidence and prevalence proportions for paternal psychiatric in- and outpatient episodes showed an increasing trend over the perinatal period and were marginally higher postpartum compared to pregnancy; e.g., median incidence proportion for inpatient treatment during pregnancy was 0.07 (95% CI: 0.04; 0.07) and 0.10 (95% CI: 0.08; 0.11) postpartum per 1000 births. No difference between the periods was found for incidence of prescriptions for psychotropic medication. Psychiatric disorders in expecting and new fathers were mainly treated in primary care with cumulative incidence of prescriptions for psychotropic medication of 14.56 per 1000 births during the first year of fatherhood., Limitations: We only capture fathers who actively sought and received treatment, and we consequently underestimate milder psychiatric episodes in expecting and new fathers., Conclusion: Becoming a father did not appear to trigger a substantially increased risk of severe psychiatric disorders, as it has been observed for new mothers., (Copyright © 2021. Published by Elsevier B.V.)

Objective: Psychiatric disorders are an established risk factor for divorce or separation. Despite the fact that 10%-15% of new mothers experience postpartum psychiatric episodes (PPEs), no previous studies have investigated the effects of PPEs on the probability of divorce in these new families. Therefore, this study aimed to investigate and quantify the probability of subsequent divorce/separation among women with either mild/moderate or severe PPE compared to mothers without PPE., Methods: This cohort study based on the national Danish registers included all cohabitating, primiparous women without previous psychiatric history who gave birth from 1996 through 2014. At 6 months postpartum, each woman's PPE status was evaluated and categorized as follows: (1) mild/moderate PPE (prescription of psychotropic medication-Anatomical Therapeutic Chemical Classification codes N03-N07), (2) severe PPE (psychiatric inpatient or outpatient treatment- International Classification of Disease, 10th Edition codes F00-F99, excluding codes for organic mental disorders, substance abuse, and mental retardation), and (3) no PPE (reference group). Subsequently, the status of cohabitation was assessed a maximum of 5 times (every January 1)., Results: A total of 266,771 new mothers were included; 4,442 had a first mild/moderate PPE and 1,141 had a first severe PPE within 6 months postpartum. Compared to mothers without PPE, women with mild/moderate PPE had a significantly higher probability of later divorce (adjusted hazard ratio [HR] = 1.23; 95% CI, 1.15-1.31); for women with severe PPE, the probability was even greater (adjusted HR = 1.64; 95% CI, 1.45-1.85)., Conclusions: Women experiencing their first-ever PPE following childbirth have a higher probability of divorce in the years following their diagnosis than mothers without PPE. Further, this study showed a dose-response relationship between the severity of PPE and the probability of divorce., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

Postpartum psychiatric disorders are heritable, but how genetic liability varies by other significant risk factors is unknown. We aimed to (1) estimate associations of genetic risk scores (GRS) for major depression (MD), bipolar disorder (BD), and schizophrenia (SCZ) with postpartum psychiatric disorders, (2) examine differences by prior psychiatric history, and (3) compare genetic and familial risk of postpartum psychiatric disorders. We conducted a nested case-control study based on Danish population-based registers of all women in the iPSYCH2012 cohort who had given birth before December 31, 2015 (n = 8850). Cases were women with a diagnosed psychiatric disorder or a filled psychotropic prescription within one year after delivery (n = 5829 cases, 3021 controls). Association analyses were conducted between GRS calculated from Psychiatric Genomics Consortium discovery meta-analyses for MD, BD, and SCZ and case-control status of a postpartum psychiatric disorder. Parental psychiatric history was associated with postpartum psychiatric disorders among women with previous psychiatric history (OR, 1.14; 95% CI 1.02-1.28) but not without psychiatric history (OR, 1.08; 95% CI: 0.81-1.43). GRS for MD was associated with an increased risk of postpartum psychiatric disorders in both women with (OR, 1.44; 95% CI: 1.19-1.74) and without (OR, 1.88; 95% CI: 1.26-2.81) personal psychiatric history. SCZ GRS was only minimally associated with postpartum disorders and BD GRS was not. Results suggest GRS of lifetime psychiatric illness can be applied to the postpartum period, which may provide clues about distinct environmental or genetic elements of postpartum psychiatric disorders and ultimately help identify vulnerable groups.

Introduction: Factors that influence antidepressant (AD) prescription and use during pregnancy are multiple including, in particular, the balance between the potential risk of untreated depression and the potential risk of AD treatment. Surveillance of temporal trends of AD use might identify areas requiring further research. We studied the use of ADs before, during, and after pregnancy using national data across two decades in Denmark., Methods: We included 1,232,233 pregnancies leading to live birth in Denmark between 1 January 1997 and 31 December 2016. Information on redemption of AD prescriptions was obtained from the Danish National Prescription Register., Results: We identified 29,504 (2.4%) pregnancies having at least one AD prescription (96,232 AD prescriptions) during pregnancy. The majority redeemed more than one prescription (69.7%) often for a single kind of AD (83.5%), and in 94% of the AD-exposed pregnancies, the estimated duration of treatment was 1 month or longer. Prescription of ADs during pregnancy increased steadily from 0.4% in 1997 to 4.6% in 2011, but decreased thereafter to 3.1% in 2016. The proportion of pregnancies with ADs in 2011 was 6.05-fold higher than that in 1997. The temporal trends in AD prescription in the years before and after pregnancy were similar to the trend during pregnancy. The decreasing use of ADs during pregnancy after 2011 was mainly driven by a decrease in the use of selective serotonin reuptake inhibitors (SSRIs), especially citalopram, the main type of SSRIs used in Denmark., Conclusion: Prescription of ADs during pregnancy in Denmark increased steadily from 1997 to 2011 but decreased sharply thereafter. More research is needed to show whether the same trend exists in other populations, like women of reproductive age, men of reproductive age, and old people, and other countries. We also need to find explanation for the decreasing trend in recent years and potential risk for untreated depression., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Objective: Postpartum psychiatric disorders are common and morbid complications of pregnancy. The authors sought to evaluate how family history of psychiatric disorders is associated with postpartum psychiatric disorders in proband mothers with and without a prior psychiatric history by assessing degree of relationship, type of disorder, and sex of family members., Method: The authors linked Danish birth and psychiatric treatment registers to evaluate familial risk of postpartum psychiatric episodes in a national population-based cohort. Probands were first-time mothers who were born in Denmark in 1970 or later and who gave birth after age 15 and before Dec. 31, 2012 (N=362,462). The primary exposure was a diagnosed psychiatric disorder in a relative. Cox regression models were used to estimate the hazard ratio of postpartum psychiatric disorders in proband mothers., Results: The relative risk of psychiatric disorders in the postpartum period was elevated when first-degree family members had a psychiatric disorder (hazard ratio=1.45, 95% CI=1.28-1.65) and highest when proband mothers had a first-degree family member with bipolar disorder (hazard ratio=2.86, 95% CI=1.88-4.35). Associations were stronger among proband mothers with no previous psychiatric history. There were no notable differences by sex of the family member., Conclusions: Family history of psychiatric disorders, especially bipolar disorder, is an important risk factor for postpartum psychiatric disorders. To assist in identification of women at risk for postpartum psychiatric disorders, questions related to female and male first-degree relatives with bipolar disorder are of the highest importance and should be added to routine clinical screening guidelines to improve prediction of risk.

Background: Childbirth is a potent trigger for the onset of psychiatric illness in women including postpartum depression (PPD) and postpartum psychosis (PP). Medical complications occurring during pregnancy and/or childbirth have been linked to postpartum psychiatric illness and sociodemographic factors. We evaluated if pregnancy and obstetrical predictors have similar effects on different types of postpartum psychiatric disorders., Method: A population-based cohort study using Danish registers was conducted in 392 458 primiparous women with a singleton delivery between 1995 and 2012 and no previous psychiatric history. The main outcome was first-onset postpartum psychiatric episodes. Incidence rate ratios (IRRs) were calculated for any psychiatric contact in four quarters for the first year postpartum., Results: PPD and postpartum acute stress reactions were associated with pregnancy and obstetrical complications. For PPD, hyperemesis gravidarum [IRR 2.69, 95% confidence interval (CI) 1.93-3.73], gestational hypertension (IRR 1.84, 95% CI 1.33-2.55), pre-eclampsia (IRR 1.45, 95% CI 1.14-1.84) and Cesarean section (C-section) (IRR 1.32, 95% CI 1.13-1.53) were associated with increased risk. For postpartum acute stress, hyperemesis gravidarum (IRR 1.93, 95% CI 1.38-2.71), preterm birth (IRR 1.51, 95% CI 1.30-1.75), gestational diabetes (IRR 1.42, 95% CI 1.03-1.97) and C-section (IRR 1.36, 95% CI 1.20-1.55) were associated with increased risk. In contrast, risk of PP was not associated with pregnancy or obstetrical complications., Conclusions: Pregnancy and obstetrical complications can increase the risk for PPD and acute stress reactions but not PP. Identification of postpartum women requiring secondary care is needed to develop targeted approaches for screening and treatment. Future work should focus on understanding the contributions of psychological stressors and underlying biology on the development of postpartum psychiatric illness.

Perinatal psychiatric episodes comprise various disorders and symptom severity, which are diagnosed and treated in multiple treatment settings. To date, no studies have quantified the incidence and prevalence of perinatal psychiatric episodes treated in primary and secondary care, which we aimed to do in the present study. We designed a descriptive prospective study and included information from Danish population registers to study first-time ever and recurrent psychiatric episodes during the perinatal period, including treatment at psychiatric facilities and general practitioners (GPs). This was done for all women who had records of one or more singleton births from 1998 until 2012. In total, we had information on 822 439 children born to 491 242 unique mothers. Results showed first-time psychiatric episodes treated at inpatient facilities were rare during pregnancy, but increased significantly shortly following childbirth (0.02 vs 0.25 per 1000 births). In comparison, first-time psychiatric episodes treated at outpatient facilities were more common, and showed little variation across pregnancy and postpartum. For every single birth resulting in postpartum episodes treated at inpatient psychiatric facilities, 2.5 births were followed by an episode treated at outpatient psychiatric facility and 12 births by GP-provided pharmacological treatment. We interpret our results the following way: treated severe and moderate psychiatric disorders have different risk patterns in relation to pregnancy and childbirth, which suggests differences in the underlying etiology. We further speculate varying treatment incidence and prevalence in pregnancy vs postpartum may indicate that the current Diagnostic and Statistical Manual of Mental Disorders-5 peripartum specifier not adequately describes at-risk periods across moderate and severe perinatal psychiatric episodes.

Background: Few studies have examined the risk of developing castration-resistant prostate cancer (CRPC), metastasis, and mortality among nonmetastatic prostate cancer (M0-PC) patients treated with androgen deprivation therapy (ADT). We estimated the incidence of these outcomes among M0-PC patients on ADT and identified prostate-specific antigen (PSA) based biomarkers for mortality and metastasis., Methods: This population-based cohort study included all nonmetastatic prostate cancer patients in Northern and Central Denmark Regions during 1997-2010, identified through registry data. Primary outcomes were metastasis, overall survival, and bone metastasis-free survival (BMFS). We estimated relative risks (RR) associated with PSA and PSA doubling-time (PSA-DT), measured as time-varying variables beginning at ADT treatment start., Results: We included 2494 M0-PC patients treated with ADT, of whom 1617 (80%) developed CRPC during follow-up. One-fourth of the patients developed metastases within 5 years; bone metastases (BM) accounted for 81% of all metastases. Median survival time was 4.4 years. Compared with PSA <8 ng/mL, PSA ≥8 ng/mL was associated with an adjusted RR of 14.0 (95% confidence interval [CI]: 10.2, 19.0) for BM, 4.4 (CI: 3.9, 5.0) for all-cause mortality, and RR of 4.8 (CI: 4.3, 5.4) for the inverse of BMFS. PSA-DT ≤6 months was associated with an adjusted RR of 7.6 (95% CI: 6.1, 9.5) for BM, RR of 5.9 (CI: 5.2, 6.6) for all-cause mortality, and RR 6.6 (CI: 5.9, 7.4) for the inverse of BMFS., Conclusions: PSA ≥8 ng/mL and PSA-DT ≤6 months are strong predictors of mortality and bone metastasis. The poor prognosis observed in this study may reflect inclusion of patients with severe prostate cancer by requiring repeated PSA measurements., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Bone metastases and skeletal-related events (SREs), including radiation therapy or surgery to bone, pathologic fracture, or spinal cord compression, among children have not been described in a population-based study. We examined the rate of bone metastasis, SREs, and survival in the Danish pediatric cancer population. We identified children below 18 years with a first-time diagnosis of cancer between January 1, 1994 and December 31, 2009 in the Danish Cancer Registry. From the Danish National Registry of Patients, we obtained bone metastasis and SRE diagnoses, and estimated incidence rates (IRs). We estimated 6-month, 1-year, and 5-year survival using Kaplan-Meier curves. Of 2652 children, 35 (1.3%) developed bone metastasis during a mean follow-up of 7.0 years (IR=1.9 per 1000 person-years [95% confidence interval (CI), 1.4-2.6]). IRs were substantially higher among children with solid tumors than those with hematologic malignancies (IR=3.2 [95% CI, 2.3-4.6] and IR=0.48 [95% CI, 0.18-1.3]). Survival was poorer for children with bone metastasis than those without bone metastasis. Among children with bone metastasis, 67% experienced an SRE during a mean follow-up of 1.1 years, yielding an IR of 590 per 1000 person-years (95% CI, 381-915). Bone metastases are rare among children with cancer, but SREs are a common consequence.

Studies have reported a 1·3- to 2·2-fold higher mortality rate among patients with primary immune thrombocytopenia (ITP) compared to the general population. However, long-term mortality estimates as well as cause-specific mortality data are sparse. In our population-based cohort of adult patients with newly diagnosed ITP and up to 37 years of follow-up, the 5-year, 10-year and 20-year mortality among the ITP patients was 22%, 34% and 49%, respectively. The mortality in the ITP cohort was consistently higher than in the in the general population cohort yielding an adjusted hazard ratio (HR) of 1·5 [95% confidence interval (CI): 1·2-1·8]. The adjusted HRs of mortality due to cardiovascular disease, infection, bleeding and haematological cancer were 1·5 (95% CI: 1·1-1·5), 2·4 (95% CI: 1·0-5·7), 6·2 (95% CI: 2·8-13·5) and 5·7 (95% CI: 2·1-15·7), respectively, whereas mortality due to solid cancer and other causes were similar in ITP patients and the general population. We conclude that mortality rates among ITP patients are higher than in the general population, predominantly as a result of increased cardiovascular disease, infection, bleeding and haematological cancer cause-specific mortalities., (© 2014 John Wiley & Sons Ltd.)

Treatment with dopamin agonists, particularly cabergoline, is the primary and preferred therapy for prolactinomas and symptomatic hyperprolactinaemia due to its effectiveness and tolerability. However, an association has been demonstrated between fibrotic heart valve disease and high-dose dopamin agonist use in patients with Parkinson's disease in several echocardiographic studies. Such observations have prompted a number of studies of valvular function in cabergoline-treated hyperprolactinaemia patients. These studies have failed to show an increased prevalence of clinically significant valvular regurgitation.

Background: Increased risk of heart valve disease during treatment with certain dopamine agonists, such as cabergoline, has been observed in patients with Parkinson's disease. The same compound is used to treat hyperprolactinemia, but it is unknown whether this also associates with heart valve disease., Objectives: The objective of the study was to assess the incidence of diagnosed heart valve disease and cardiac valve surgery among patients with hyperprolactinemia, compared with a general population cohort in Denmark., Design: This was a nationwide, population-based, cohort study based on a nationwide hospital registry., Methods: We identified 2381 hyperprolactinemia patients with a first-time diagnosis recorded from 1994 through 2010 in the registry, with no previous hospital diagnosis of heart valve disease. Each patient was compared with 10 age- and gender-matched comparison cohort members from the general population. The association between hyperprolactinemia and heart valve disease was analyzed with Cox's proportional hazards regression, controlling for potential confounding factors. To assess the risk of cardiac valve surgery and avoid ascertainment bias, a subanalysis was made in a cohort of 2,387 hyperprolactinemia patients with no previous cardiac valve surgery and 23,870 comparison cohort members., Results: Nineteen hyperprolactinemic patients (0.80%) were diagnosed with heart valve disease during a total of 17,759.8 yr of follow-up, compared with 75 persons (0.31%) in the comparison cohort during 179,940.6 yr of follow-up [adjusted hazard ratio 2.27 (95% confidence interval 1.35-3.82)]. Seven of the 10 patients treated with cabergoline and diagnosed with heart valve disease were asymptomatic and diagnosed on the basis of an echocardiography performed as a safety measure. However, only two patients with hyperprolactinemia (0.08%) underwent surgery, compared with 28 persons in the general population cohort (0.12%) [adjusted hazard ratio 0.55 (95% confidence interval 0.13-2.42)]., Conclusions: Data from the present register-based study do not support that hyperprolactinemia or its treatment is associated with an increased risk of clinically significant heart valve disease.