Identification of women at high risk of postpartum psychiatric episodes: A population-based study quantifying relative and absolute risks following exposure to selected risk factors and genetic liability.

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.

Twenty-year mortality of adult patients with primary immune thrombocytopenia: a Danish population-based cohort study.

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.

Pregnancy and postpartum psychiatric episodes in fathers: A population-based study on treatment incidence and prevalence.

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.

Trend of antidepressants before, during, and after pregnancy across two decades-A population-based study.

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.

Survival and PSA-markers for mortality and metastasis in nonmetastatic prostate cancer treated with androgen deprivation therapy.

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.

Validation of algorithms to detect distant metastases in men with prostate cancer using routine registry data in Denmark.

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.

[Dopamin agonist treatment and fibrotic heart valve disease in hyperprolactinaemia patients]. / Behandling med dopaminagonister og udvikling af hjerteklapsygdom hos patienter med hyperprolaktinæmi.

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.

Correspondence between general practitioner-reported medication use and timing of prescription dispensation.

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.

Heart valve disease among patients with hyperprolactinemia: a nationwide population-based cohort study.

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.