Changing prescribing practice for rapid tranquillization-a quality improvement project based on the Plan-Do-Study-Act method.

PURPOSE: It is unclear how the evidence from clinical trials best translates into complex clinical settings. The aim of this quality improvement (QI) project was to change prescribing practice for rapid tranquillization in inpatient mental health care services examining the effectiveness of the Plan-Do-Study-Act (PDSA) method. METHODS: A prospective QI project was conducted to ensure that intramuscular (IM) diazepam was substituted with IM lorazepam for benzodiazepine rapid tranquillization in inpatient mental health care. We monitored the prescription and administration of medication for rapid tranquillization before (N = 371), during (N = 1130) and after (N = 364) the QI intervention. Seven iterative PDSA cycles with a multiple-component intervention approach were conducted to gradually turn the prescribing practice in the desired direction. Simultaneously, a standard monitoring regimen was introduced to ensure patient safety. RESULTS: Lorazepam administrations gradually replaced diazepam during the intervention period which was sustained post-intervention where lorazepam comprised 96% of benzodiazepine administrations for rapid tranquillization. The mean dose of benzodiazepine administered remained stable from pre (14.40 mg diazepam equivalents) to post (14.61 mg) intervention phase. Close to full compliance (> 80%) with vital signs monitoring was achieved by the end of the observation period. CONCLUSION: It was possible to increase the quality of treatment of acute agitation in a large inpatient mental health care setting using a stepwise approach based on iterative PDSA cycles and continuous data feedback. This approach might be valuable in other prescribing practice scenarios with feedback from local stakeholders and opinion leaders.

Effect of Influenza Vaccination on Risk of Coronavirus Disease 2019: A Prospective Cohort Study of 46†000 Healthcare Workers.

BACKGROUND: The purpose of this study was to assess whether influenza vaccination has an impact on the risk of coronavirus disease 2019 (COVID-19). METHODS: A cohort of 46 112 healthcare workers were tested for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and filled in a survey on COVID-19 symptoms, hospitalization, and influenza vaccination. RESULTS: The risk ratio of hospitalization due to SARS-CoV-2 for influenza vaccinated compared with unvaccinated participants was 1.00 for the seasonal vaccination in 2019/2020 (confidence interval, .56-1.78, P = 1.00). Likewise, no clinical effect of influenza vaccination on development of antibodies against SARS-CoV-2 was found. CONCLUSIONS: The present findings indicate that influenza vaccination does not affect the risk of SARS-CoV-2 infection or COVID-19.

At the Core of Depression: A Diagnostic Interview of the Core Features of Depression.

INTRODUCTION: Valid and reliable methods for diagnosing depression are essential. The present study aimed to test the performance of a new diagnostic interview for depression focusing on the core symptoms of depression. METHOD: We developed a diagnostic interview for depression: the CORE Diagnostic Interview, CORE-DI, which assesses each of the core features of depression on the four dimensions: quality, reactivity, globality, and fluctuations over time. The diagnostic performance of this interview was tested in a clinical study including 83 individuals presenting with various depressive symptoms, who were interviewed independently (1) by means of the CORE-DI and the Mini-International Neuropsychiatric Interview (M.I.N.I.), and (2) by highly skilled specialists in depression representing gold standard diagnoses. RESULTS: We compared the outcome of the CORE-DI, the M.I.N.I., and the diagnosis made by clinicians, respectively, versus the gold standard diagnosis, using diagnostic efficiency statistics. The CORE-DI diagnosed depression with a high specificity (0.91, 95% CI: 0.85-0.97, for International Classification of Diseases [ICD]-10 criteria and 0.88, 95% CI: 0.81-0.95, for Diagnostic and Statistical Manual of Mental Disorders [DSM-5] criteria) compared to both M.I.N.I (specificity 0.44, 95% CI: 0.33-0.55) and clinical diagnoses (specificity 0.76, 95% CI: 0.67-0.85). The sensitivity of the CORE-DI was 0.61 (95% CI: 0.55-0.72) for ICD-10 criteria and 0.67 (95% CI: 0.57-0.77) for DSM-5 criteria. DISCUSSION/CONCLUSION: The CORE-DI increased the specificity of the depression diagnosis substantially compared to clinical diagnoses and the diagnoses obtained by M.I.N.I. The results point to the usefulness of an elaborated and systematic assessment of the core symptoms in the examination of patients with depressive symptoms and thereby indicate a way for further development of specific diagnostic tools for depression in both clinical and research settings. However, it should be noted that the sensitivity of the CORE-DI was modest, and the psychometric properties of the CORE-DI might be different in other settings with higher or lower prevalence or severity of depressive symptoms.

Light therapy for seasonal affective disorder in visual impairment and blindness - a pilot study.

OBJECTIVE: Seasonal and non-seasonal depression are prevalent conditions in visual impairment (VI). We assessed the effects and side effects of light therapy in persons with severe VI/blindness who experienced recurrent depressive symptoms in winter corresponding to seasonal affective disorder (SAD) or subsyndromal SAD (sSAD). RESULTS: We included 18 persons (11 with severe VI, 3 with light perception and 4 with no light perception) who met screening criteria for sSAD/SAD in a single-arm, assessor-blinded trial of 6 weeks light therapy. In the 12 persons who completed the 6 weeks of treatment, the post-treatment depression score was reduced (p < 0.001), and subjective wellbeing (p = 0.01) and sleep quality were improved (p = 0.03). In 6/12 participants (50%), the post-treatment depression score was below the cut-off set for remission. In four participants with VI, side effects (glare or transiently altered visual function) led to dropout or exclusion. CONCLUSION: Light therapy was associated with a reduction in depressive symptoms in persons with severe VI/blindness. Eye safety remains a concern in persons with residual sight.

Relation Between Infant Microbiota and Autism?: Results from a National Cohort Sibling Design Study.

BACKGROUND: Hypotheses concerning adverse effects of changes in microbiota have received much recent attention, but unobserved confounding makes them difficult to test. We investigated whether surrogate markers for potential adverse microbiota change in infancy affected autism risk, addressing unobserved confounding using a sibling study design. METHODS: This is a population-based, prospective cohort study including all singleton live births in Denmark from 1997 to 2010. The exposure variables were cesarean delivery and antibiotic use in the first 2 years of life. The outcome was a subsequent autism diagnosis. We used the between- and within-sibling model and compared it with sibling-stratified Cox models and simpler standard Cox models that ignored sibship. RESULTS: Of our study population including 671,606 children, who were followed for up to 15 years (7,341,133 person-years), 72% received antibiotics, 17.5% were delivered by cesarean, and 1.2% (8,267) developed autism. The standard Cox models predicted that both cesarean (compared with vaginal) delivery and antibiotics increased the risk of autism. In the sibling-stratified Cox model, only broader spectrum antibiotics were associated with increased risk of autism: hazard ratio (HR) = 1.16 (95% confidence interval = 1.01, 1.36). The between-within model estimated no exposure effects: intrapartum cesarean HR = 1.06 (0.89, 1.26); prelabor cesarean HR = 0.97 (0.83, 1.15); exclusively penicillin HR = 1.05 (0.93, 1.18); and broader spectrum antibiotics HR = 1.05 (0.95, 1.16). CONCLUSIONS: The between-within model rendered more precise estimates than sibling-stratified Cox models, and we believe that it also provided more valid estimates. Results from these preferred models do not support a causal relation between antibiotic treatment during infancy, cesarean delivery, and autism. See video abstract at, http://links.lww.com/EDE/B432.

Investigating the effects of cesarean delivery and antibiotic use in early childhood on risk of later attention deficit hyperactivity disorder.

BACKGROUND: Increasing attention deficit hyperactivity disorder (ADHD) incidence has been proposed to be caused by factors influencing microbiota in early life. We investigated the potential causality between ADHD and two surrogate markers for changes in children's microbiota: birth delivery mode and early childhood antibiotic use. METHOD: This population-based, prospective cohort study linked nationwide registers of data for native Danish singleton live births in Denmark from 1997 to 2010. Exposure variables were delivery mode and antibiotic use during the first 2 years of life. The main outcome measure was ADHD diagnosis or redeemed ADHD medication prescriptions. For statistical analysis, we used both advanced sibling models and a more traditional approach. RESULTS: We included 671,592 children, followed from their second birthday in the period 1999-2014 for 7,300,522 person-years. ADHD was diagnosed in 17,971. In total, 17.5% were born by cesarean delivery, and 72% received antibiotic treatment within their first 2 years of life. In the adjusted between-within sibling survival model, mode of delivery or antibiotics had no effect on ADHD when compared with vaginal delivery or no antibiotic treatment as hazard ratios were 1.09 (95% confidence interval 0.97-1.24) for intrapartum cesarean, 1.03 (0.91-1.16) for prelabor cesarean, 0.98 (0.90-1.07) for penicillin, and 0.99 (0.92-1.06) for broader spectrum antibiotics. In a sibling-stratified Cox regression, intrapartum cesarean was associated with increased ADHD risk, but other exposures were not. In a descriptive, nonstratified Cox model, we found increased risk for ADHD for all exposures. CONCLUSIONS: Detailed family confounder control using the superior between-within model indicates that cesarean delivery or use of antibiotics during the first 2 years of life does not increase ADHD risk. Therefore, our study suggests that changes in children's microbiota related to cesarean delivery or antibiotic use, do not cause ADHD.

Circadian reinforcement therapy in combination with electronic self-monitoring to facilitate a safe post-discharge period of patients with depression by stabilizing sleep: protocol of a randomized controlled trial.

BACKGROUND: The transition phase from inpatient to outpatient care for patients suffering from Major Depressive Disorder represents a vulnerable period associated with a risk of depression worsening and suicide. Our group has recently found that the sleep-wake cycle in discharged depressive patients became irregular and exhibited a drift towards later hours, associated with worsening of depression. In contrast, an advancement of sleep phase has earlier been shown to have an antidepressant effect. Thus, methods to prevent drift of the sleep-wake cycle may be promising interventions to prevent or reduce worsening of depression after discharge. METHODS: In this trial, we apply a new treatment intervention, named Circadian Reinforcement Therapy (CRT), to patients discharged from inpatient psychiatric wards. CRT consists of a specialized psychoeducation on the use of regular time signals (zeitgebers): daylight exposure, exercise, meals, and social contact. The aim is to supply stronger and correctly timed zeitgebers to the circadian system to prevent sleep drift and worsening of depression. The CRT is used in combination with an electronic self-monitoring system, the Monsenso Daybuilder System (MDB). By use of the MDB system, all patients self-monitor their sleep, depression level, and activity (from a Fitbit bracelet) daily. Participants can inspect all their data graphically on the MDB interface and will have clinician contact. The aim is to motivate patients to keep a stable sleep-wake cycle. In all, 130 patients referred to an outpatient service will be included. Depression rating is blinded. Patients will be randomized 1:1 to a Standard group or a CRT group. The intervention period is 4 weeks covering the transition phase from inpatient to outpatient care. The primary outcome is score change in interviewer rated levels of depression on the Hamilton Depression Rating Scale. A subset of patients will be assessed with salivary Dim Light Melatonin Onset (DLMO) as a validator of circadian timing. The trial was initiated in 2016 and will end in 2020. DISCUSSION: If the described intervention is beneficial it could be incorporated into usual care algorithms for depressed patients to facilitate a better and safer transition to outpatient treatment. TRIAL REGISTRATION: Posted prospectively at ClinicalTrials.gov at February 10, 2016 with identifier NCT02679768 .

Do emotion regulation, attentional control, and attachment style predict response to cognitive behavioral therapy for anxiety disorders? - an investigation in clinical settings.

Objective: Approximately, 50% of all individuals with anxiety disorders do not benefit from the "gold standard" treatment, namely cognitive behavioral therapy (CBT). Reliable predictors of treatment effect are lacking. The primary aim of this study was to investigate the predictive value of emotion regulation, attentional control, and attachment style for group-based CBT outcomes in routine clinical settings. Method: A total of 76 patients with anxiety disorders received manual-based group CBT at psychiatric outpatient clinics. Emotion regulation, attachment style, and attentional control were assessed with self-report measures and with an experimental computer-based attentional control task at baseline. The severity of anxiety was assessed at intake, post-treatment, and at a 6-month follow-up. Results: Attentional control, emotion regulation, and attachment avoidance did not predict treatment outcomes. Higher attachment anxiety at baseline was significantly related to poorer outcome. Conclusion: In routine clinical settings, high attachment anxiety may predict poorer outcomes for group-based CBT.

Mortality in Women Treated With Assisted Reproductive Technology-Addressing the Healthy Patient Effect.

In previous studies, investigators have reported reduced mortality among women undergoing assisted reproductive technology (ART) treatment, possibly related to selection of healthy women into ART treatment. Our aim in this study was to explore the impact of relevant selection factors on the association between ART treatment and mortality and to explore effect modification by parity. Women treated with ART in fertility clinics in Denmark during 1994-2009 (n = 42,897) were age-matched with untreated women from the background population (n = 204,514) and followed until December 31, 2010. With adjustment for relevant confounders, the risk of death was lower among ART-treated women during the first 2 years after ART treatment (hazard ratio (HR) = 0.68, 95% confidence interval (CI): 0.63, 0.74), but there was no apparent difference after 10 years (HR = 0.92, 95% CI: 0.79, 1.07). Having children prior to ART treatment was associated with markedly reduced mortality (HR = 0.45, 95% CI: 0.38, 0.53), possibly due to better health among fertile women. While the frequencies of previous medical and psychiatric diagnoses among ART-treated and untreated women were similar, differences in disease severity could explain the reduced mortality among ART-treated women, as poor prognosis would make initiation of ART treatment unlikely. The survival advantage among ART-treated women is likely a selection phenomenon rather than a biological phenomenon.

Erythropoietin prevents the effect of chronic restraint stress on the number of hippocampal CA3c dendritic terminals-relation to expression of genes involved in synaptic plasticity, angiogenesis, inflammation, and oxidative stress in male rats.

Stress-induced allostatic load affects a variety of biological processes including synaptic plasticity, angiogenesis, oxidative stress, and inflammation in the brain, especially in the hippocampus. Erythropoietin (EPO) is a pleiotropic cytokine that has shown promising neuroprotective effects. Recombinant human EPO is currently highlighted as a new candidate treatment for cognitive impairment in neuropsychiatric disorders. Because EPO enhances synaptic plasticity, attenuates oxidative stress, and inhibits generation of proinflammatory cytokines, EPO may be able to modulate the effects of stress-induced allostatic load at the molecular level. The aim of this study was therefore to investigate how EPO and repeated restraint stress, separately and combined, influence (i) behavior in the novelty-suppressed feeding test of depression/anxiety-related behavior; (ii) mRNA levels of genes encoding proteins involved in synaptic plasticity, angiogenesis, oxidative stress, and inflammation; and (iii) remodeling of the dendritic structure of the CA3c area of the hippocampus in male rats. As expected, chronic restraint stress lowered the number of CA3c apical dendritic terminals, and EPO treatment reversed this effect. Interestingly, these effects seemed to be mechanistically distinct, as stress and EPO had differential effects on gene expression. While chronic restraint stress lowered the expression of spinophilin, tumor necrosis factor α, and heat shock protein 72, EPO increased expression of hypoxia-inducible factor-2α and lowered the expression of vascular endothelial growth factor in hippocampus. These findings indicate that the effects of treatment with EPO follow different molecular pathways and do not directly counteract the effects of stress in the hippocampus.

Daylight Savings Time Transitions and the Incidence Rate of Unipolar Depressive Episodes.

BACKGROUND: Daylight savings time transitions affect approximately 1.6 billion people worldwide. Prior studies have documented associations between daylight savings time transitions and adverse health outcomes, but it remains unknown whether they also cause an increase in the incidence rate of depressive episodes. This seems likely because daylight savings time transitions affect circadian rhythms, which are implicated in the etiology of depressive disorder. Therefore, we investigated the effects of daylight savings time transitions on the incidence rate of unipolar depressive episodes. METHODS: Using time series intervention analysis of nationwide data from the Danish Psychiatric Central Research Register from 1995 to 2012, we compared the observed trend in the incidence rate of hospital contacts for unipolar depressive episodes after the transitions to and from summer time to the predicted trend in the incidence rate. RESULTS: The analyses were based on 185,419 hospital contacts for unipolar depression and showed that the transition from summer time to standard time were associated with an 11% increase (95% CI = 7%, 15%) in the incidence rate of unipolar depressive episodes that dissipated over approximately 10 weeks. The transition from standard time to summer time was not associated with a parallel change in the incidence rate of unipolar depressive episodes. CONCLUSION: This study shows that the transition from summer time to standard time was associated with an increase in the incidence rate of unipolar depressive episodes. Distress associated with the sudden advancement of sunset, marking the coming of a long period of short days, may explain this finding. See video abstract at, http://links.lww.com/EDE/B179.

Seasonal difference in brain serotonin transporter binding predicts symptom severity in patients with seasonal affective disorder.

Cross-sectional neuroimaging studies in non-depressed individuals have demonstrated an inverse relationship between daylight minutes and cerebral serotonin transporter; this relationship is modified by serotonin-transporter-linked polymorphic region short allele carrier status. We here present data from the first longitudinal investigation of seasonal serotonin transporter fluctuations in both patients with seasonal affective disorder and in healthy individuals. Eighty (11)C-DASB positron emission tomography scans were conducted to quantify cerebral serotonin transporter binding; 23 healthy controls with low seasonality scores and 17 patients diagnosed with seasonal affective disorder were scanned in both summer and winter to investigate differences in cerebral serotonin transporter binding across groups and across seasons. The two groups had similar cerebral serotonin transporter binding in the summer but in their symptomatic phase during winter, patients with seasonal affective disorder had higher serotonin transporter than the healthy control subjects (P = 0.01). Compared to the healthy controls, patients with seasonal affective disorder changed their serotonin transporter significantly less between summer and winter (P < 0.001). Further, the change in serotonin transporter was sex- (P = 0.02) and genotype- (P = 0.04) dependent. In the patients with seasonal affective disorder, the seasonal change in serotonin transporter binding was positively associated with change in depressive symptom severity, as indexed by Hamilton Rating Scale for Depression - Seasonal Affective Disorder version scores (P = 0.01). Our findings suggest that the development of depressive symptoms in winter is associated with a failure to downregulate serotonin transporter levels appropriately during exposure to the environmental stress of winter, especially in individuals with high predisposition to affective disorders.media-1vid110.1093/brain/aww043_video_abstractaww043_video_abstract.

Usability, Acceptability, and Adherence to an Electronic Self-Monitoring System in Patients With Major Depression Discharged From Inpatient Wards.

BACKGROUND: Patients suffering from depression have a high risk of relapse and readmission in the weeks following discharge from inpatient wards. Electronic self-monitoring systems that offer patient-communication features are now available to offer daily support to patients, but the usability, acceptability, and adherence to these systems has only been sparsely investigated. OBJECTIVE: We aim to test the usability, acceptability, adherence, and clinical outcome of a newly developed computer-based electronic self-assessment system (the Daybuilder system) in patients suffering from depression, in the period from discharge until commencing outpatient treatment in the Intensive Outpatient Unit for Affective Disorders. METHODS: Patients suffering from unipolar major depression that were referred from inpatient wards to an intensive outpatient unit were included in this study before their discharge, and were followed for four weeks. User satisfaction was assessed using semiqualitative questionnaires and the System Usability Scale (SUS). Patients were interviewed at baseline and at endpoint with the Hamilton depression rating scale (HAM-D17), the Major Depression Inventory (MDI), and the 5-item World Health Organization Well-Being Index (WHO-5). In this four-week period patients used the Daybuilder system to self-monitor mood, sleep, activity, and medication adherence on a daily basis. The system displayed a graphical representation of the data that was simultaneously displayed to patients and clinicians. Patients were phoned weekly to discuss their data entries. The primary outcomes were usability, acceptability, and adherence to the system. The secondary outcomes were changes in: the electronically self-assessed mood, sleep, and activity scores; and scores from the HAM-D17, MDI, and WHO-5 scales. RESULTS: In total, 76% of enrolled patients (34/45) completed the four-week study. Five patients were readmitted due to relapse. The 34 patients that completed the study entered data for mood on 93.8% of the days (872/930), sleep on 89.8% of the days (835/930), activity on 85.6% of the days (796/930), and medication on 88.0 % of the days (818/930). SUS scores were 86.2 (standard deviation [SD] 9.7) and 79% of the patients (27/34) found that the system lived up to their expectations. A significant improvement in depression severity was found on the HAM-D17 from 18.0 (SD 6.5) to 13.3 (SD 7.3; P<.01), on the MDI from 27.1 (SD 13.1) to 22.1 (SD 12.7; P=.006), and in quality of life on the WHO-5 from 31.3 (SD 22.9) to 43.4 (SD 22.1; P<.001) scales, but not on self-assessed mood (P=.08). Mood and sleep parameters were highly variable from day-to-day. Sleep-offset was significantly delayed from baseline, averaging 48 minutes (standard error 12 minutes; P<.001). Furthermore, when estimating delay of sleep-onset (with sleep quality included in the model) during the study period, this showed a significant negative effect on mood (P=.03). CONCLUSIONS: The Daybuilder systems performed well technically, and patients were satisfied with the system and had high adherence to self-assessments. The dropout rate and the gradual delay in sleep emphasize the need for continued clinical support for these patients, especially when considering sleep guidance.

High prevalence of seasonal affective disorder among persons with severe visual impairment.

BACKGROUND: Light severely affects the occurrence of seasonal affective disorder (SAD). AIMS: To compare the prevalence of SAD in persons with severe visual impairment and persons with full sight, and in persons with severe visual impairment with or without light perception. METHOD: This cross-sectional study assessed the Global Seasonality Score (GSS) and the prevalence of SAD among 2781 persons with visual impairment and 4099 persons with full sight using the Seasonal Pattern Assessment Questionnaire (SPAQ). RESULTS: Respondents with visual impairment had significantly higher GSS and prevalence of SAD compared with full sight controls, P<0.001. Light perception respondents were more vulnerable to seasonal change than both full sight and no light perception respondents. CONCLUSIONS: The study showed a highly significant association between visual impairment and SPAQ-defined SAD parameters, supporting the hypothesis that decreased retinal light input plays a role in the pathogenesis of SAD.

Depressed Patients Hospitalized in Southeast-Facing Rooms Are Discharged Earlier than Patients in Northwest-Facing Rooms.

BACKGROUND AND AIM: Improvement in patients admitted to inpatient wards with severe depression is slow, and such patients are often discharged with residual symptoms which put them at risk for relapse. New treatments that can speed up recovery are highly desired. This naturalistic follow-up study in a specialized affective disorders unit investigated the impact of daylight on the length of hospital stay and improvement of depression. METHODS: For a period of 1 year, we collected data on sociodemographics, length of stay, vitamin D, and depression severity for patients in an inpatient affective disorders unit. The ward is located with one facade that faces southeast (SE); the opposite one faces northwest (NW) and receives far less light and no direct sunlight during winter. RESULTS: SE-facing rooms received far more daylight than NW-facing rooms. The length of stay was significantly lower in the SE rooms, i.e., 29.2 (±26.8) versus 58.8 (±42.0) days in the NW rooms (p = 0.01). There was a statistically nonsignificant greater reduction of 52.2% in depression severity for the patients staying in the SE rooms compared to 42.2% in the NW rooms, which may nevertheless be clinically relevant. CONCLUSION: Due to the study design, no causality for the observed difference in length of stay can be given, but the results support findings in previous studies of the importance of architectural orientation providing natural daylight as a factor for improvement.

Development and psychometric validation of the verbal affective memory test.

We here present the development and validation of the Verbal Affective Memory Test-24 (VAMT-24). First, we ensured face validity by selecting 24 words reliably perceived as positive, negative or neutral, respectively, according to healthy Danish adults' valence ratings of 210 common and non-taboo words. Second, we studied the test's psychometric properties in healthy adults. Finally, we investigated whether individuals diagnosed with Seasonal Affective Disorder (SAD) differed from healthy controls on seasonal changes in affective recall. Recall rates were internally consistent and reliable and converged satisfactorily with established non-affective verbal tests. Immediate recall (IMR) for positive words exceeded IMR for negative words in the healthy sample. Relatedly, individuals with SAD showed a significantly larger decrease in positive recall from summer to winter than healthy controls. Furthermore, larger seasonal decreases in positive recall significantly predicted larger increases in depressive symptoms. Retest reliability was satisfactory, rs ≥ .77. In conclusion, VAMT-24 is more thoroughly developed and validated than existing verbal affective memory tests and showed satisfactory psychometric properties. VAMT-24 seems especially sensitive to measuring positive verbal recall bias, perhaps due to the application of common, non-taboo words. Based on the psychometric and clinical results, we recommend VAMT-24 for international translations and studies of affective memory.

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.

Effect of melatonin on depressive symptoms and anxiety in patients undergoing breast cancer surgery: a randomized, double-blind, placebo-controlled trial.

Depression, anxiety and sleep disturbances are known problems in patients with breast cancer. The effect of melatonin as an antidepressant in humans with cancer has not been investigated. We investigated whether melatonin could lower the risk of depressive symptoms in women with breast cancer in a three-month period after surgery and assessed the effect of melatonin on subjective parameters: anxiety, sleep, general well-being, fatigue, pain and sleepiness. Randomized, double-blind, placebo-controlled trial undertaken from July 2011 to December 2012 at a department of breast surgery in Copenhagen, Denmark. Women, 30-75 years, undergoing surgery for breast cancer and without signs of depression on Major Depression Inventory (MDI) were included 1 week before surgery and received 6 mg oral melatonin or placebo for 3 months. The primary outcome was the incidence of depressive symptoms measured by MDI. The secondary outcomes were area under the curve (AUC) for the subjective parameters. 54 patients were randomized to melatonin (n = 28) or placebo (n = 26) and 11 withdrew from the study (10 placebo group and 1 melatonin group, P = 0.002). The risk of developing depressive symptoms was significantly lower with melatonin than with placebo (3 [11 %] of 27 vs. 9 [45 %] of 20; relative risk 0.25 [95 % CI 0.077-0.80]), giving a NNT of 3.0 [95 % CI 1.7-11.0]. No significant differences were found between AUC for the subjective parameters. No differences in side effects were found (P = 0.78). Melatonin significantly reduced the risk of depressive symptoms in women with breast cancer during a three-month period after surgery.

Effects of erythropoietin on cognitive impairment and prefrontal cortex activity across affective disorders: A randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Persistent cognitive impairment is frequent across bipolar disorder (BD) and major depressive disorder (MDD), highlighting an urgent need for pro-cognitive treatments. AIM: This study investigated effects of erythropoietin (EPO) on cognitive impairment and dorsal prefrontal cortex (dPFC) activity in affective disorders. METHODS: In this randomized, double-blinded, placebo-controlled trial, cognitively impaired patients with remitted BD or MDD received 1 weekly recombinant human EPO (40,000 IU/mL) or saline infusion for a 12-week period. Assessments were conducted at baseline, after 2 weeks of treatment (week 3), immediately after treatment (week 13) and at 6-months follow-up. Participants underwent functional MRI during performance on a n-back working memory (WM) task at baseline and week 3, and for a subgroup 6 weeks post-treatment (week 18). The primary outcome was a cognitive composite score at week 13, whereas secondary outcomes comprised sustained attention and functioning. WM-related dPFC activity was a tertiary outcome. RESULTS: Data were analysed for 101 of the 103 included patients (EPO, n = 58; saline, n = 43). There were no effects of EPO over saline on any cognitive or functional outcomes or on WM-related dPFC activity. CONCLUSIONS: The absence of treatment-related changes in cognition and neural activity was unexpected and contrasts with multiple previous preclinical and clinical studies. It is possible that the lack of effects resulted from a recent change in the manufacturing process for EPO. Nevertheless, the findings support the validity of dPFC target engagement as a biomarker model for pro-cognitive effects, according to which treatments that do not improve cognition should not modulate dPFC activity. TRIAL REGISTRATIONS: EudraCT no.: 2016-004023-24; ClinicalTrials.gov identifier: NCT03315897.