Dialysis withdrawal and symptoms of anxiety and depression: a prospective cohort study.

BACKGROUND: An important aspect of end-of-life decisions in dialysis patients is elective withdrawal from dialysis therapy. Several studies have shown that clinical factors, such as comorbidity, play a role in dialysis withdrawal. The role of symptoms of anxiety and depression is largely unknown. The. METHODS: A prospective multi-center study has been set up to investigate anxiety and depressive symptoms longitudinally in dialysis patients. Anxiety and depressive symptoms were investigated using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) as baseline. Adverse events, including dialysis withdrawal and mortality were registered during follow-up. Multivariable cox proportional hazard models were used with anxiety and depression as the independent variable and dialysis withdrawal as the outcome variable. Models included age, sex, ethnicity and a set of clinical comorbidities. RESULTS: A total of 687 patients were included between 2012 and 2017, with a median follow-up of 3.2 years. A total of 48 patients (7%) withdrew from dialysis therapy, and subsequently deceased. Anxiety and depressive symptoms at baseline showed an association with dialysis withdrawal with hazard ratios of 2.31 (1.09-4.88) for anxiety and 2.56 (1.27-5.15) for depressive symptoms, independent of somatic comorbidities. DISCUSSION: Withdrawal from dialysis therapy is associated with anxiety and depressive symptoms. Dialysis patients with more severe depressive and anxiety symptoms were more vulnerable for dialysis withdrawal. Insight in factors that play a role in dialysis withdrawal could aid patients and clinicians making an informed decision and develop clinical guidelines.

Brain development after intrauterine exposure to lithium: A magnetic resonance imaging study in school-age children.

OBJECTIVE: Lithium is often continued during pregnancy to reduce the risk of perinatal mood episodes for women with bipolar disorder. However, little is known about the effect of intrauterine lithium exposure on brain development. The aim of this study was to investigate brain structure in children after intrauterine exposure to lithium. METHODS: Participants were offspring, aged 8-14 years, of women with a diagnosis of bipolar spectrum disorder. In total, 63 children participated in the study: 30 with and 33 without intrauterine exposure to lithium. Global brain volume outcomes and white matter integrity were assessed using structural MRI and diffusion tensor imaging, respectively. Primary outcomes were total brain, cortical and subcortical gray matter, cortical white matter, lateral ventricles, cerebellum, hippocampus and amygdala volumes, cortical thickness, cortical surface area and global fractional anisotropy, and mean diffusivity. To assess how our data compared to the general population, global brain volumes were compared to data from the Generation R study (N = 3243). RESULTS: In our primary analyses, we found no statistically significant associations between intrauterine exposure to lithium and structural brain measures. There was a non-significant trend toward reduced subcortical gray matter volume. Compared to the general population, lithium-exposed children showed reduced subcortical gray and cortical white matter volumes. CONCLUSION: We found no differences in brain structure between lithium-exposed and non-lithium-exposed children aged 8-14 years following correction for multiple testing. While a rare population to study, future and likely multi-site studies with larger datasets are required to validate and extend these initial findings.

Neurodevelopment in school-aged children after intrauterine exposure to antipsychotics.

OBJECTIVE: Antipsychotics are increasingly prescribed in pregnancy, yet little is known about potential long-term developmental effects on children. In this study, we investigated the effect of prenatal antipsychotic exposure on neurodevelopmental functioning in school-aged children. METHODS: We performed a cross-sectional neurodevelopmental assessment of 91 children aged 6-14 years whose mothers had severe mental illness and were either exposed or unexposed to antipsychotic medication during pregnancy. Neurodevelopmental outcomes were assessed using validated neurodevelopmental assessment instruments to examine the child's IQ and global cognitive functioning, and the presence of any psychiatric disorders and/or learning problems in the child was assessed by parental report. RESULTS: No statistically significant associations were found between antipsychotic exposure during pregnancy and either adverse neurodevelopmental outcomes (IQ, neuropsychological function), likelihood of psychiatric diagnosis, or learning problems based on parental report. Analyses were likely limited in power to detect subtler differences in neurodevelopmental functioning because of small sample size and heterogeneity of the sample. CONCLUSIONS: In this exploratory cohort study, intrauterine exposure to antipsychotics was not associated with any adverse effect on IQ or neurodevelopmental functioning in a cohort of school-aged children (6-14 years).

Construct Validity and Responsiveness of Instruments Measuring Depression and Anxiety in Pregnancy: A Comparison of EPDS, HADS-A and CES-D.

Depression and anxiety occur frequently in pregnancy and may have unfavourable consequences for mother and child. Therefore, adequate symptom measurement seems important. Commonly used instruments are the Center for Epidemiologic Studies Depression Scale (CES-D), the Edinburgh Postpartum Depression Scale (EPDS), and the Hospital Anxiety and Depression Scale, anxiety subscale (HADS-A). We compared the (1) structural and (2) longitudinal validity of these instruments. The data originated from a study on the effectiveness of an Internet intervention for pregnant women with affective symptoms. (1) A confirmatory factor analysis was used to estimate the construct validity. The theoretical factorial structure that was defined in earlier studies of the CES-D and the EPDS, but not the HADS-A, could be sufficiently replicated with acceptable CFI and RMSEA values. (2) Since there were two measurements in time, the hypotheses concerning plausible directions of the change scores of subscales that were (un)related to each other could be formulated and tested. In this way, longitudinal validity in the form of responsiveness was estimated. Ten of sixteen hypotheses were confirmed, corroborating the longitudinal validity of all constructs, except anhedonia, probably due to inconsistent conceptualization. The HADS-A seems less suitable to screen for anxiety in pregnancy. Anhedonia needs better conceptualisation to assess the change of symptoms over time with the CES-D and the EPDS.

Complications and Healthcare Consumption of Pregnant Women with a Migrant Background: Could There be an Association with Psychological Distress?

OBJECTIVE: Previous studies reported less prenatal healthcare consumption and more perinatal complications in women with a migrant background. Hence, we investigated in a country with free healthcare access whether women with a migrant background differed with respect to pregnancy complications, healthcare consumption and in terms of associations with psychological distress in comparison to native Dutch. METHODS: We included 324 native Dutch and 303 women with a migrant background, who visited two hospitals in Amsterdam for antenatal care between 2014 and 2015. Participants completed the Edinburgh Postnatal Depression Scale, the Hospital Depression and Anxiety Scale, and sociodemographic questions. Complications and healthcare consumption during pregnancy were extracted from medical records. Regression analyses were used with adjustment for covariates. RESULTS: Except for gestational diabetes [adjusted OR = 3.09; 95% CI = (1.51, 6.32)], no differences were found between groups in perinatal complications [OR = 1.15; 95% CI = (0.80, 1.64)], nor in healthcare consumption [OR = 0.87; 95% CI = (0.63, 1.19)]. Women with a migrant background reported more depressive symptoms [Cohen's d = 0.25; 95% CI = (0.10, 0.41)], even after adjustment for socio-economic factors. Psychological distress was associated with more hospital admissions during pregnancy. When experiencing depressive symptoms, women with a migrant background had an increased risk to be admitted [OR = 1.11; 95% CI = (1.01, 1.21)]. CONCLUSIONS FOR PRACTICE: This cohort study found no differences in pregnancy-related complications, except for diabetes, nor different healthcare consumption, in women with a migrant background versus native Dutch, in a country with free health care access. However, women with a migrant background experienced more depressive symptoms, and when depressed their risk for hospital admission increased. Additional research is warranted to improve healthcare for this population.

The effect of prenatal lithium exposure on the neuropsychological development of the child.

OBJECTIVES: Lithium is an effective treatment for bipolar disorder, also during pregnancy to prevent the recurrence of episodes in the perinatal period. Little is known about the neuropsychological development of lithium-exposed offspring. The current study was designed to investigate neuropsychological functioning in lithium-exposed children with the aim to provide further knowledge on the long-term effects of lithium use during pregnancy. METHODS: Participants were offspring of women with a diagnosis of bipolar spectrum disorder, aged 6-14 years. In total, 99 children participated in the study, 56 were exposed to lithium in utero and 43 were not exposed to lithium. Neuropsychological tests were administered, including the Snijders-Oomen Nonverbal Intelligence Test and the NEPSY-II-NL assessment. Linear and negative binomial regression models were used to investigate the association between prenatal lithium exposure and neuropsychological functioning. In secondary analyses, the association between lithium blood level during pregnancy and neuropsychological functioning was assessed. Additionally, norm scores and percentiles for task outcomes were calculated. RESULTS: Lithium use during pregnancy was associated with the total number of mistakes made on the Auditory Attention task, but not statistically significant after full adjustment for potential confounding factors. No association between prenatal lithium exposure and IQ was found. Also, no relationship between lithium blood level during pregnancy and neuropsychological functioning was found after adjustment for potential confounders. Task outcomes in both groups were comparable to the general population. CONCLUSION: In this study, we found no evidence for significantly altered neuropsychological functioning of lithium-exposed children at the age of 6-14 years, when compared to non-lithium-exposed controls.

The course of bipolar disorder in pregnant versus non-pregnant women.

BACKGROUND AND RATIONALE: Although it has been suggested that pregnancy may influence the course of bipolar disorder (BD), studies show contradictory results. Until now, no studies included a finegrained validated method to report mood symptoms on a daily basis, such as the lifechart method (LCM). The aim of the present study is to investigate the course of BD during pregnancy by comparing LCM scores of pregnant and non-pregnant women. METHODS: Study design: Comparison of LCM scores of two prospective observational BD cohort studies, a cohort of pregnant women (n = 34) and a cohort of non-pregnant women of childbearing age (n = 52). Main study parameters are: (1) proportions of symptomatic and non-symptomatic days; (2) symptom severity, frequency, and duration of episodes; (3) state sequences, longitudinal variation of symptom severity scores. RESULTS: No differences in clinical course variables (symptomatic days, average severity scores, frequency, and duration of episodes in BD were found between pregnant and non-pregnant women. With a combination of State Sequence Analysis (SSA) and cluster analysis on the sequences of daily mood scores three comparable clusters were found in both samples: euthymic, moderately ill and severely ill. The distribution differences between pregnant and non-pregnant women were significant, with a majority of the pregnant women (68%) belonging to the moderately ill cluster and a majority of the non-pregnant women (46%) to the euthymic cluster. In pregnant women the average daily variation in mood symptoms as assessed with Shannon's entropy was less than in non-pregnant women (respectively 0.43 versus 0.56). CONCLUSIONS: Although the use of daily mood scores revealed no difference in overall course of BD in pregnant versus non-pregnant women, more pregnant than non-pregnant women belonged to the moderately ill cluster, and during pregnancy the variation in mood state was less than in non-pregnant women. Further research is necessary to clarify these findings.

Treatment of current depressive symptoms in dialysis patients: A systematic review and meta-analysis.

OBJECTIVE: Symptoms of depression are highly prevalent and undertreated in dialysis patients. To aid clinicians in offering treatment to patients with depression, we conducted a systematic review and meta-analysis on the treatment of current depressive symptoms in dialysis patients. METHODS: Nine databases were searched on January 8th 2020 for randomized controlled trials on the treatment of depressive symptoms in dialysis patients. In contradiction to previous reviews, we only included studies who selected patients with a score above a defined cut-off for depressive symptoms and used an inactive control group, to investigate the effectiveness of treatments in currently depressed patients. All interventions aimed to treat depressive symptoms were accepted for inclusion. Standardized mean differences were calculated in a random effect meta-analysis. RESULTS: Seventeen studies were included in the systematic review (1640 patients). Nine studies could be included in the meta-analysis. A pooled analysis of 7 studies on psychotherapy showed a standardized mean difference of -0.48 [-0.87; -0.08], with a moderate heterogeneity (I2 = 52%, X2 = 12.56, p = .05). All studies on psychotherapy performed a per protocol analysis and scored high on potential bias. A pooled analysis of two studies on SSRI's showed no statistically significant improvement of depressive symptoms (SMD -0.57 [-6.17; 5.02], I2 = 71%, X2 = 0.2474, p = .06). CONCLUSIONS: Psychotherapy is a promising treatment for currently depressed dialysis patients, although quality of evidence is low. More evidence is needed regarding the efficacy of SSRI's, exercise therapy and dietary supplements in this population. PROSPERO: CRD42018073969.

The influence of perioperative interventions targeting psychological distress on clinical outcome after total knee arthroplasty.

Our aim was to assess the effect of perioperative interventions targeting psychological distress on clinical outcome after total knee arthroplasty (TKA). We searched studies on the effect of perioperative interventions focused on psychological distress used in conjunction with TKA on pain, function, and quality of life (QoL) on PubMed, Embase.com, PsycINFO/OVID, CENTRAL, the Cochrane Database of Systematic Reviews, Scopus, and Web of Science. We included 40 studies (22 RCTs, ten cohort studies, and eight quasi-experimental studies) with a total of 3846 patients. We graded the quality of evidence as low for pain and function and as moderate for QoL. Patients receiving music, education, cognitive behavioural therapy, guided imagery, pain coping skills training, Reiki, occupational therapy with self-monitoring, and biofeedback-assisted progressive muscles relaxing training had lower pain scores or declined opioid prescriptions after TKA. Pain coping skills training, audio recording-guided imagery scripts, video promoting self-confidence, psychological therapies by video, Reiki, music, occupational therapy with self-monitoring, education, and psychotherapy improved postoperative functional outcome. Education through an app improved QoL after TKA. The studies in our systematic review show that perioperative interventions targeting psychological distress for patients receiving TKA seem to have a positive effect on postoperative pain, function, and QoL. RCTs with strict methodological safeguards are still needed to determine if perioperative interventions focused on psychological distress should be used in conjunction with TKA. These studies should also assess which type of intervention will be most effective in improving patient-reported outcome measures and declining opioid prescriptions.

General distress and symptoms of anxiety and depression: A factor analysis in two cohorts of dialysis patients.

OBJECTIVE: Depression and anxiety often coexist in patients with end-stage-kidney disease. Recently, studies showed that a composite 'general distress score' which combines depression and anxiety symptoms provides a good fit in dialysis and oncology patients. We aim to investigate if the three most frequently used self-report questionnaires to measure depression and anxiety in dialysis patients are sufficiently unidimensional to warrant the use of such a general distress score in two cohorts of dialysis patients. METHODS: This study includes two prospective observational cohorts of dialysis patients (total n = 749) which measured depression and anxiety using Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Hospital Anxiety and Depression Scale (HADS). Confirmatory factor analyses was used to investigate both a strictly unidimensional model and a multidimensional bifactor model that includes a general distress, depression and anxiety factor. The comparative fit index (CFI) and The Root Mean Square Error of Approximation (RMSEA) were used as model fit indices. RESULTS: Factor analysis did not show a good fit for a strictly unidimensional general distress factor for both the BDI/BAI and HADS (CFI 0.690 and 0.699, RMSEA 0.079 and 0.125 respectively). The multidimensional model performed better with a moderate fit for the BDI/BAI and HADS (CFI 0.873 and 0.839, RMSEA 0.052 and 0.102). CONCLUSIONS: This data shows that the BDI/BAI and HADS are insufficiently unidimensional to warrant the use of a general distress score in dialysis patients without also investigating anxiety and depression separately. Future research is needed whether the use of a general distress score might be beneficial to identify patients in need of additional (psychological) support.

Symptom dimensions of anxiety and their association with mortality, hospitalization and quality of life in dialysis patients.

OBJECTIVE: Symptoms of anxiety are highly prevalent in dialysis patients and are associated with adverse clinical outcomes. Identifying symptom dimensions may help to understand the pathophysiology, improve screening and guide treatment. Currently, there are no data on symptom dimensions of anxiety in dialysis patients. This study aimed to identify the best fitting dimensional model for anxiety in dialysis patients and assess the association between symptom dimensions of anxiety and adverse clinical outcomes. METHODS: This study is a prospective observational cohort study including patients from 10 urban dialysis centers between 2012 and 2017. Anxiety symptoms were measured using the self-reported questionnaire Beck Anxiety Inventory. Confirmatory factor analysis was used to identify symptom dimensions. The association between dimensions and mortality, hospitalization and quality of life was investigated using stepwise cox, poisson and lineair regression models. Multivariable models included demographic, social, laboratory and clinical variables to adjust for possible confounding. RESULTS: In total 687 chronic dialysis patients were included. A Somatic and Subjective anxiety dimension were identified. Only Somatic anxiety symptoms showed an association with increased risk of hospitalization and mortality (Rate Ratio 1.73 (1.45-2.06) p = .007 and Hazard Ratio 1.65 (1.15-2.37) p = .007 respectively). These associations were independent from somatic comorbidity. All symptom dimensions of anxiety showed an association with Quality of Life. CONCLUSION: This study shows that anxiety is common in chronic dialysis patients and comprises of a somatic, subjective, and a total score. The discrimination between anxiety dimensions can be useful for clinical practice, as they are related to different clinical outcomes.

Diurnal rhythmicity in breast-milk glucocorticoids, and infant behavior and sleep at age 3 months.

PURPOSE: In previous studies, associations between breast-milk cortisol levels obtained on one occasion and infant neurodevelopment were demonstrated. However, more recent evidence indicates that breast-milk cortisol and cortisone concentrations follow the diurnal rhythm of maternal hypothalamus-pituitary-adrenal axis, peaking in the early morning and with a nadir at midnight. We studied associations between breast-milk glucocorticoid (GC) rhythmicity, and infant behavior and sleep. METHODS: We included 59 mothers, and their infants, of whom 17 had consulted an expert center during pregnancy for an increased risk of psychological distress. At 1 month postpartum, breast milk was sampled (on average six times) over a 24 h period for assessment of cortisol and cortisone using LC-MS/MS, and experienced maternal distress was assessed using the Hospital Anxiety and Depression Scale questionnaire. Three months after birth, infant behavior was assessed with the Infant Behavior Questionnaire, and infant sleep pattern was quantified by questionnaire. Associations between breast-milk GC rhythm parameters (maximum, delta, and Area Under the Curve increase and ground) and infant behavior and sleep were tested with linear regression analyses. RESULTS: No consistent associations between breast-milk GC rhythm parameters and infant behavior or sleep were found. CONCLUSIONS: Breast-milk GC rhythmicity at 1 month postpartum was not associated with infant behavior or sleep at the age of 3 months. Findings from previous studies linking breast-milk cortisol to infant neurodevelopment might be biased by the lack of GC measurements across the full diurnal cycle, and should therefore be interpreted with caution.

The Effectiveness of a Guided Internet-Based Tool for the Treatment of Depression and Anxiety in Pregnancy (MamaKits Online): Randomized Controlled Trial.

BACKGROUND: Pregnant women with symptoms of depression or anxiety often do not receive adequate treatment. In view of the high incidence of these symptoms in pregnancy and their impact on pregnancy outcomes, getting treatment is of the utmost importance. A guided internet self-help intervention may help to provide more women with appropriate treatment. OBJECTIVE: This study aimed to examine the effectiveness of a guided internet intervention (MamaKits online) for pregnant women with moderate to severe symptoms of anxiety or depression. Assessments took place before randomization (T0), post intervention (T1), at 36 weeks of pregnancy (T2), and 6 weeks postpartum (T3). We also explored effects on perinatal child outcomes 6 weeks postpartum. METHODS: This randomized controlled trial included pregnant women (<30 weeks) with depressive symptoms above threshold (ie, Center for Epidemiological Studies Depression scale [CES-D] >16) or anxiety above threshold (ie, Hospital Anxiety and Depression Scale-Anxiety subscale [HADS-A] >8) or both of them. Participants were recruited via general media and flyers in prenatal care waiting rooms or via obstetricians and midwives. After initial assessment, women were randomized to (1) MamaKits online in addition to treatment as usual or (2) treatment as usual (control condition). MamaKits online is a 5-week guided internet intervention based on problem solving treatment. Guidance was was provided by trained students pursuing a Master's in Psychology. Outcomes were based on a Web-based self-report. Women in the control condition were allowed to receive the intervention after the last assessment (6 weeks postpartum). RESULTS: Of the 159 included women, 79 were randomized to MamaKits online, 47% (79/37) of whom completed the intervention. Both groups showed a substantial decrease in affective symptoms on the CES-D, HADS-A, and Edinburgh Postnatal Depression Scale over time. In the intervention group, affective symptoms decreased more than that in the control group, but between-group effect sizes were small to medium (Cohen d at T3=0.45, 0.21, and 0.23 for the 3 questionnaires, respectively) and statistically not significant. Negative perinatal child outcomes did not differ between the 2 groups (χ21=0.1; P=.78). Completer analysis revealed no differences in outcome between the treatment completers and the control group. The trial was terminated early for reasons of futility based on the results of an interim analysis, which we performed because of inclusion problems. CONCLUSIONS: Our study did show a significant reduction in affective symptoms in both groups, but the differences in reduction of affective symptoms between the intervention and control groups were not significant. There were also no differences in perinatal child outcomes. Future research should examine for which women these interventions might be effective or if changes in the internet intervention might make the intervention more effective. TRIAL REGISTRATION: Netherlands Trial Register NL4162; https://tinyurl.com/sdckjek.

Biphasic Glucocorticoid Rhythm in One-Month-Old Infants: Reflection of a Developing HPA-Axis?

CONTEXT: The hypothalamus-pituitary-adrenal (HPA) axis displays a diurnal rhythm. However, little is known about its development in early life. OBJECTIVE: To describe HPA-axis activity and study possible influencing factors in 1-month-old infants. DESIGN: Observational. SETTING: Amsterdam University Medical Center, location VU University Medical Center (VUMC), and Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam. PARTICIPANTS: Fifty-five mother-infant pairs. INTERVENTIONS: Collection of breast milk and infants' saliva 1 month postpartum for analysis of glucocorticoids (GCs; ie, cortisol and cortisone) using liquid chromatography- tandem mass spectrometry. MAIN OUTCOME MEASURE: GC rhythm in infants' saliva and associations with vulnerability for maternal psychological distress (increased Hospital Anxiety and Depression Scale [HADS] score) or consultation at the Psychiatric Obstetric Pediatric (POP clinic), season at sampling, sex, and breast milk GC rhythmicity analyzed with SigmaPlot 14.0 software (Systat Software, San Jose, CA, USA) and regression analyses. RESULTS: A significant biphasic GC rhythm was detected in infants, with mean peaks [standard error of the mean, SEM] at 6:53 am [1:01] and 18:36 pm [1:49] for cortisol, and at 8:50 am [1:11] and 19:57 pm [1:13] for cortisone. HADS score, POP consultation, season at sampling, and sex were not associated with the infants' GC rhythm. Breast milk cortisol maximum was positively associated with infants' cortisol area-under-the-curve (AUC) increase and maximum. Higher breast milk cortisone AUC increase, AUC ground, and maximum were associated with an earlier maximum in infants. Breast milk and infant GC concentrations were associated between 6:00 am and 9:00 am. CONCLUSIONS: A biphasic GC rhythm, peaking in the morning and evening, was seen in 1-month-old infants at a group level. Breast milk GC parameters might be associated with the infants' GC rhythm, possibly caused by a signaling effect of breast milk GCs, or as an associative effect of increased mother-infant synchrony. These results contribute to an increased understanding of early life HPA-axis development.

The (cost) effectiveness of guided internet-based self-help CBT for dialysis patients with symptoms of depression: study protocol of a randomised controlled trial.

BACKGROUND: Only a minority of dialysis patients with depressive symptoms are diagnosed and receive treatment. Depressive symptoms are highly prevalent in this population and are associated with adverse clinical outcomes. Underlying factors for this undertreatment may be the lack of evidence for the safety and effectivity of antidepressant medication, the reluctance of patients to adhere to antidepressant medication, the lack of mental healthcare provision in somatic healthcare environments and end-stage renal disease (ESRD) related physical limitations that complicate face-to-face psychotherapy. Guided Internet-based self-help treatment has demonstrated to be effective for depressive symptoms in other chronic patient populations and may overcome these barriers. The aim of this study is to investigate the (cost) effectiveness of a guided Internet-based self-help intervention for symptoms of depression in dialysis patients. METHODS: This study is a cluster randomized controlled trial (RCT) that investigates the effectiveness of a 5-week Internet-based self-help Problem Solving Therapy (PST) for depressive symptoms in dialysis patients. Depressive symptoms will be measured using the Beck Depression Inventory - second edition (BDI-II), with a cut-off score of ≥10. We aim to include 206 dialysis patients with depressive symptoms who will be cluster randomized to the intervention or the Care as Usual (CAU) control group. Secondary outcomes will include anxiety symptoms, quality of life, economic costs and clinical outcomes, such as inflammatory factors and hair cortisol levels. Assessments will take place at baseline (T0), 2 weeks after intervention (T1) and 6 months (T2), 12 months (T3) and 18 months (T4) after intervention. The control group will be measured at the same time points. Analysis will be based on the intention-to-treat principle. Mixed models will be used to assess the changes within each condition between pre-treatment and post-treatment. DISCUSSION: If demonstrated to be (cost) effective, Internet-based PST will offer new possibilities to treat dialysis patients with depressive symptoms and to improve their quality of care. TRIAL REGISTRATION: Dutch Trial Register: Trial NL6648 (NTR6834) (prospectively registered 13th November 2017).

Diabetes distress is associated with adverse pregnancy outcomes in women with gestational diabetes: a prospective cohort study.

BACKGROUND: Around 12% of pregnant women develop gestational diabetes mellitus (GDM), which is associated with increased health risks for both mother and child and pre- and postpartum depression. Little is known about the relationship of GDM with diabetes-specific emotional distress (diabetes distress). The aims of this study are to assess the prevalence of diabetes distress in GDM and its association with adverse pregnancy outcomes. METHODS: A prospective cohort study was carried out in an Amsterdam based teaching hospital with an ethnic diverse population. Women diagnosed with GDM completed a set of questionnaires at three time points. Questionnaires consisted of Problem Areas in Diabetes Scale 5 (PAID-5) for diabetes distress (T0-T1), Patient Health Questionnaire 9 (PHQ-9) for depressive symptoms (T0-T2), and questions to assess adverse pregnancy outcomes (T2). Adverse pregnancy outcomes (collected via self-report and if feasible from the medical records) were defined as hypertension, pre-eclampsia, caesarean section, severe perineal tearing, postpartum hemorrhage, postpartum depression, shoulder dystocia, neonatal hospitalization, macrosomia, jaundice, hypoglycemia and other (among which low heart rate, fever, hypoxia). Adverse pregnancy outcomes were dichotomized into none and 1 or more. Additional information was collected from the medical charts. Missing data were imputed via predictive mean matching and a multivariable logistic regression analysis was performed with diabetes distress, depressive symptoms, socioeconomic status, parity and ethnicity as predictors and age, HbA1c, and BMI as covariates. RESULTS: A total of 100 women were included, mean age 32.5 (4.1), mean BMI 26.7 (4.8), 71% were of non-Dutch ethnic background. Elevated diabetes distress (PAID score ≥ 8) was reported by 36% of the women. Multivariable logistic regression analyses revealed that both high diabetes distress (OR 4.70, p = .02) and parity (OR 0.21, p = .02) but not antepartum depressive symptoms were related to adverse pregnancy outcomes. CONCLUSIONS: Diabetes distress is likely in women with GDM and our findings suggest an association between both diabetes distress, parity and adverse pregnancy outcomes in women with GDM. This warrants replication and further research into the underlying mechanisms explaining the impact of diabetes distress in GDM and potential interventions to reduce distress.

Ethnic Differences in the Association of Depressive Symptoms with Clinical Outcome in Dialysis Patients.

BACKGROUND: Studies show mixed results on the association between depressive symptoms and adverse clinical outcomes in patients on dialysis therapy. Ethnicity may play a role in these heterogeneous results. No studies have investigated the interplay between ethnicity and depressive symptoms on clinical outcome in this patient population. This study aims to examine interaction between ethnicity and depressive symptoms on hospitalization and mortality in dialysis patients. METHODS: A multi-ethnic cohort in 10 dialysis centers included 687 dialysis patients between 2012 and 2017, with an average follow-up of 3.2 years. Depressive symptoms were measured using the Beck Depression Inventory. Interaction was assessed by investigating excess risk on an additive scale using both absolute rates and relative risks. Multivariable regression models included demographic, social, and clinical variables. RESULTS: Adverse outcomes are more pronounced in native patients, compared to immigrant patients. The risk for mortality and hospitalization is considerably higher in native patients compared to immigrants. An excess risk on an additive scale indicates the presence of possible causal interaction. CONCLUSIONS: Depressive symptoms are a risk factor for hospitalization and mortality, especially in native dialysis patients. Adverse clinical events associated with depressive symptoms differ among ethnic groups. This differential association could play a role in the conflicting findings in literature. Ethnicity is an important factor when investigating depressive symptoms and clinical outcome in dialysis patients. Future research should focus on the possible mechanisms and pathways involved in these differential associations.

Dimensions of Depressive Symptoms and Their Association With Mortality, Hospitalization, and Quality of Life in Dialysis Patients: A Cohort Study.

OBJECTIVE: Unraveling specific dimensions of depressive symptoms may help to improve screening and treatment in dialysis patients. We aimed to identify the best-fitting factorial structure for the Beck Depression Inventory-II (BDI) in dialysis patients and to assess the relation of these structure dimensions with quality of life (QoL), hospitalization, and mortality. METHODS: This prospective study included chronic dialysis patients from 10 dialysis centers in five hospitals between 2012 and 2017. Dimensions of depressive symptoms within the BDI were analyzed using confirmatory factor analysis. To investigate the clinical impact of these dimensions, the associations between symptom dimensions and QoL, hospitalization rate, and mortality were investigated using logistic, Poisson, and Cox proportional hazard regression models. Multivariable regression models included demographic, social, and clinical variables. RESULTS: In total, 687 dialysis patients were included. The factor model that included a general and a somatic factor provided the best-fitting structure of the BDI-II. Only the somatic dimension scores were associated with all-cause mortality (hazard ratio of 1.7 [1.2-2.5], p < .007) in the multivariable model. All dimensions were associated with increased hospitalization rate and reduced QoL. CONCLUSIONS: The somatic dimension of the BDI-II in dialysis patients was associated with all-cause mortality, increased hospitalization rate, and reduced QoL. Other dimensions were associated with hospitalization rate and decreased QoL. These findings show that symptom dimensions of depression have differential association with adverse clinical outcomes. Future studies should take symptom dimensions into account when investigating depression-related pathways, screening, and treatment effects in dialysis patients.

Anxiety Symptoms, Mortality, and Hospitalization in Patients Receiving Maintenance Dialysis: A Cohort Study.

RATIONALE & OBJECTIVE: Anxiety symptoms are common in dialysis patients and have a large impact on quality of life. The association of anxiety symptoms with adverse clinical outcomes in dialysis patients is largely unknown. This study examined the association of anxiety symptoms with hospitalization and mortality in patients receiving maintenance dialysis. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Maintenance dialysis patients treated at 10 dialysis centers in the Netherlands between 2012 and 2016. EXPOSURES: Time-varying symptoms of anxiety and depression using the Beck Anxiety Inventory and Beck Depression Inventory. OUTCOMES: All-cause mortality, 1-year hospitalization rate, and hospital length of stay. ANALYTICAL APPROACH: Cox proportional hazards and Poisson regression models adjusted for sociodemographic and clinical variables. Sensitivity analyses included multiple imputation of missing data and restriction to incident patients only. RESULTS: 687 patients were included, composed of 433 prevalent and 242 incident dialysis patients. Median follow-up time was 3.1 (IQR, 3.0-3.5) years, during which 172 deaths occurred. 22% of patients had anxiety symptoms and 42% had depressive symptoms. Anxiety symptoms were associated with all-cause mortality and 1-year hospitalization rate and length of stay in all multivariable models. Anxiety symptoms showed a clear dose-response relationship with mortality. LIMITATIONS: Depression and anxiety often coexist and share symptoms. The observational design of this study limits inferences about causal mechanisms between anxiety and clinical outcomes. CONCLUSIONS: Anxiety symptoms are independently associated with increased risk for mortality and 1-year hospitalization. Anxiety symptoms are a clinically relevant risk factor for morbidity and mortality in dialysis patients and warrant further research on effective treatment.

Risk of recurrence of mood disorders during pregnancy and the impact of medication: A systematic review.

BACKGROUND: Mood disorders can be difficult to treat during pregnancy. There is still lack of evidence whether pregnancy influences their natural course and whether continuation of pharmacotherapy, despite potential risks for the unborn child, is beneficial in preventing recurrence of mood episodes during pregnancy. METHODS: Systematic review conducted according to the PRISMA guidelines, searching Pubmed, PsycINFO, Embase and Cochrane databases up till January 9th, 2018. Recurrence rates and various measures of risk were calculated. RESULTS: Out of 1387 articles from an initial search 22 studies met the inclusion criteria. Included studies reported a wide variation in the recurrence rate of bipolar disorder and major depressive disorder during pregnancy (BD: mean = 19%, range = 4%-73%; MDD: mean = 8%, range = 1%-75%). Observational data showed a relative risk reduction of maintenance therapy during pregnancy of 66% in women with BD and 54% for women with MDD, a significant difference (95% CI 9.4-14.6; p < 0.001). LIMITATIONS: heterogeneous samples, study designs, and reported outcomes in included studies. CONCLUSIONS: Despite the importance of the topic there is a paucity of evidence on recurrence rates of mood episodes during pregnancy among women with MDD or BD. Unlike the impact of the postpartum period, it is still uncertain whether the course of mood disorders is influenced by pregnancy. Non-randomized studies show that maintenance pharmacotherapy during pregnancy in women with mood disorders significantly (p < 0.01) reduces the risk of recurrence.