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BACKGROUND: Women with bipolar I disorder are at high risk for severe episodes after childbirth, but there is no study that provides an overview on bipolar episode risk both during pregnancy and after childbirth, miscarriage and induced abortion. The aim of this study was to determine the episode risk during all pregnancy outcomes subdivided by first and subsequent pregnancies. METHODS: Participants were 436 women with bipolar I disorder from the Dutch Bipolar Cohort, having 919 pregnancies of which 762 resulted in a live childbirth, 118 ended in a miscarriage and 39 ended in induced abortion. Women reported on the occurrence of manic or depressed episodes during the perinatal period. Information about medication use was obtained by questionnaires. RESULTS: Episode risk was 5.2% during pregnancy, and 30.1% in the postpartum period, with a peak in the early postpartum period. Risk of an episode was highest after live birth (34.4%), and lower after miscarriage (15.2%) and induced abortion (27.8%). Women with an episode during pregnancy or postpartum were less likely to have a second child compared to women with an uneventful first pregnancy (cOR=0.34; 95%CI: 0.22-0.51; p

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.

Objective: The primary indication for electroconvulsive therapy is medication-resistant major depression. There is some evidence that combining electroconvulsive therapy with an antidepressant, instead of electroconvulsive therapy monotherapy, might improve remission rates. However, data on this topic have not been systematically studied. We undertook a systematic review and meta-analysis to determine the effectiveness of an adjuvant antidepressant during electroconvulsive therapy for major depression. Methods: Embase, Medline Ovid, Web of Science, Cochrane Central, PsychINFO Ovid and Google Scholar were searched up to January 2019. Randomized controlled trials and cohort studies reporting on the influence of an adjuvant antidepressant on the efficacy of electroconvulsive therapy for major depression were included. Authors independently screened records, extracted data and assessed study quality. We reported this systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Nine studies were included in the meta-analysis. The meta-analysis revealed a significant advantage of adjuvant antidepressants versus placebo. The overall effect size per category of antidepressant was as follows: tricyclic antidepressants: Hedges’ g 0.32 (95% confidence interval: [0.14, 0.51]) ( k = 6) with low heterogeneity ( I2: 4%, p = 0.39); selective serotonin reuptake inhibitors/serotonin noradrenaline reuptake inhibitors: Hedges’ g 0.27 (95% confidence interval: [0.03, 0.52]) ( k = 2) with a lack of heterogeneity ( I2: 0%, p = 0.89); and monoamine oxidase inhibitors: Hedges’ g 0.35 (95% confidence interval: [−0.07, 0.77]) with moderate heterogeneity ( I2: 43%, p = 0.17) ( k = 3). Conclusion: An adjuvant antidepressant enhances the efficacy of electroconvulsive therapy for major depression. Tricyclic antidepressants, selective serotonin reuptake inhibitors/serotonin noradrenaline reuptake inhibitors and monoamine oxidase inhibitors showed the same effect size. However, the effect sizes of tricyclic antidepressants and monoamine oxidase inhibitors are most likely underestimated, due to insufficient doses in most of the included studies. We recommend the routine use of an adequately dosed antidepressant during electroconvulsive therapy for major depression.

Antidepressant use during pregnancy has increased over the last decades, while safety has been under debate. Our aim was to measure the international prevalence of antidepressant use before, during, and after pregnancy and examine timing, type of prescriptions and geographic variability.We searched Embase, Medline Ovid, Web of Science, Cochrane Central and Google Scholar from their inception until February 19, 2019. We determined pooled prevalence estimates of antidepressants before, during, and after pregnancy, as well as stratified according to substantive variables.We identified 40 cohorts from 15 countries, together reporting on 14,072,251 pregnancies. Included studies had a low risk of bias, often reporting on large representative cohorts. Selective serotonin reuptake inhibitors (SSRIs) were the most commonly used antidepressants during pregnancy, with an international prevalence estimate of 3.0% (95%CI 2.3;3.7). While Europe and Australasia had pooled prevalence estimates of 1.6% and 1.3% respectively, Northern America had a prevalence estimate of 5.5% (Q-value = 126.19; df = 2; p-value0.01). Highest SSRI prevalence rates were found for sertraline (1.10%), followed by citalopram and fluoxetine (0.77% and 0.76% respectively) (Q-value = 121.25; df = 5; p-value0.01). Qualitative analysis indicated an increase in antidepressant use over subsequent calendar years.Substantial heterogeneity remained unaccounted for throughout the analyses, even after accounting for hypothetical contributors.This meta-analysis revealed substantial regional differences in antidepressant use around pregnancy, which could be due to variability in prescription behavior, healthcare seeking behavior and organization of healthcare. There is an urgent need for evidence on effectiveness, benefit, and harm of antidepressants during pregnancy to guide clinical practice.

Despite increased prevalence of domestic violence and abuse (DVA), victimization through DVA often remains undetected in mental health care. To estimate the effectiveness of a system provider level training intervention by comparing the detection and referral rates of DVA of intervention community mental health (CMH) teams with rates in control CMH teams. We also aimed to determine whether improvements in knowledge, skills and attitudes to DVA were greater in clinicians working in intervention CMH teams than those working in control teams. We conducted a cluster randomized controlled trial in two urban areas of the Netherlands. Detection and referral rates were assessed at baseline and at 6 and 12 months after the start of the intervention. DVA knowledge, skills and attitudes were assessed using a survey at baseline and at 6 and 12 months after start of the intervention. Electronic patient files were used to identify detected and referred cases of DVA. Outcomes were compared between the intervention and control teams using a generalized linear mixed model. During the 12-month follow-up, detection and referral rates did not differ between the intervention and control teams. However, improvements in knowledge, skills and attitude during that follow-up period were greater in intervention teams than in control teams: β 3.21 (95% CI 1.18-4.60). Our trial showed that a training program on DVA knowledge and skills in CMH teams can increase knowledge and attitude towards DVA. However, our intervention does not appear to increase the detection or referral rates of DVA in patients with a severe mental illness. A low detection rate of DVA remains a major problem. Interventions with more obligatory elements and a focus on improving communication between CMH teams and DVA services are recommended.The trial has been registered on the ISRCTN register, number: ISRCTN14115257.

Background: While antidepressant use during pregnancy is increasingly common, there is concern about the possible effects of in-utero antidepressant exposure on the child. Our objective was to examine whether there is a dose-effect of maternal serotonin reuptake inhibitors (SRI) during pregnancy on birth outcomes. Methods: Women between 12 and 16 weeks of gestation, who were using an SRI, were eligible for participation in this nation-wide prospective observational cohort study. Recruitment took place between April 2015 and February 2018 (n = 145). SRI exposure and psychopathology symptoms were assessed throughout pregnancy. Exposure was defined as SRI standardized dose at 36 weeks of gestation and mean SRI standardized dose over total pregnancy. Multivariable linear and logistic regression were used to examine the associations with birth weight, gestational age at birth, and being small for gestational age. Results: Maternal SRI dose at 36 weeks of gestation was significantly associated with birth weight (adjusted ß = -180.7, 95%CI -301.1;-60.2, p-value < 0.01) as was mean SRI standardized dose during total pregnancy (adjusted ß = -187.3, 95%CI -322.0;-52.6, p-value < 0.01). No significant associations between maternal SRI dose and gestational age or being small for gestational age were observed. Limitations: Although prospective, we cannot make full causal inferences given that we did not randomize women to different dosages. Conclusion: These findings suggest that careful dosing of SRI use during pregnancy may prevent a negative impact on birth weight and indicate the need for further investigation of causality.

International audience; Microfluidic droplet generators excel in generating monodisperse micrometer-sized droplets and particles. However, the low throughput of conventional droplet generators hinders their clinical and industrial translation. Current approaches to parallelize microdevices are challenged by the two-dimensional nature of the standard fabrication methods. Here, we report the facile production of three-dimensionally (3D) parallelized microfluidic droplet generators consisting of stacked and radially multiplexed channel designs. Computational fluid dynamics simulations form the design basis for a microflow distributor that ensures similar flow rates through all droplet generators. Stereolithography is the selected technique to fabricate microdevices, which enables the manufacturing of hollow channels with dimensions as small as 50 μm. The microdevices could be operated up to 4 bars without structural damage, including deformation of channels, or leakage of the on-chip printed Luer-Lok type connectors. The printed microdevices readily enable the production of water-in-oil emulsions, as well as polymer containing droplets that act as templates for both solid and core-shell hydrogel microparticles. The cytocompatibility of the 3D printed device is demonstrated by encapsulating mesenchymal stem cells in hydrogel microcapsules, which results in the controllable formation of stem cell spheroids that remain viable and metabolically active for at least 21 days. Thus, the unique features of stereolithography fabricated microfluidic devices allow for the parallelization of droplet generators in a simple yet effective manner by enabling the realization of (complex) 3D designs.

Gastroesophageal reflux (GER), excessive crying, and constipation are common gastrointestinal symptoms in infancy of multifactorial origin in which psychosocial stress factors play an important role. The aims of this observational study were to investigate the presence of gastrointestinal symptoms in infants of mothers with or without a history of a psychiatric disorder, their association with maternal depressive symptoms, and the possible mediating role of bonding.One hundred one mothers with a history of a psychiatric disorder and 60 control mothers were included. Infant gastrointestinal symptoms, maternal depressive symptoms, and mother-infant bonding were assessed using validated questionnaires and diagnostic criteria at 1.5 months postpartum.The mean total score on the Infant Gastroesophageal Reflux Questionnaire Revised reported in infants of mothers with psychiatric disorder (13.4 standard deviation 5.4) was significantly higher than that in infants of control mothers (10.8 standard deviation 5.4; P = .003). No significant differences were found in the presence of excessive crying (modified Wessel criteria and subjective experience) and constipation (ROME IV criteria) between both groups. Infant GER was associated with maternal depressive symptoms (P = 0.027) and bonding problems (P = 0.001). Constipation was related to maternal depressive symptoms (P = 0.045), and excessive crying (Wessel and subjective criteria) was associated with bonding problems (P = 0.022 and P = 0.002, respectively). The effect of maternal depressive symptomatology on infant GER symptoms and excessive crying was mediated by bonding problems.Maternal psychiatric history is associated with infant gastrointestinal symptoms, in which mother-infant bonding is a mediating factor.

While it is not only important to synthesize instruments, controls, and robotics, it is also essential to connect these elements to people to achieve the future of automation. Whether in an operating room with surgical robots or in an earthquake disaster zone where an operator is aided by search and rescue drones, interaction between machines and humans is becoming central to increasing productivity. Industry 4.0 trends such as Internet of Things (IoT) and digital manufacturing are the early adopters of human-machine interfaces that support manufacturing automation. Such models must consider various aspects of process implementation such as explicit, implicit, and tacit knowledge to properly mimic a human’s performance. However, most inquiries in this field use expressed information instead of tacit knowledge due to an unfulfilled need for an industrial tacit knowledge framework. Tacit knowledge is difficult to learn and transfer if an operator’s logic is never revealed. In response, this research provides a knowledge model to structure, categorize, and reuse tacit knowledge for advanced manufacturing operations. The model is implemented in a human-robot interaction by capturing valuable experiences using digital tools such as Tecnomatix for further reuse in a variety of industrial applications.

Industry 4.0 is an important manufacturing paradigm driving research and the enhancement of Industrial Internet of Things (IIoT) technologies on a global scale. The expanding capabilities of IIoT technologies has risen to meet customer demand for intelligent, interconnected devices. Legacy Programmable Logic Controllers (PLCs) remain the industry standard for manufacturing and process control even though Free and Open Source Software (FOSS) has emerged as a feature-rich market alternative. This paper compares and contrasts traditional closed systems and new FOSS in the context of Industry 4.0 trends through a literature review and reports on the resultant capabilities of their synthesis. A methodology for linking these previously independent systems through IIoT is presented via case study using a mobile autonomous robot to interact automatically with a custom process control training bench (PCTB) in a scenario analogous to a mobile delivery robot. The novelty of this research is the synthesis of traditional closed and open systems across a new class of smart device, the semi-proprietary IIoT network bridge. Hybridization, it is concluded, presents the most advantageous features of both proprietary systems and FOSS without many of the trade-offs typically encountered when employing technologies under either paradigm.

Following the Industry 4.0 paradigm with the rise of smart factories, there is a growing need in exploring digital manufacturing tools compatible with Industrial Internet of Things (IIoT) functionalities. This paper discusses the concept of Virtual Commissioning (VC) including applications in present and near-future advanced automation and production. Specifically, global trends towards Industry 4.0 and virtual manufacturing processes are explored in addition to how and why these emerging technologies could be applied. Furthermore, the advantages of VC processes are contrasted to Traditional Physical Commissioning (TPC) to highlight the evolution of Product Lifecycle Management (PLM) software and the optimization of manufacturing processes since the turn of the century. This research aims to use state-of-the-art PLM software to replicate a physical prototype in near-perfect functionality to demonstrate the effectiveness of VC in an industrial setting. Developing a methodology for this research, the analysis is followed by a case study involving a Mini Festo Pick-and-Place (P&P) unit simulated in Siemens Tecnomatix Process Simulate and controlled via ladder logic executed in Totally Integrated Automation (TIA) Portal. As expected, the results of this case study validate the potential for optimized contemporary manufacturing solutions in which higher-quality goods are reliably produced with minimal delays at all-time low principal investments through the use of VC tools.

Objective We aimed to investigate the outcome of postpartum psychosis over a four-year follow-up, and to identify potential clinical markers of mood/psychotic episodes outside of the postpartum period. Methods One hundred and six women with a diagnosis of first-onset mania or psychosis during the postpartum period were included in this prospective longitudinal study. Women were categorized into either (1) recurrence of non-postpartum mood/psychotic episodes or (2) mania/psychosis limited to the postpartum period. We summarize the longitudinal course of the illness per group. We used a logistic regression model to identify clinical predictors of recurrence of mood/psychotic episodes outside of the postpartum period. Results Over two thirds of the women included in this study did not have major psychiatric episodes outside of the postpartum period during follow-up. The overall recurrence rate of mood/psychotic episodes outside the postpartum period was ~ 32%. Of these women, most transitioned to a bipolar disorder diagnosis. None of the women fulfilled diagnostic criteria for schizophrenia or schizophreniform disorder. No clinical markers significantly predicted recurrence outside of the postpartum period. Conclusions For the majority of women with first-onset postpartum psychosis, the risk of illness was limited to the period after childbirth. For the remaining women, postpartum psychosis was part of a mood/psychotic disorder with severe non-postpartum recurrence, mainly in the bipolar spectrum. No clinical predictors for risk of severe episodes outside the postpartum period emerged. Our findings add to previous evidence suggesting a fundamental link between postpartum psychosis and bipolar disorder, which may represent two distinct diagnoses within the same spectrum.

Background. Maternal psychopathology is associated with altered HPA axis functioning in offspring. Most studies have focused on mildly affected populations, but less is known about the effect of severe maternal psychopathology. In our explorative study we investigated in a heterogenic sample of mothers with severe and long-lasting psychiatric disorders, if a diagnosis of depression and severity of general maternal psychiatric symptomatology were associated with infant salivary cortisol reactivity to the Face-to-Face Still-Face (FFSF) paradigm at 6 months of age. Methods. A clinical sample of 36 mother-infant dyads was explored. All mothers fulfilled criteria for a severe psychiatric disorder and had psychiatric complaints for the last two consecutive years. Maternal diagnosis was established during pregnancy using a diagnostic interview and general maternal psychiatric symptom severity was established by self-report at the time of the FFSF procedure. The FFSF paradigm was used to assess infants’ response to social stress at the age of 6 months. Infant saliva samples were collected at three time points: 5 min before and 15 and 30 min after the social stressor. Cortisol reactivity was operationalized as incremental Area Under the Curve (AUCi). Potential confounders were identified and adjusted for. Results. In regression analyses, a negative relationship was found between infant cortisol reactivity (AUCi) during the FFSF paradigm at 6 months and general maternal symptom severity at time of the FFSF paradigm (unadjusted n = 36, s = −0.331, B = −9.758, SE 4.8, p = .048; adjusted n = 36, s = −0.335, B = −9.868, SE 4.5, p = .039) and for diagnosis of perinatal depression at trend level (unadjusted n = 36, s = −0.293, B = −8.640, SE 4.8, p = .083; adjusted n = 36, s = −0.317, B = −9.347, SE 4.6, p = .052). Analyses were adjusted for gestational age. Conclusions. Preliminary results on cortisol reactivity in 6-month-old infants of mothers with severe and long-lasting psychiatric disorders show a significant reduction in the group of mothers who experienced a high level of psychiatric symptoms in the post-partum period, compared to mothers with lower levels of psychiatric symptomatology. The same trend was found for mothers with and without a diagnosis of perinatal depression. Since these infants are considered to be at increased risk for later psychopathology, our study suggests that future longitudinal studies should investigate whether reduced cortisol reactivity in babies could be a marker for any adverse outcomes, besides other possible risk factors (e.g. (epi)genetic phenomena).

Probabilistic fasteners are known to provide strong attachment onto their respective surfaces. Examples are Velcro® and the "3M dual lock"system. However, these systems typically only function using specific counter surfaces and are often destructive to other surfaces such as fabrics. Moreover, the design parameters to optimize their functionality are not obvious. Here, we present a surface patterned with soft micrometric features inspired by the mushroom shape showing a nondestructive mechanical interlocking and thus attachment to fabrics. We provide a scalable experimental approach to prepare these surfaces and quantify the attachment strength with rheometric and video-based analysis. In these "probabilistic fasteners,"we find that higher feature densities result in higher attachment force; however, the individual feature strength is higher on a low feature density surface. We interpret our results via a load-sharing principle common in fiber bundle models. Our work provides new handles for tuning the mechanical attachment properties of soft patterned surfaces that can be used in various applications including soft robotics.

Recent advances in optical coding, drug delivery, diagnostics, tissue engineering, shear-induced gelation, and functionally engineered rheology crucially depend on microparticles and microfibers with tunable shape, size, and composition. However, scalable manufacturing of the required complex micromaterials remains a long-standing challenge. Here in-air polymerization of liquid jets is demonstrated as a novel platform to produce microparticles and microfibers with tunable size, shape, and composition at high throughput (>100 mL h-1 per nozzle). The polymerization kinetics is quantitatively investigated and modeled as a function of the ink composition, the UV light intensity, and the velocity of the liquid jet, enabling engineering of complex micromaterials in jetting regimes. The size, morphology, and local chemistry of micromaterials are independently controlled, as highlighted by producing micromaterials using 5 different photopolymers as well as multi-material composites. Simultaneous optimization of these control parameters yields rapid fabrication of stimuli-responsive Janus fibers that function as soft actuators. Finally, in-air photopolymerization enables control over the curvature of printed droplets, as highlighted by high-throughput printing of microlenses with tunable focal distance. The combination of rapid processing and tunability in composition and architecture opens a new route toward applications of tailored micromaterials in soft matter, medicine, pharmacy, and optics.

Engineering of biomimetic tissue implants provides an opportunity for repairing volumetric muscle loss (VML), beyond a tissue’s innate repair capacity. Here, we present thick, suturable, and pre-vascularized 3D muscle implants containing human induced pluripotent stem cell-derived myogenic precursor cells (hiPSC-MPCs), which can differentiate into skeletal muscle cells while maintaining a self-renewing pool. The formation of contractile myotubes and millimeter-long fibers from hiPSC-MPCs is achieved in chemically, mechanically, and structurally tailored extracellular matrix-based hydrogels, which can serve as scaffolds to ultimately organize the linear fusion of myoblasts. Embedded multi-material bioprinting is used to deposit complex patterns of perfusable vasculatures and aligned hiPSC-MPC channels within an endomysium-like supporting gel to recapitulate muscle architectural integrity in a facile yet highly rapid manner. Moreover, we demonstrate successful graft-host integration and de novo muscle formation upon in vivo implantation of pre-vascularized constructs within a VML model. This work pioneers the engineering of large pre-vascularized hiPSC-derived muscle tissues toward next generation VML regenerative therapies.

Objectives: The authors sought to evaluate the impact of ischemic burden reduction after chronic total occlusion (CTO) percutaneous coronary intervention (PCI) on long-term prognosis and cardiac symptom relief. Background: The clinical benefit of CTO PCI is questioned. Methods: In a high-volume CTO PCI center, 212 patients prospectively underwent quantitative [ 15O]H 2O positron emission tomography perfusion imaging before and three months after successful CTO PCI between 2013-2019. Perfusion defects (PD) (in segments) and hyperemic myocardial blood flow (hMBF) (in ml · min −1 · g −1) allocated to CTO areas were related to prognostic outcomes using unadjusted (Kaplan-Meier curves, log-rank test) and risk-adjusted (multivariable Cox regression) analyses. The prognostic endpoint was a composite of all-cause death and nonfatal myocardial infarction. Results: After a median [interquartile range] of 2.8 years [1.8 to 4.3 years], event-free survival was superior in patients with ≥3 versus −1 · g −1) versus below the population median (p < 0.01; risk-adjusted p < 0.01; HR: 0.16 [95% CI: 0.05 to 0.54]) after CTO PCI. Furthermore, event-free survival was superior in patients without versus any residual PD (p < 0.01; risk-adjusted p = 0.02; HR: 0.22 [95% CI: 0.06 to 0.76]) or with a residual hMBF level >2.3 versus ≤2.3 ml · min −1 · g −1 (p < 0.01; risk-adjusted p = 0.03; HR: 0.25 [95% CI: 0.07 to 0.91]) at follow-up positron emission tomography. Patients with residual hMBF >2.3 ml · min −1 · g −1 were more frequently free of angina and dyspnea on exertion at long-term follow-up (p = 0.04). Conclusions: Patients with extensive ischemic burden reduction and no residual ischemia after CTO PCI had lower rates of all-cause death and nonfatal myocardial infarction. Long-term cardiac symptom relief was associated with normalization of hMBF levels after CTO PCI.

Background Sheltered housing is associated with quality-of-life improvements for individuals with serious mental illness (SMI). However, there are equivocal findings around safety outcomes related to this type of living condition. Aims We aimed to investigate raw differences in prevalence and incidence of crime victimisation in sheltered housing compared with living alone or with family; and to identify groups at high risk for victimisation, using demographic and clinical factors. We do so by reporting estimated victimisation incidents for each risk group. Method A large, community-based, cross-sectional survey of 956 people with SMI completed the Dutch Crime and Victimisation Survey. Data was collected on victimisation prevalence and number of incidents in the past year. Results Victimisation prevalence was highest among residents in sheltered housing (50.8%) compared with persons living alone (43%) or with family (37.8%). We found that sheltered housing was associated with increased raw victimisation incidence (incidence rate ratio: 2.80, 95% CI 2.36–3.34 compared with living with family; 1.87, 95% CI 1.59–2.20 compared with living alone). Incidence was especially high for some high-risk groups, including men, people with comorbid post-traumatic stress disorder and those with high levels of education. However, women reported less victimisation in sheltered housing than living alone or with family, if they also reported drug or alcohol use. Conclusions The high prevalence and incidence of victimisation among residents in sheltered housing highlights the need for more awareness and surveillance of victimisation in this population group, to better facilitate a recovery-enabling environment for residents with SMI.

Background Maternal psychopathology during pregnancy is associated with negative outcomes in offspring. Increased placental transfer of maternal cortisol may contribute to mediate this association. Hair cortisol concentrations (HCCs) appear to be a good biomarker of long-term prenatal stress exposure. Little is known about the associations between severe maternal psychopathology and perinatal infant HCCs. Aims We assessed HCCs in the perinatal period in mother–infant dyads with and without severe psychiatric disorders. Method We examined group differences in HCCs of mother–infant dyads (n = 18) subjected to severe maternal psychiatric disorders versus healthy control dyads (n = 27). We assessed the correlation of HCCs between mother and infant within both groups, and the association between current maternal symptoms and HCCs in patient dyads. Results Median (interquartile range) and distribution of HCC differed in patients compared with control mothers (U = 468.5, P = 0.03). HCCs in infants of patients did not differ from control infants (U = 250.0, P = 0.67). Subsequently, we found that HCCs within healthy control dyads were correlated (n = 27, r 0.55 (0.14), P = 0.003), but were not within patient dyads (n = 18, r 0.082 (0.13), P = 0.746). HCCs in infants of patients showed a positive correlation with maternal symptoms (n = 16, r = 0.63 (0.06), P = 0.008). Conclusions These preliminary findings suggest that infant HCC reflect perinatal stress exposure. In infants, these early differences could influence lifetime hypothalamic–pituitary–adrenal axis functioning, which might be associated with increased susceptibility to later disease.

Background Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) leads to major reductions in ischemic burden. However, to date, studies investigating if more ischemia reduction after CTO PCI translates into an improved patient prognosis, are lacking. Purpose To evaluate if change in absolute myocardial perfusion after CTO PCI is related to patient prognosis. Methods Between 2013–2019, 219 prospectively recruited patients with a CTO underwent quantitative [15O]H2O positron emission tomography perfusion imaging before and 3 months after successful CTO PCI in a single high-volume CTO PCI center (175 procedures/year). Changes in perfusion defect size (in myocardial segments) and hyperemic myocardial blood flow (MBF, in mL min–1 g–1) within the CTO territory after PCI were related to the combined endpoint of death or myocardial infarction (MI). Kaplan-Meier curves (log-rank test) and multivariable Cox regression (including covariates age, gender, prior MI, and left ventricular function) were used to analyze unadjusted and risk-adjusted event-free survivals with HR [95% CI]. Results Out of 213 (97%) patients with a median follow-up of 3.2 [2.1–4.7] years, 22 (10%) patients experienced the composite of death (19, 9%) or MI (5, 2%). Event-free survival was significantly improved in patients with a perfusion defect size reduction of ≥3 segments (N=132, 62%) after CTO PCI compared to 1.13 mL min–1 g–1) as compared to below the median (p2.30 mL min–1 g–1 (N=105, 49%) showed a better event-free survival compared to patients with lower residual hyperemic MBF levels (p=0.02, risk-adjusted: p=0.04 with HR 0.33 [0.12–0.95]). Conclusions Patients with more ischemic burden reduction and less residual ischemia following CTO PCI showed a major improved survival free of death or MI. A limitation was the low absolute number of events that prohibited more extensive risk-adjustment of the analyses. Funding Acknowledgement Type of funding source: None

Summary:. Hyperbaric oxygen therapy (HBOT) serves as “primary” or “adjunctive” therapy in a wide range of pathologies. It is considered the mainstay of management for potentially life-threatening conditions such as carbon monoxide poisoning, decompression illness, and gas embolisms. Moreover, HBOT has been utilized for decades as an adjunctive therapy in a variety of medical disciplines, including chronic wounds, which affect approximately 6.5 million Americans annually. In general, chronic wounds are characterized by hypoxia, impaired angiogenesis, and prolonged inflammation, all of which may theoretically be ameliorated by HBOT. Nonetheless, the cellular, biochemical, and physiological mechanisms by which HBOT achieves beneficial results in chronic wounds are not fully understood, and there remains significant skepticism regarding its efficacy. This review article provides a comprehensive overview of HBOT, and discusses its history, mechanisms of action, and its implications in management of chronic wounds. In particular, we discuss the current evidence regarding the use of HBOT in diabetic foot ulcers, while digging deeply into the roots of controversy surrounding its efficacy. We discuss how the paucity of high-quality research is a tremendous challenge, and offer future direction to address existing obstacles.

Mother-to-infant bonding is important for long-term child development. The aim of this study was to investigate bonding in women admitted to a Mother and Baby Unit with postpartum depression (PD, n = 64) and postpartum psychosis (PP, n = 91). Participants completed the Postpartum Bonding Questionnaire (PBQ), the Edinburgh Postnatal Depression Scale (EPDS) and the Young Mania Rating Scale (YMRS) weekly during admission. At admission, 57.1% of women with PD had impaired bonding, compared to only 17.6% of women with PP (p-value < 0.001). At discharge, only 18.2% of women with PD and 5.9% of women with PP still experienced impaired bonding (p-value = 0.02). There was a strong association between decrease of depressive and manic symptoms and improved bonding over an eight-week admission period. In a small group of women (5.7%) impaired bonding persisted despite being in remission of their psychiatric disorder. The results from our study show that impaired bonding is a more present and evidently severe problem in postpartum depression but not so much in postpartum psychosis. Treatment of depressive symptoms will improve bonding in almost all women, but clinicians should assess if impaired bonding is still present after remission because for a small group special care and treatment focused on bonding might be required.

Recent studies have provided new data on the teratogenicity of lithium. Less is known about the risk of miscarriage after lithium use during pregnancy. The aim of this study was to investigate the association between lithium use during pregnancy and miscarriage. Participants were women with bipolar I disorder and one or more pregnancies, of which information on medication use and pregnancy outcome was available (n = 443). The unadjusted odds ratios for miscarriage after lithium use during pregnancy was calculated. Multilevel logistic regression was used to calculate the odds ratio, adjusted for the age at conception and the clustering of pregnancies per woman. Miscarriages occurred in 20.8% of the lithium-exposed pregnancies (16/77), compared with 10.9% of the unexposed pregnancies (40/366) (OR = 2.14; 95% CI: 1.13–4.06). The adjusted odds ratio of miscarriage after lithium use during pregnancy was 2.94 (95% CI: 1.39–6.22). Lithium use during pregnancy may increase the risk of miscarriage.

To investigate whether older age predicts a higher efficacy of electroconvulsive therapy (ECT) in severely depressed patients. Also, to analyze whether psychomotor disturbance and/or psychotic features might explain the potential higher efficacy of ECT in older age.A total of 96 patients with major depressive disorder treated with bilateral ECT were evaluated. The 17-item HAM-D and the MADRS were used to evaluate the efficacy of ECT and time to remission, respectively. Psychomotor disturbance was defined according the HAM-D.Middle-aged (MA; 50-70 years) and older-aged (OA; ≥70 years) patients had a non-significant larger symptom reduction compared with young-aged (YA;50 years) patients. Medium effect size was found in favor of MA (d = 0.44) and small effect size in favor of OA (d = 0.30), when compared to YA. Patients with psychotic features and patients with psychomotor retardation had a significantly larger symptom reduction (p 0.001 and p = 0.005, respectively; d = 0.88 and d = 0.66, respectively). The association between age and ECT efficacy is mediated by psychomotor retardation (p = 0.049) and in lesser extent by psychotic features (p = 0.071).The results show that psychomotor retardation and psychotic features are strong predictors of ECT efficacy and explain the association between age and ECT efficacy. Instead of focusing on the age of a patient, clinicians should focus on the presence of psychomotor disturbances and psychotic features of depression, when considering ECT treatment.

Objective: To investigate whether early improvement, measured after two electroconvulsive therapy (ECT) sessions, is a good predictor of eventual remission in severely depressed in-patients receiving ECT. Method: A prospective cohort study was performed that included 89 major depressive disorder in-patients treated with bilateral ECT. Sensitivity, specificity, and predictive values were computed for various definitions of early improvement (15%, 20%, 25%, and 30% reduction on the Montgomery Asberg depression rating scale (MADRS) score) after 1 week (i.e. two sessions) of ECT regarding prediction of remission (final MADRS score ≤ 9). Results: A 15% reduction in MADRS score appeared to be the best definition of early improvement, with modest sensitivity (51%) and relatively good specificity (79%). Kaplan–Meier analysis showed a more than 2-week shorter time to remission in patients with early improvement compared with patients lacking early improvement. Conclusion: Early improvement during an ECT course may be assessed after two ECT sessions. Such improvement, defined as a 15% reduction in the MADRS score, is a moderately sensitive predictor for eventual remission in an in-patient population with severe major depression.

OBJECTIVE: There is limited information on the longitudinal disease course after first-onset postpartum psychosis (PP). Some women will experience severe affective episodes outside the postpartum period, while for other women their vulnerability to mania and psychosis may be restricted to the postpartum period. This meta-analysis estimates the risk of recurrence after first-onset PP. DATA SOURCES: A computerized literature search was conducted using Embase, MEDLINE, Web of Science, PsycINFO, Cochrane Central, PubMed, and Google Scholar (first 100 hits) combining key terms regarding longitudinal studies of first-onset PP from inception through May 9, 2019. Two levels of screening were used on 2,807 citations. STUDY SELECTION: A total of 6 English-language articles including patients with a first-onset PP within 1 year after childbirth and a minimum follow-up period of 18 months or more after the index episode were included in the quantitative analysis. DATA EXTRACTION: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines were used for data extraction, and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were used to independently assess the quality of the included studies. The primary outcome was recurrence, defined as any subsequent psychiatric episode after first-onset PP. RESULTS: Six studies and 645 patients could be included in the quantitative analyses; follow-up periods were 11-26 years. Of these patients, 279 did not experience subsequent severe episodes outside the postpartum period. Meta-analysis using random-effect estimation resulted in a weighted estimate of 43.5% (95% CI, 37.7% to 49.4%). CONCLUSIONS: In this meta-analysis, more than 40% of women were classified as having "isolated postpartum psychosis," which could be considered a distinct diagnostic category with a more favorable prognosis. The remaining women had severe non-puerperal psychiatric episodes during longitudinal follow-up.

OBJECTIVE: Several clinical variables assumed to be predictive of electroconvulsive therapy (ECT) outcome in major depressive disorder show substantial interrelations. The current study tries to disentangle this interdependence to distill the most important predictors of treatment success to help improve patient-treatment matching. METHODS: We constructed a conceptual framework of interdependence capturing age, episode duration, and treatment resistance, all variables associated with ECT outcome, and the clinical symptoms of what we coin core depression, ie, depression with psychomotor agitation, retardation, psychotic features, or a combination of the three. The model was validated in a sample of 73 patients with a major depressive episode according to DSM-5 treated twice weekly with ECT (August 2015-January 2018) using path analyses, with the size and direction of all direct and indirect paths being estimated using structural equation modeling. Reduction in Montgomery-Asberg Depression Rating Scale (MADRS)scores during treatment was the ECT outcome measure. RESULTS: The baseline presence of psychomotor agitation, retardation, and/or psychotic symptoms strongly correlated with beneficial ECT outcome (z = 0.84 [SE = 0.17]; P < .001), and the association between age and the effect of ECT appears to be mediated by their presence (z = 0.53 [SE = 0.18]; P = .004). There was no direct correlation between age and ECT response (P = .479), but there was for episode duration and ECT outcome (z = -0.38 [SE = 0.08]; P < .001). CONCLUSIONS: ECT is a very effective treatment option for severe depressive disorder, especially for patients suffering from severe depression characterized by the presence of psychomotor agitation, psychomotor retardation, psychotic symptoms, or a combination of these 3 features, with the chance of a beneficial outcome being reduced in patients with a longer episode duration. Age may heretofore have been given too much weight in ECT decision making. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02562846.

Designer microparticles and multiscale materials can be fabricated in one step by microfluidic processing in the air., Microfluidic chips provide unparalleled control over droplets and jets, which have advanced all natural sciences. However, microfluidic applications could be vastly expanded by increasing the per-channel throughput and directly exploiting the output of chips for rapid additive manufacturing. We unlock these features with in-air microfluidics, a new chip-free platform to manipulate microscale liquid streams in the air. By controlling the composition and in-air impact of liquid microjets by surface tension–driven encapsulation, we fabricate monodisperse emulsions, particles, and fibers with diameters of 20 to 300 μm at rates that are 10 to 100 times higher than chip-based droplet microfluidics. Furthermore, in-air microfluidics uniquely enables module-based production of three-dimensional (3D) multiscale (bio)materials in one step because droplets are partially solidified in-flight and can immediately be printed onto a substrate. In-air microfluidics is cytocompatible, as demonstrated by additive manufacturing of 3D modular constructs with tailored microenvironments for multiple cell types. Its in-line control, high throughput and resolution, and cytocompatibility make in-air microfluidics a versatile platform technology for science, industry, and health care.

Objective:Several countries have developed Clinical Practice Guidelines regarding treatment of perinatal depressive symptoms and perinatal use of antidepressant. We aimed to compare guidelines to guide clinicians in best clinical practice.Methods:An extensive search in guideline databases, MEDLINE and PsycINFO was performed. When no guidelines were (publicly) available online, we contacted psychiatric-, obstetric-, perinatal- and mood disorder societies of all first world countries and the five largest second world countries. Only Clinical Practice Guidelines adhering to quality criteria of the Appraisal of Guidelines for Research and Evaluation instrument and including a systematic review of evidence were included. Data extraction focussed on recommendations regarding continuation or withdrawal of antidepressants and preferred treatment in newly depressed patients.Results:Our initial search resulted in 1094 articles. After first screening, 40 full-text articles were screened. Of these, 24 were excluded for not being an official Clinical Practice Guidelines. In total, 16 Clinical Practice Guidelines were included originating from 12 countries. Eight guidelines were perinatal specific and eight were general guidelines.Conclusion:During pregnancy, four guidelines advise to continue antidepressants, while there is a lack of evidence supporting this recommendation. Five guidelines do not specifically advise or discourage continuation. For new episodes, guidelines agree on psychotherapy (especially cognitive behavioural therapy) as initial treatment for mild to moderate depression and antidepressants for severe depression, with a preference for sertraline. Paroxetine is not preferred treatment for new episodes but switching antidepressants for ongoing treatment is discouraged (three guidelines). If mothers use antidepressants, observation of the neonate is generally recommended and breastfeeding encouraged.

Lithium and antipsychotics are often prescribed to treat bipolar disorder or psychotic disorders in women of childbearing age. Little is known about the consequences of these medications during pregnancy for the developing child. The objective of this article is to systematically review findings from preclinical and clinical studies that have examined the neurodevelopmental consequences of intrauterine exposure to lithium and antipsychotics. A systematic search was performed in Embase, Medline, Web of Science, PsychINFO, Cochrane, and Google Scholar. Clinical and experimental studies were selected if they investigated neurodevelopment of offspring exposed to lithium or antipsychotics during gestation. Quality of clinical and preclinical studies was assessed by the Newcastle–Ottawa Scale and the SYRCLE’s risk of Bias tool, respectively. In total, 73 studies were selected for qualitative synthesis and three studies were selected for quantitative synthesis. Of preclinical studies, 93% found one or more adverse effects of prenatal exposure to antipsychotics or lithium on neurodevelopment or behaviour. Only three clinical cohort studies have investigated the consequences of lithium exposure, all of which reported normal development. In 66% of clinical studies regarding antipsychotic exposure, a transient delay in neurodevelopment was observed. The relative risk for neuromotor deficits after in utero exposure to antipsychotics was estimated to be 1.63 (95% CI 1.22–2.19; I2 = 0%). Preclinical studies suggest long-term adverse neurodevelopmental consequences of intrauterine exposure to either lithium or antipsychotics. However, there is a lack of high-quality clinical studies. Interpretation is difficult, since most studies have compared exposed children with their peers from the unaffected population, which did not allow correction for potential influences regarding genetic predisposition or parental psychiatric illness.

BackgroundDuring the postpartum period, women are at risk for the new onset of both auto-immune thyroid disorders and depression. The presence of thyroid peroxidase antibodies (TPO-ab) during early gestation is predictive for postpartum auto-immune thyroid dysfunction. The aim of this study was to investigate the association between TPO-ab status during early gestation and first-onset postpartum depression.MethodsProspective cohort study (n = 1075) with follow-up during pregnancy up to one year postpartum. Thyroid function and TPO-ab status were measured during early gestation. Depressive symptomatology was assessed during each trimester and at four time points postpartum with the Edinburgh Depression Scale (EDS). Women with antenatal depression were not eligible for inclusion. Self-reported postpartum depression was defined with an EDS cut-off of ≥ 13.ResultsThe cumulative incidence of self-reported first-onset depression in the first postpartum year was 6.3%. A positive TPO-ab status was associated with an increased risk for self-reported first-onset depression at four months postpartum (adjusted OR 3.8; 95% CI 1.3–11.6), but not at other postpartum time points. Prevalence rates of self-reported postpartum depression declined after four months postpartum in the TPO-ab positive group, but remained constant in the TPO-ab negative group.LimitationsDepression was defined with a self-rating questionnaire (EDS).ConclusionsWomen with an increased TPO-ab titer during early gestation are at increased risk for self-reported first-onset depression. The longitudinal pattern of self-reported postpartum depression in the TPO-ab positive group was similar to the typical course of postpartum TPO-ab titers changes. This suggests overlap in the etiology of first-onset postpartum depression and auto-immune thyroid dysfunction. Thyroid function should be evaluated in women with first-onset postpartum depression.

Background Maternal use of benzodiazepines during pregnancy is common and has increased over the last decades. In this systematic review and meta-analysis, we studied the literature to estimate the worldwide use of benzodiazepines before, during and after pregnancy, which could help to estimate benzodiazepine exposure and to prioritize and guide future investigations. Methods We systematically searched Embase, Medline Ovid, Web of Science and Cochrane Central up until July 2019 for studies reporting on benzodiazepine use before (12 months), during and after pregnancy (12 months). Random effects meta-analysis was conducted to calculate pooled prevalence estimates, as well as stratified according to substantive variables. Results We identified 32 studies reporting on 28 countries, together reporting on 7,343,571 pregnancies. The worldwide prevalence of benzodiazepine use/prescriptions during pregnancy was 1.9% (95%CI 1.6%-2.2%; I2 97.48%). Highest prevalence was found in the third trimester (3.1%; 95%CI 1.8%-4.5%; I2 99.83%). Lorazepam was the most frequently used/prescribed benzodiazepine (1.5%; 95%CI 0.5%-2.5%; I2 99.87%). Highest prevalence was found in Eastern Europe (14.0%; 95%CI 12.1%-15.9%; I2 0.00%). Limitations All analyses revealed considerable heterogeneity. Conclusions Our meta-analysis confirmed that benzodiazepine use before, during and after pregnancy is prevalent. The relatively common use of benzodiazepines with possible risks for both mother and (unborn) child is worrying and calls for prescription guidelines for women, starting in the preconception period. Given the substantial proportion of children exposed to benzodiazepines in utero, future research should continue to study the short- and long-term safety of maternal benzodiazepine use during pregnancy and to explore non-pharmacological alternative treatments.

ObjectivesApproximately 11%–13% of pregnant women suffer from depression. Bright light therapy (BLT) is a promising treatment, combining direct availability, sufficient efficacy, low costs and high safety for both mother and child. Here, we examined the effects of BLT on depression during pregnancy.DesignRandomised, double-blind controlled trial.SettingPrimary and secondary care in The Netherlands, from November 2016 to March 2019.Participants67 pregnant women (12–32 weeks gestational age) with a DSM-5 diagnosis of depressive disorder (Diagnostic and Statistical Manual of Mental Disorders).InterventionsParticipants were randomly allocated to treatment with either BLT (9000 lux, 5000 K) or dim red light therapy (DRLT, 100 lux, 2700 K), which is considered placebo. For 6 weeks, both groups were treated daily at home for 30 min on awakening. Follow-up took place weekly during the intervention, after 6 weeks of therapy, 3 and 10 weeks after treatment and 2 months postpartum.Primary and secondary outcome measuresDepressive symptoms were measured primarily with the Structured Interview Guide for the Hamilton Depression Scale—Seasonal Affective Disorder. Secondary measures were the Hamilton Rating Scale for Depression and the Edinburgh Postnatal Depression Scale. Changes in rating scale scores of these questionnaires over time were analysed using generalised linear mixed models.ResultsMedian depression scores decreased by 40.6%–53.1% in the BLT group and by 50.9%–66.7% in the DRLT group. We found no statistically significant difference in symptom change scores between BLT and DRLT. Sensitivity and post-hoc analyses did not change our findings.ConclusionsDepressive symptoms of pregnant women with depression improved in both treatment arms. More research is necessary to determine whether these responses represent true treatment effects, non-specific treatment responses, placebo effects or a combination hereof.Trial registration numberNTR5476.

Rationale: Despite interventions to improve detection rates, domestic violence, and abuse (DVA) remains largely undetected by healthcare services. We therefore aimed to examine the acceptability, feasibility, and sustainability of an intervention aiming to improve DVA detection rates, which included a clear referral pathway (i.e., the BRAVE intervention) and to explore the acceptability and feasibility of DVA management and referrals in general, in the context of low detection rates. Methods: Qualitative study design with four focus groups of 16 community mental health (CMH) clinicians from both control and intervention arms. The focus groups discussed managing DVA in clinical practice and staff experiences with the BRAVE intervention in particular. Focus groups continued until saturation of the subject was reached. Interviews were analyzed using a thematic analysis approach. Results: DVA was seen to be highly relevant to mental healthcare but is also a very sensitive subject. Barriers in CMH professionals, institutions, and society meant CMH professionals often refrained from asking about DVA in patients. Barriers included communication difficulties between CMH professionals and DVA professionals, a fear of disrupting the therapeutic alliance with the patient, and a lack of appropriate services to help victims of DVA. Conclusion: The BRAVE intervention was acceptable but not feasible or sustainable. Personal, institutional, and public barriers make it not feasible for CMH professionals to detect DVA in mental healthcare. To increase the detection of DVA, professional standards should be combined with training, feedback sessions with peers and DVA counselors, and routine enquiry about DVA. Clinical Trial Registration: ISRCTN, trial registration number: ISRCTN14115257.

Geographical indications (GIs) and innovation do not seem to fit well together. The system of acquiring a geographical indication requires applicants to stipulate product specifications with which all producers that want to use the GI must comply. These criteria provide certainty that the GI-protected product displays the characteristics and quality it is supposed to have. However, they also constitute a hurdle for changing characteristics of the product, for example in the vein of innovative solutions and improvement. This limited flexibility of adapting the product specifications therefore may be argued to hamper innovation rather than fostering it. While the above-stated problem is true, it may be short-sighted. Even in a rigid system as that of GI protection, innovation and improvements can take place. This Chapter therefore aims at analysing how the system of protecting geographical indications allows for innovation to happen, and whether it stimulates such efforts. This is mainly done from a theoretical perspective, assessing the rationales on which the GI system is based and the legal rules applicable to the governance structure.

Background Premenstrual syndrome is characterized by the cyclic occurrence of physical, behavioral and psychological symptoms during the luteal phase of the menstrual cycle disappearing within a few days of the onset of menstruation. Generally symptoms are mild, but 5–8% of women suffer from severe PMS. Apart from conventional drugs, like serotonin reuptake inhibitors and oral contraceptives, complementary and alternative medicines such as Vitex agnus castus are used by many women experiencing PMS. Objective Our objective was to determine the efficacy, tolerability, and acceptability of Vitex agnus castus preparations for treatment of premenstrual syndrome. Study Design All journals in the Ovid software from inception through January 2016 were searched, including the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and PsycINFO. Gray literature was searched by Google Scholar and manufacturers of Vitex agnus castus preparations were contacted for information about unpublished trials. We included randomized controlled trials with Vitex agnus castus in women with premenstrual syndrome and/or premenstrual dysphoric disorder with a minimal duration of 2 menstrual cycles. The eligibility of the manuscripts was assessed by 2 reviewers independently. The data abstracted included characteristics of the study design, characteristics of the patient population, intervention details, type of comparator, method of diagnosis, and outcome measures. We adhered to the PRISMA guidelines. Results We found 17 randomized controlled trials of Vitex agnus castus in the treatment of premenstrual syndrome. Fourteen of these could be included in the quantitative analysis. Thirteen of 14 studies with placebo, dietary supplements, or herbal preparations as controls reported positive effects of Vitex agnus castus on total premenstrual syndrome symptoms. Unfortunately most of the trials are associated with a high risk of bias. The pooled effect of Vitex agnus castus in placebo-controlled trials was large (Hedges g, –1.21; 95% confidence interval, –1.53 to –0.88), but heterogeneity was extremely high (I 2 , 91%). We were unable to single out factors that could explain this heterogeneity satisfactorily. The funnel plot and Egger tests suggest the presence of publication bias. Conclusion Although meta-analysis shows a large pooled effect of Vitex agnus castus in placebo-controlled trials, the high risk of bias, high heterogeneity, and risk of publication bias of the included studies preclude a definitive conclusion. The pooled treatment effects should be viewed as merely explorative and, at best, overestimating the real treatment effect of Vitex agnus castus for premenstrual syndrome symptoms. There is a clear need for high-quality trials of appropriate size examining the effect of standardized extracts of Vitex agnus castus in comparison to placebo, selective serotonin reuptake inhibitors, and oral contraceptives to establish relative efficacy.

__Objective:__ Postpartum psychosis is an acute and severe mood disorder. Although the prognosis is generally good, postpartum psychosis is a highly stressful life-event presumed to have a major impact on functioning and well-being beyond the acute stage of the illness. We studied functional recovery, including psychosocial functioning and the presence of psychological distress, in patients with a recent diagnosis of postpartum psychosis. __Methods:__ Seventy-eight patients with postpartum psychosis consecutively admitted for inpatient hospitalization between 2005 and 2011 were assessed 9 months postpartum. Included were patients with DSM-IV-TR diagnoses of psychotic disorder not otherwise specified, brief psychotic disorder, or mood disorder with psychotic features, each requiring the additional specifier “with postpartum onset.” Functioning was assessed in 4 domains by the Longitudinal Interval Follow-up Evaluation–Range of Impaired Functioning Tool (LIFE-RIFT). Symptomatology was measured by the Brief Symptom Inventory and compared to a matched population-based cohort. __Results:__ Nine months postpartum, 74% (58/78) of women with postpartum psychosis reported good functioning on the domains of work, interpersonal relations, recreation, and global satisfaction. Moreover, 88% (69/78) of patients with postpartum psychosis had resumed their premorbid employment and household responsibilities. Compared to the general population, patients with postpartum psychosis reported a higher burden of depression and anxiety (effect sizes r ≤ 0.14). Patients who had a relapse episode (18%) experienced considerable functional impairments across several domains. __Conclusions:__ Nine months postpartum, the majority of patients with postpartum psychosis reported good functional recovery. Our relatively improved functional outcomes compared to nonpostpartum onset could be attributed to the postpartum onset and/or more favorable risk factor profile.

We use regular solution theory and implement a three-gradient model for a liquid/vapour system in contact with a complex surface topology to study the shape of a liquid drop in advancing and receding wetting scenarios. More specifically, we study droplets on an inverse opal: spherical cavities in a hexagonal pattern. In line with experimental data, we find that the surface may switch from hydrophilic (contact angle on a smooth surface θY < 90°) to hydrophobic (effective advancing contact angle θ > 90°). Both the Wenzel wetting state, that is cavities under the liquid are filled, as well as the Cassie–Baxter wetting state, that is air entrapment in the cavities under the liquid, were observed using our approach, without a discontinuity in the water front shape or in the water advancing contact angle θ. Therefore, air entrapment cannot be the main reason why the contact angle θ for an advancing water front varies. Rather, the contact line is pinned and curved due to the surface structures, inducing curvature perpendicular to the plane in which the contact angle θ is observed, and the contact line does not move in a continuous way, but via depinning transitions. The pinning is not limited to kinks in the surface with angles θkink smaller than the angle θY. Even for θkink > θY, contact line pinning is found. Therefore, the full 3D-structure of the inverse opal, rather than a simple parameter such as the wetting state or θkink, determines the final observed contact angle.

Poor sleep quality during pregnancy is associated with both antepartum and postpartum depression and adverse birth outcomes. This study evaluated both objective and subjective sleep quality and the effects on the subsequent course of antepartum depressive symptoms in psychiatric patients. This observational explorative study was embedded in an ongoing study focusing on pregnant women with a mental disorder and was performed in 18 patients (24&ndash, 29 weeks pregnant). Depressive symptoms were assessed throughout pregnancy using the Edinburgh Postnatal Depression Scale (EPDS) with 5-week intervals. Sleep was assessed with actigraphy, the Pittsburgh Sleep Quality Index (PSQI) and sleep diaries at the start of the study. We studied correlations between sleep parameters and EPDS scores cross-sectionally using Spearman correlation. Next, we studied the course of antepartum EPDS scores over time per sleep parameter using generalized linear mixed modelling analysis. Objectively measured fragmentation index, total PSQI score and 4 PSQI subscales (sleep quality, sleep duration, sleep disturbances and daytime dysfunctions) were significantly correlated with EPDS scores when measured cross-sectionally at the start. Six objectively and subjectively measured sleep parameters had moderate to large effects on the course of depressive symptoms through the third trimester, but these effects were not statistically significant. More research is necessary to explore the causality of the direction between sleep problems and antepartum depressive symptoms we found in psychiatric patients.

ObjectiveAntidepressant medication is commonly used for the prevention of depression recurrence in the perinatal period, yet it is unknown what vulnerability markers may play a role in recurrence. The objective of the current study was to provide a descriptive overview of the associated characteristics of women who experienced a perinatal recurrence of depression despite ongoing antidepressant use, and further, to identify clinically measurable vulnerability markers associated with recurrence.MethodsEighty-five pregnant women with a history of depression who used antidepressants (e.g. Selective Serotonin Reuptake Inhibitors or Serotonin and Noradrenaline Reuptake Inhibitors) at the start of the study were included. Clinical features, including information on psychiatric history and antidepressant use, were collected throughout the perinatal period (in this study defined as the period between 12 weeks of pregnancy untill three months postpartum). The clinical features of women experiencing recurrence of depression were described in detail. To identify vulnerability markers associated with recurrence of depression, we performed exploratory univariable logistic regression analyses.ResultsEight women (9.4%) experienced a recurrence of depression; two during pregnancy and six in the first 12 weeks postpartum. All women with recurrence of depression had first onset of depression during childhood or adolescence and had at least 2 psychiatric co-morbidities. Identification of vulnerability markers associated with recurrence of depression yielded associations with depressive symptoms around 16 weeks of pregnancy (OR 1.28, 95%CI 1.08-1.52), number of psychiatric co-morbidities (OR 1.89, 95%CI 1.16-3.09) and duration of antidepressant use (OR 1.01, 95%CI 1.00-1.02).ConclusionImplementing adequate risk assessment in pregnant women who use antidepressants can help identify predictors for recurrence of depression in future studies and thus ultimately lead to improved care.

Objective: Using outcome data collected routinely over a continuous two-year treatment period, we wished to distinguish homogeneous subgroups of patients with a severe mental illness whose psychosocial problems followed a similar pattern over time. By identifying the effectiveness of health services for different patient groups, this approach allowed us to identify patients at risk of deterioration and those recovering from their symptoms.Methods: In total we included 2,660 patients who were in two-year continuous contact with a Flexible Assertive Community Treatment team (FACT). We collected outcome data on psychosocial functioning, needs for care and quality of life. We performed a latent class growth analysis (LCGA).Results: The LCGA identified six homogenous patient subgroups using trajectories of HoNOS scores. On the basis of the patterns of patients’ psychosocial problems over time, we labelled these as follows: 1) stable at a low problem-severity level (N = 709; 27%); 2) stable at a low medium problem-severity level (N = 1,208; 45%); 3) stable at a high medium problem-severity level (N = 528; 20%); 4) stable at a high problem-severity level (N = 116; 4%); 5) amelioration of problems (N = 42; 2%); and 6) deterioration of problems (N = 57; 2%). Patients with stable and a high severity of psychosocial problems had more practical and somatic unmet needs than those in other subgroups, and also had the fewest decrease in the number of unmet needs.Discussion: After linking patient subgroups with clinical features such as the need for care, we found that, over two years, most patients remained relatively stable in terms of psychosocial functioning, but that their unmet needs decreased over time. However, in terms of needs for treatment during two years of contact with a FACT team, patients in the subgroup with a stable and high problem-severity level tended to derive little or no benefit.

Microfluidic manufacturing platforms have advanced the production of monodisperse, shape-controlled, and chemically defined micromaterials. However, conventional microfabrication platforms are typically designed and fabricated as single-purpose and single-use tools, which limits their efficiency, versatility, and overall potential. We here present an on-the-fly exchangeable nozzle concept that operates in a transparent, 3D, and reusable microfluidic device produced without cleanroom technology. The facile exchange and repositioning of the nozzles readily enables the production of monodisperse water-in-oil and oil-in-water emulsions, solid and core-shell microspheres, microfibers, and even Janus type micromaterials with controlled diameters ranging from 10 to 1000 μm using a single microfluidic device.

Background Depressive symptoms in pregnant women, which are common and debilitating, are often co-morbid with other mental disorders (e.g. anxiety and personality disorders), and related to low socioeconomic status (SES). This situation may hamper treatment outcome, which has often been neglected in previous studies on the treatment of depression during pregnancy. We developed a new group-based multicomponent treatment (GMT) comprising cognitive behavioral therapy, psycho-education and body-oriented therapy and compared the effect on depressive symptoms with individual counseling (treatment as usual, TAU) in a heterogeneous group of pregnant women with co-morbid mental disorders and/or low SES. Methods An outpatient sample from a university hospital of 158 pregnant women who met DSM-IV criteria for mental disorders were included and 99 participants were randomized to GMT or TAU from January 2010 until January 2013. The Edinburgh Depression Scale (EDS) was used at baseline, every 5 weeks during pregnancy and as the primary outcome measure of depressive symptoms at 6 weeks postpartum. Secondary outcome measures included the clinician-reported Hamilton Depression Rating Scale (HDRS), obstetric outcomes and a ‘Patient Satisfaction’ questionnaire. Results 155 participants were included the intention-to-treat (ITT)-analysis. GMT was not superior above TAU according to estimated EDS (β = 0.13, CI = − 0.46–0.71, p = 0.67) and HDRS scores (β = − 0.39, CI = − 0.82–0.05, p = 0.08) at 6 weeks postpartum. There were no differences in secondary outcomes between the GMT and TAU, nor between the randomized condition and patient-preference condition. Limitations The ability to detect an effect of GMT may have been limited by sample size, missing data and the ceiling effect of TAU. Conclusions GMT is an acceptable treatment for a heterogeneous group of pregnant women with depressive symptoms and co-morbid mental disorders and/or low SES, but not superior to TAU. Further research should focus on understanding and treating co-morbid disorders and psychosocial problems during pregnancy. Clinical trials registration Dutch trial registry, www.trialregister.nl under reference number: NTR3015.

BackgroundElectroconvulsive therapy (ECT) is considered to be the most effective treatment in severe major depression. The identification of reliable predictors of ECT response could contribute to a more targeted patient selection and consequently increased ECT response rates.AimsTo investigate the predictive value of age, depression severity, psychotic and melancholic features for ECT response and remission in major depression.MethodA meta-analysis was conducted according to the PRISMA statement. A literature search identified recent studies that reported on at least one of the potential predictors.ResultsOf the 2193 articles screened, 34 have been included for meta-analysis. Presence of psychotic features is a predictor of ECT remission (odds ratio (OR) = 1.47,P= 0.001) and response (OR = 1.69,P< 0.001), as is older age (standardised mean difference (SMD) = 0.26 for remission and 0.35 for response (P< 0.001)). The severity of depression predicts response (SMD = 0.19,P= 0.001), but not remission. Data on melancholic symptoms were inconclusive.ConclusionsECT is particularly effective in patients with depression with psychotic features and in elderly people with depression. More research on both biological and clinical predictors is needed to further evaluate the position of ECT in treatment protocols for major depression.Declaration of interestNone.