Preventive interventions for paternal perinatal depression: a scoping review protocol.

INTRODUCTION: The objective of this scoping review is to map the literature describing preventive interventions for paternal perinatal depression. Depression is a common mental disorder experienced by fathers as well as mothers around childbirth. Perinatal depression has negative consequences for men, and suicide is the most serious adverse effect. Impaired father-child relationships can also result from perinatal depression, negatively impacting child health and development. Considering its severe effects, early prevention of perinatal depression is important. However, little is known about preventive interventions for paternal perinatal depression including Asian populations. METHODS AND ANALYSIS: This scoping review will consider studies of preventive interventions for perinatal depression in men with a pregnant wife or partner, and new fathers (less than 1 year post partum). Preventive intervention includes any form of intervention intended to prevent perinatal depression. Primary prevention intended to promote mental health will also be included if depression is included as an outcome. Interventions for those with a formal diagnosis of depression will be excluded. MEDLINE (EBSCOhost), CINAHL (EBSCOhost), APA PsycINFO (EBSCOhost), Cochrane Central Register of Controlled Trials and Ichushi-Web (Japan's medical literature database) will be searched for published studies, and Google Scholar and ProQuest Health and Medical Collection will be searched for grey literature. Beginning in 2012, the search will include the last 10 years of research. Screening and data extraction will be performed by two independent reviewers. Data will be extracted using a standardised data extraction tool and presented in diagrammatic or tabular form, accompanied by a narrative summary. ETHICS AND DISSEMINATION: As this study involves no human participants, approval from a human research ethics committee is not required. Findings of the scoping review will be disseminated through conference presentations and publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: https://osf.io/fk2qe/.

Experiences of transition to motherhood among pregnant women following assisted reproductive technology: a systematic review protocol of qualitative evidence.

OBJECTIVE: This systematic review aims to identify and synthesize available qualitative evidence related to the experiences of transition to motherhood during pregnancy in women who conceived through assisted reproductive technology (ART). INTRODUCTION: Women who conceived through ART experience pregnancy-specific anxiety and paradoxical feelings, and face unique challenges in their identity transition to motherhood. It is important for healthcare professionals working with these women to understand the context and complexity of this special path to parenthood, including the emotional adaptation to pregnancy following ART. A qualitative systematic review can provide the best available evidence to inform development of nursing interventions to meet the needs of pregnant women after ART. INCLUSION CRITERIA: This review will consider any qualitative research data from empirical studies published from 1992-2019 in English or Japanese that described experiences of transition to motherhood during pregnancy in women who conceived with ART. METHODS: This review will follow the JBI approach for qualitative systematic reviews. Databases that will be searched for published and unpublished studies include MEDLINE, CINAHL, PsycINFO, ProQuest Health & Medical Collection, Google Scholar and Open Access Theses and Dissertations (in English), and Ichushi-Web, CiNii and the Institutional Repositories Database (in Japanese). Titles and abstracts will be screened by two independent reviewers in full. The full-text of selected studies will be assessed in detail, and findings and their illustrations will be extracted and aggregated. Any disagreements between the reviewers that arise at each stage will be resolved through discussion, or by a third reviewer.

Application of unbound liver-to-plasma concentration ratio to quantitative projection of cytochrome P450-mediated drug-drug interactions using physiologically based pharmacokinetic modelling approach.

1. This study evaluated the prediction accuracy of cytochrome P450 (CYP)-mediated drug-drug interaction (DDI) using minimal physiologically-based pharmacokinetic (PBPK) modelling incorporating the hepatic accumulation factor of an inhibitor (i.e. unbound liver/unbound plasma concentration ratio [Kp,uu,liver]) based on 22 clinical DDI studies. 2. Kp,uu,liver values were estimated using three methods: (1) ratio of cell-to-medium ratio in human cryopreserved hepatocytes (C/Mu) at 37 °C to that on ice (Kp,uu,C/M), (2) multiplication of total liver/unbound plasma concentration ratio (Kp,u,liver) estimated from C/Mu at 37 °C with unbound fraction in human liver homogenate (Kp,uu,cell) and (3) observed Kp,uu,liver in rats after intravenous infusion (Kp,uu,rat). 3. PBPK model using each Kp,uu,liver projected the area under the curve (AUC) increase of substrates more accurately than the model assuming a Kp,uu,liver of 1 for the average fold error and root mean square error did. Particularly, the model with a Kp,uu,liver of 1 underestimated the AUC increase of triazolam following co-administration with CYP3A4 inhibitor itraconazole by five-fold, whereas the AUC increase projected using the model incorporating the Kp,uu,C/M, Kp,uu,cell, or Kp,uu,rat of itraconazole and hydroxyitraconazole was within approximately two-fold of the actual value. 4. The results indicated that incorporating Kp,uu,liver into the PBPK model improved the accuracy of DDI projection.

Discovery of Novel 5-(Piperazine-1-carbonyl)pyridin-2(1H)-one Derivatives as Orally eIF4A3-Selective Inhibitors.

Starting from our previous eIF4A3-selective inhibitor 1a, a novel series of (piperazine-1-carbonyl)pyridin-2(1H)-one derivatives was designed, synthesized, and evaluated for identification of orally bioavailable probe molecules. Compounds 1o and 1q showed improved physicochemical and ADMET profiles, while maintaining potent and subtype-selective eIF4A3 inhibitory potency. In accord with their promising PK profiles and results from initial in vivo PD studies, compounds 1o and 1q showed antitumor efficacy with T/C values of 54% and 29%, respectively, without severe body weight loss. Thus, our novel series of compounds represents promising probe molecules for the in vivo pharmacological study of selective eIF4A3 inhibition.

Risk Assessment Using Cytochrome P450 Time-Dependent Inhibition Assays at Single Time and Concentration in the Early Stage of Drug Discovery.

In this article, we proposed a risk assessment strategy for CYP3A time-dependent inhibition (TDI) during drug discovery based on a thorough retrospective study of 13 reference drugs, some of which are known to have in vitro TDI potential but have unknown clinical relevance. First, the traditional parameter kinact/KI, recommended by regulatory authorities for necessity decision making in clinical drug-drug interaction (DDI) studies, was investigated as a predictive index for clinical TDI liability. The cutoff value of 1.1 for kinact/KI, established by the Food and Drug Administration, tended to produce false-positive prediction results for clinical DDI occurrence. The value of 1.25 recommended in the European Medicines Evaluation Agency draft guideline yielded better predictions with only 1 false negative for diltiazem. Second, to enable earlier risk assessment, remaining activity, defined as the residual CYP3A activity in vitro obtained in the screening conditions, was investigated as an alternative index. As a result, the ratios of unbound Cmax or area under the curve to remaining activity precisely predicted clinical DDI occurrence. In conclusion, we demonstrated the predictive power of kinact/KI and remaining activity values for clinical DDIs. These findings provide insights that enable TDI risk assessment, even during drug discovery.