Brexanolone Treatment in a Real-World Patient Population: A Case Series and Pilot Feasibility Study of Precision Neuroimaging.

PURPOSE/BACKGROUND: Brexanolone is approved for postpartum depression (PPD) by the United States Food and Drug Administration. Brexanolone has outperformed placebo in clinical trials, but less is known about the efficacy in real-world patients with complex social and medical histories. Furthermore, the impact of brexanolone on large-scale brain systems such as changes in functional connectivity (FC) is unknown. METHODS/PROCEDURES: We tracked changes in depressive symptoms across a diverse group of patients who received brexanolone at a large medical center. Edinburgh Postnatal Depression Scale (EPDS) scores were collected through chart review for 17 patients immediately prior to infusion through approximately 1 year postinfusion. In 2 participants, we performed precision functional neuroimaging (pfMRI), including before and after treatment in 1 patient. pfMRI collects many hours of data in individuals for precision medicine applications and was performed to assess the feasibility of investigating changes in FC with brexanolone. FINDINGS/RESULTS: The mean EPDS score immediately postinfusion was significantly lower than the mean preinfusion score (mean change [95% CI]: 10.76 [7.11-14.40], t (15) = 6.29, P < 0.0001). The mean EPDS score stayed significantly lower at 1 week (mean difference [95% CI]: 9.50 [5.23-13.76], t (11) = 4.90, P = 0.0005) and 3 months (mean difference [95% CI]: 9.99 [4.71-15.27], t (6) = 4.63, P = 0.0036) postinfusion. Widespread changes in FC followed infusion, which correlated with EPDS scores. IMPLICATIONS/CONCLUSIONS: Brexanolone is a successful treatment for PPD in the clinical setting. In conjunction with routine clinical care, brexanolone was linked to a reduction in symptoms lasting at least 3 months. pfMRI is feasible in postpartum patients receiving brexanolone and has the potential to elucidate individual-specific mechanisms of action.

Exploring Australian university students' and staff members' perspectives on an animal-assisted intervention as a health promotion initiative on campus.

ISSUE ADDRESSED: The university campus environment is unique and complex, with students and staff members experiencing increasing levels of stress and anxiety over time. One intervention being used internationally to alleviate stress and anxiety is an Animal Assisted Intervention (AAI). This research aimed to explore Australian university students' and staff members' perspectives on an AAI prior to implementation. METHODS: This study used an explanatory mixed methods approach. Student participants were recruited through posts on a university's subject sites and via social media. University staff member participants were recruited through emails from managers or department newsletters. Data were collected through an online anonymous survey and subsequent semi-structured interviews. Quantitative data were analysed with SPSS and qualitative data were analysed via thematic analysis. RESULTS: Data included 344 survey responses and 45 semi-structured interviews. Survey responses indicated a large majority of participants believe an AAI could promote health on campus. This was due to the range of benefits participants felt an AAI could have on campus (such as reducing stress and anxiety, providing opportunities for a break from work or study, social benefits, and enhancing the university environment). In interviews, participants suggested an AAI could contribute towards a positive university environment and help promote other services on campus; provided it considers those not interested in participating. SO WHAT?: If implemented sustainably, an AAI has potential to contribute towards a positive university environment for both staff and students, by potentially reducing the high rates of stress and anxiety the university community are currently experiencing. An AAI could also help to raise awareness of other health services on campus, further contributing towards promoting positive mental health and wellbeing.

Buprenorphine Extended-Release Treatment for Opioid Use Disorder in the Postpartum Period.

Buprenorphine extended-release (XR) is an extended-release monthly injection to treat opioid use disorder (OUD). This retrospective case series includes 15 postpartum patients who were treated with buprenorphine-XR at a single center and reports on their outcomes. The average total daily sublingual buprenorphine dose before initiation of buprenorphine-XR was 16.25 mg (SD±7.76, range 2-32 mg). Overall, 137 total doses of buprenorphine-XR were administered between May 17, 2021, and April 11, 2023. Urine toxicology test results were negative for opioids other than buprenorphine in the majority (80.0%) of patients once appropriate maintenance doses were achieved. Euphoria and intoxication were not reported. A minority of patients (20.0%) discontinued buprenorphine-XR. Although more extensive research is needed before widespread use, buprenorphine-XR may be a favorable treatment for OUD in this high-risk population.

Employees' support strategies for mental wellbeing during and beyond the COVID-19 pandemic: Recommendations for employers in the UK workforce.

Throughout the COVID-19 pandemic, and beyond for many businesses, employees have had to adapt to new ways of working due to disruptions in traditional practices. It is therefore crucial to understand the new challenges that employees are facing when it comes to taking care of their mental wellbeing at work. To that end, we distributed a survey to full-time UK employees (N = 451) to explore how supported they felt throughout the pandemic, and to identify whether there are any additional types of support they would like to receive. We also compared employees' intentions to seek help before versus during the COVID-19 pandemic, and assessed their current attitudes toward mental health. Based on direct employee feedback, our results show remote workers felt more supported throughout the pandemic compared to hybrid workers. We also found that employees who had previously experienced an episode of anxiety or depression were significantly more likely to want extra support at work compared to those who had not. Furthermore, employees were significantly more likely to seek help for their mental health during the pandemic compared to before. Interestingly, the largest increase in intentions to seek help during the pandemic compared to before was with digital health solutions. Finally, we found that the strategies managers have adopted to better support their employees, an employee's mental health history, and their attitude to mental health all contributed to significantly increasing the likelihood that an employee would disclose a mental health concern to their line manager. We provide recommendations that encourage organisations to make changes to better support their employees, and we highlight the importance of mental health awareness training for both managers and employees. This work is of particular interest to organisations who are looking to tailor their current employee wellbeing offer to a post-pandemic world.

Animal-assisted interventions in universities: a scoping review of implementation and associated outcomes.

With levels of stress and anxiety rising among the university community, universities worldwide are implementing animal-assisted interventions (AAIs) on campus. However, to date, little is known about how to implement these initiatives. Questions also remain as to the impact of evaluated AAIs on health and wellbeing. Therefore, this study sought to review the implementation and effectiveness of previous AAIs in university settings. Electronic databases ProQuest Central, Gale and 16 databases within EBSCOHost were searched with key words, such as AAI, and university or college students for relevant articles. Inclusion criteria included primary research studies that measured a health, wellbeing or behavioural outcome. A total of 47 articles met inclusion criteria, including 24 RCTs. There was limited reporting on the implementation of AAIs in the higher education setting. A total of 11 different mental health and behavioural outcomes have been summarized, with stress, anxiety and mood providing favourable results. An AAI on campus may provide a form of stress and anxiety relief for the university community. Other mental health and behavioural outcomes require further research to determine their effectiveness. These findings highlight that an AAI on campus could potentially provide a form of stress and anxiety relief, and could be a strategy for addressing rising levels of psychological stress and mental health issues among university students and staff in Australia and internationally.

Informing Implementation: Perspectives from the Australian University Community Regarding an Animal Assisted Intervention.

Animal Assisted Interventions (AAIs) have become increasingly popular in the university setting; however, there is limited research exploring their potential on an Australian university campus and participants' views prior to implementation. Therefore, this study aimed to explore university staff members' and students' interest in participating in an AAI and their perspectives on intervention characteristics. This was a mixed methods study, using an online survey and semi-structured interviews. The survey had 344 responses, and 45 interviews were conducted. A large majority of participants (86%) were interested in participating in an AAI. In the survey, participants indicated their preferred intervention characteristics for the location of the intervention, frequency of participating, and ways of hearing about the intervention. Participants also expressed concerns regarding therapy animal welfare. In interviews, participants discussed various considerations which may impact the intervention (such as the accessibility of the location, the impact of workload on participating, the effectiveness of promotion strategies, and factors that may assist therapy animal welfare, such as the therapy animals' handlers). Gaining an insight into the university community's views prior to implementation may ensure the intervention is feasible to implement and can be beneficial to both humans and therapy animals.

Exploring Implementation of Animal-Assisted Interventions as Health Promotion Initiatives on University Campuses.

In this study, we aimed to inform implementation of an animal-assisted intervention (AAI) in an Australian university setting by exploring previously implemented university AAIs. Universities internationally have attempted to address growing concerns around student and staff stress and anxiety by adopting AAIs. However, despite stress and anxiety being common among Australian students and staff, studies are yet to investigate the implementation of an AAI as a strategy to promote health and well-being in this context. Twelve academics who had previously implemented AAIs were recruited via purposeful intensity sampling, with data collected via semistructured interviews. Our findings highlight several facilitators to successful implementation of an AAI, along with strategies used to overcome barriers. Understanding how to amplify strengths and minimize challenges will support Australian universities to implement successful AAIs on campus and, in turn, assist in promoting improved student and staff well-being.

Intravenous versus Oral Iron for Iron-Deficiency Anemia in Pregnancy (IVIDA): A Randomized Controlled Trial.

OBJECTIVE: Iron-deficiency anemia (IDA) can have serious consequences for mothers and babies. Iron supplementation is recommended, but the administration route is controversial. We sought to conduct a randomized controlled trial (RCT) testing the effectiveness and safety of intravenous (IV) iron compared with oral iron on perinatal outcomes in pregnant women with IDA. STUDY DESIGN: This open-label RCT randomized patients with IDA (hemoglobin [hgb] <10 g/dL and ferritin <30 ng/mL) at 24 to 34 weeks' to oral iron or single 1,000-mg dose of IV low-molecular weight iron dextran over one hour. The primary outcome was maternal anemia at delivery (hgb < 11 g/dL). Secondary outcomes were mild/moderate or severe adverse reactions, maternal hgb and ferritin at delivery, blood transfusion, gestational age at delivery, birth weight, neonatal hgb and ferritin, and composite neonatal morbidity. Analysis was as per protocol. RESULTS: The trial was stopped early for logistical reasons, and the data analyzed as preliminary data to inform a larger, potentially externally funded, definitive trial. Of 55 patients approached, 38 consented. Of these, 15 were withdrawn: 5 received IV iron from their primary obstetrician after being randomized to oral iron and 10 declined to receive IV iron. Of the remaining 23 patients, who were included in the analytic population, 13 received oral iron and 10 received IV iron. The rate of maternal anemia at delivery (hgb < 11 g/dL) was high overall but significantly reduced with IV iron (40 vs. 85%, p = 0.039). Rates of maternal hgb < 10 g/dL were significantly lower in the IV iron group (10 vs. 54%, p = 0.029). There were no severe adverse reactions and similar rates of mild/moderate reactions between groups. CONCLUSION: IV iron reduces rates of anemia at the time of admission for delivery, supporting a larger RCT comparing IV versus oral iron for the treatment of IDA of pregnancy powered for definitive clinical outcomes. However, issues uncovered in this RCT suggest that patient, clinician, and systems-level barriers associated with different IDA treatment modalities must be considered prior to conducting a larger RCT. This study is registered with clinicaltrials.gov with identifier no.: NCT03438227. KEY POINTS: · IV iron decreases rates of anemia on admission for delivery compared with oral iron.. · In an unblinded randomized trial, a significant proportion of patients preferred alternate therapy.. · Future RCTs should incorporate double-blinded technique to reduce risk of patient crossover.. · Results from feasibility trial support a larger RCT comparing IV to oral iron for IDA in pregnancy..

Review of Allopregnanolone Agonist Therapy for the Treatment of Depressive Disorders.

OBJECTIVE: This paper reviews the current literature available for the efficacy and safety of allopregnanolone agonists and discusses considerations for their place in therapy. LITERATURE SEARCH: A literature search was conducted utilizing PubMed, clinicaltrials.gov, and the manufacturer's website. DATA SYNTHESIS: One phase II trial and two phase III trials evaluating the efficacy and safety of brexanolone were identified. Brexanolone demonstrated efficacy through significantly reduced Hamilton Depression Rating Scale (HAM-D) scores compared to placebo in the treatment of postpartum depression (PPD). Noted adverse effects were somnolence and dizziness, excessive sedation, and loss of consciousness. One published phase II study and the interim results of two phase III trials and one phase II trial on zuranolone were included in this review. Zuranolone, an oral allopregnanolone agonist, is given as a single, 14-day course. A significant reduction in HAM-D scores was demonstrated in patients with major depressive disorder (MDD) at 15 and 28 days compared to placebo. Interim results for zuranolone in PPD and bipolar disorder (BPD) show promising reductions in HAM-D scores. Adverse effects included sedation, dizziness, and headache. PLACE IN THERAPY: Allopregnanolone agonists seem to have a role in PPD when weighing the quick onset of action and potential risks of untreated PPD. The class of medications is limited by the single course for this indication and may fit as a bridge to maintenance therapy with selective serotonin reuptake inhibitors (SSRIs). Brexanolone, specifically, is hindered by the long infusion time, hospitalization associated with administration, and risk evaluation and mitigation strategy program. Zuranolone may also have a role in MDD or BPD, but more data are needed. CONCLUSION: Allopregnanolone agonists present a novel mechanism of action in the treatment of depressive disorders. Clinical trials and interim results support significant reductions in depression scores for brexanolone in PPD, and for zuranolone in PPD, MDD, and BPD.

The feasibility of a Pet Support Program in an Australian university setting.

ISSUE ADDRESSED: Internationally, universities have recognised the benefits of Pet Support Programs (PSPs). However, existing literature has predominately focused on quantitatively measuring health outcomes associated with a PSP amongst student populations. This research aimed to explore the feasibility of a PSP within an Australian university, as there is a need to explore practical considerations involved in implementation. METHODS: This research used a qualitative descriptive approach. Participants were recruited via purposive snowball sampling. The sample included 17 participants across eight administrative divisions within an Australian university. Semi-structured individual interviews were used to collect data. Data were analysed using thematic analysis. RESULTS: Three main themes emerged from the data: Organisational Change, Program Management and Perceived Outcomes. Findings suggest several considerations from both an organisational and program level that need to be addressed prior to implementation, including the university's policies, the location and animal welfare. The main perceived outcomes were stress relief and social support. Ways to minimise risks to those who may have an aversion towards animals were also discussed. CONCLUSIONS: Participants believed implementing a PSP would be feasible in the university setting, provided all aforementioned considerations were adequately addressed. Considerations identified have the potential to act as a barrier or a facilitator depending on how they are managed. SO WHAT?: Where feasible and later implemented, a PSP could provide Australian university students and staff with an alternative means of improving mental health, providing stress relief and contributing towards the Health Promoting University framework.

Multicolor FRET-FLIM Microscopy to Analyze Multiprotein Interactions in Live Cells.

The need to describe and understand signaling pathways in live cell is seen as a primary route to identifying and developing targeted medicines. Signaling cascade is also seen as a complex communication and involves interactions between multiple interconnecting proteins. Where subcellularly and how different proteins interact need to be preserved during investigation. Furthermore, these complex events occurring simultaneously may lead to a single or multiple end point or cell function such as protein synthesis, cell cytoskeleton formation, DNA damage repair, or autophagy. There is therefore a need of real-time noninvasive methods for protein assays to enable direct visualization of the interactions in their natural environment and hence overcome the limitations of methods that rely on invasive cell disruption techniques. Förster resonance energy transfer (FRET) coupled with fluorescence lifetime imaging microscopy (FLIM) is an advanced imaging method to observe protein-protein interactions at nanometer scale inside single living cells in real-time. Here we describe the development and use of two-channel pulsed interleave excitation (PIE) for multiple protein interactions in the mTORC1 pathway. The proteins were first tagged with multiple color fluorescent protein derivatives. The FRET-FLIM combination means that the information gained from using standard steady-state FRET between interacting proteins is considerably improved by monitoring changes in the excited-state lifetime of the donor fluorophore where its quenching in the presence of the acceptor is evidence for a direct physical interaction.

Use of Nonselective ß-Blockers in Patients With End-Stage Liver Disease and Select Complications.

Objective: To review the literature and recommendations for nonselective ß-blockers (NSBBs) in the setting of variceal bleeding prophylaxis and decompensated liver disease. Data Sources: Literature search of MEDLINE was performed (1988 to October 2019) using the following search terms: cirrhosis, advanced cirrhosis, ß-blocker, decompensation, prophylaxis. Abstracts, peer-reviewed publications, clinical practice guidelines, and product monographs were reviewed. Study Selection and Data Extraction: Relevant English language studies and those conducted in humans were considered for analysis and inclusion. Data Synthesis: Evidence that suggests that NSBBs are harmful in advanced cirrhosis is overshadowed by confounding variables and small patient populations. The majority of the available evidence suggests neutral or beneficial effects on mortality with continuation of NSBBs despite liver disease progression. Based on the available literature, guidelines, and expert consensuses, NSBBs can be considered within this patient population and may have a positive impact on the majority of these patients. Relevance to Patient Care and Clinical Practice: This review summarizes current place in therapy for NSBBs in the setting of cirrhosis and variceal bleeding prophylaxis. It also includes a discussion of the literature for use of NSBBs within the setting of different acute decompensations in which the data and recommendations for use are less clear. Conclusions: Recent evidence shows neutral or positive results for NSBB use in particular decompensation subgroups, which suggests that NSBBs can be used cautiously with close monitoring in patients with advanced cirrhosis. Questions still remain regarding optimal agent and dose and whether agents can be safely restarted after an acute decompensation episode.

Intravenous compared with oral iron for the treatment of iron-deficiency anemia in pregnancy: a systematic review and meta-analysis.

OBJECTIVE: To assess the effect of intravenous versus oral iron on hematologic indices and clinical outcomes for iron-deficiency anemia (IDA) in pregnancy. STUDY DESIGN: Searches in Ovid Medline, Embase, SCOPUS, Cochrane Database, and ClinicalTrials.gov identified randomized-controlled trials comparing intravenous to oral iron for treating IDA in pregnancy. Primary outcomes were maternal hematologic indices at delivery. Secondary outcomes were blood transfusion, cesarean delivery, neonatal outcomes, and medication reactions. RESULTS: Of 15,637 studies, 20 randomized trials met inclusion criteria and were analyzed. Mean hemoglobin at delivery (9 studies: WMD 0.66 g/dL (95% confidence Interval 0.31 -1.02 g/dL)) was significantly higher after intravenous iron therapy. Intravenous iron was associated with higher birthweight (8 studies: WMD 58.25 g (95% CI: 5.57-110.94 g)) but no significant differences in blood transfusion, cesarean delivery, or neonatal hemoglobin. There were fewer medication reactions with intravenous iron (21 studies: RR 0.34% (95% CI: 0.20-0.57)). CONCLUSION: Intravenous iron therapy is associated with higher maternal hemoglobin at delivery with no difference in blood transfusion and fewer mild medication reactions.

A low-glycemic-load versus low-fat diet in the treatment of fatty liver in obese children.

BACKGROUND: Fatty liver is highly prevalent among obese children and represents a major risk factor for chronic liver diseases and severe metabolic complications. METHODS: We randomly assigned 17 obese children 8-17 years of age with fatty liver to either an experimental low-glycemic-load or conventional low-fat diet for 6 months. Participants in both groups received nutrition education and behavioral counseling of equal intensity. The primary outcome was hepatic lipid content measured by proton magnetic resonance spectroscopy. Secondary outcomes included change in visceral fat, BMI, anthropometrics, alanine aminotransferase (ALT), and insulin resistance. RESULTS: A total of 16 participants completed the study. Reported glycemic load decreased in the low-glycemic-load group and reported dietary fat decreased in the low-fat group. At baseline, liver fat was 23.8% [standard deviation (SD) 12.2] in the low-glycemic-load group and 29.3% (14.1) in the low-fat group. Liver fat decreased substantially in both groups at 6 months expressed as absolute percentage change, with no between-group differences [-8.8 (standard error (SE) 4.1) vs. -10.5 (3.7)%, respectively, p=0.76 for group×time interaction]. Secondary outcomes also improved on both diets, with no between-group differences. Baseline and change in ALT were strongly associated with hepatic fat content. CONCLUSIONS: Weight-reducing diets focused either on glycemic load or dietary fat improved hepatic steatosis over 6 months. Additional research is needed to determine whether these diets differ in effectiveness over the long term. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00480922.