Intra- and Inter-Network connectivity of the default mode network differentiates Treatment-Resistant depression from Treatment-Sensitive depression.

Understanding why some patients with depression remain resistant to antidepressant medication could be elucidated by investigating their associated neural features. Although research has consistently demonstrated abnormalities in the anterior cingulate cortex (ACC) - a region that is part of the default mode network (DMN) - in treatment-resistant depression (TRD), a considerable research gap exists in discerning how these neural networks distinguish TRD from treatment-sensitive depression (TSD). We aimed to evaluate the resting-state functional connectivity (rsFC) of the ACC with other regions of the DMN to better understand the role of this structure in the pathophysiology of TRD. 35 TRD patients, 35 TSD patients, and 38 healthy controls (HC) underwent a resting-state functional MRI protocol. Seed-based functional connectivity analyses were performed, comparing the three groups for the connectivity between two subregions of the ACC (the subgenual ACC (sgACC) and the rostral ACC (rACC)) and the DMN (p < 0.05 FWE corrected). Furthermore, inter-network connectivity of the DMN with other neural networks was explored by independent component (ICA) analyses (p < 0.01, FDR corrected). The results demonstrated hyperconnectivity between the rACC and the posterior cingulate cortex in TRD relative to TSD and HC (F(2,105) = 5.335, p < 0.05). ICA found DMN connectivity to regions of the visual network (TRDTSD), differentiating the two clinical groups. These results provide confirmatory evidence of DMN hyperconnectivity and preliminary evidence for its interactions with other neural networks as key neural mechanisms underlying treatment non-responsiveness.

Developing and validating a discrete-event simulation model of multiple myeloma disease outcomes and treatment pathways using a national clinical registry.

Multiple myeloma is a haematological malignancy typically characterised by neoplastic plasma cell infiltration of the bone marrow. Treatment for multiple myeloma consists of multi-line chemotherapy with or without autologous stem cell transplantation and has been rapidly evolving in recent years. However, clinical trials are unable to provide patients and clinicians with long-term prognostic information nor policymakers with the full body of evidence needed to perform economic evaluation of new therapies or make reimbursement decisions. To address these limitations of the available evidence, this study aimed to develop and validate the EpiMAP Myeloma model, a discrete-event simulation model of multiple myeloma disease outcomes and treatment pathways. Risk equations were estimated using the Australian and New Zealand Myeloma & Related Diseases Registry after multiple imputation of missing data. Risk equation coefficients were combined with multiple myeloma patients at diagnosis from the Registry to perform the simulation. The model was validated with 100 bootstraps of an out-of-sample prediction analysis using a 70/30 split of the 4,121 registry patients diagnosed between 2009 and 2023, resulting in 2,884 and 1,237 patients in the training and validation cohorts, respectively. For 90% of the 120 months in the 10-year post-diagnosis period, there was no significant difference in overall survival between the validation and simulated cohorts. These results highlight that the EpiMAP Myeloma model is robust at predicting multiple myeloma disease outcomes and treatment pathways in Australia & New Zealand. In the future, clinicians will be able to use the EpiMAP Myeloma model to provide personalised estimates of life expectancy to patients based on their specific characteristics, disease stage, and response to treatment. Policymakers will also be able to use the model to perform economic evaluation, to forecast the number of patients receiving treatment at different stages, and to determine the downstream impact of listing new, effective therapies.

Sample-to-Answer Detection of SARS-CoV-2 Viremia Using Thermally Responsive Alkane Partitions.

The diagnosis of bloodborne viral infections (viremia) is currently relegated to central laboratories because of the complex procedures required to detect viruses in blood samples. The development of point-of-care diagnostics for viremia would enable patients to receive a diagnosis and begin treatment immediately instead of waiting days for results. Point-of-care systems for viremia have been limited by the challenges of integrating multiple precise steps into a fully automated (i.e., sample-to-answer), compact, low-cost system. We recently reported the development of thermally responsive alkane partitions (TRAPs), which enable the complete automation of diagnostic assays with complex samples. Here we report the use of TRAPs for the sample-to-answer detection of viruses in blood using a low-cost portable device and easily manufacturable cassettes. Specifically, we demonstrate the detection of SARS-CoV-2 in spiked blood samples, and we show that our system detects viremia in COVID-19 patient samples with good agreement to conventional RT-qPCR. We anticipate that our sample-to-answer system can be used to rapidly diagnose SARS-CoV-2 viremia at the point of care, leading to better health outcomes for patients with severe COVID-19 disease, and that our system can be applied to the diagnosis of other life-threatening bloodborne viral diseases, including Hepatitis C and HIV.

Multi-signal regulation of the GSK-3ß homolog Rim11 controls meiosis entry in budding yeast.

Starvation in diploid budding yeast cells triggers a cell-fate program culminating in meiosis and spore formation. Transcriptional activation of early meiotic genes (EMGs) hinges on the master regulator Ime1, its DNA-binding partner Ume6, and GSK-3ß kinase Rim11. Phosphorylation of Ume6 by Rim11 is required for EMG activation. We report here that Rim11 functions as the central signal integrator for controlling Ume6 phosphorylation and EMG transcription. In nutrient-rich conditions, PKA suppresses Rim11 levels, while TORC1 retains Rim11 in the cytoplasm. Inhibition of PKA and TORC1 induces Rim11 expression and nuclear localization. Remarkably, nuclear Rim11 is required, but not sufficient, for Rim11-dependent Ume6 phosphorylation. In addition, Ime1 is an anchor protein enabling Ume6 phosphorylation by Rim11. Subsequently, Ume6-Ime1 coactivator complexes form and induce EMG transcription. Our results demonstrate how various signaling inputs (PKA/TORC1/Ime1) converge through Rim11 to regulate EMG expression and meiosis initiation. We posit that the signaling-regulatory network elucidated here generates robustness in cell-fate control.

Food consumption patterns, seasonal dietary diversity, and factors affecting food intake in rural Eastern Uganda: A mixed-methods cross-sectional study.

This mixed-methods cross-sectional study examines food consumption patterns, dietary diversity, and factors affecting food intake and malnutrition in the rural Mbale District in Eastern Uganda, during both wet and dry seasons. Participants (n = 100; 66% females) completed a food frequency questionnaire identifying foods and beverages consumed in the preceding 12 months. Individual interviews (n = 8) were conducted with key workers. Analysis of seventeen food items revealed seasonal variations in carbohydrate and protein sources. During the dry season, staples like matooke (mashed boiled plantains) and sweet and Irish potatoes were affected, while protein-rich foods such as beans and groundnuts saw increased consumption in the wet season. Fruit and vegetable intake also rose during the wet season. The main causes of malnutrition that emerged from the interviews were the lack of knowledge about food and nutrition, financial struggles, climate impact, and cultural beliefs. The last theme covered strategies to combat malnutrition. Although carbohydrate intake remains consistent throughout seasons due to reliance on posho (maize flour porridge) and cassava, variations in the number of meals and protein sources, particularly beans and groundnuts, were observed. Both of these, being the primary protein sources in rural households' diets, are highly susceptible to climate fluctuations. This may pose significant implications for food security, as heightened climate instability may impede their production. Solutions to combat malnutrition discussed by the interviewees include education, employment, family planning, and healthcare improvements. Professionals emphasise the need for comprehensive approaches to address these complex issues. In addition, data on food consumption during the dry and wet seasons should be collected as a difference in food consumption during the seasons may become more prominent with the need to implement tailored interventions.

Validating cognitive screening in young people with first-episode psychosis: The CogScreen protocol.

AIM: Cognitive impairments are a core feature of first-episode psychosis (FEP) and one of the strongest predictors of long-term psychosocial functioning. Cognition should be assessed and treated as part of routine clinical care for FEP. Cognitive screening offers the opportunity to rapidly identify and triage those in most need of cognitive support. However, there are currently no validated screening measures for young people with FEP. CogScreen is a hybrid effectiveness-implementation study which aims to evaluate the classification accuracy (relative to a neuropsychological assessment as a reference standard), test-retest reliability and acceptability of two cognitive screening tools in young people with FEP. METHODS: Participants will be 350 young people (aged 12-25) attending primary and specialist FEP treatment centres in three large metropolitan cities (Adelaide, Sydney, and Melbourne) in Australia. All participants will complete a cross-sectional assessment over two sessions including two cognitive screening tools (Screen for Cognitive Impairment in Psychiatry and Montreal Cognitive Assessment), a comprehensive neuropsychological assessment battery, psychiatric and neurodevelopmental assessments, and other supplementary clinical measures. To determine the test-retest reliability of the cognitive screening tools, a subset of 120 participants will repeat the screening measures two weeks later. RESULTS: The protocol, rationale, and hypotheses for CogScreen are presented. CONCLUSIONS: CogScreen will provide empirical evidence for the validity and reliability of two cognitive screening tools when compared to a comprehensive neuropsychological assessment. The screening measures may later be incorporated into clinical practice to assist with rapid identification and treatment of cognitive deficits commonly experienced by young people with FEP.

Examining the impact of a group treatment using cognitive and social cognition remediation for young offenders: The justice health NSW school-link advantage pilot study.

AIM: Young offenders experience higher rates of neurodevelopmental and mental health disorders than the general population, and significant access barriers to health treatment. Treatment combining Cognitive Remediation Therapy (CRT) and Social Cognition Remediation Therapy (SCRT) has demonstrated benefits for functional improvements and social development. However, there is limited information regarding group treatment programs in custodial settings for young offenders. This pilot study explores the effectiveness and feasibility of a group treatment program for youth offenders with cognitive deficits and mental health concerns in youth detention. METHODS: The School-Link Advantage pilot study designed and tested a 10-week group treatment program combining CRT and SCRT for young offenders in custody. The closed groups incorporated interactive activities focussed on emotional recognition and regulation skills, optimizing executive functioning, understanding values, exploring belief systems, improving relationships, and safety planning. RESULTS: Of the 22 male participants recruited in an Australian Youth Justice Centre, 12 completed all aspects of the treatment program, reflecting a 54.5% completion rate in a typically challenging to engage population cohort. Results demonstrated significant improvements in the ability to store and retrieve information, recognize information, and control emotions. Planning and organizing skills also showed considerable development. CONCLUSIONS: This pilot study suggests that a combined CRT and SCRT group treatment program has the potential to effectively target cognitive challenges associated with mental health disorders in young offenders in custody. These promising outcomes suggest exploring randomized controlled trials with increased cultural sensitivity for diverse populations.

Implementation of supplemental physiotherapy following hip fracture surgery: a protocol for the process evaluation of a randomised controlled trial.

BACKGROUND: Patient outcomes following low-trauma hip fracture are suboptimal resulting in increased healthcare costs and poor functional outcomes at 1 year. Providing early and intensive in-hospital physiotherapy could help improve patient outcomes and reduce costs following hip fracture surgery. The HIP fracture Supplemental Therapy to Enhance Recovery (HIPSTER) trial will compare usual care physiotherapy to intensive in-hospital physiotherapy for patients following hip fracture surgery. The complex environments in which the intervention is implemented present unique contextual challenges that may impact intervention effectiveness. This study aims to complete a process evaluation to identify barriers and facilitators to implementation and explore the patient, carer and clinician experience of intensive therapy following hip fracture surgery. METHODS AND ANALYSIS: The process evaluation is embedded within a two-arm randomised, controlled, assessor-blinded trial recruiting 620 participants from eight Australian hospitals who have had surgery for a hip fracture sustained via a low-trauma injury. A theory-based mixed method process evaluation will be completed in tandem with the HIPSTER trial. Patient and carer semi-structured interviews will be completed at 6 weeks following hip fracture surgery. The clinician experience will be explored through online surveys completed pre- and post-implementation of intensive therapy and mapped to domains of the Theoretical Domains Framework (TDF). Translation and behaviour change success will be assessed using the Reach Effectiveness-Adoption Implementation Maintenance (RE-AIM) framework and a combination of qualitative and quantitative data collection methods. These data will assist with the development of an Implementation Toolkit aiding future translation into practice. DISCUSSION: The embedded process evaluation will help understand the interplay between the implementation context and the intensive therapy intervention following surgery for low-trauma hip fracture. Understanding these mechanisms, if effective, will assist with transferability into other contexts and wider translation into practice. TRIAL REGISTRATION: ACTRN 12622001442796.

Continuation or maintenance ECT for schizophrenia: A narrative review of case report data.

OBJECTIVE: This review aimed to address the limited evidence on the efficacy of continuation or maintenance electroconvulsive therapy (C/M-ECT) in schizophrenia, with a focus on international case reports and series due to the scarcity of randomised controlled trials. MATERIALS AND METHODS: Electronic database searches were conducted to identify case reports or series evaluating the efficacy of C/M-ECT in patients with schizophrenia or schizoaffective disorder. RESULTS: C/M-ECT treatment span varied from 3 months to 36 years (Median = 30 months; M = 43.9 months; SD = 63.0) and was effective in maintaining remission for most patients with schizophrenia in combination with antipsychotic medication. Reporting of adverse events including cognitive adverse effects was infrequent. CONCLUSIONS: Collation of case reports and series data indicated that C/M-ECT, when combined with antipsychotics, appears to be a safe and effective strategy for maintaining remission, even over several years. Caution is warranted due to the potential influence of publication bias.

Evaluation of hospital-onset bacteraemia and fungaemia in the USA as a potential healthcare quality measure: a cross-sectional study.

BACKGROUND: Hospital-onset bacteraemia and fungaemia (HOB) is being explored as a surveillance and quality metric. The objectives of the current study were to determine sources and preventability of HOB in hospitalised patients in the USA and to identify factors associated with perceived preventability. METHODS: We conducted a cross-sectional study of HOB events at 10 academic and three community hospitals using structured chart review. HOB was defined as a blood culture on or after hospital day 4 with growth of one or more bacterial or fungal organisms. HOB events were stratified by commensal and non-commensal organisms. Medical resident physicians, infectious disease fellows or infection preventionists reviewed charts to determine HOB source, and infectious disease physicians with training in infection prevention/hospital epidemiology rated preventability from 1 to 6 (1=definitely preventable to 6=definitely not preventable) using a structured guide. Ratings of 1-3 were collectively considered 'potentially preventable' and 4-6 'potentially not preventable'. RESULTS: Among 1789 HOB events with non-commensal organisms, gastrointestinal (including neutropenic translocation) (35%) and endovascular (32%) were the most common sources. Overall, 636/1789 (36%) non-commensal and 238/320 (74%) commensal HOB events were rated potentially preventable. In logistic regression analysis among non-commensal HOB events, events attributed to intravascular catheter-related infection, indwelling urinary catheter-related infection and surgical site infection had higher odds of being rated preventable while events with neutropenia, immunosuppression, gastrointestinal sources, polymicrobial cultures and previous positive blood culture in the same admission had lower odds of being rated preventable, compared with events without those attributes. Of 636 potentially preventable non-commensal HOB events, 47% were endovascular in origin, followed by gastrointestinal, respiratory and urinary sources; approximately 40% of those events would not be captured through existing healthcare-associated infection surveillance. DISCUSSION: Factors identified as associated with higher or lower preventability should be used to guide inclusion, exclusion and risk adjustment for an HOB-related quality metric.

Effects of neural oscillation power and phase on discrimination performance in a visual tilt illusion.

Neural oscillations reflect fluctuations in the relative excitation/inhibition of neural systems1,2,3,4,5 and are theorized to play a critical role in canonical neural computations6,7,8,9 and cognitive processes.10,11,12,13,14 These theories have been supported by findings that detection of visual stimuli fluctuates with the phase of oscillations prior to stimulus onset.15,16,17,18,19,20,21,22,23 However, null results have emerged in studies seeking to demonstrate these effects in visual discrimination tasks,24,25,26,27 raising questions about the generalizability of these phenomena to wider neural processes. Recently, we suggested that methodological limitations may mask effects of phase in higher-level sensory processing.28 To test the generality of phasic influences on perception requires a task that involves stimulus discrimination while also depending on early sensory processing. Here, we examined the influence of oscillation phase on the visual tilt illusion, in which a center grating has its perceived orientation biased away from the orientation of a surround grating29 due to lateral inhibitory interactions in early visual processing.30,31,32 We presented center gratings at participants' subjective vertical angle and had participants report whether the grating appeared tilted clockwise or counterclockwise from vertical on each trial while measuring their brain activity with electroencephalography (EEG). In addition to effects of alpha power and aperiodic slope, we observed robust associations between orientation perception and alpha and theta phase, consistent with fluctuating illusion magnitude across the oscillatory cycle. These results confirm that oscillation phase affects the complex processing involved in stimulus discrimination, consistent with its purported role in canonical computations that underpin cognition.

A multi-center validation of the electronic health record admission source and discharge location fields against the clinical notes for identifying inpatients with long-term care facility exposure.

Identifying long-term care facility (LTCF)-exposed inpatients is important for infection control research and practice, but ascertaining LTCF exposure is challenging. Across a large validation study, electronic health record data fields identified 76% of LTCF-exposed patients compared to manual chart review. OBJECTIVE: Residence or recent stay in a long-term care facility (LTCF) is an important risk factor for antibiotic-resistant bacterial colonization. However, absent dedicated intake questionnaires or resource-intensive chart review, ascertaining LTCF exposure in inpatients is challenging. We aimed to validate the electronic health record (EHR) admission and discharge location fields against the clinical notes for identifying LTCF-exposed inpatients. METHODS: We conducted a retrospective study of 1020 randomly sampled adult admissions between 2016 and 2021 across 12 University of Maryland Medical System hospitals. Using study-developed guidelines, we categorized the following data for LTCF exposure: each admission's history & physical (H&P) note, each admission's EHR-extracted "Admission Source," and (3) the EHR-extracted admission and discharge locations for previous admissions (≤90 days). We estimated sensitivities, with 95% CIs, of H&P notes and of EHR admission/discharge location fields for detecting "current" and "any recent" (≤90 days, including current) LTCF exposure. RESULTS: For detecting current LTCF exposure, the sensitivity of the index admission's EHR-extracted "Admission Source" was 46% (95% CI: 35%­58%) and of the H&P note was 92% (83%­97%). For detecting any recent LTCF exposure, the sensitivity of "Admission Source" across the index and previous admissions was 32% (24%­41%), "Discharge Location" across previous admission(s) was 57% (47%­66%), and of the H&P note was 68% (59%­76%). The combined sensitivity of admission source and discharge location for detecting any recent LTCF exposure was 76% (67%­83%). CONCLUSIONS: The EHR-obtained admission source and discharge location fields identified 76% of LTCF-exposed patients compared to chart review but disproportionately missed currently exposed patients.

Integrating smartwatches in community mental health services for severe mental illness for detecting relapse and informing future intervention: A case series.

OBJECTIVE: This case series explored the integration of smartwatches in a community mental health service to support severe mental illness (SMI) management and intervention. We examined whether biometric data provided by smartwatches could help to predict relapse and inform treatment decisions. METHOD: Four Australian SMI outpatients of mixed diagnoses (age range = 19-24) were selected from a prior study. Clinicians accessed patients' biometric data (activity, sleep, heart rate, and electrodermal activity) through smartwatches. RESULTS: Changes in circadian rhythm and electrodermal activity preceded hospitalization in two cases. Additionally, smartwatch data was effectively used to guide targeted interventions, improving patient treatment outcomes. CONCLUSION: Integrating smartwatches in community mental health services offers promise as adjunct tools for SMI management. However, ethical considerations on data privacy and technology reliance require further evaluation. Additionally, as this is a small case series, randomized controlled trials with larger sample sizes are required to provide evidence for generalisability of results.

Healthcare personnel opinions regarding the feasibility of a risk-tailored approach to contact precautions for methicillin-resistant Staphylococcus aureus in the acute care setting.

"All or none" approaches to the use of contact precautions for methicillin-resistant Staphylococcus aureus (MRSA) both fail to recognize that transmission risk varies. This qualitative study assessed healthcare personnel perspectives regarding the feasibility of a risk-tailored approach to use contact precautions for MRSA more strategically in the acute care setting.