Cost-utility analysis of a telehealth psychological support intervention for people with primary brain tumor: Telehealth Making Sense of brain tumor.

OBJECTIVE: To undertake an economic evaluation of a telehealth psychological support intervention for patients with primary brain tumor (PBT). METHODS: A within-trial cost-utility analysis over 6 months was performed comparing a tailored telehealth-psychological support intervention with standard care (SC) in a randomized control trial. Data were sourced from the Telehealth Making Sense of Brain Tumor (Tele-MAST) trial survey data, project records, and administrative healthcare claims. Quality-adjusted life years (QALYs) were calculated based on the EuroQol-5D-5L. Non-parametric bootstrapping with 2000 iterations was used to determine sampling uncertainty. Multiple imputation was used for handling missing data. RESULTS: The Tele-MAST trial included 82 participants and was conducted in Queensland, Australia during 2018-2021. When all healthcare claims were included, the incremental cost savings from Tele-MAST were -AU$4,327 (95% CI: -$8637, -$18) while incremental QALY gains were small at 0.03 (95% CI: -0.02, 0.08). The likelihood of Tele-MAST being cost-effective versus SC was 87% at a willingness-to-pay threshold of AU$50,000 per QALY gain. When psychological-related healthcare costs were included only, the incremental cost per QALY gain was AU$10,685 (95% CI: dominant, $24,566) and net monetary benefits were AU$534 (95% CI: $466, $602) with a 65% likelihood of the intervention being cost-effective. CONCLUSIONS: Based on this small randomized controlled trial, the Tele-MAST intervention is a cost-effective intervention for improving the quality of life of people with PBT in Australia. Patients receiving the intervention incurred significantly lower overall healthcare costs than patients in SC. There was no significant difference in costs incurred for psychological health services.

Rapid detection of viable microbes with 5-cyano-2,3-di-(p-tolyl)tetrazolium chloride and 5(6)-carboxyfluorescein diacetate using a fibre fluorescence spectroscopy system.

AIMS: To assess the efficacy of two commercially available viability dyes, 5-cyano-2,3-di-(p-tolyl)tetrazolium chloride (CTC) and 5(6)-carboxyfluorescein diacetate (CFDA), in reporting on viable cell concentration and species using an all-fibre fluorometer. METHODS AND RESULTS: Four bacterial species (two Gram-positive and two Gram-negative) commonly associated with food poisoning or food spoilage (Escherichia coli, Salmonella enterica, Staphylococcus aureus, and Bacillus cereus) were stained with CTC or CFDA and the fibre fluorometer was used to collect full fluorescence emission spectra. A good correlation between concentration and fluorescence intensity was found for Gram-negative bacteria between 107 and 108 colony-forming units (CFU) ml-1. There was no correlation with concentration for Gram-positive bacteria; however, the information in the CTC and CFDA spectra shows the potential to distinguish Gram-negative cells from Gram-positive cells, although it may simply reflect the overall bacterial metabolic activity under staining conditions from this study. CONCLUSIONS: The limit of detection (LoD) is too high in the dip-probe approach for analysis; however, the development of an approach measuring the fluorescence of single cells may improve this limitation. The development of new bacteria-specific fluorogenic dyes may also address this limitation. The ability to differentiate bacteria using these dyes may add value to measurements made to enumerate bacteria using CTC and CFDA.

Evaluation of the telehealth making sense of brain tumor psychological support intervention for people with primary brain tumor and their caregivers: A randomized controlled trial.

OBJECTIVE: This pragmatic randomized control trial aimed to evaluate clinical efficacy of the Making Sense of Brain Tumour program delivered via videoconferencing (Tele-MAST) for improving mental health and quality of life (QoL) relative to standard care in individuals with primary brain tumor (PBT). METHOD: Adults with PBT experiencing at least mild distress (Distress Thermometer ≥4) and caregivers were randomly allocated to the 10-session Tele-MAST program or standard care. Mental health and QoL were assessed pre-intervention, post-intervention (primary endpoint), and 6-weeks and 6-months follow-up. The primary outcome was clinician-rated depressive symptoms on the Montgomery-Asberg Depression Rating Scale. RESULTS: 82 participants with PBT (34% benign, 20% lower-grade glioma, 46% high-grade glioma) and 36 caregivers were recruited (2018-2021). Controlling for baseline functioning, Tele-MAST participants with PBT had lower depressive symptoms at post-intervention (95% CI: 10.2-14.6, vs. 15.2-19.6, p = 0.002) and 6-weeks post-intervention (95% CI: 11.5-15.8 vs. 15.6-19.9, p = 0.010) than standard care, and were almost 4 times more likely to experience clinically reduced depression (OR, 3.89; 95% CI: 1.5-9.9). Tele-MAST participants with PBT also reported significantly better global QoL, emotional QoL and lower anxiety at post-intervention and 6-weeks post-intervention than standard care. There were no significant intervention effects for caregivers. At 6-months follow-up participants with PBT who received Tele-MAST reported significantly better mental health and QoL relative to pre-intervention. CONCLUSIONS: Tele-MAST was found to be more effective for reducing depressive symptoms at post-intervention than standard care for people with PBT but not caregivers. Tailored and extended psychological support may be beneficial for people with PBT.

Use of telehealth platforms for delivering supportive care to adults with primary brain tumors and their family caregivers: A systematic review.

OBJECTIVE: Telehealth platforms have potential utility for providing remote access to supportive care to people with brain tumour. This systematic review aimed to evaluate the feasibility, acceptability and efficacy of delivering supportive care via telehealth platforms to adults with primary brain tumour and family caregivers. METHODS: A systematic search of PsycINFO, MEDLINE, CINAHL, Embase, Scopus and Cochrane Library was conducted from 1980 to 1st June 2020 to identify eligible studies. Methodological quality was assessed by two independent reviewers. RESULTS: Seventeen articles, reporting on 16 studies, evaluated telephone-based support (5 studies), videoconferencing (3 studies), web-based programs and resources (7 studies) or combined use of videoconferencing and web-based modules (1 study) to deliver supportive care remotely. Caregivers were involved in 31% of interventions. Mean rates of accrual (68%) and adherence (74%) were moderate, whereas acceptability or satisfaction for those completing the interventions was typically high (M satisfied or very satisfied = 81%). Adherence rates were generally higher and clinical gains were more evident for interventions involving real-time interaction as opposed to self-guided interventions. CONCLUSIONS: Telehealth delivery of supportive care is feasible and acceptable to a high proportion of individuals with primary brain tumour and their caregivers. It is recommended that future research focuses on implementation outcomes, including factors influencing the uptake and sustainability of telehealth platforms in practice.

Evaluation of a telehealth psychological support intervention for people with primary brain tumour and their family members: Study protocol for a randomised controlled trial.

OBJECTIVE: There is a lack of research on interventions that address the specific psychosocial needs of people with brain tumour and their families. This paper describes the protocol for a pragmatic randomised control trial (RCT) evaluating the clinical efficacy and cost-effectiveness of the Making Sense of Brain Tumour program delivered via telehealth (Tele-MAST) relative to standard care. METHODS: The 148 adults with primary brain tumour will be randomly allocated to the 10-session Tele-MAST videoconferencing program or standard care from a cancer counselling service. The primary outcome is level of depression and secondary outcomes are quality of life, mental health and incremental cost per quality-adjusted life year. The mental health and quality of life of family members will also be assessed. Assessments will be conducted at pre-intervention, post-intervention (primary endpoint), 6-weeks post-intervention and 6-months post-intervention. The main analysis will determine whether the Tele-MAST intervention is more effective than standard care at post-intervention, and whether these effects are sustained at follow-up. CONCLUSION: Results will indicate whether the Tele-MAST program is associated with better clinical outcomes and is more cost-effective than existing cancer support services. Such outcomes will contribute to effective and accessible psychosocial care for the brain tumour population.

Endonuclease G preferentially cleaves 5-hydroxymethylcytosine-modified DNA creating a substrate for recombination.

5-hydroxymethylcytosine (5hmC) has been suggested to be involved in various nucleic acid transactions and cellular processes, including transcriptional regulation, demethylation of 5-methylcytosine and stem cell pluripotency. We have identified an activity that preferentially catalyzes the cleavage of double-stranded 5hmC-modified DNA. Using biochemical methods we purified this activity from mouse liver extracts and demonstrate that the enzyme responsible for the cleavage of 5hmC-modified DNA is Endonuclease G (EndoG). We show that recombinant EndoG preferentially recognizes and cleaves a core sequence when one specific cytosine within that core sequence is hydroxymethylated. Additionally, we provide in vivo evidence that EndoG catalyzes the formation of double-stranded DNA breaks and that this cleavage is dependent upon the core sequence, EndoG and 5hmC. Finally, we demonstrate that the 5hmC modification can promote conservative recombination in an EndoG-dependent manner.

Development of an Interprofessional Psychosocial Interventions Framework.

To meet the increasingly complex needs of mental health consumers, it is essential for multidisciplinary clinicians to have capabilities across a range of psychosocial interventions. Despite this, there is scant evidence investigating the existing levels of knowledge and skills of specialties within multidisciplinary mental health teams. The purpose of this paper was to describe the self-reported capabilities of mental health clinicians, and to provide a rationale for the Psychosocial Interventions Framework Assessment (PIFA), which aims to enhance the access to, and quality of, evidence-informed practice for consumers of mental health services (MHSs) by strengthening workforce capabilities and leadership for psychosocial therapies. Using the Delphi method, the team developed a 75-item survey based on the 10-point Mental Health Recovery Star (MHRS). Participants completed a self-administered survey indicating their perceived capabilities in the PIFA items. The findings revealed lower-than-expected average scores between 'novice' and 'proficient', highlighting the need for further development of specific training and education modules for individual teams. This is the first framework of its nature to use the Recovery StarTM to determine the psychosocial areas and domains for the assessment of practitioners' strengths and needs for skill development.

Factors associated with Health of the Nation Outcomes Scales (HoNOS) in an acute young adult psychiatric unit.

The transition from adolescence to adulthood is a highly vulnerable period for mental health concerns and is a key life-stage, fundamental to later health and quality of life. Scant research has investigated the health outcomes of young adults admitted to a specialised acute psychiatric unit for this cohort. Understanding health and functional outcomes for young adults admitted to a specialised acute mental health inpatient unit is beneficial in identifying treatment effectiveness and vulnerable groups. The study examines the relationship between demographic and clinical factors with admission, discharge and change in Health of the Nation Outcomes Scale (HoNOS) scores in patients admitted to an acute young adult psychiatric unit. The HoNOS was completed at admission and discharge for patients admitted to an acute young adult psychiatric unit in Australia. Descriptive statistics, paired t-tests, generalised estimating equations, independent samples t-tests and correlations were completed. Patients (N = 130) were aged between 18 and 25 years old (M = 21.26 years old, SD = 2.31). Patients were diagnosed with mood disorders (21.54%), substance abuse disorders (20.00%), personality disorders (19.23%), and psychotic disorders (17.69%). HoNOS scores across all subscales improved from admission to discharge, when controlling for confounding variables. Admission, discharge and change in HoNOS scores were associated with gender, country of birth, number of admissions, mental health act, diagnosis and socioeconomic status. This study is the first to explore HoNOS scores, demographic factors and clinical variables in young adults admitted to a specialised psychiatric inpatient unit for this age group. While further research is required, the findings identifies vulnerable subgroups (e.g., individuals with personality disorders, individuals with substance use, those admitted involuntarily, those readmitted) that may benefit from increased tailored support to foster more optimal health outcomes.

Developing video resources to reduce the burden of caring for persons with brain cancer.

PURPOSE: Co-designed and accessible video resources improve an understanding of health information and can reduce unmet needs for caregivers of persons with brain cancer. This study developed and evaluated video resources that provide health information for persons caring for someone with brain cancer. METHOD: A co-design approach with consumers was used to design, develop, and evaluate video resources. RESULTS: Twelve videos were designed with persons with brain cancer, caregivers, and health professionals. The video design and topics were informed by current literature. The videos were filmed with consumers to ensure authenticity. The evaluation was completed using data analytics and seven interviews with consumers. Content analysis identified four themes: needing information, authenticity, visual engagement, and key messages. The video length and presentation were important aspects to engage the caregiver, particularly when dealing with stress. The storage on YouTube enabled accessibility and various presentation formats met different learning styles. CONCLUSION: The development of co-designed health information videos provided resources to improve caregivers understanding of the information provided by the health professionals. The videos were easy to access and able to be viewed at home with family.

The presence of 5-hydroxymethylcytosine at the gene promoter and not in the gene body negatively regulates gene expression.

5-Hydroxymethylcytosine (5hmC) was recently described as a stable modification in mammalian DNA. 5hmC is formed by the enzymatic oxidation of 5-methylcytosine (5meC). Overwhelming evidence supports the notion that 5meC has a negative effect on transcription; however, only recently has the effect that 5hmC has on transcription begun to be studied. Using model substrates including the CMV(IE) promoter and a generic gene body we have directly assessed the effect that 5hmC, both at the promoter and in the gene body, has on in vitro gene transcription. We show that the presence of the 5hmC modifications strongly represses transcription. We also demonstrate that the inhibition of transcriptional activity is primarily due to the presence of 5hmC in the promoter and that 5hmC in the gene body has a minimal effect on transcription. Thus, we propose that the presence of 5hmC in promoter prevents the binding of essential transcription factors or recruits factors that repress transcription.

Rapid Detection of Escherichia coli Antibiotic Susceptibility Using Live/Dead Spectrometry for Lytic Agents.

Antibiotic resistance is a serious threat to public health. The empiric use of the wrong antibiotic occurs due to urgency in treatment combined with slow, culture-based diagnostic techniques. Inappropriate antibiotic choice can promote the development of antibiotic resistance. We investigated live/dead spectrometry using a fluorimeter (Optrode) as a rapid alternative to culture-based techniques through application of the LIVE/DEAD® BacLightTM Bacterial Viability Kit. Killing was detected by the Optrode in near real-time when Escherichia coli was treated with lytic antibiotics-ampicillin and polymyxin B-and stained with SYTO 9 and/or propidium iodide. Antibiotic concentration, bacterial growth phase, and treatment time used affected the efficacy of this detection method. Quantification methods of the lethal action and inhibitory action of the non-lytic antibiotics, ciprofloxacin and chloramphenicol, respectively, remain to be elucidated.

Species Dependence of SYTO 9 Staining of Bacteria.

SYTO 9 is a fluorescent nucleic acid stain that is widely used in microbiology, particularly for fluorescence microscopy and flow cytometry analyzes. Fluorimetry-based analysis, i.e., analysis of fluorescence intensity from a bulk sample measurement, is more cost effective, rapid and accessible than microscopy or flow cytometry but requires application-specific calibration. Here we show the relevance of SYTO 9 for food safety analysis. We stained four bacterial species of relevance to food safety (Bacillus cereus, Escherichia coli, Salmonella enterica subspecies enterica ser. Typhimurium, Staphylococcus aureus) with different concentrations of SYTO 9, with and without the presence of ethylenediaminetetraacetic acid (EDTA), for varying amounts of time, to investigate the effect of these treatment parameters on fluorescence intensity. The addition of EDTA and an increased staining duration did not significantly affect fluorescence intensity, and over the bacterial cell concentration range investigated (∼105-108 CFU/ml) there was no significant difference in using 0.5 or 1 µM SYTO 9. The effect of bacterial cell concentration on fluorescence intensity was species specific. At different bacterial cell concentrations, the effect of species on fluorescence intensity is different. This interaction complicates the development of a general fluorimetry-based protocol for the determination of bacterial cell concentration in a mixed bacterial suspension, as would be expected from samples taken from food safety settings.

Determination of human teratogenicity by the astute clinician method: review of illustrative agents and a proposal of guidelines.

BACKGROUND: The determination that an exposure is a human teratogen is a complex process involving the application of the principles of teratology, epidemiology, biology, and clinical medicine. Shepard suggested that the "rare exposure/rare defect" or "case report method", the astute clinician model, was one approach for establishing teratogenicity. The purpose of this article is to review selected exposures with the goal of identifying principles that lead to a working proposal for the application of this approach. METHODS: We selected three known exposures--penicillamine, fluconazole and mycophenolate mofetil--for detailed review. These agents were chosen because their evidence for causation arises mostly from clinical observations in the context of biologic plausibility. RESULTS: All three agents were originally detected based on astute observations by clinicians reporting on individual cases of a distinctive pattern of malformation or, in the case of penicillamine distinctive phenotype, after the rare exposure. All three have varying degrees of biologic evidence that support the hypothesis that each represents a human teratogen. All three meet Shepard's criteria for "proof." CONCLUSIONS: The basic premise of this approach depends on the rarity of both the exposure and the outcome. We propose guidelines for utilization of this approach in the determination of human teratogenicity.

Optimisation of the Protocol for the LIVE/DEAD® BacLightTM Bacterial Viability Kit for Rapid Determination of Bacterial Load.

Rapid antimicrobial susceptibility testing is needed to reduce prescription of inappropriate antibiotics. A rapid alternative to standard culture-based testing is to determine reductions in cell viability using the LIVE/DEAD® BacLightTM Bacterial Viability Kit. We optimised the kit protocol for this application, focusing on simplifying the process by minimising the steps involved and on determining the optimal analytical parameters for fluorescence measurements from the dyes SYTO 9 and propidium iodide (PI). We demonstrate that for our experimental system, the intensity of emissions should be integrated from 505-515 nm for SYTO 9 and 600-610 nm for PI, and the proportion of live cells calculated from a new dye ratio formula, termed the adjusted dye ratio. We show that the pre-staining washing step is not necessary if a non-fluorescent growth media is used; however, staining must be done for each sampling as prolonged exposure to the dyes negatively impacts cell viability. The optimised methodology was able to reproducibly detect reductions in culture viability when the proportion of live cells in a sample of 1 × 108 cells/ml fell below ∼50% live in a media that supports the growth required for detecting antibiotic killing. Finally, we show that the interaction of fluorescence emission spectra from SYTO 9 and PI stained Escherichia coli cells is influenced by the proportion of dead cells in a sample. The excitation of PI by SYTO 9 was found to occur in populations containing sufficient numbers of dead cells (>25%), whereas in populations with low numbers of dead cells the dye interaction was additive in regard to red emissions, indicating that these dye interactions may offer another dimension to live/dead analysis. Fluorescence measurements from samples established according to the optimised protocol can be taken using a flow cytometer, spectrofluorometer, microplate reader, and the Optrode, a fibre-based spectroscopic system developed at the University of Auckland.

Psychometric and Faciometric Support for Observable Facial Feminization in Gay Men.

Though male homosexuality appears to be evolutionarily paradoxical, phenotypic feminization has been offered as a route for three current models positing a genetic basis for male homosexuality. We tested whether facial feminization is observable in gay men in two studies. In Study 1, using two composite images of gay and of heterosexual men, naive participants (N = 308) rated the "gay" face more highly on stereotypically feminine traits and actual femininity and the "heterosexual" face more highly on stereotypically masculine traits and actual masculinity. In Study 2, faciometrics of 428 Internet images of gay (N = 219) and heterosexual men were analyzed along six sexually dimorphic ratios. The faciometrics of gay men were more feminine, both in gestalt terms and for five of the six individual traits. The studies offer objective support for a more feminized facial phenotype in gay males that is difficult to explain through cultural or behavioral cues.

5-hydroxymethylcytosine Marks Mammalian Origins Acting as a Barrier to Replication.

In most mammalian cells, DNA replication occurs once, and only once between cell divisions. Replication initiation is a highly regulated process with redundant mechanisms that prevent errant initiation events. In lower eukaryotes, replication is initiated from a defined consensus sequence, whereas a consensus sequence delineating mammalian origin of replication has not been identified. Here we show that 5-hydroxymethylcytosine (5hmC) is present at mammalian replication origins. Our data support the hypothesis that 5hmC has a role in cell cycle regulation. We show that 5hmC level is inversely proportional to proliferation; indeed, 5hmC negatively influences cell division by increasing the time a cell resides in G1. Our data suggest that 5hmC recruits replication-licensing factors, then is removed prior to or during origin firing. Later we propose that TET2, the enzyme catalyzing 5mC to 5hmC conversion, acts as barrier to rereplication. In a broader context, our results significantly advance the understating of 5hmC involvement in cell proliferation and disease states.

Investigation of Polyaniline and a Functionalised Derivative as Antimicrobial Additives to Create Contamination Resistant Surfaces.

Antimicrobial surfaces can be applied to break transmission pathways in hospitals. Polyaniline (PANI) and poly(3-aminobenzoic acid) (P3ABA) are novel antimicrobial agents with potential as non-leaching additives to provide contamination resistant surfaces. The activity of PANI and P3ABA were investigated in suspension and as part of absorbent and non-absorbent surfaces. The effect of inoculum size and the presence of organic matter on surface activity was determined. PANI and P3ABA both demonstrated bactericidal activity against Escherichia coli and Staphylococcus aureus in suspension and as part of an absorbent surface. Only P3ABA showed antimicrobial activity in non-absorbent films. The results that are presented in this work support the use of P3ABA to create contamination resistant surfaces.

Sexually Dimorphic Faciometrics in Black Racial Groups From Early Adulthood to Late Middle Age.

An increasing body of research focusing on gender-related traits has utilized faciometrics in order to consider sexual dimorphism: Aspects as diverse as social heuristics, facial attractiveness, sexual orientation, aggression, and trustworthiness have all been investigated. However, the majority of these studies have tended to focus on White or Caucasian student populations and have paid little regard to either older populations or racial background. The current study therefore investigated sexual dimorphism in 450 participants (225 women) from a Black population across four age groups (20s, 30s, 40s, and 50s). In line with much previous research using White or Caucasian faces, the expected sexual dimorphism was seen in the younger age-group in three of the four indices (cheekbone prominence, facial width to lower facial height, and lower face height to full face height). However, consistent with more recent literature, the facial width to height ratio (fWHR) was not found to be significantly different between men and women in this age-group. Contrary to previous research, when considering broader age groups, the three established measures of facial sexual dimorphism, when looked at independently, remained static over time, but this was not true for fWHR. It is concluded that facial structure does not follow the same aging trajectory in all populations and care should be taken in choice of facial metric, depending on the nature of the sample under investigation.

The antimicrobial action of polyaniline involves production of oxidative stress while functionalisation of polyaniline introduces additional mechanisms.

Polyaniline (PANI) and functionalised polyanilines (fPANI) are novel antimicrobial agents whose mechanism of action was investigated. Escherichia coli single gene deletion mutants revealed that the antimicrobial mechanism of PANI likely involves production of hydrogen peroxide while homopolymer poly(3-aminobenzoic acid), P3ABA, used as an example of a fPANI, disrupts metabolic and respiratory machinery, by targeting ATP synthase and causes acid stress. PANI was more active against E. coli in aerobic, compared to anaerobic, conditions, while this was apparent for P3ABA only in rich media. Greater activity in aerobic conditions suggests involvement of reactive oxygen species. P3ABA treatment causes an increase in intracellular free iron, which is linked to perturbation of metabolic enzymes and could promote reactive oxygen species production. Addition of exogenous catalase protected E. coli from PANI antimicrobial action; however, this was not apparent for P3ABA treated cells. The results presented suggest that PANI induces production of hydrogen peroxide, which can promote formation of hydroxyl radicals causing biomolecule damage and potentially cell death. P3ABA is thought to act as an uncoupler by targeting ATP synthase resulting in a futile cycle, which precipitates dysregulation of iron homeostasis, oxidative stress, acid stress, and potentially the fatal loss of proton motive force.