Economic evaluation of interventions for treatment-resistant depression: A systematic review.

Background: The extraordinarily high prevalence of treatment-resistant depression (TRD), coupled with its high economic burden to both healthcare systems and society, underscore how critical it is that resources are managed optimally to address the significant challenge it presents. Objective: To review the literature on economic evaluation in TRD systematically, with the aim of informing future studies by identifying key challenges specific to the area, and highlighting good practices. Methods: A systematic literature search across seven electronic databases was conducted to identify both within-trial and model-based economic evaluations in TRD. Quality of reporting and study design was assessed using the Consensus Health Economic Criteria (CHEC). A narrative synthesis was conducted. Results: We identified 31 evaluations, including 11 conducted alongside a clinical trial and 20 model-based evaluations. There was considerable heterogeneity in the definition of treatment-resistant depression, although with a trend for more recent studies to use a definition of inadequate response to two or more antidepressive treatments. A broad range of interventions were considered, including non-pharmacological neuromodulation, pharmacological, psychological, and service-level interventions. Study quality as assessed by CHEC was generally high. Frequently poorly reported items related to discussion of ethical and distributional issues, and model validation. Most evaluations considered comparable core clinical outcomes - encompassing remission, response, and relapse. There was good agreement on the definitions and thresholds for these outcomes, and a relatively small pool of outcome measures were used. Resource criteria used to inform the estimation of direct costs, were reasonably uniform. Predominantly, however, there was a high level of heterogeneity in terms of evaluation design and sophistication, quality of evidence used (particularly health state utility data), time horizon, population considered, and cost perspective. Conclusion: Economic evidence for interventions in TRD is underdeveloped, particularly so for service-level interventions. Where evidence does exist, it is hampered by inconsistency in study design, methodological quality, and availability of high quality long-term outcomes evidence. This review identifies a number of key considerations and challenges for the design of future economic evaluations. Recommendations for research and suggestions for good practice are made. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=259848&VersionID=1542096, identifier CRD42021259848.

A systematic review of the impact of carer interventions on outcomes for patients with eating disorders.

PURPOSE: Eating disorder (ED) prevalence and illness severity is rapidly increasing. The complicated interplay of factors contributing to the maintenance of EDs, including family/carer influences, highlights the importance of carer interventions within ED treatment. Carer interventions demonstrate positive outcomes for carers themselves, though are also hypothesised to benefit the patient indirectly. A systematic review was conducted to greater understand the impact of carer interventions on ED patient outcomes. METHODS: Eight databases, including CINAHL, MEDLINE and PsychINFO, were systematically searched. Intervention studies for parent(s)/carer(s) of a patient with an ED were included, provided they reported outcomes for the patient. No publication date restrictions were set. Included studies were quality appraised. RESULTS: Twenty-eight studies met inclusion for the review; all of which varied in intervention type, duration, content and setting. Patient diagnosis and treatment setting were mixed across studies, though the majority focused on Anorexia Nervosa within outpatient settings. Intervention content broadly included consideration of relationship issues and interactional patterns, psychoeducation, skill development, behavioural management, and peer support. Therapeutic models utilised were diverse, including but not limited to: family, interpersonal, cognitive, and psychodynamic approaches. CONCLUSION: Several carer interventions showed positive outcomes for patients with EDs, with small group treatment formats being commonly used and proving effective through intervention content alongside a peer support element. Separate family therapy was suggested to be of equal efficacy, if not better, than family therapy alongside the patient. Recommendations for clinical practice and future research are considered. LEVEL OF EVIDENCE: 1: Systematic review, evidence mostly obtained from randomised controlled trials.

The MindfulBreather: Motion Guided Mindfulness.

For millennia, humans have focused their attention on the breath to develop mindfulness, but finding a scientific way to harness mindful breathing has proven elusive. Existing attempts to objectively measure and feedback on mindfulness have relied on specialist external hardware including electroencephalograms or respirometers that have been impractical for the majority of people learning to meditate. Consequently, training in the key skill of breath-awareness has lacked practical objective measures and guidance to enhance training. Here, we provide a brief technology report on an invention, The MindfulBreather® that addresses these issues. The technology is available to download embedded in a smartphone app that targets, measures and feedbacks on mindfulness of breathing in realtime to enhance training. The current article outlines only the technological concept with future studies quantifying efficacy, validity and reliability to be reported elsewhere. The MindfulBreather works by generating Motion Guided Mindfulness through interacting gyroscopic and touchscreen sensors in a three phase process: Mindfulness Induction (Phase I) gives standardized instruction to users to place their smartphone on their abdomen, breathe mindfully and to tap only at the peak of their inhalation. The smartphone's gyroscope detects periodic tilts during breathing to generate sinusoidal waveforms. Waveform-tap patterns are analyzed to determine whether the user is mindfully tapping only at the correct phase of the breathing cycle, indicating psychobiological synchronization. Mindfulness Maintenance (Phase II) provides reinforcing pleasant feedback sounds each time a breath is mindfully tapped at the right time, and the App records a mindful breath. Lastly, data-driven Insights are fed back to the user (Phase III), including the number of mindful breaths tapped and breathing rate reductions associated with parasympathetic engagement during meditation. The new MGM technology is then evaluated and contrasted with traditional mindfulness approaches and a novel Psychobiological Synchronization Model is proposed. In summary, unlike existing technology, the MindfulBreather requires no external hardware and repurposes regular smartphones to deliver app-embedded Motion-Guided Mindfulness. Technological applications include reducing mindwandering and down-regulation of the brain's default mode through enhanced mindful awareness. By objectively harnessing breath awareness, The MindfulBreather aims to realize the ancient human endeavor of mindfulness for the 21st century.

Experiences of Sex Education and Sexual Awareness in Young Adults with Autism Spectrum Disorder.

The research investigated feelings towards sex education and sexual awareness in young adults with autism spectrum disorder (ASD). Data were generated from the sexual knowledge, experiences, feelings and needs questionnaire (McCabe et al. 1999), the sexual awareness questionnaire (Snell et al. 1991) and semi-structured interviews. Twenty typically developing and 20 ASD individuals participated. Feelings toward sex education did not differ between the groups, but the groups differed significantly on measures of sexual awareness. Negative experiences of sex education and issues of vulnerability, social anxiety, and confused sexuality were prominent features of the qualitative interviews. This report suggest that mainstream sex and relationship education is not sufficient for people with ASD, specific methods and curricular are necessary to match their needs.

Primary cilium suppression by SREBP1c involves distortion of vesicular trafficking by PLA2G3.

Distortion of primary cilium formation is increasingly recognized as a key event in many human pathologies. One of the underlying mechanisms involves aberrant activation of the lipogenic transcription factor sterol regulatory element-binding protein 1c (SREBP1c), as observed in cancer cells. To gain more insight into the molecular pathways by which SREBP1c suppresses primary ciliogenesis, we searched for overlap between known ciliogenesis regulators and targets of SREBP1. One of the candidate genes that was consistently up-regulated in cellular models of SREBP1c-induced cilium repression was phospholipase A2 group III (PLA2G3), a phospholipase that hydrolyzes the sn-2 position of glycerophospholipids. Use of RNA interference and a chemical inhibitor of PLA2G3 rescued SREBP1c-induced cilium repression. Cilium repression by SREBP1c and PLA2G3 involved alterations in endosomal recycling and vesicular transport toward the cilium, as revealed by aberrant transferrin and Rab11 localization, and was largely mediated by an increase in lysophosphatidylcholine and lysophosphatidylethanolamine levels. Together these findings indicate that aberrant activation of SREBP1c suppresses primary ciliogenesis by PLA2G3-mediated distortion of vesicular trafficking and suggest that PLA2G3 is a novel potential target to normalize ciliogenesis in SREBP1c-overexpressing cells, including cancer cells.

Specific cell targeting with nanobody conjugated branched gold nanoparticles for photothermal therapy.

Branched gold nanoparticles are potential photothermal therapy agents because of their large absorption cross section in the near-infrared window. Upon laser irradiation they produce enough heat to destroy tumor cells. In this work, branched gold nanoparticles are biofunctionalized with nanobodies, the smallest fully functional antigen-binding fragments evolved from the variable domain, the VHH, of a camel heavy chain-only antibody. These nanobodies bind to the HER2 antigen which is highly expressed on breast and ovarian cancer cells. Flow cytometric analysis and dark field images of HER2 positive SKOV3 cells incubated with anti-HER2 conjugated branched gold nanoparticles show specific cell targeting. Laser irradiation studies reveal that HER2 positive SKOV3 cells exposed to the anti-HER2 targeted branched gold nanoparticles are destroyed after five minutes of laser treatment at 38 W/cm(2) using a 690 nm continuous wave laser. Starting from a nanoparticle optical density of 4, cell death is observed, whereas the control samples, nanoparticles with anti-PSA nanobodies, nanoparticles only, and laser only, do not show any cell death. These results suggest that this new type of bioconjugated branched gold nanoparticles are effective antigen-targeted photothermal therapeutic agents for cancer treatment.