A Multimodal Generative AI Copilot for Human Pathology.

The field of computational pathology[1,2] has witnessed remarkable progress in the development of both task-specific predictive models and task-agnostic self-supervised vision encoders[3,4]. However, despite the explosive growth of generative artificial intelligence (AI), there has been limited study on building general purpose, multimodal AI assistants and copilots[5] tailored to pathology. Here we present PathChat, a vision-language generalist AI assistant for human pathology. We build PathChat by adapting a foundational vision encoder for pathology, combining it with a pretrained large language model and finetuning the whole system on over 456,000 diverse visual language instructions consisting of 999,202 question-answer turns. We compare PathChat against several multimodal vision language AI assistants and GPT4V, which powers the commercially available multimodal general purpose AI assistant ChatGPT-4[7]. PathChat achieved state-of-the-art performance on multiple-choice diagnostic questions from cases of diverse tissue origins and disease models. Furthermore, using open-ended questions and human expert evaluation, we found that overall PathChat produced more accurate and pathologist-preferable responses to diverse queries related to pathology. As an interactive and general vision-language AI Copilot that can flexibly handle both visual and natural language inputs, PathChat can potentially find impactful applications in pathology education, research, and human-in-the-loop clinical decision making.

A model approach to show that monocytes can enter microporous ß-TCP ceramics.

ß-TCP ceramics are versatile bone substitute materials and show many interactions with cells of the monocyte-macrophage-lineage. The possibility of monocytes entering microporous ß-TCP ceramics has however not yet been researched. In this study, we used a model approach to investigate whether monocytes might enter ß-TCP, providing a possible explanation for the origin of CD68-positive osteoclast-like giant cells found in earlier works.We used flow chambers to unidirectionally load BC, PRP, or PPP into slice models of either 2 mm or 6 mm ß-TCP. Immunofluorescence for CD68 and live/dead staining was performed after the loading process.Our results show that monocytes were present in a relevant number of PRP and BC slices representing the inside of our 2 mm slice model and also present on the actual inside of our 6 mm model. For PPP, monocytes were not found beyond the surface in either model.Our results indicate the possibility of a new and so far neglected constituent in ß-TCP degradation, perhaps causing the process of ceramic degradation also starting from inside the ceramics as opposed to the current understanding. We also demonstrated flow chambers as a possible new in vitro model for interactions between blood and ß-TCP.

Age at first drink and its influence on alcohol use behaviours in young adulthood: Evidence from an Australian household-based panel study.

BACKGROUND: Public health guidelines recommend delaying the initiation age for alcohol. However, the causal link between age-at-first-drink (AFD) and future alcohol use in young adulthood is uncertain. This study examined the association between AFD and alcohol-related outcomes at age 20 years using an Australian sample. METHODS: Data were obtained from Waves 1-19 (years 2001-2019) of the Household, Income and Labour Dynamics in Australia Survey on 20-year-olds with responses across ≥3 consecutive waves (n = 2278). The AFD for each respondent (between 15 and 20 years) was analysed relative to Australian legal drinking age (18 years). Inverse probability treatment weighting was used to evaluate associations between AFD and four outcomes at age 20 years: risk of current alcohol use; quantity of weekly alcohol consumption; risk of binge drinking; and frequency of binge drinking. Adjustments were made for confounders (e.g., heavy drinking by parents). Robustness of study findings was evaluated using several diagnostic tests/sensitivity analyses. RESULTS: Among 20-year-olds, those with an AFD of 15-16 years consumed significantly more alcohol per week compared to an AFD of 18 years. Additionally, 20-year-old drinkers with an AFD of 16 years were significantly more likely to binge drink (though this association was likely confounded). An inverse dose-response relationship was observed between AFD and weekly alcohol consumption at 20 years, where a higher AFD led to lower alcohol consumption. CONCLUSION: Study findings indicate an association between a higher AFD and consuming less alcohol in young adulthood, which could potentially support the scale-up of prevention programs to delay AFD among Australian adolescents.

Economic costs associated with unhealthy weight control behaviors among Australian adolescents.

OBJECTIVE: This study explored the relationship between unhealthy weight control behaviors (UWCBs) and their associated economic costs among adolescents using the 2014-2018 Longitudinal Study of Australian Children (LSAC). METHODS: LSAC data in Wave 6 (n = 3538 adolescents aged 14-15 years), Wave 7 n = 3089 adolescents aged 16-17 years), and Wave 8 (n = 3037 adolescents aged 18-19 years) were derived from a representative sample of Australian adolescents. UWCBs were measured using the self-reported Branched Eating Disorder Test questionnaire. UWCBs were sub-classified into having fasting behaviors, using weight loss supplements or purging behaviors. Economic costs include healthcare and productivity costs to caregivers. Healthcare costs were measured using data from the Medicare and Pharmaceutical Benefits, which includes both medical and pharmaceutical costs. Productivity losses were measured using caregivers' lost leisure time due to UWCBs among adolescents. RESULTS: The mixed effect model identified statistically significant higher economic costs (mean difference = $453, 95% CIs $154, $752), higher health care costs (mean difference = $399, 95% CIs $102, $695), and higher productivity costs (mean difference = $59, 95% CIs $29, $90) for adolescents with UWCBs compared to their peers with no UWCBs. Subgroup analysis revealed that higher costs were associated with fasting and purging behaviors. DISCUSSION: UWCBs were associated with increased economic costs during adolescence. Our finding suggests there should be a policy focus on tackling UWCBs to reduce the economic burden on the healthcare system and society. PUBLIC SIGNIFICANCE: The study contributes to existing knowledge by investigating the direct healthcare costs and productivity losses associated with unhealthy weight control behaviors in Australian adolescents (14-18 years old) using a dataset that follows Australian adolescents over time. We found that engaging in unhealthy weight control behaviors such as fasting, using weight loss supplements, and purging was linked to higher costs among adolescents, suggesting policies should focus on addressing these behaviors.

The Modeled Cost-Effectiveness of a Prevention Program Targeting Both Eating Disorders and High BMI.

OBJECTIVE: Prevention programs for eating disorders (EDs) and high body index mass (BMI) have the potential to reduce the onset of these interconnected public health concerns. However, it remains unclear whether routine implementation of such programs would be cost-effective. This study aims to determine the cost-effectiveness of an intervention that aims to prevent both ED and high BMI. METHOD: A Markov model was developed to evaluate the incremental cost-effectiveness of a targeted school-based program, Healthy Weight, that aims to prevent both EDs and high BMI among Australian adolescents with body image concerns (aged 15-18 years), versus a "no intervention" comparator. A cost-utility analysis was conducted from a "healthcare and education" sector perspective with costs (measured in 2019 Australian dollars) and health impacts modeled over the lifetime of the target population. An incremental cost-effectiveness ratio (ICER), expressed as cost per health-adjusted life year (HALY) gained, was calculated. Sensitivity analyses were done to test model assumptions. RESULTS: The mean intervention cost and HALYs gained were AUD$2.13 million (95% CI, AUD$1.83-2.43 million) and 146 (95% CI, 90-209), respectively. With healthcare cost-savings (AUD$3.97 million) included, the intervention was predicted to be cost-saving (AUD$1.83 million; 95% CI, AUD$0.51-3.21 million). Primary findings were robust to extensive sensitivity analyses. DISCUSSION: The Healthy Weight intervention is likely to represent good value-for-money. To ensure the successful implementation of this program at the population level, further research on its feasibility and acceptability among schools and the wider community is required.

Economic evidence for prevention and treatment of eating disorders: An updated systematic review.

OBJECTIVE: This systematic review updates an existing review examining the cost-effectiveness of interventions to prevent and treat eating disorders (EDs). METHOD: Literature search was conducted in Academic Search Complete, MEDLINE, CINAHL, PsycINFO, EconLit, Global Health, ERIC, Health Business Elite, and Health Policy Reference Center electronic databases, capturing studies published between March 2017 to April 2023. Hand-searching was conducted as supplementary including gray literature search. Included articles were (1) full economic evaluations or return-on-investment studies, (2) in English and (3) aimed at prevention and treatment of any ED. Included studies were added and synthesized with previously reviewed studies. Screening and extraction followed PRISMA guidelines. Quality assessment was conducted using the Drummond checklist. PROSPERO registration CRD42021287464. RESULTS: A total of 28 studies were identified, including 15 published after the previous review. There were nine prevention, seven anorexia nervosa (AN) treatment, five bulimia nervosa (BN) treatment, four binge-eating disorder (BED), and three non-specific ED treatment studies. Findings indicate value-for-money evidence supporting all interventions. Quality assessment showed studies were fair-to-good quality. DISCUSSION: There has been significant growth in cost-effectiveness studies over the last 5 years. Findings suggest that interventions to prevent and treat ED offer value for money. Interventions such as Featback (ED prevention and non-specific ED treatment); focal psychodynamic therapy, enhanced cognitive behavioral therapy, and high-calorie refeeding (AN treatment); stepped-care with assisted self-help and internet-based cognitive behavioral therapy (BN treatment); and cognitive behavioral therapy guided self-help intervention (BED treatment) have good quality economic evidence. Further research in implementation of interventions is required. PUBLIC SIGNIFICANCE STATEMENT: The increasing prevalence of ED globally has significant impact on healthcare systems, families, and society. This review is showcasing the value for money of interventions of eating disorders prevention and treatment. This review found that existing interventions offers positive economic benefit for the healthcare system.

OBJETIVO: Esta revisión sistemática actualiza una revisión existente que examina la rentabilidad de las intervenciones para prevenir y tratar los trastornos de la conducta alimentaria (TCA). MÉTODO: Se realizó una búsqueda bibliográfica en las bases de datos electrónicas Academic Search Complete, MEDLINE, CINAHL, PsycINFO, EconLit, Global Health, ERIC, Health Business Elite y Health Policy Reference Center, abarcando estudios publicados entre marzo de 2017 y abril de 2023. Se realizó una búsqueda manual como complemento, incluyendo la búsqueda de literatura gris. Los artículos incluidos eran (1) evaluaciones económicas completas o estudios de retorno de inversión, (2) en inglés y (3) dirigidos a la prevención y tratamiento de cualquier TCA. Los estudios incluidos se añadieron y sintetizaron con estudios previamente revisados. El cribado y la extracción siguieron las pautas PRISMA. La evaluación de la calidad se realizó utilizando la lista de verificación de Drummond. Registro en PROSPERO CRD42021287464. RESULTADOS: Se identificaron 28 estudios, incluyendo 15 publicados después de la revisión anterior. Hubo nueve estudios de prevención, siete de tratamiento de anorexia nerviosa (AN), cinco de tratamiento de bulimia nerviosa (BN), cuatro de trastorno por atracón (TpA) y tres de tratamiento de TCA no especificados. Los hallazgos indican evidencia de valor por dinero que respalda todas las intervenciones. La evaluación de la calidad mostró que los estudios eran de calidad aceptable a buena. DISCUSIÓN: Ha habido un crecimiento significativo en los estudios de rentabilidad en los últimos cinco años. Los hallazgos sugieren que las intervenciones para prevenir y tratar los TCA ofrecen valor por dinero. Intervenciones como Featback (prevención de TCA y tratamiento de TCA no específicos); terapia psicodinámica focal, terapia cognitivo-conductual mejorada y rehabilitación nutricional con alto contenido calórico (tratamiento de AN); atención escalonada con autoayuda asistida y terapia cognitivo-conductual en línea (tratamiento de BN); y terapia cognitivo-conductual guiada de autoayuda (tratamiento de TpA) tienen una buena evidencia económica de calidad. Se requiere más investigación en la implementación de intervenciones.

Health service and medication costs associated with common mental disorders and subthreshold symptoms in women: Findings from the Geelong Osteoporosis Study in Australia.

OBJECTIVE: This analysis estimated 2013 annual healthcare costs associated with the common mental disorders of mood and anxiety disorders and psychological symptoms within a representative sample of Australian women. METHODS: Data from the 15-year follow-up of women in the Geelong Osteoporosis Study were linked to 12-month Medicare Benefits Schedule and Pharmaceutical Benefits Scheme data. A Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Non-patient edition identified common mental disorders and the General Health Questionnaire 12 assessed psychological symptoms. Participants were categorised into mutually exclusive groups: (1) common mental disorder (past 12 months), (2) subthreshold (no common mental disorder and General Health Questionnaire 12 score ⩾4) or (3) no common mental disorder and General Health Questionnaire 12 score <4. Two-part and hurdle models estimated differences in service use, and adjusted generalised linear models estimated mean differences in costs between groups. RESULTS: Compared to no common mental disorder, women with common mental disorders utilised more Medicare Benefits Schedule services (mean 26.9 vs 20.0, p < 0.001), had higher total Medicare Benefits Schedule cost ($1889 vs $1305, p < 0.01), received more Pharmaceutical Benefits Scheme prescriptions (35.8 vs 20.6, p < 0.001), had higher total Pharmaceutical Benefits Scheme cost ($1226 vs $740, p < 0.05) and had significantly higher annual out-of-pocket costs for Pharmaceutical Benefits Scheme prescriptions ($249 vs $162, p < 0.001). Compared to no common mental disorder, subthreshold women were less likely to use any Medicare Benefits Schedule service (89.6% vs 97.0%, p < 0.01), but more likely to use mental health services (11.4% vs 2.9%, p < 0.01). The subthreshold group received more Pharmaceutical Benefits Scheme prescriptions (mean 43.3 vs 20.6, p < 0.001) and incurred higher total Pharmaceutical Benefits Scheme cost ($1268 vs $740, p < .05) compared to no common mental disorder. CONCLUSIONS: Common mental disorders and subthreshold psychological symptoms place a substantial economic burden on Australian healthcare services and consumers.

Physician Empathy in Doctor-Patient Communication: A Systematic Review.

Physician empathy is at the heart of doctor-patient communication and significantly influences patient outcomes. However, the research on how physicians express their empathy and how physician empathy affects patient outcomes and doctor-patient communication has not been well summarized in the latest literature. Thus, we conducted a systematic review to synthesize existing studies on physician empathy and its value to patient outcomes and doctor-patient communication. The systematic review consisted of studies published in English peer-reviewed journals between January 2017 and October 2021. Following the PRISMA procedure, a total of 3055 articles were retrieved, and 11 articles were retained. The thematic analysis revealed three emergent themes: physicians' empathic expressions; patient outcomes (patient functional status, patient safety, and patient satisfaction); and empathy enhancing doctor-patient communication. This study highlighted the different ways empathy may be expressed by physicians and its positive effects on patient outcomes and doctor- patient communication. This study also suggested the under-researched areas that can be expanded in the future.

Barriers to and facilitators of user engagement with web-based mental health interventions in young people: a systematic review.

Many young people (YP) are diagnosed with mental illnesses and require support. Web-based mental health interventions (W-MHIs) have been increasingly utilized by YP, healthcare providers, and parents due to reasons including convenience and anonymity. W-MHIs are effective in improving mental health in YP. However, real-world engagement with W-MHIs remains low. Therefore, understanding barriers/facilitators of user engagement with W-MHIs is necessary to promote W-MHIs and help users gain optimal benefits through higher engagement. This review aims to identify barriers/facilitators of user engagement with W-MHIs in YP aged 10-24 years. A systematic search of five databases for English language, peer-reviewed publications was conducted between January 2010 and February 2023. Studies examining factors influencing user engagement with W-MHIs, described as barriers or facilitators, were included. Study quality was assessed using the Mixed Methods Appraisal Tool. A narrative synthesis was performed. Of 4088 articles identified, 69 studies were included. Barriers/facilitators were reported by young people (63 studies), providers (17 studies), and parents/caregivers (8 studies). YP perceived that usefulness and connectedness were the most common facilitators, whereas low-perceived need was the most reported barrier. Both providers and parents reported that perceived usefulness for YP was the most common facilitator, whereas concerns about program effectiveness and privacy were noted as barriers. This review found that program- and individual-related factors were important determinants of engagement with W-MHIs. This review provides guidance on the future design and development of new interventions, narrowing the gap between existing W-MHIs and unmet needs of users.

Spatial and temporal-trend assessment of desertification-sensitive land using the desertification sensitivity index in the provincial Ninh Thuan, Vietnam.

Desertification is a specific land-degrading process, reducing soil productivity and potentially threatening global food security. Therefore, spatially and temporally identifying and mapping desertification-sensitive areas is essential for better management. The current study aimed to (1) assess spatial areas sensitive to desertification and (2) examine the changing tendency of the desertification-sensitive areas over the past 25 years in the provincial Ninh Thuan. The desertification sensitivity index (DSI) was computed based on the Medalus model using 10 quantitative parameters, grouped into the soil, climate, and vegetation quality indexes, computed for the years 1996, 2005, 2010, and 2016. GIS was used to map desertification-sensitive areas associated with five DSI classes. Results showed that classes II and III had the highest area percentage, followed by classes IV and V, and class I. The classes most sensitive to desertification (classes IV and V) covered around 13 to 17%, and classes II and III were 25 to 32% of the total study area, respectively. The coastal areas located in the southeastern parts were more sensitive to desertification than the other parts. Over the four examined periods, the areas of classes IV and V increased while those of classes II and I decreased. These indicated that the study province tended to increase in its desertification sensitivity with a severe increase in the coastal areas over the past 25 years. The key factors involved in these changes could be related the human activities and climate variation, which could be more serious in southeastern areas than in the other areas.

Hexavalent Chromium Inhibited Zebrafish Embryo Development by Altering Apoptosis- and Antioxidant-Related Genes.

This study aimed to assess the effects of hexavalent chromium on zebrafish (Danio rerio) embryo development. The zebrafish embryos were treated with solutions containing chromium at different concentrations (0.1, 1, 3.125, 6.25, 12.5, 50, and 100 µg/mL). The development of zebrafish embryos was estimated by the determination of survival rate, heart rate, and the measurement of larvae body length. Real time RT-PCR and Western blot were performed to assess the expression of apoptosis- and antioxidant-related genes. The results showed that the reduced survival rate of zebrafish embryos and larvae was associated with an increase in chromium concentration. The exposure of higher concentrations resulted in a decrease in body length of zebrafish larvae. In addition, a marked increase in heart rate was observed in the zebrafish larvae under chromium treatment, especially at high concentrations. The real-time RT-PCR analysis showed that the transcript expressions for cell-cycle-related genes (cdk4 and cdk6) and antioxidant-related genes (sod1 and sod2) were downregulated in the zebrafish embryos treated with chromium. Western blot analysis revealed the upregulation of Caspase 3 and Bax, while a downregulation was observed in Bcl2. These results indicated that hexavalent chromium induced changes in zebrafish embryo development by altering apoptosis- and antioxidant-related genes.

Modeled health economic and equity impact on dental caries and health outcomes from a 20% sugar sweetened beverages tax in Australia.

Dental caries is the most prevalent oral disease across the life course. This study modeled the population health and economic impact of a 20% sugar sweetened beverages tax (SSB) for preventing dental caries compared to no intervention (societal and healthcare perspective). A cost-effectiveness analysis according to quintiles of area-level socioeconomic disadvantage was performed for the 2020 Australian population (0-100 years old) using a closed cohort Markov model. A qualitative assessment of implementation considerations (e.g., acceptability, equity, sustainability) was undertaken. Health outcomes were modeled as decayed teeth prevented and disability-adjusted life years (DALYs) averted. The 10-year and lifetime scenarios were modeled with probabilistic sensitivity analysis (Monte Carlo simulation, 2000 cycles). The 10-year scenario from a societal perspective yielded cost-savings of AUD$63.5M, healthcare cost-savings of AUD$42.2M, 510,977 decayed teeth averted and 98.1 DALYs averted. The lifetime scenario resulted in societal cost savings of AUD$176.6M, healthcare cost-savings of AUD$122.5M, 1,309,211 decayed teeth averted and 254.9 DALYs averted. Modeling indicated 71.5% and 74.5% cost-effectiveness for the 10-year and lifetime scenarios, respectively. A three-fold health benefit for the least advantaged was found compared to the most advantaged. A 20% SSB tax in Australia is cost-effective and promotes health equity.

Health-related quality of life in children, adolescents and young adults with self-harm or suicidality: A systematic review.

OBJECTIVE: Self-harm and suicidality are associated with substantial social and economic burden, especially among children, adolescents and young adults. The aim of this review was to systematically synthesize the literature on the association between health-related quality of life and self-harm/suicidality in children, adolescents and young adults. METHODS: Searches were conducted via MEDLINE, PsycINFO, CINAHL, EconLit and EMBASE. Search terms were the combination of the following blocks: (1) self-harm/suicidality, (2) health-related quality of life/well-being/life satisfaction and (3) children/adolescents/young adults. The quality of studies was assessed using the Effective Public Health Practice Project tool. RESULTS: We identified 23 relevant studies. Findings showed that participants who reported self-harm had lower well-being, life satisfaction or overall health-related quality of life compared to those without self-harm. There was also evidence supporting the association between health-related quality of life and suicidal attempt. However, the results for the association with suicidal ideation remained inconsistent. Additionally, mental health, emotional well-being, physical health, oral health, existential well-being and family quality of life were found to be significant domains associated with self-harm or suicidality. Regarding the quality of included studies, 35% (n = 8), 39% (n = 9) and 26% (n = 6) of studies were scored as 'Strong', 'Moderate' and 'Weak', respectively. CONCLUSION: Findings from the review showed that health-related quality of life varied according to the severity of suicidality (from ideation to attempt). There was also no evidence to infer the direction of causality between health-related quality of life and self-harm/suicidality. The findings suggest a need for further research, in particular longitudinal studies to fill identified gaps in the literature.

Mental health systems modelling for evidence-informed service reform in Australia.

Australia's Fifth National Mental Health Plan required governments to report, not only on the progress of changes to mental health service delivery, but to also plan for services that should be provided. Future population demand for treatment and care is challenging to predict and one solution involves modelling the uncertain demands on the system. Modelling can help decision-makers understand likely future changes in mental health service demand and more intelligently choose appropriate responses. It can also support greater scrutiny, accountability and transparency of these processes. Australia has an emerging national capacity for systems modelling in mental health which can enhance the next phase of mental health reform. This paper introduces concepts useful for understanding mental health modelling and identifies where modelling approaches can support health service planners to make evidence-informed decisions regarding planning and investment for the Australian population.

Sharing health information across online platforms: A systematic review.

Advanced Web 2.0 communication technologies have facilitated health-related information (HRI) sharing on the Internet. Especially, the COVID-19 pandemic and lockdowns around the world have forced more people to turn to the Internet for HRI. A better understanding of users' sharing content and sharing behavior can help communicators improve health literacy, raise community awareness, and facilitate social support exchanges. This paper reports the results of a systematic review of online HRI sharing literature, including key research topics, theories and methods used in past studies, and key factors of sharing behavior across online platforms. Following the PRISMA procedure for a systematic review, 58 articles were identified and analyzed using keyword matching, thematic analysis, and expert review. Guided by the platform theory, our findings differentiated five types of online platforms that differently influenced online users' sharing content and sharing purposes, including micro-blogs, social network sites, online health communities, social question and answer sites, and Wikis. The findings also clarify five main research topics and applicable theories used in each topic, including personal health sharing, health-related knowledge sharing, general health message diffusion, outcomes of HRI sharing, and exploratory research. Key factors of sharing behavior and potential sharing outcomes are also reviewed and summarized in the research framework developed from the motivation theory. Our study contributes to the understanding of online sharing behavior and provides implications for health communicators to develop effective health campaigns. Potential research directions are also identified and discussed.

Burden and preference-based quality of life associated with bullying in children.

The objectives of this study are to assess the association between childhood bullying and preference-based health-related quality of life (QoL) in Australian school children and their parents and estimate quality-adjusted life years (QALYs) associated with bullying chronicity. Children aged 8-10 years completed the child health utilities (CHU-9D), while parents completed the Australian quality of life (AQoL-8D). Children were grouped into four categories of bullying involvement (no bullying, victim, perpetrator, or both perpetrator and victim) based on the Revised Olweus Bully/Victim Questionnaire. Parental data were compared across two bullying involvement groups (bullying vs. no bullying). QALYs were calculated for children over two years and comparisons made based on the number of assessments where bullying was reported (baseline, 1- and 2-year follow up). Children who were involved in bullying (victims and/or perpetrators) reported statistically significantly lower mean utility scores compared to children who were not involved in bullying. Parents whose child was involved in bullying had significantly lower mean utility scores compared to parents of children not involved with bullying. There appeared to be a dose-response relationship, with higher QALY losses associated with increasing frequency of reported bullying. Bullying among Australian school children was associated with significantly lower preference-based QoL for themselves and their parents. This study also confirmed the significant burden of disease for bullying among children measured by an incremental decrease in QALY with an increasing chronicity of bullying over time.

Results from Viet Nam's 2022 report card on physical activity for children and youth.

Background: The Active Healthy Kids 2022 Viet Nam Report Card provides an evidence-based assessment of 10 indicators of community and government-led initiatives that impact the physical activity levels of children and youth in Vietnam. Methods: A systematic framework developed by the Active Healthy Kids Global Alliance was used. Each indicator: Overall Physical Activity, Organized Sport Participation, Active Play, Active Transportation, Sedentary Behaviors, Physical Fitness, Family and Peers, School, Community and Environment, and Government, and a new indicator: Obesity was assessed against predefined benchmarks. EBSCOhost databases and Google Scholar were searched for relevant academic and grey literature (e.g., government reports) respectively to inform indicator grading. Results: The School indicator received the highest grade 'A', followed by the Government indicator which was graded as 'B-'. Three indicators (Sedentary Behaviors, Family and Peers, Community and Environment) received 'C' grades. Active Transportation was graded 'D+'. Overall Physical Activity received the lowest grade of 'F'. Organized Sport and Physical Activity, Active Play, and Physical Fitness were not graded due to lack of data. Obesity was graded B-. Conclusions: This is the first physical activity report card for children and adolescents in Viet Nam. Evidence suggests that Vietnamese children and adolescents have low physical activity levels and high levels of sedentary behaviors. Initiatives to promote physical activity in children predominantly focus on promoting physical education in schools. Increased community-based programs promoting physical activity outside of school settings are required. Future research should address the surveillance gap in Organized Sport and Physical Activity, Active Play, and Physical Fitness.

Implementation and Clinical Adoption of Precision Oncology Workflows Across a Healthcare Network.

BACKGROUND: Precision oncology relies on molecular diagnostics, and the value-proposition of modern healthcare networks promises a higher standard of care across partner sites. We present the results of a clinical pilot to standardize precision oncology workflows. METHODS: Workflows are defined as the development, roll-out, and updating of disease-specific molecular order sets. We tracked the timeline, composition, and effort of consensus meetings to define the combination of molecular tests. To assess clinical impact, we examined order set adoption over a two-year period (before and after roll-out) across all gastrointestinal and hepatopancreatobiliary (GI) malignancies, and by provider location within the network. RESULTS: Development of 12 disease center-specific order sets took ~9 months, and the average number of tests per indication changed from 2.9 to 2.8 (P = .74). After roll-out, we identified significant increases in requests for GI patients (17%; P < .001), compliance with testing recommendations (9%; P < .001), and the fraction of "abnormal" results (6%; P < .001). Of 1088 GI patients, only 3 received targeted agents based on findings derived from non-recommended orders (1 before and 2 after roll-out); indicating that our practice did not negatively affect patient treatments. Preliminary analysis showed 99% compliance by providers in network sites, confirming the adoption of the order sets across the network. CONCLUSION: Our study details the effort of establishing precision oncology workflows, the adoption pattern, and the absence of harm from the reduction of non-recommended orders. Establishing a modifiable communication tool for molecular testing is an essential component to optimize patient care via precision oncology.

Identification of fusions with potential clinical significance in melanoma.

Though uncommon in melanoma, gene fusions may have therapeutic implications. Next generation sequencing-based clinical assays, designed to detect relevant gene fusions, mutations, and copy number changes, were performed on 750 melanomas (375 primary and 375 metastases) at our institution from 2014-2021. These included 599 (80%) cutaneous, 38 (5%) acral, 11 (1.5%) anorectal, 23 (3%) sinonasal, 27 (3.6%) eye (uveal/ conjunctiva), 11 (1.5%) genital (vulva/penile), and 41 (5.5%) melanomas of unknown primary. Sixteen fusions (2%) were detected in samples from 16 patients: 12/599 (2%) cutaneous, 2/38 (5%) acral, 1/9 (11%) vulva, 1/23(4.3%) sinonasal; and 12/16 (75%) fusions were potentially targetable. We identified two novel rearrangements: NAGS::MAST2 and NOTCH1::GNB1; and two fusions that have been reported in other malignancies but not in melanoma: CANT1::ETV4 (prostate cancer) and CCDC6::RET (thyroid cancer). Additional fusions, previously reported in melanoma, included: EML4::ALK, MLPH::ALK, AGAP3::BRAF, AGK::BRAF, CDH3::BRAF, CCT8::BRAF, DIP2B::BRAF, EFNB1::RAF1, LRCH3::RAF1, MAP4::RAF1, RUFY1::RAF1, and ADCY2::TERT. Fusion positive melanomas harbored recurrent alterations in TERT and CDKN2A, among others. Gene fusions were exceedingly rare (0.2%) in BRAF/RAS/NF1-mutant tumors and were detected in 5.6% of triple wild-type melanomas. Interestingly, gene rearrangements were significantly enriched within the subset of triple wild-type melanomas that harbor TERT promoter mutations (18% versus 2%, p < 0.0001). Thirteen (81%) patients were treated with immunotherapy for metastatic disease or in the adjuvant setting. Six of 12 (50%) patients with potentially actionable fusions progressed on immunotherapy, and 3/6 (50%) were treated with targeted agents (ALK and MEK inhibitors), 2 off-label and 1 as part of a clinical trial. One patient with an AGAP3::BRAF fusion positive melanoma experienced a 30-month long response to trametinib. We show that, detecting fusions, especially in triple wild-type melanomas with TERT promoter mutations, may have a clinically significant impact in patients with advanced disease who have failed front-line immunotherapy.

Economics of sedentary behaviour: A systematic review of cost of illness, cost-effectiveness, and return on investment studies.

AIMS: METHODS: RESULTS: We identified nine articles (conducted in Australia (n = 5), Europe (n = 3) and China (n = 1)); three reported healthcare costs associated with excessive sedentary time, whilst six were economic evaluations of interventions targeting sedentary behaviour. Healthcare costs associated with excessive sedentary time as reported in cost of illness studies were substantial; however, none explored non-health sector costs. In contrast, all full economics evaluations adopted a societal perspective; however, costs included differed depending on the intervention context. One sedentary behaviour intervention in children was cost-saving. The five interventions targeting occupational sitting time of adults in office workplaces were cost-effective. Physical environmental changes such as sit-stand desks, active workstations etc., were the key cost driver. CONCLUSIONS: Sedentary behaviour is likely associated with excess healthcare costs, although future research should also explore costs across other sectors. Cost-effectiveness evidence of sedentary behaviour reduction interventions in workplaces is limited but consistent. Key gaps relate to the economic credentials of interventions targeting children, and modelling of long-term health benefits of interventions.