Cysteine induces mitochondrial reductive stress in glioblastoma through hydrogen peroxide production.

Glucose and amino acid metabolism are critical for glioblastoma (GBM) growth, but little is known about the specific metabolic alterations in GBM that are targetable with FDA-approved compounds. To investigate tumor metabolism signatures unique to GBM, we interrogated The Cancer Genome Atlas for alterations in glucose and amino acid signatures in GBM relative to other human cancers and found that GBM exhibits the highest levels of cysteine and methionine pathway gene expression of 32 human cancers. Treatment of patient-derived GBM cells with the FDA-approved single cysteine compound N-acetylcysteine (NAC) reduced GBM cell growth and mitochondrial oxygen consumption, which was worsened by glucose starvation. Normal brain cells and other cancer cells showed no response to NAC. Mechanistic experiments revealed that cysteine compounds induce rapid mitochondrial H2O2 production and reductive stress in GBM cells, an effect blocked by oxidized glutathione, thioredoxin, and redox enzyme overexpression. From analysis of the clinical proteomic tumor analysis consortium (CPTAC) database, we found that GBM cells exhibit lower expression of mitochondrial redox enzymes than four other cancers whose proteomic data are available in CPTAC. Knockdown of mitochondrial thioredoxin-2 in lung cancer cells induced NAC susceptibility, indicating the importance of mitochondrial redox enzyme expression in mitigating reductive stress. Intraperitoneal treatment of mice bearing orthotopic GBM xenografts with a two-cysteine peptide induced H2O2 in brain tumors in vivo. These findings indicate that GBM is uniquely susceptible to NAC-driven reductive stress and could synergize with glucose-lowering treatments for GBM.

Centering Health Equity in the Implementation of the Hospital Incident Command System: A Qualitative Case Comparison Study.

OBJECTIVE: Disasters exacerbate inequities in health care. Health systems use the Hospital Incident Command System (HICS) to plan and coordinate their disaster response. This study examines how 2 health systems prioritized equity in implementing the Hospital Incident Command System (HICS) during the coronavirus disease 2019 (COVID-19) pandemic and identifies factors that influenced implementation. METHODS: This is a qualitative case comparison study, involving semi-structured interviews with 29 individuals from 2 US academic health systems. Strategies for promoting health equity were categorized by social determinants of health. The Consolidated Framework for Implementation Research (CFIR) guided analysis using a hybrid inductive-deductive approach. RESULTS: The health systems used various strategies to incorporate health equity throughout implementation, addressing all 5 social determinants of health domains. Facilitators included HICS principles, external partnerships, community relationships, senior leadership, health equity experts and networks, champions, equity-stratified data, teaming, and a culture of health equity. Barriers encompassed clarity of the equity representative role, role ambiguity for equity representatives, tokenism, competing priorities, insufficient resource allocation, and lack of preparedness. CONCLUSIONS: These findings elucidate how health systems centered equity during HICS implementation. Health systems and regulatory bodies can use these findings as a foundation to revise the HICS and move toward a more equitable disaster response.

Embedding Equity into the Hospital Incident Command System: A Narrative Review.

BACKGROUND: Disasters exacerbate health inequities, with historically marginalized populations experiencing unjust differences in health care access and outcomes. Health systems plan and respond to disasters using the Hospital Incident Command System (HICS), an organizational structure that centralizes communication and decision-making. The HICS does not have an equity role or considerations built into its standard structure. The authors conducted a narrative review to identify and summarize approaches to embedding equity into the HICS. METHODS: The peer-reviewed (PubMed, SCOPUS) and gray literature was searched for articles from high-income countries that referenced the HICS or Incident Command System (ICS) and equity, disparities, or populations that experience inequities in disasters. The primary focus of the search strategy was health care, but the research also included governmental and public health system articles. Two authors used inductive thematic analysis to assess commonalities and refined the themes based on feedback from all authors. RESULTS: The database search identified 479 unique abstracts; 76 articles underwent full-text review, and 11 were included in the final analysis. The authors found 5 articles through cited reference searching and 13 from the gray literature search, which included websites, organizations, and non-indexed journal articles. Three themes from the articles were identified: including equity specialists in the HICS, modifying systems to promote equity, and sensitivity to the local community. CONCLUSION: Several efforts to embed equity into the HICS and disaster preparedness and response were discovered. This review provides practical strategies health system leaders can include in their HICS and emergency preparedness plans to promote equity in their disaster response.

Astrocytes as Drivers and Disruptors of Behavior: New Advances in Basic Mechanisms and Therapeutic Targeting.

Astrocytes are emerging as key regulators of cognitive function and behavior. This review highlights some of the latest advances in the understanding of astrocyte roles in different behavioral domains across lifespan and in disease. We address specific molecular and circuit mechanisms by which astrocytes modulate behavior, discuss their functional diversity and versatility, and highlight emerging astrocyte-targeted treatment strategies that might alleviate behavioral and cognitive dysfunction in pathologic conditions. Converging evidence across different model systems and manipulations is revealing that astrocytes regulate behavioral processes in a precise and context-dependent manner. Improved understanding of these astrocytic functions may generate new therapeutic strategies for various conditions with cognitive and behavioral impairments.

Gut microbiota profiles in two New Zealand cohorts with overweight and prediabetes: a Tu Ora/PREVIEW comparative study.

Obesity-related metabolic diseases such as type 2 diabetes (T2D) are major global health issues, affecting hundreds of millions of people worldwide. The underlying factors are both diverse and complex, incorporating biological as well as cultural considerations. A role for ethnicity - a measure of self-perceived cultural affiliation which encompasses diet, lifestyle and genetic components - in susceptibility to metabolic diseases such as T2D is well established. For example, Asian populations may be disproportionally affected by the adverse 'TOFI' (Thin on the Outside, Fat on the Inside) profile, whereby outwardly lean individuals have increased susceptibility due to excess visceral and ectopic organ fat deposition. A potential link between the gut microbiota and metabolic disease has more recently come under consideration, yet our understanding of the interplay between ethnicity, the microbiota and T2D remains incomplete. We present here a 16S rRNA gene-based comparison of the fecal microbiota of European-ancestry and Chinese-ancestry cohorts with overweight and prediabetes, residing in New Zealand. The cohorts were matched for mean fasting plasma glucose (FPG: mean ± SD, European-ancestry: 6.1 ± 0.4; Chinese-ancestry: 6.0 ± 0.4 mmol/L), a consequence of which was a significantly higher mean body mass index in the European group (BMI: European-ancestry: 37.4 ± 6.8; Chinese-ancestry: 27.7 ± 4.0 kg/m2; p < 0.001). Our findings reveal significant microbiota differences between the two ethnicities, though we cannot determine the underpinning factors. In both cohorts Firmicutes was by far the dominant bacterial phylum (European-ancestry: 93.4 ± 5.5%; Chinese-ancestry: 79.6 ± 10.4% of 16S rRNA gene sequences), with Bacteroidetes and Actinobacteria the next most abundant. Among the more abundant (≥1% overall relative sequence abundance) genus-level taxa, four zero-radius operational taxonomic units (zOTUs) were significantly higher in the European-ancestry cohort, namely members of the Subdoligranulum, Blautia, Ruminoclostridium, and Dorea genera. Differential abundance analysis further identified a number of additional zOTUs to be disproportionately overrepresented across the two ethnicities, with the majority of taxa exhibiting a higher abundance in the Chinese-ancestry cohort. Our findings underscore a potential influence of ethnicity on gut microbiota composition in the context of individuals with overweight and prediabetes.

Assessing US Small Animal Veterinary Clinic Adaptations and Their Impacts on Workforce COVID-19 Preparedness and Response.

Veterinary personnel are an essential yet often underappreciated workforce, critical for zoonotic disease prevention and response efforts that impact human health. During the early COVID-19 pandemic, the veterinary workforce supported emergency responses by promoting zoonotic disease risk communication, sharing animal health expertise, and boosting laboratory surge capacity against SARS-CoV-2 in animals and people. However, small animal veterinary workers (SAVWs), similar to healthcare workers, faced organizational challenges in providing clinical care to family pets, including those susceptible to SARS-CoV-2. We analyzed a cross-sectional survey of 1,204 SAVWs in the United States to assess veterinary clinic adaptations and their associations with SAVWs' self-perceived readiness, willingness, and ability to respond to the COVID-19 pandemic as a workforce. SAVWs who worked fewer hours than before the pandemic (ready, OR 0.59; willing, OR 0.66; able, OR 0.52) or used personal protective equipment less frequently for protection in the clinic (ready, OR 0.69; willing, OR 0.69; able, OR 0.64) felt less ready, willing, and able to respond to COVID-19. SAVWs working remotely felt less ready (OR 0.46) but not less willing or able to respond to COVID-19. Lastly, SAVWs with dependents felt less ready (OR 0.67) and able (OR 0.49) to respond to COVID-19 than SAVWs without dependents. Our findings highlight the importance of proactively managing work schedules, having access to personal protective equipment, and addressing caregiving concerns to enhance SAVW preparedness and response outcomes. SAVWs are knowledgeable, motivated personnel who should be integrated into local public health emergency preparedness and response plans, supporting a One Health framework that unites multidisciplinary teams to respond to future zoonotic disease threats.

Sociodemographic and Health Indicators of Diet Quality in Pre-Frail Older Adults in New Zealand.

This study aimed to identify sociodemographic and health indicators of diet quality in pre-frail community-dwelling older adults. Pre-frail older adults are those at risk of progression to clinical manifestations of frailty and are targets for preventative intervention. We previously reported that pre-frail older adults have reasonably good overall diet quality. However, further analyses found a low intake of energy, protein and several micronutrients. METHODS: We collected detailed dietary intake from pre-frail (FRAIL scale 1-2) older adults using NZ Intake24, an online version of 24 h multiple pass dietary recall. Diet quality was ascertained with the Diet Quality Index-International (DQI-I). We used regression generalized linear models to determine predictors of diet quality as well as classification and regression tree (CART) analysis to examine the complex relationships between predictors and identified profiles of sub-groups of older adults that predict diet quality. RESULTS: The median age in this sample (n = 468) was 80.0 years (77.0-84.0). Living with others, a high deprivation index and a higher BMI were independent predictors of poorer diet quality. With CART analysis, we found that those with a BMI > 29 kg/m2, living with others and younger than 80 years were likely to have a lower diet quality. CONCLUSIONS: We found that BMI, living arrangement and socioeconomic status were independent predictors of diet quality in pre-frail older adults, with BMI being the most important variable in this sample when the interaction of these variables was considered. Future research is needed to determine the similarities and/or differences in the profile of subgroups of older adults with poorer diet quality.

Decision-Making Prepandemic: University Curtailment of Academic Operations Closure Processes During the Novel Coronavirus Disease 2019 (COVID-19) Outbreak.

OBJECTIVE: Through in-depth interviews, this study aimed to understand perspectives of key stakeholders regarding the decision to curtail academic operations in the setting of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak before the declaration of a pandemic on March 11, 2020, and how such processes may be optimized in the future to best protect public health and safety. METHODS: Virtual interviews with key stakeholders from 4 academic institutions were conducted from September to December 2020 using a standardized interview question template. The interviews lasted approximately 30-45 minutes and each interview was recorded with permission. The interviews were then transcribed and reviewed for qualitative analysis. RESULTS: The decision to curtail academic operations involved several common themes, such as discussing how institutions would control the outbreak and the process of transitioning to virtual learning and remote work. Universities were monitoring other universities' responses as well as evaluating the prevalence of cases nationally and globally. Risks and challenges identified included housing for international students, financial implications, and loss of academic productivity. CONCLUSIONS: The decision-making process may be optimized in the future by focusing on communication within a smaller committee, prioritizing epidemiology over fiscal implications, and embracing an openness to consider new strategies. Further research regarding this topic should be pursued to best protect public health and safety.

Effect of a 12-Week Polyphenol Rutin Intervention on Markers of Pancreatic ß-Cell Function and Gut Microbiota in Adults with Overweight without Diabetes.

Supplementation with prebiotic polyphenol rutin is a potential dietary therapy for type 2 diabetes prevention in adults with obesity, based on previous glycaemic improvement in transgenic mouse models. Gut microbiota are hypothesised to underpin these effects. We investigated the effect of rutin supplementation on pancreatic ß-cell function measured as C-peptide/glucose ratio, and 16S rRNA gene-based gut microbiota profiles, in a cohort of individuals with overweight plus normoglycaemia or prediabetes. Eighty-seven participants were enrolled, aged 18-65 years with BMI of 23-35 kg/m2. This was a 12-week double-blind randomised controlled trial (RCT), with 3 treatments comprising (i) placebo control, (ii) 500 mg/day encapsulated rutin, and (iii) 500 mg/day rutin-supplemented yoghurt. A 2-h oral glucose tolerance test (OGTT) was performed at baseline and at the end of the trial, with faecal samples also collected. Compliance with treatment was high (~90%), but rutin in both capsule and dietary format did not alter pancreatic ß-cell response to OGTT over 12 weeks. Gut bacterial community composition also did not significantly change, with Firmicutes dominating irrespective of treatment. Fasting plasma glucose negatively correlated with the abundance of the butyrate producer Roseburia inulinivorans, known for its anti-inflammatory capacity. This is the first RCT to investigate postprandial pancreatic ß-cell function in response to rutin supplementation.

Enhancing a Willingness to Respond to Disasters and Public Health Emergencies Among Health Care Workers, Using mHealth Intervention: A Multidisciplinary Approach.

Health care workers (HCWs) are increasingly faced with the continuous threat of confronting acute disasters, extreme weather-related events, and protracted public health emergencies. One of the major factors that determines emergency-department-based HCWs' willingness to respond during public health emergencies and disasters is self-efficacy. Despite increased public awareness of the threat of disasters and heightened possibility of future public health emergencies, the emphasis on preparing the health care workforce for such disasters is inadequate in low-and-middle-income countries (LMICs). Interventions for boosting self-efficacy and response willingness in public health emergencies and disasters have yet to be implemented or examined among emergency HCWs in LMICs. Mobile health (mHealth) technology seems to be a promising platform for such interventions, especially in a resource-constrained setting. This paper introduces an mHealth-focused project that demonstrates a model of multi-institutional and multidisciplinary collaboration for research and training to enhance disaster response willingness among emergency department workers in Pakistan.

The Role of Self-Efficacy and Risk Perception in the Willingness to Respond to Weather Disasters Among Emergency Medicine Health Care Workers in Pakistan.

OBJECTIVE: Optimizing health care workers' (HCWs) willingness to respond (WTR) is critical in low-and-middle-income countries (LMICs) for proper health system functioning during extreme weather events. Pakistan frequently experiences weather-related disasters, but limited evidence is available to examine HCW willingness. Our study examined the association between WTR and behavioral factors among emergency department HCWs. METHODS: A cross-sectional survey was conducted from August to September 2022 among HCWs from 2 hospitals in Karachi, Pakistan. Non-probability purposive sampling was used to recruit participants. A survey tool was informed by Witte's Extended Parallel Process Model (EPPM). Multivariate logistic regression analyses were performed to examine the association between WTR and attitudes/beliefs as well as EPPM profiles. RESULTS: Twenty-nine percent of HCWs indicated a low WTR. HCWs using public transportation had a higher WTR. Perceived knowledge and skills, self-efficacy, and perceived impact of one's response showed positive associations with WTR if required. Perception that one's colleagues would report to work positively predicted WTR if asked. Consistent with the EPPM, HCWs with high efficacy and perceived threat were willing to respond to weather disasters. CONCLUSIONS: Our findings highlight the need of strengthening WTR by promoting self-efficacy and enhancing accurate risk perception as a response motivator, among emergency department HCWs in Pakistan.

Social network analysis of COVID-19 vaccine YouTube videos in Odisha, India: mapping the channel network and analyzing comment sentiment.

India has reported more than 35 million confirmed cases of COVID-19 and nearly half a million cumulative deaths. Although vaccination rates for the first vaccine dose are quite high, one-third of the population has not received a second shot. Due to its widespread use and popularity, social media can play a vital role in enhancing vaccine acceptance. This study in a real-world setting utilizes YouTube videos in Odisha, India where the platform has deep penetration among the 18-35 target population, and secondarily their family and peers. Two contrasting videos were launched on the YouTube platform to examine how those videos operate within the broader recommender and subscription systems that determine the audience reach. Video analytics, algorithms for recommended videos, visual representation of connections created, centrality between the networks, and comment analysis was conducted. The results indicate that the video with a non-humorous tone and collectivistic appeal delivered by a female protagonist performed best with regard to views and time spent watching the videos. The results are of significance to health communicators who seek to better understand the platform mechanisms that determine the spread of videos and measures of viewer reactions based on viewer sentiment.

Production of vaccination videos in India: learnings from a science-art partnership.

BACKGROUND: Cross-cultural communication, often conceptualized along culture and language dimensions, is an important issue for collaborative teams that include both scientists and artists. Such teams must balance the standardization needs of rigorous scientific methods, on the one hand, with openness for artistic creativity, on the other. The scientific literature does not provide clear guidance on how to structure such collaborations. DISCUSSION: We created eight videos manipulating the type of appeal, message tone, and gender of the vaccine promoter in a 2 × 2 × 2 between-subjects experiment. The four stages of the filmmaking process were 1) conceptualizing filmmaking and script writing through a scientific lens, 2) pilot testing and finalizing the script, 3) video production and editing, and 4) dissemination. We describe the process and learnings from a collaboration that included filmmakers, researchers, and vaccine experts from India and the United States in producing, disseminating, and evaluating videos that promoted vaccine uptake in Odisha, India. CONCLUSIONS: When projects require close collaborations between scientists and artists, committing to a unified vision is essential for facilitating open, bidirectional communication and building trust between the partners. Clearly denoting research boundaries ensures that the scientific needs of the project are met while simultaneously welcoming space for the filmmakers' creativity, fostering a sense of ownership, and enhancing the final product.

Differentiating radiation necrosis from tumor recurrence: a systematic review and diagnostic meta-analysis comparing imaging modalities.

PURPSOSE: Cerebral radiation necrosis (RN) is often a delayed phenomenon occurring several months to years after the completion of radiation treatment. Differentiating RN from tumor recurrence presents a diagnostic challenge on standard MRI. To date, no evidence-based guidelines exist regarding imaging modalities best suited for this purpose. We aim to review the current literature and perform a diagnostic meta-analysis comparing various imaging modalities that have been studied to differentiate tumor recurrence and RN. METHODS: A systematic search adherent to PRISMA guidelines was performed using Scopus, PubMed/MEDLINE, and Embase. Pooled sensitivities and specificities were determined using a random-effects or fixed-effects proportional meta-analysis based on heterogeneity. Using diagnostic odds ratios, a diagnostic frequentist random-effects network meta-analysis was performed, and studies were ranked using P-score hierarchical ranking. RESULTS: The analysis included 127 studies with a total of 220 imaging datasets, including the following imaging modalities: MRI (n = 10), MR Spectroscopy (MRS) (n = 28), dynamic contrast-enhanced MRI (n = 7), dynamic susceptibility contrast MRI (n = 36), MR arterial spin labeling (n = 5), diffusion-weighted imaging (n = 13), diffusion tensor imaging (DTI) (n = 2), PET (n = 89), and single photon emission computed tomography (SPECT) (n = 30). MRS had the highest pooled sensitivity (90.7%). DTI had the highest pooled specificity (90.5%). Our hierarchical ranking ranked SPECT and MRS as most preferable, and MRI was ranked as least preferable. CONCLUSION: These findings suggest SPECT and MRS carry greater utility than standard MRI in distinguishing RN from tumor recurrence.

PP1ß opposes classic PP1 function, inhibiting spine maturation and promoting LTP.

Protein phosphatase 1 (PP1) regulates synaptic plasticity and has been described as a molecular constraint on learning and memory. There are three neuronal isoforms, PP1α, PP1ß, and PP1γ, but little is known about their individual functions. PP1α and PP1γ are assumed to mediate the effects of PP1 on learning and memory based on their enrichment at dendritic spines and their preferential binding to neurabin and spinophilin, major PP1 synaptic scaffolding proteins. However, it was recently discovered that human de novo PP1ß mutations cause intellectual disability, suggesting an important but ill-defined role for PP1ß. In this study, we investigated the functions of each PP1 isoform in hippocampal synaptic physiology using conditional CA1-specific knockout mice. In stark contrast to classic PP1 function, we found that PP1ß promotes synaptic plasticity as well as spatial memory. These changes in synaptic plasticity and memory are accompanied by changes in GluA1 phosphorylation, GluN2A levels, and dendritic spine density and morphology, including silent synapse number. These functions of PP1ß reveal a previously unidentified signaling pathway regulating spine maturation and plasticity, broadening our understanding of the complex role of PP1 in synaptic physiology.

Exploring U.S. Food System Workers' Intentions to Work While Ill during the Early COVID-19 Pandemic: A National Survey.

With "stay at home" orders in effect during early COVID-19, many United States (U.S.) food system workers attended in-person work to maintain national food supply chain operations. Anecdotally, many encountered barriers to staying home despite symptomatic COVID-19 illness. We conducted a national, cross-sectional, online survey between 31 July and 2 October 2020 among 2535 respondents. Using multivariable regression and free-text analyses, we investigated factors associated with workers' intentions to attend work while ill (i.e., presenteeism intentions) during the early COVID-19 pandemic. Overall, 8.8% of respondents intended to attend work with COVID-19 disease symptoms. Almost half (41.1%) reported low or very low household food security. Workers reporting a higher workplace safety climate score were half as likely to report presenteeism intentions (adjusted odds ratio [aOR] 0.52, 95% confidence interval (CI) 0.37, 0.75) relative to those reporting lower scores. Workers reporting low (aOR 2.06, 95% CI 1.35, 3.13) or very low (aOR 2.31, 95% CI 1.50, 3.13) household food security levels had twice the odds of reporting presenteeism intentions relative to those reporting high/marginal food security. Workplace culture and safety climate could enable employees to feel like they can take leave when sick during a pandemic, which is critical to maintaining individual and workplace health. We stress the need for strategies which address vulnerabilities and empower food workers to make health-protective decisions.

A Scoping Review of the Essential Components of Emergency Medical Response Systems for Mass Casualty Incidents.

OBJECTIVE: Emergency medical (EM) response systems require extensive coordination, particularly during mass casualty incidents (MCIs). The recognition of preparedness gaps and contextual priorities to MCI response capacity in low- and middle-income countries (LMICs) can be better understood through the components of EM reponse systems. This study aims to delineate essential components and provide a framework for effective emergency medical response to MCIs. METHODS: A scoping review was conducted using 4 databases. Title and abstract screening was followed by full-text review. Thematic analysis was conducted to identify themes pertaining to the essential components and integration of EM response systems. RESULTS: Of 20,456 screened citations, 181 articles were included in the analysis. Seven major and 40 sub-themes emerged from the content analysis as the essential components and supportive elements of MCI medical response. The essential components of MCI response were integrated into a framework demonstrating interrelated connections between essential and supportive elements. CONCLUSIONS: Definitions of essential components of EM response to MCIs vary considerably. Most literature pertaining to MCI response originates from high income countries with far fewer reports from LMICs. Integration of essential components is needed in different geopolitical and economic contexts to ensure an effective MCI emergency medical response.

Creation, dissemination, and evaluation of videos to promote COVID-19 vaccination in India: A research protocol.

Background: Vaccine hesitancy is one of the greatest challenges to the success of coronavirus disease 2019 (COVID-19) vaccination campaigns. Videos promoting vaccines have a narrow scope focusing solely on facts, and less on the emotional and narrative elements of communication that can be equally persuasive. The role of humor, for example, has remained largely unexplored.   Objective: This study investigates whether theory-based videos can change people's attitudes, beliefs, and intentions to receive the second COVID-19 vaccine. Our primary research question is: How do collectivistic and individualistic appeals, humor, and protagonist gender individually and jointly affect vaccination attitudes, beliefs, and intentions?   Methods: This project tapped into the underutilized Indian film industry-the world's largest film producer-to promote vaccination messaging through short videos. Feedback from a community advisory board was utilized to inform the video scripts that were then shot by a production team. Eight videos were filmed and shared by adopting a 2 (appeal: individualistic or collectivistic) x 2 (tone: humor or non-humor) x 2 (protagonist gender: male or female) between-subjects design approach. Our sample includes Odia-speaking participants aged between 18 - 35 years old randomly assigned to watch one of the eight study videos. An online survey questionnaire, social media network analysis, and small group qualitative interviews will be utilized to explore how the entertainment-education videos can be used to reduce vaccine hesitancy.  Discussion: Vaccine messages do not fall into a cultural or cognitive vacuum. People process and make sense of information based on their prior experience, properties of the message, and their social environment. Yet, these considerations have taken secondary importance in vaccine communications. This research shows that it is possible to deliver high-caliber videos created in accordance with the audience's cultural and cognitive background.   Conclusions: This study will inform future health promotion messaging through brief videos on the internet.

Effectiveness of a complex intervention of group-based nutrition and physical activity to prevent frailty in pre-frail older adults (SUPER): a randomised controlled trial.

BACKGROUND: The increasing prevalence of frailty with age is becoming a public health priority in countries with ageing populations. Pre-frailty presents a window of opportunity to prevent the development of frailty in community-dwelling older adults. This study aimed to examine the effectiveness of a complex intervention that combined a nutrition-based intervention and a physical activity intervention, along with the effectiveness of each intervention individually, to reduce physical frailty in pre-frail older adults over 2 years. METHODS: In this single-blind, 2 x 2 factorial, randomised, controlled trial, we recruited pre-frail community-dwelling older adults in Aotearoa New Zealand via mail through general medical practices. To be eligible, participants had to be pre-frail according to self-reported FRAIL scores of 1 or 2, aged 75 years or older (or 60 years or older for Maori and Pacific Peoples), not terminally ill or with advanced dementia as judged by a general practitioner, able to stand, medically safe to participate in low-intensity exercise, and able to use kitchen utensils safely. Participants were randomly allocated to receive an 8-week Senior Chef programme (SC group), a 10-week Steady As You Go programme (SAYGO group), a 10-week combined SC and SAYGO intervention (combined group), or a 10-week social programme (control group), using computer-generated block randomisation administered through an electronic data capture system by local study coordinators. Assessors were masked to group allocation for all assessments. SC is a group-based nutrition education and cooking class programme (3 h weekly), SAYGO is a group-based strength and balance exercise programme (1 h weekly), and the social control programme was a seated, group socialising activity (once a week). Masked assessors ascertained Fried frailty scores at baseline, end of intervention, and at 6, 12, and 24 months after the programme. The primary outcome was change in Fried frailty score at 2 years. Intention-to-treat analyses were completed for all randomised participants, and all participants who had a high (≥75%) adherence were analysed per protocol. This study is registered at ANZCTR, ACTRN12614000827639. FINDINGS: Between May 12, 2016 and April 9, 2018, we assessed 2678 older adults for eligibility, of whom 468 (17%) consented and completed baseline assessment, with a mean age of 80·3 years (SD 5·1) and a mean Fried score of 1·9 (1·2); 59% were women. We randomly allocated these participants into the four groups: 117 in the SC group, 118 in the SAYGO group, 118 in the combined group, and 115 in the control group; 318 participants attended the 24-month follow-up: 89 in the SC group, 78 in the SAYGO group, 73 in the combined group, and 78 in the control group. At the 24-month follow-up, there were no differences in mean Fried scores between the intervention groups and the control group. No adverse events were reported. INTERPRETATION: The study did not find that the combined SC and SAYGO programme was effective in reducing frailty in pre-frail older adults. Although some short-term benefits were observed in each individual programme, there was no clear evidence of long-term impact. Further research is needed to evaluate combinations of group-based programmes for community-dwelling older adults to optimise their physical function. FUNDING: Health Research Council New Zealand and Ageing Well Challenge (Ministry of Business Innovation and Employment).