Quality indicators to monitor the quality and safety of care for older people: a scoping review protocol.

OBJECTIVE: The objective of this review is to identify quality indicators used to monitor the quality and safety of care provided to older people (≥ 65 years old) in 8 care settings: primary care; hospital/acute care; aged care (including residential aged care and home or community care); palliative care; rehabilitation care; care transitions; dementia care; and care in rural areas. INTRODUCTION: There is a need for high-quality, holistic, person-centered aged and health care for older people. Older people receive care across multiple care settings, and population-level monitoring of quality and safety of care across settings represents a significant challenge. INCLUSION CRITERIA: National and international quality indicators used to monitor and evaluate quality and safety of care at the population level for older individuals in the 8 key care settings will be considered for inclusion. English-language quantitative and mixed method studies published from 2012 will be considered. METHODS: Academic (MEDLINE, Embase) and gray (government websites, clinical guidelines, Google) literature searches will be conducted. A standardized data extraction tool will be used to describe the identified quality indicators and associated tools. Quality indicators will be categorized by key domains (ie, pain, function, consumer experience, service delivery), quality indicator type (structure, process, outcome) and the Institute of Medicine's 6 dimensions of care quality (eg, efficiency, effectiveness, appropriateness, accessibility, acceptability/person-centered, safety). The scoping review will be conducted in accordance with the JBI methodology for scoping reviews and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). REVIEW REGISTRATION: Open Science Framework osf.io/8czun.

Sexual Victimization, Emotion Dysregulation, and Sexual Consent Feelings and Communication During a Recent Sexual Encounter.

Sexual consent has been a major focus of campus campaigns to reduce sexual violence (SV). However, these campaigns often educate students about consent with little attention to the complex ways consent can be experienced, expressed, and interpreted by others. Further, little research has focused on the consent feelings and communication cues of students who have a history of SV, nor have studies examined how the ability to attend to and regulate emotions relates to internal feelings or external communication of consent. This secondary analysis examined SV histories, emotion dysregulation, and internal and external consent cues in a sample of 610 college students (72% women) who completed an online self-report survey. Findings revealed that students with SV histories (n = 257) reported greater emotion dysregulation, lower internal consent, and greater use of passive external consent cues compared to students without SV histories; greater emotion dysregulation was associated with lower internal consent. In a path model, SV history was indirectly related to use of direct nonverbal and passive consent cues through greater emotion dysregulation and lower internal consent. Contrary to expectations, higher internal consent was associated with greater use of passive external consent cues. Consent programming could be augmented to encourage attention to and regulation of emotions in sexual situations to improve communication and sexual well-being.

"I Didn't Realize How Common it Was:" A Mixed-Methods Study Examining Changes in Perceptions of Sexual Assault, Sex and Consent, and Sexual Behavior as a Function of the #Metoo Movement.

This mixed-methods study examined awareness and perceived legitimacy of the #MeToo movement and how #MeToo changed perceptions of sexual assault and consent, as well as sexual interactions, in the United States. Adults residing in the U.S. were recruited through CloudResearch to complete an online survey in 2021. Quantitative data from 680 participants (M age = 45.8, 60% women, 77.4% White) indicated moderate awareness and perceived legitimacy of the #MeToo movement; Black, LGBQ+, and more politically liberal respondents had greater #MeToo awareness while younger, more liberal respondents, and those with greater rejection of rape myths rated #MeToo more legitimate. Among 354 participants (M age = 45.0, 65.3% women, 76.4% White) who answered at least one open-ended question with regard to changes resulting from the #MeToo movement, thematic analysis revealed nine primary themes: (1) Describing change; (2) Change in understanding; (3) More cautious; (4) Wrong or requires reporting/punishment; (5) Gendered social norms; (6) Easier to talk about; (7) #MeToo rhetoric; (8) Consequences for survivors, and (9) Empowerment. Several sub-themes were identified among the primary themes and implications for sexual assault prevention and response were discussed. The study findings are contextualized by social constructionism, with a particular focus on gender-based power dynamics, contributing to a growing literature documenting the cultural impact of the #MeToo movement.

Effect of Low-Dose Aspirin on the Course of Age-Related Macular Degeneration: A Secondary Analysis of the ASPREE Randomized Clinical Trial.

Importance: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in old age. There is no proven intervention to prevent AMD and, apart from lifestyle, nutritional, and supplement advice, there is no intervention to delay its progression. Objective: To determine the impact of long-term low-dose aspirin on the incidence and progression of AMD. Design, Setting and Participants: The Aspirin in Reducing Events in the Elderly-AMD (ASPREE-AMD) study was an Australian-based substudy of the ASPREE trial, a multicenter, international, randomized, double-masked, placebo-clinical trial investigating the efficacy of low-dose aspirin in prolonging disability-free survival among older individuals. Retinal photography was conducted at baseline from March 2010 to January 2015, then 3 and 5 years after randomization. AMD status was determined using color retinal images and treatment records. Australian participants in ASPREE aged 70 years and older without dementia, independence-limiting physical disability, cardiovascular disease, or chronic illness limiting 5-year survival and with gradable retinal images at baseline were included. Data were analyzed from December 2022 to December 2023. Interventions: Aspirin (100 mg daily, enteric coated) or placebo. Main Outcomes and Measures: Incidence of AMD and progression from early/intermediate to late AMD. Outcomes were analyzed by modified intention-to-treat analysis. Results: A total of 4993 participants were enrolled in this substudy. Baseline characteristics were similar between groups. At the time of sponsor-determined trial termination, retinal follow-up data were available for 3208 participants, 3171 of whom were analyzed for AMD incidence and progression, with a median (IQR) age of 73.5 (71.5-76.4) years and even sex distribution (1619 [51%] female). Median (IQR) follow-up time was 3.1 (3.0-3.5) years. Cumulative AMD incidence was 195 of 1004 (19.4%) in the aspirin group and 187 of 979 (19.1%) in the placebo group (relative risk [RR], 1.02; 95% CI, 0.85-1.22; P = .86). Cumulative progression from early/intermediate AMD to late AMD was observed in 14 of 615 (2.3%) participants in the aspirin group and 18 of 573 (3.1%) in the placebo group (RR, 0.72; 95% CI, 0.36-1.44; P = .36). Conclusions and Relevance: In this trial, low-dose aspirin administered for 3 years did not affect the incidence of AMD. The evidence was weaker for progression of AMD due to low number of progressed cases. Overall, these results do not support suggestion that low-dose daily aspirin prevents the development or progression of AMD. Trial Registration: anzctr.org Identifier: ACTRN12613000755730.

National surveillance using a clinical quality indicator for prolonged antipsychotic use among older Australians with dementia who access aged care services.

OBJECTIVES: Dementia guidelines recommend antipsychotics are only used for behavioral and psychological symptoms when non-drug interventions fail, and to regularly review use. Population-level clinical quality indicators (CQIs) for dementia care in permanent residential aged care (PRAC) typically monitor prevalence of antipsychotic use but not prolonged use. This study aimed to develop a CQI for antipsychotic use >90 days and examine trends, associated factors, and variation in CQI incidence; and examine duration of the first episode of use among individuals with dementia accessing home care packages (HCPs) or PRAC. METHODS: Retrospective cohort study, including older individuals with dementia who accessed HCPs (n = 50,257) or PRAC (n = 250,196). Trends in annual CQI incidence (2011-12 to 2015-16) and associated factors were determined using Poisson regression. Funnel plots examined geographical and facility variation. Time to antipsychotic discontinuation was estimated among new antipsychotic users accessing HCP (n = 2367) and PRAC (n = 15,597) using the cumulative incidence function. RESULTS: Between 2011-12 and 2015-16, antipsychotic use for >90 days decreased in HCP recipients from 10.7% (95% CI 10.2-11.1) to 10.1% (95% CI 9.6-10.5, adjusted incidence rate ratio (aIRR) 0.97 (95% CI 0.95-0.98)), and in PRAC residents from 24.5% (95% CI 24.2-24.7) to 21.8% (95% CI 21.5-22.0, aIRR 0.97 (95% CI 0.96-0.98)). Prior antipsychotic use (both cohorts) and being male and greater socioeconomic disadvantage (PRAC cohort) were associated with higher CQI incidence. Little geographical/facility variation was observed. Median treatment duration in HCP and PRAC was 334 (interquartile range [IQR] 108-958) and 555 (IQR 197-1239) days, respectively. CONCLUSIONS: While small decreases in antipsychotic use >90 days were observed between 2011-12 and 2015-16, findings suggest antipsychotic use among aged care recipients with dementia can be further minimized.

Allergic Rhinitis: A Review.

Importance: Allergic rhinitis affects an estimated 15% of the US population (approximately 50 million individuals) and is associated with the presence of asthma, eczema, chronic or recurrent sinusitis, cough, and both tension and migraine headaches. Observations: Allergic rhinitis occurs when disruption of the epithelial barrier allows allergens to penetrate the mucosal epithelium of nasal passages, inducing a T-helper type 2 inflammatory response and production of allergen-specific IgE. Allergic rhinitis typically presents with symptoms of nasal congestion, rhinorrhea, postnasal drainage, sneezing, and itching of the eyes, nose, and throat. In an international study, the most common symptoms of allergic rhinitis were rhinorrhea (90.38%) and nasal congestion (94.23%). Patients with nonallergic rhinitis present primarily with nasal congestion and postnasal drainage frequently associated with sinus pressure, ear plugging, muffled sounds and pain, and eustachian tube dysfunction that is less responsive to nasal corticosteroids. Patients with seasonal allergic rhinitis typically have physical examination findings of edematous and pale turbinates. Patients with perennial allergic rhinitis typically have erythematous and inflamed turbinates with serous secretions that appear similar to other forms of chronic rhinitis at physical examination. Patients with nonallergic rhinitis have negative test results for specific IgE aeroallergens. Intermittent allergic rhinitis is defined as symptoms occurring less than 4 consecutive days/week or less than 4 consecutive weeks/year. Persistent allergic rhinitis is defined as symptoms occurring more often than 4 consecutive days/week and for more than 4 consecutive weeks/year. Patients with allergic rhinitis should avoid inciting allergens. In addition, first-line treatment for mild intermittent or mild persistent allergic rhinitis may include a second-generation H1 antihistamine (eg, cetirizine, fexofenadine, desloratadine, loratadine) or an intranasal antihistamine (eg, azelastine, olopatadine), whereas patients with persistent moderate to severe allergic rhinitis should be treated initially with an intranasal corticosteroid (eg, fluticasone, triamcinolone, budesonide, mometasone) either alone or in combination with an intranasal antihistamine. In contrast, first-line therapy for patients with nonallergic rhinitis consists of an intranasal antihistamine as monotherapy or in combination with an intranasal corticosteroid. Conclusions and Relevance: Allergic rhinitis is associated with symptoms of nasal congestion, sneezing, and itching of the eyes, nose, and throat. Patients with allergic rhinitis should be instructed to avoid inciting allergens. Therapies include second-generation H1 antihistamines (eg, cetirizine, fexofenadine, desloratadine, loratadine), intranasal antihistamines (eg, azelastine, olopatadine), and intranasal corticosteroids (eg, fluticasone, triamcinolone, budesonide, mometasone) and should be selected based on the severity and frequency of symptoms and patient preference.

A 10-week intergenerational program bringing together community-living older adults and preschool children (INTERACTION): a pilot feasibility non-randomised clinical trial.

BACKGROUND: Social isolation and low levels of physical activity are strong drivers for frailty, which is linked to poor health outcomes and transition to long-term care. Frailty is multifactorial, and thus an integrated approach is needed to maintain older adults' health and well-being. Intergenerational programs represent a novel multifactorial approach to target frailty, social isolation and physical decline but these have not yet been rigorously tested in Australia. Here, we present the results of our pilot study which aimed to test the feasibility of a 10-week intergenerational program between older adults and preschool children. METHODS: A non-randomised wait-listed controlled trial was conducted. Participants were allocated to either the intervention or wait-list control group. The intervention group received 10 weekly 2-h intergenerational sessions led by trained child educators; the control group continued with their usual routine and received their intergenerational program after the 10-week control period. All participants were assessed at baseline and 10 weeks. The primary outcome was the feasibility and acceptability of the program including measures of recruitment eligibility, adherence and effective data collection across the multiple domains important for frailty, including functional mobility and balance, grip strength, cognitive function, mood, social engagement, quality of life and concerns about falling. RESULTS: Nineteen adults were included, with nine in the intervention and ten in the control group. A total of 42% of older adults screened were eligible, 75% of participants were present at each intervention session and the overall attrition rate was 21% (n = 4). The reasons for participant absence were primarily health-related. Missing data was minimal for the majority of assessments but more apparent for the cognitive testing where completion rates ranged from 53 to 79% for baseline tests and 73 to 100% for those who received follow-up testing. CONCLUSIONS: The high program compliance and low attrition show that a 10-week intergenerational program embedded in the local community, designed for community-living older adults and preschool children, is feasible and acceptable to older adults. Our next trial will test the efficacy of intergenerational programs in this setting.

Evaluating the implementation of a prescription only regulatory model for nicotine vaping products: A qualitative study on the experiences and views of healthcare professionals.

BACKGROUND: Deciding how to regulate nicotine vaping products (NVPs) is a challenge for many countries. Balanced regulation should consider the potential harms to young people from uptake of NVPs alongside the possible benefits of NVPs as a smoking cessation aid. One option is to make NVPs only available via medical prescription to adults who smoke. From October 2021, Australia adopted a unique model that allows prescription access to NVPs that meet a product standard without requiring the NVPs to be approved as therapeutic goods. This research explored the impact of this regulatory model on the smoking cessation practices of health professionals, and their views on the model. METHODS: Semi-structured interviews were conducted with 39 Australian health professionals recruited from professional networks and social media. Health professionals were eligible if they provided smoking cessation advice as part of their role, and included medical practitioners (n = 9), pharmacists (n = 9), and other health professionals that provided smoking cessation counselling (n = 21). Interviews were mostly completed by phone and online teleconferencing software. Questions focused on smoking cessation practices, advice and information provided to patients about NVPs, views about the effectiveness of the model for supporting use of NVPs for smoking cessation and preventing youth uptake, and barriers and facilitators to prescribing and dispensing NVPs. Coding and analysis used a combination of inductive and deductive approaches. RESULTS: Findings indicated a lack of consensus amongst the participants about NVPs as a cessation or harm reduction tool. Participants broadly agreed that the model has not been effective in improving quality control of NVPs, or in reducing youth access. Many participants eligible to prescribe or dispense NVPs felt that the current regulatory model placed an undue time and responsibility burden on clinicians. CONCLUSION: Our research identified several limitations associated with the current Australian prescription-only regulatory model. These were perceived by healthcare professionals to limit the potential for the regulations to reduce youth use and to increase access to safer NVP products for people who smoke to use for smoking cessation.

A novel, multidomain, primary care nurse-led and mHealth-assisted intervention for dementia risk reduction in middle-aged adults (HAPPI MIND): study protocol for a cluster randomised controlled trial.

INTRODUCTION: Middle-aged multidomain risk reduction interventions targeting modifiable risk factors for dementia may delay or prevent a third of dementia cases in later life. We describe the protocol of a cluster randomised controlled trial (cRCT), HAPPI MIND (Holistic Approach in Primary care for PreventIng Memory Impairment aNd Dementia). HAPPI MIND will evaluate the efficacy of a multidomain, nurse-led, mHealth supported intervention for assessing dementia risk and reducing associated risk factors in middle-aged adults in the Australian primary care setting. METHODS AND ANALYSIS: General practice clinics (n≥26) across Victoria and New South Wales, Australia, will be recruited and randomised. Practice nurses will be trained to implement the HAPPI MIND intervention or a brief intervention. Patients of participating practices aged 45-65 years with ≥2 potential dementia risk factors will be identified and recruited (approximately 15 patients/clinic). Brief intervention participants receive a personalised report outlining their risk factors for dementia based on Australian National University Alzheimer's Disease Risk Index (ANU-ADRI) scores, education booklet and referral to their general practitioner as appropriate. HAPPI MIND participants receive the brief intervention as well as six individualised dementia risk reduction sessions with a nurse trained in motivational interviewing and principles of behaviour change, a personalised risk reduction action plan and access to the purpose-built HAPPI MIND smartphone app for risk factor self-management. Follow-up data collection will occur at 12, 24 and 36 months. Primary outcome is ANU-ADRI score change at 12 months from baseline. Secondary outcomes include change in cognition, quality of life and individual risk factors of dementia. ETHICS AND DISSEMINATION: Project approved by Monash University Human Research Ethics Committee (ID: 28273). Results will be disseminated in peer-reviewed journals and at healthcare conferences. If effective in reducing dementia risk, the HAPPI MIND intervention could be integrated into primary care, scaled up nationally and sustained over time. TRIAL REGISTRATION NUMBER: ACTRN12621001168842.

Tackling Dementia Together via The Australian Dementia Network (ADNeT): A Summary of Initiatives, Progress and Plans.

In 2018, the Australian Dementia Network (ADNeT) was established to bring together Australia's leading dementia researchers, people with living experience and clinicians to transform research and clinical care in the field. To address dementia diagnosis, treatment, and care, ADNeT has established three core initiatives: the Clinical Quality Registry (CQR), Memory Clinics, and Screening for Trials. Collectively, the initiatives have developed an integrated clinical and research community, driving practice excellence in this field, leading to novel innovations in diagnostics, clinical care, professional development, quality and harmonization of healthcare, clinical trials, and translation of research into practice. Australia now has a national Registry for Mild Cognitive Impairment and dementia with 55 participating clinical sites, an extensive map of memory clinic services, national Memory and Cognition Clinic Guidelines and specialized screening for trials sites in five states. This paper provides an overview of ADNeT's achievements to date and future directions. With the increase in dementia cases expected over coming decades, and with recent advances in plasma biomarkers and amyloid lowering therapies, the nationally coordinated initiatives and partnerships ADNeT has established are critical for increased national prevention efforts, co-ordinated implementation of emerging treatments for Alzheimer's disease, innovation of early and accurate diagnosis, driving continuous improvements in clinical care and patient outcome and access to post-diagnostic support and clinical trials. For a heterogenous disorder such as dementia, which is now the second leading cause of death in Australia following cardiovascular disease, the case for adequate investment into research and development has grown even more compelling.

Clinical Quality Indicators for Monitoring Hospitalizations Among Older People with Dementia Accessing Aged Care Services.

BACKGROUND: There is a need for clinical quality indicators (CQIs) that can be applied to dementia quality registries to monitor care outcomes for people with Alzheimer's disease and other forms of dementia. OBJECTIVE: To develop tertiary and primary care-based dementia CQIs for application to clinical registries for individuals with dementia accessing aged care services and determine 1) annual trends in CQI incidence between 2011-2012 and 2015-2016, 2) associated factors, and 3) geographic and facility variation in CQI incidence. METHODS: This retrospective repeated cross-sectional study included non-Indigenous individuals aged 65-105 years who lived with dementia between July 2008-June 2016, were assessed for government-funded aged care services, and resided in New South Wales or Victoria (n = 180,675). Poisson or negative binomial regression models estimated trends in annual CQI incidence and associated factors. Funnel plots examined CQI variation. RESULTS: Between 2011-2012 and 2015-2016, CQI incidence increased for falls (11.0% to 13.9%, adjusted incidence rate ratio (aIRR) 1.05 (95% CI 1.01-1.06)) and delirium (4.7% to 6.7%, aIRR 1.09 (95% CI 1.07-1.10)), decreased for unplanned hospitalizations (28.7% to 27.9%, aIRR 0.99 (95% CI 0.98-0.99)) and remained steady for fracture (6.2% to 6.5%, aIRR 1.01 (95% CI 0.99-1.01)) and pressure injuries (0.5% to 0.4%, aIRR 0.99 (95% CI 0.96-1.02)). Being male, older, having more comorbidities and living in a major city were associated with higher CQI incidence. Considerable geographical and facility variation was observed for unplanned hospitalizations and delirium CQIs. CONCLUSIONS: The CQI results highlighted considerable morbidity. The CQIs tested should be considered for application in clinical quality registries to monitor dementia care quality.

Ubiquitin-specific protease 11 structure in complex with an engineered substrate mimetic reveals a molecular feature for deubiquitination selectivity.

Ubiquitin-specific proteases (USPs) are crucial for controlling cellular proteostasis and signaling pathways but how deubiquitination is selective remains poorly understood, in particular between paralogues. Here, we developed a fusion tag method by mining the Protein Data Bank and trapped USP11, a key regulator of DNA double-strand break repair, in complex with a novel engineered substrate mimetic. Together, this enabled structure determination of USP11 as a Michaelis-like complex that revealed key S1 and S1' binding site interactions with a substrate. Combined mutational, enzymatic, and binding experiments identified Met77 in linear diubiquitin as a significant residue that leads to substrate discrimination. We identified an aspartate "gatekeeper" residue in the S1' site of USP11 as a contributing feature for discriminating against linear diubiquitin. When mutated to a glycine, the corresponding residue in paralog USP15, USP11 acquired elevated activity toward linear diubiquitin in-gel shift assays, but not controls. The reverse mutation in USP15 confirmed that this position confers paralog-specific differences impacting diubiquitin cleavage rates. The results advance our understanding of the molecular basis for the higher selectivity of USP11 compared to USP15 and may aid targeted inhibitor development. Moreover, the reported carrier-based crystallization strategy may be applicable to other challenging targets.

Acceptability of Personal Sensing Among People With Alcohol Use Disorder: Observational Study.

BACKGROUND: Personal sensing may improve digital therapeutics for mental health care by facilitating early screening, symptom monitoring, risk prediction, and personalized adaptive interventions. However, further development and the use of personal sensing requires a better understanding of its acceptability to people targeted for these applications. OBJECTIVE: We aimed to assess the acceptability of active and passive personal sensing methods in a sample of people with moderate to severe alcohol use disorder using both behavioral and self-report measures. This sample was recruited as part of a larger grant-funded project to develop a machine learning algorithm to predict lapses. METHODS: Participants (N=154; n=77, 50% female; mean age 41, SD 11.9 years; n=134, 87% White and n=150, 97% non-Hispanic) in early recovery (1-8 weeks of abstinence) were recruited to participate in a 3-month longitudinal study. Participants were modestly compensated for engaging with active (eg, ecological momentary assessment [EMA], audio check-in, and sleep quality) and passive (eg, geolocation, cellular communication logs, and SMS text message content) sensing methods that were selected to tap into constructs from the Relapse Prevention model by Marlatt. We assessed 3 behavioral indicators of acceptability: participants' choices about their participation in the study at various stages in the procedure, their choice to opt in to provide data for each sensing method, and their adherence to a subset of the active methods (EMA and audio check-in). We also assessed 3 self-report measures of acceptability (interference, dislike, and willingness to use for 1 year) for each method. RESULTS: Of the 192 eligible individuals screened, 191 consented to personal sensing. Most of these individuals (169/191, 88.5%) also returned 1 week later to formally enroll, and 154 participated through the first month follow-up visit. All participants in our analysis sample opted in to provide data for EMA, sleep quality, geolocation, and cellular communication logs. Out of 154 participants, 1 (0.6%) did not provide SMS text message content and 3 (1.9%) did not provide any audio check-ins. The average adherence rate for the 4 times daily EMA was .80. The adherence rate for the daily audio check-in was .54. Aggregate participant ratings indicated that all personal sensing methods were significantly more acceptable (all P<.001) compared with neutral across subjective measures of interference, dislike, and willingness to use for 1 year. Participants did not significantly differ in their dislike of active methods compared with passive methods (P=.23). However, participants reported a higher willingness to use passive (vs active) methods for 1 year (P=.04). CONCLUSIONS: These results suggest that active and passive sensing methods are acceptable for people with alcohol use disorder over a longer period than has previously been assessed. Important individual differences were observed across people and methods, indicating opportunities for future improvement.

New botulinum neurotoxin constructs for treatment of chronic pain.

Chronic pain affects one in five people across human societies, with few therapeutic options available. Botulinum neurotoxin (BoNT) can provide long-lasting pain relief by inhibiting local release of neuropeptides and neurotransmitters, but its highly paralytic nature has limited its analgesic potential. Recent advances in protein engineering have raised the possibility of synthesising non-paralysing botulinum molecules for translation to pain sufferers. However, the synthesis of these molecules, via several synthetic steps, has been challenging. Here, we describe a simple platform for safe production of botulinum molecules for treating nerve injury-induced pain. We produced two versions of isopeptide-bonded BoNT from separate botulinum parts using an isopeptide bonding system. Although both molecules cleaved their natural substrate, SNAP25, in sensory neurons, the structurally elongated iBoNT did not cause motor deficit in rats. We show that the non-paralytic elongated iBoNT targets specific cutaneous nerve fibres and provides sustained pain relief in a rat nerve injury model. Our results demonstrate that novel botulinum molecules can be produced in a simple and safe manner and be useful for treating neuropathic pain.

Statins for extension of disability-free survival and primary prevention of cardiovascular events among older people: protocol for a randomised controlled trial in primary care (STAREE trial).

INTRODUCTION: The world is undergoing a demographic transition to an older population. Preventive healthcare has reduced the burden of chronic illness at younger ages but there is limited evidence that these advances can improve health at older ages. Statins are one class of drug with the potential to prevent or delay the onset of several causes of incapacity in older age, particularly major cardiovascular disease (CVD). This paper presents the protocol for the STAtins in Reducing Events in the Elderly (STAREE) trial, a randomised double-blind placebo-controlled trial examining the effects of statins in community dwelling older people without CVD, diabetes or dementia. METHODS AND ANALYSIS: We will conduct a double-blind, randomised placebo-controlled trial among people aged 70 years and over, recruited through Australian general practice and with no history of clinical CVD, diabetes or dementia. Participants will be randomly assigned to oral atorvastatin (40 mg daily) or matching placebo (1:1 ratio). The co-primary endpoints are disability-free survival defined as survival-free of dementia and persistent physical disability, and major cardiovascular events (cardiovascular death or non-fatal myocardial infarction or stroke). Secondary endpoints are all-cause death, dementia and other cognitive decline, persistent physical disability, fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, heart failure, atrial fibrillation, fatal and non-fatal cancer, all-cause hospitalisation, need for permanent residential care and quality of life. Comparisons between assigned treatment arms will be on an intention-to-treat basis with each of the co-primary endpoints analysed separately in time-to-first-event analyses using Cox proportional hazards regression models. ETHICS AND DISSEMINATION: STAREE will address uncertainties about the preventive effects of statins on a range of clinical outcomes important to older people. Institutional ethics approval has been obtained. All research outputs will be disseminated to general practitioner co-investigators and participants, published in peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION NUMBER: NCT02099123.

Socioeconomic, Behavioural, and Social Health Correlates of Optimism and Pessimism in Older Men and Women: A Cross-Sectional Study.

BACKGROUND: Optimism is a disposition characterised by positive future expectancies, while pessimism is characterised by expecting the worst. High optimism and low pessimism promote the health of older adults and may potentiate full engagement in life. We identified socioeconomic, behavioural, and social factors associated with optimism and pessimism in older adults. METHODS: Participants included 10,146 community-dwelling, apparently healthy Australian adults aged 70 years and over from the ASPREE Longitudinal Study of Older Persons (ALSOP). Optimism and pessimism were measured using the revised Life Orientation Test. Cross-sectional ordinal logistic regression was used to determine the socioeconomic, behavioural, and social health factors associated with optimism and pessimism. RESULTS: Higher education, greater physical activity, lower loneliness, and volunteering were associated with higher optimism and lower pessimism. Low social support was associated with higher pessimism. Higher socioeconomic advantage, greater income, and living alone were associated with lower pessimism. Women were more optimistic and less pessimistic than men. The association of age, smoking status, and alcohol consumption with optimism and pessimism differed for men and women. CONCLUSIONS: Factors associated with higher optimism and lower pessimism were also those demonstrated to support healthy ageing. Health-promotion action at the individual level (e.g., smoking cessation or regular physical activity), health professional level (e.g., social prescribing or improving access and quality of care for all older adults), and community level (e.g., opportunities for volunteer work or low-cost social activities for older adults) may improve optimism and reduce pessimism, possibly also promoting healthy ageing.

Factors contributing to school food program acceptance: a Review of Canadian literature.

Diet quality and food security are a concern in school-aged children in Canada. In 2019, the Canadian federal government announced the intention to work towards a national school food program. Understanding the factors that impact school food program acceptability can inform planning to ensure that students are willing to participate. A scoping review of school food programs in Canada completed in 2019 identified 17 peer-reviewed and 18 grey literature publications. Of these, five peer-reviewed and nine grey literature publications included a discussion of factors that impact the acceptance of school food programs. These factors were thematically analyzed into categories: stigmatization, communication, food choice and cultural considerations, administration, location and timing, and social considerations. Considering these factors while planning can help to maximize program acceptability.

Diet quality and having sufficient food to eat are concerns in school-aged children in Canada. In 2019, the Canadian federal government announced the intention to work towards a national school food program. Providing food to children in schools can only address diet concerns if children participate. Understanding the factors that impact school food program acceptability can inform planning to contribute to program acceptance. Themes of factors contributing to school food program acceptance discussed in 14 publications were identified. Themes included stigmatization, communication, food choice and cultural considerations, administration, location and timing, and social considerations. Considering these factors while planning can help to maximize school food program acceptability.

The association between sex hormones and the change in brain-predicted age difference in older women.

OBJECTIVE: The role of circulating sex hormones on structural brain ageing is yet to be established. This study explored whether concentrations of circulating sex hormones in older women are associated with the baseline and longitudinal changes in structural brain ageing, defined by the brain-predicted age difference (brain-PAD). DESIGN: Prospective cohort study using data from NEURO and Sex Hormones in Older Women; substudies of the ASPirin in Reducing Events in the Elderly clinical trial. PATIENTS: Community-dwelling older women (aged 70+ years). MEASUREMENTS: Oestrone, testosterone, dehydroepiandrosterone (DHEA), and sex-hormone binding globulin (SHBG) were quantified from plasma samples collected at baseline. T1-weighted magnetic resonance imaging was performed at baseline, 1 and 3 years. Brain age was derived from whole brain volume using a validated algorithm. RESULTS: The sample comprised of 207 women not taking medications known to influence sex hormone concentrations. A statistically higher baseline brain-PAD (older brain age relative to chronological age) was seen for women in the highest DHEA tertile compared with the lowest in the unadjusted analysis (p = .04). This was not significant when adjusted for chronological age, and potential confounding health and behavioural factors. Oestrone, testosterone and SHBG were not associated with brain-PAD cross-sectionally, nor were any of the examined sex hormones or SHBG associated with brain-PAD longitudinally. CONCLUSION: No strong evidence of an association between circulating sex hormones and brain-PAD. Given there is prior evidence to suggests sex hormones may be important for brain ageing, further studies of circulating sex hormones and brain health in postmenopausal women are warranted.

Carer-reported measures for a dementia registry: A systematic scoping review and a qualitative study.

OBJECTIVES: Informal carers play a critical role in supporting people with dementia. We conducted a scoping review and a qualitative study to inform the identification and development of carer-reported measures for a dementia clinical quality registry. METHODS: Phase 1-Scoping review: Searches to identify carer-reported health and well-being measures were conducted in three databases (MEDLINE, PsycINFO and Embase). Data were extracted to record how the measures were administered, the domains of quality-of-life addressed and whether they had been used in a registry context. Phase 2-Qualitative study: Four focus groups were conducted with carers to examine the acceptability of selected measures and to identify outcomes that were important but missing from these measures. RESULTS: Phase 1: Ninety-nine carer measures were identified with the top four being the Zarit Burden Interview (n = 39), the Short-Form12/36 (n = 14), the Brief Coping Orientation to Problems Experienced scale and the Sense of Coherence scale (both n = 9). Modes of administration included face-to-face (n = 50), postal (n = 11), telephone (n = 8) and online (n = 5). No measure had been used in a registry context. Phase 2: Carers preferred brief measures that included both outcome and experience questions, reflected changes in carers' circumstances and included open-ended questions. CONCLUSIONS: Carer-reported measures for a dementia clinical quality registry need to include both outcome and experience questions to capture carers' perceptions of the process and outcomes of care and services. Existing carer-reported measures have not been used in a dementia registry context and adaption and further research are required.

PDLIM2 is highly expressed in Breast Cancer tumour-associated macrophages and is required for M2 macrophage polarization.

The PDZ-LIM domain-containing protein 2 (PDLIM2) regulates cell polarity and the protein stability of key transcription factors in epithelial and hemopoietic cells. We previously reported that PDLIM2 is more highly expressed in Triple Negative Breast Cancer (TNBC) than in other breast cancer types or normal breast tissue. In the course of the TNBC study, it was noted that PDLIM2 was highly expressed in the stroma of PDLIM2-expressing tumours. Here, we investigated the phenotype of these stromal cells and whether any infiltrating immune population was linked to PDLIM2 expression. We found that high PDLIM2 expression in breast tumours was associated with higher levels of infiltrating M2 macrophages, but was not associated with infiltrating T cell sub-populations. We then tested whether PDLIM2 contributes to macrophage differentiation or function by using cultures of bone marrow-derived macrophages from wildtype and Pdlim2 knockout mice. This demonstrated that PDLIM2 is required for naïve macrophage migration and for the full adoption of IL-4-induced M2 polarization, including expression of M2 phenotypic markers, cell adhesion and cell migration. TLR4-, TLR3- or IFNγ-induced M1 macrophage activity was less dependent on PDLIM2. Finally, analysis of publicly available breast cancer datasets showed that high PDLIM2 expression is associated with increased M2 macrophage infiltration. We conclude that PDLIM2 expression influences the tumour associated stroma and, in particular, M2 macrophage infiltration that may contribute to the progression of TNBC or other subsets of breast cancer.