STAREE-Mind Imaging Study: a randomised placebo-controlled trial of atorvastatin for prevention of cerebrovascular decline and neurodegeneration in older individuals.

Introduction: Cerebrovascular disease and neurodegeneration are causes of cognitive decline and dementia, for which primary prevention options are currently lacking. Statins are well-tolerated and widely available medications that potentially have neuroprotective effects. The STAREE-Mind Imaging Study is a randomised, double-blind, placebo-controlled clinical trial that will investigate the impact of atorvastatin on markers of neurovascular health and brain atrophy in a healthy, older population using MRI. This is a nested substudy of the 'Statins for Reducing Events in the Elderly' (STAREE) primary prevention trial. Methods: Participants aged 70 years or older (n=340) will be randomised to atorvastatin or placebo. Comprehensive brain MRI assessment will be undertaken at baseline and up to 4 years follow-up, including structural, diffusion, perfusion and susceptibility imaging. The primary outcome measures will be change in brain free water fraction (a composite marker of vascular leakage, neuroinflammation and neurodegeneration) and white matter hyperintensity volume (small vessel disease). Secondary outcomes will include change in perivascular space volume (glymphatic drainage), cortical thickness, hippocampal volume, microbleeds and lacunae, prefrontal cerebral perfusion and white matter microstructure. Ethics and dissemination: Academic publications from this work will address the current uncertainty regarding the impact of statins on brain structure and vascular integrity. This study will inform the utility of repurposing these well-tolerated, inexpensive and widely available drugs for primary prevention of neurological outcomes in older individuals. Ethics approval was given by Monash University Human Research Ethics Committee, Protocol 12206. Trial registration number: ClinicalTrials.gov Identifier: NCT05586750.

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.

Alcohol availability and prevalent Chlamydia trachomatis in young Australians: a multi-level analysis.

Background Prevalence of sexually transmissible infections (STIs) has been associated with availability of alcohol. This paper investigates potential associations between prevalent cases of chlamydia in young people in Australia and the availability of alcohol within their local area, defined as postcode of residence. Methods Alcohol availability was determined at the postcode level using liquor licensing data, classified as total number of licences, number of 'take-away' licences and number of licenses by population. Participant data were drawn from a survey targeting Australians aged 16-29years in rural and regional Australia, capturing demographic details including postcode of residence, indicators of sexual behaviour including condom use and chlamydia test results. Mixed-effects logistic regression was used to examine potential associations between first, alcohol availability and chlamydia, and second, between condom use and chlamydia. Results We found little evidence of associations between alcohol availability and chlamydia in either unadjusted or adjusted models. After adjusting for alcohol availability, we observed significant associations between inconsistent condom use and chlamydia prevalence, whether alcohol availability was measured as total number (adjusted odds ratio (AOR) 2.20; 95% confidence interval (CI) 1.20, 3.70), number of take-away licenses (AOR 2.19; 95% CI1.30, 3.69) or licenses per 1000 population (AOR 2.19; 95% CI 1.30, 3.68). Conclusion Little evidence of association between alcohol availability and chlamydia at the postcode level was found. Further research is required to determine appropriate measures of 'local area' and how characteristics thereof may impact on sexual health.

Intensified partner notification and repeat testing can improve the effectiveness of screening in reducing Chlamydia trachomatis prevalence: a mathematical modelling study.

BACKGROUND: The Australian Chlamydia Control Effectiveness Pilot (ACCEPt) was a cluster randomised controlled trial designed to assess the effectiveness of annual chlamydia testing through general practice in Australia. The trial showed that testing rates increased among sexually active men and women aged 16-29 years, but after 3 years the estimated chlamydia prevalence did not differ between intervention and control communities. We developed a mathematical model to estimate the potential longer-term impact of chlamydia testing on prevalence in the general population. METHODS: We developed an individual-based model to simulate the transmission of Chlamydia trachomatis in a heterosexual population, calibrated to ACCEPt data. A proportion of the modelled population were tested for chlamydia and treated annually at coverage achieved in the control and intervention arms of ACCEPt. We estimated the reduction in chlamydia prevalence achieved by increasing retesting and by treating the partners of infected individuals up to 9 years after introduction of the intervention. RESULTS: Increasing the testing coverage in the general Australian heterosexual population to the level achieved in the ACCEPt intervention arm resulted in reduction in the population-level prevalence of chlamydia from 4.6% to 2.7% in those aged 16-29 years old after 10 years (a relative reduction of 41%). The prevalence reduces to 2.2% if the proportion retested within 4 months of treatment is doubled from the rate achieved in the ACCEPt intervention arm (a relative reduction of 52%), and to 1.9% if the partner treatment rate is increased from 30%, as assumed in the base case, to 50% (a relative reduction of 59%). CONCLUSION: A reduction in C. trachomatis prevalence could be achieved if the level of testing as observed in the ACCEPt intervention arm can be maintained at a population level. More substantial reductions can be achieved with intensified case management comprising retesting of those treated and treatment of partners of infected individuals.

Incomplete recording of Indigenous identification status under-estimates the prevalence of Indigenous population attending Australian general practices: a cross sectional study.

BACKGROUND: Australian Aboriginal and Torres Strait Islander (Indigenous) peoples face major health disadvantage across many conditions. Recording of patients' Indigenous status in general practice records supports equitable delivery of effective clinical services. National policy and accreditation standards mandate recording of Indigenous status in patient records, however for a large proportion of general practice patient records it remains incomplete. We assessed the completeness of Indigenous status in general practice patient records, and compared the patient self-reported Indigenous status to general practice medical records. METHODS: A cross sectional analysis of Indigenous status recorded at 95 Australian general practices, participating in the Australian Chlamydia Control Effectiveness Pilot (ACCEPt) in 2011. Demographic data were collected from medical records and patient surveys from 16 to 29 year old patients at general practices, and population composition from the 2011 Australian census. General practitioners (GPs) at the same practices were also surveyed. Completeness of Indigenous status in general practice patient records was measured with a 75% benchmark used in accreditation standards. Indigenous population composition from a patient self-reported survey was compared to Indigenous population composition in general practice records, and Australian census data. RESULTS: Indigenous status was complete in 56% (median 60%, IQR 7-81%) of general practice records for 109,970 patients aged 16-29 years, and Indigenous status was complete for 92.5% of the 3355 patients aged 16-29 years who completed the survey at the same clinics. The median proportion per clinic of patients identified as Indigenous was 0.9%, lower than the 1.8% from the patient surveys and the 1.7% in clinic postcodes (ABS). Correlations between the proportion of Indigenous people self-reporting in the patient survey (5.2%) compared to status recorded in all patient records (2.1%) showed a fair association (r = 0.6468; p < 0.01). After excluding unknown /missing data, correlations weakened. CONCLUSIONS: Incomplete Indigenous status records may under-estimate the true proportion of Indigenous people attending clinics but have higher association with self-reported status than estimates which exclude missing/unknown data. The reasons for incomplete Indigenous status recording in general practice should be explored so efforts to improve recording can be targeted and strengthened. TRIAL REGISTRATION: ACTRN12610000297022 . Registered 13th April 2010.

Comparing two methods for delivering clinical trial informed consent information to older adults: singular versus stepped approach.

BACKGROUND: Adapting the informed consent process to the needs of older adults may enhance engagement and willingness to participate in a clinical trial. A key aspect of the process is being provided with written clinical trial information and consent documents and having an opportunity to discuss the information with the researcher. However, there are no guidelines on the most appropriate method for delivering this information to older adults and it is not known whether the delivery method is a facilitator or barrier towards clinical trial participation. AIMS: To compare two delivery methods of informed consent on recruitment, refusal to continue and randomisation rates in a general practice-based clinical trial involving older adults. METHODS: In a matched cohort sub-study as part of the STAtins in Reducing Events in the Elderly clinical trial, 520 participants were allocated into two groups by age, gender and attending general practice location, to receive the trial information and consent form in the mail (Method 1) prior to the first baseline visit or in person (Method 2) at the visit where a comprehensive informed consent process took place. RESULTS: Compared with Method 1, potential participants assigned to Method 2 were more likely to agree to attend the first baseline screening visit (refusal rate 20% vs 13.5%, respectively, p = 0.05). However, there was no significant difference in the proportion of participants recruited into the trial by providing written informed consent at the first baseline screening visit. For each informed consent delivery method, similar proportions of participants refused to take part in the trial by the end of the screening phase. Randomisation rates in the two groups were also similar. Time to conduct the informed consent procedure took significantly longer with Method 2 compared with Method 1 (median time 20 vs 15 min, respectively, p < 0.01). Interest in the research trial topic was the main reason cited (33.4%) for considering trial participation. CONCLUSION: Later delivery of informed consent documents to potential participants in this trial was associated with a small increase in attendance at the first, in person, screening visit. However, the randomisation rate of participants into the trial was not affected by the method and timing of delivery of informed consent information. Similar randomisation rates occurred whether potential participants were mailed informed consent documents prior to the first in person screening visit or were given the information at the screening visit.

Impact of informed consent content and length on recruitment of older adults into a community based primary prevention trial.

AIMS: To compare recruitment, refusal and randomisation rates of older adults into a general practice-based clinical trial with two versions (varied format, content and language) of the Participant Information and Consent Form (PICF). METHODS: This prospective PICF study was conducted within the STAREE (STAtins in Reducing Events in the Elderly) clinical trial. Participants phone screened between October 2015 to February 2016 formed Group 1 and were mailed the extended PICF version and participants phone screened between October 2016 to February 2017 formed Group 2 and were mailed the shortened PICF version. Participants who attended a subsequent baseline screening visit were guided through a comprehensive informed consent process. RESULTS: During the screening phase of the trial, the likelihood of refusing trial participation was lower in Group 2 compared to Group 1 equating to an overall 23% reduction in risk (RR 0.77, P = 0.005, 95% CI 0.62-0.95). Group 2 had a 6.4% higher randomisation rate compared with Group 1 (65.3% versus 58.9% respectively) but this difference was not statistically significant. Factors associated with trial participation were male gender, age between 70 and 75 years and living alone (all p < .0.05). CONCLUSIONS: Whilst avoiding lengthy and complex PICF documents may assist with initial trial engagement, it needs to be supplemented with other strategies to support ongoing trial interest to randomisation and beyond. Participants refused trial participation throughout the screening phase indicating that the PICF was only one factor among several affecting an individual's decision to participate in this clinical trial.

Socio-demographic and structural barriers to being tested for chlamydia in general practice.

OBJECTIVES: To investigate socio-demographic and structural factors associated with not providing a specimen for chlamydia testing following a request by a general practitioner. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional analysis of chlamydia testing data for men and women aged 16-29 years attending general practice clinics participating in a cluster randomised controlled trial evaluating the effectiveness of a chlamydia testing intervention. The study period was the 2013 calendar year. OUTCOME: The proportion of chlamydia test requests for which the patient did not provide a specimen for testing. RESULTS: During the study period, there were 13 225 chlamydia test requests, for which a chlamydia test was not performed in 2545 instances (19.2%; 95% CI, 16.5-22.3%). Multivariate analysis indicated that the odds for not undertaking a requested test were higher for men (adjusted odds ratio [aOR], 1.4; 95% CI, 1.3-1.6), those aged 16-19 years (aOR, 1.3; 95% CI, 1.1-1.4), those living in areas of greater socio-economic disadvantage (aOR, 1.2; 95% CI, 1.1-1.4 for each additional quintile of Index of Relative Socio-economic Disadvantage), and those attending clinics without on-site pathology collection (aOR, 1.4; 95% CI, 1.0-1.9). CONCLUSION: One in five young people did not submit a specimen for chlamydia testing despite their GP requesting it. This highlights the need for clinics to establish systems which ensure that men and those aged 16-19 years undertake chlamydia tests requested by a GP.

Using computer-assisted survey instruments instead of paper and pencil increased completeness of self-administered sexual behavior questionnaires.

OBJECTIVES: To compare the data quality, logistics, and cost of a self-administered sexual behavior questionnaire administered either using a computer-assisted survey instrument (CASI) or by paper and pencil in a primary care clinic. STUDY DESIGN AND SETTING: A self-administered sexual behavior questionnaire was administered to 16-29 year olds attending general practice. Questionnaires were administered by either paper and pencil (paper) or CASI. A personal digital assistant was used to self-administer the CASI. RESULTS: A total of 4,491 people completed the questionnaire, with 46.9% responses via CASI and 53.2% by paper. Completion of questions was greater for CASI than for paper for sexual behavior questions: number of sexual partners [odds ratio (OR), 6.85; 95% confidence interval (CI): 3.32, 14.11] and ever having had sex with a person of the same gender (OR, 2.89; 95% CI: 1.52, 5.49). The median number of questions answered was higher for CASI than for paper (17.6 vs. 17.2; P < 0.01). CASI was cheaper to run at $8.18 per questionnaire compared with $11.83 for paper. CONCLUSION: Electronic devices using CASI are a tool that can increase participants' questionnaire responses and deliver more complete data for a sexual behavior questionnaire in primary care clinics.

Improving chlamydia knowledge should lead to increased chlamydia testing among Australian general practitioners: a cross-sectional study of chlamydia testing uptake in general practice.

BACKGROUND: Female general practitioners (GPs) have higher chlamydia testing rates than male GPs, yet it is unclear whether this is due to lack of knowledge among male GPs or because female GPs consult and test more female patients. METHODS: GPs completed a survey about their demographic details and knowledge about genital chlamydia. Chlamydia testing and consultation data for patients aged 16-29 years were extracted from the medical records software for each GP and linked to their survey responses. Chi-square tests were used to determine differences in a GP's knowledge and demographics. Two multivariable models that adjusted for the gender of the patient were used to investigate associations between a GP and their chlamydia testing rates - Model 1 included GPs' characteristics such as age and gender, Model 2 excluded these characteristics to specifically examine any associations with knowledge. RESULTS: Female GPs were more likely than male GPs to know when to re-test a patient after a negative chlamydia test (18.8% versus 9.7%, p = 0.01), the correct symptoms suggestive of PID (80.5% versus 67.8%, p = 0.01) and the correct tests for diagnosing PID (57.1% versus 42.6%, p = 0.01). Female GPs tested 6.5% of patients, while male GPs tested 2.2% (p < 0.01). Model 1 found factors associated with chlamydia testing were being a female GP (OR = 2.5, 95% CI: 1.9, 3.3) and working in a metropolitan clinic (OR = 3.2; 95% CI: 2.4, 4.3). Model 2 showed that chlamydia testing increased as knowledge of testing guidelines improved (3-5 correct answers - AOR = 2.0, 95% CI: 1.0, 4.2; 6+ correct answers - AOR = 2.9, 95% CI: 1.4, 6.2). CONCLUSIONS: Higher rates of chlamydia testing are strongly associated with GPs who are female, based in a metropolitan clinic and among those with more knowledge of the recommended guidelines. Improving chlamydia knowledge among male GPs may increase chlamydia testing.