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Plain Language Summary Through living with conditions and/or engaging with health and social care services patients, public and service users become experts by experience. In Canada and the UK, the active involvement of experts by experience in ophthalmology research (as well as in other specialties) positively benefits all stages of the research cycle; improves the experience and outcomes for patients taking part in research; drives better engagement between researchers, the public and other key stakeholders; and benefits these expert’s own sense of wellbeing and achievement. At the moment, the extent to which experts by experience are active in ophthalmology research around the world is unclear, but likely to be minimal. To enable more research to benefit from the contribution of experts by experience, global efforts to improve the continuity and quality of reporting and evidence of impact are needed.

Aims: Current guidelines recommend measuring carotid intima-media thickness (IMT) at the far wall of the common carotid artery (CCA). We aimed to precisely quantify associations of near vs. far wall CCA-IMT with the risk for atherosclerotic cardiovascular disease (CVD, defined as coronary heart disease or stroke) and their added predictive values., Methods and Results: We analysed individual records of 41 941 participants from 16 prospective studies in the Proof-ATHERO consortium {mean age 61 years [standard deviation (SD) = 11]; 53% female; 16% prior CVD}. Mean baseline values of near and far wall CCA-IMT were 0.83 (SD = 0.28) and 0.82 (SD = 0.27) mm, differed by a mean of 0.02 mm (95% limits of agreement: -0.40 to 0.43), and were moderately correlated [ r = 0.44; 95% confidence interval (CI): 0.39-0.49). Over a median follow-up of 9.3 years, we recorded 10 423 CVD events. We pooled study-specific hazard ratios for CVD using random-effects meta-analysis. Near and far wall CCA-IMT values were approximately linearly associated with CVD risk. The respective hazard ratios per SD higher value were 1.18 (95% CI: 1.14-1.22; I ² = 30.7%) and 1.20 (1.18-1.23; I ² = 5.3%) when adjusted for age, sex, and prior CVD and 1.09 (1.07-1.12; I ² = 8.4%) and 1.14 (1.12-1.16; I ²=1.3%) upon multivariable adjustment (all P < 0.001). Assessing CCA-IMT at both walls provided a greater C-index improvement than assessing CCA-IMT at one wall only [+0.0046 vs. +0.0023 for near ( P < 0.001), +0.0037 for far wall ( P = 0.006)]., Conclusions: The associations of near and far wall CCA-IMT with incident CVD were positive, approximately linear, and similarly strong. Improvement in risk discrimination was highest when CCA-IMT was measured at both walls., Competing Interests: Conflict of interest: M.J.S. is a full-time employee of AstraZeneca. The other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development. Methods and Results We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I 2 =63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I 2 =59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I 2 =57.1%; 14 studies; 17 352 participants; 6991 incident plaques). Conclusions Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.

Purpose: The health of parents prior to conception, a woman's health during pregnancy and the infant's environment across their first months and years collectively have profound effects on the child's health across the lifespan. Since there are very few cohort studies in early pregnancy, gaps remain in our understanding of the mechanisms underpinning these relationships, and how health may be optimised. 'BABY1000', a pilot prospective longitudinal birth cohort study, aims to (1) identify factors before and during pregnancy and early life that impact longer-term health and (2) assess the feasibility and acceptability of study design to inform future research., Participants: Participants were based in Sydney, Australia. Women were recruited at preconception or 12 weeks' gestation, and data were collected from them throughout pregnancy and postpartum, their children until the age of 2 years, and dietary information from a partner (if able) at the last study visit. The pilot aimed to recruit 250 women. However, recruitment ceased earlier than planned secondary to limitations from the COVID-19 pandemic and the final number of subjects was 225., Findings to Date: Biosamples, clinical measurements and sociodemographic/psychosocial measures were collected using validated tools and questionnaires. Data analysis and 24-month follow-up assessments for children are ongoing. Key early findings presented include participant demographics and dietary adequacy during pregnancy. The COVID-19 pandemic and associated public health and research restrictions affected recruitment of participants, follow-up assessments and data completeness., Future Plans: The BABY1000 study will provide further insight into the developmental origins of health and disease and inform design and implementation of future cohort and intervention studies in the field. Since the BABY1000 pilot was conducted across the COVID-19 pandemic, it also provides unique insight into the early impacts of the pandemic on families, which may have effects on health across the lifespan., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Quantitative rankings of multiple dietary patterns for their effects on non-communicable disease (NCD) biomarkers is lacking and would inform primary prevention strategies. Accordingly, a network meta-analysis (NMA) was conducted to compare and rank the effects of different dietary patterns on NCD biomarkers, and associations of dietary patterns’ underlying macronutrient composition with NCD biomarkers were determined by a nutritional geometry approach. Randomised controlled trials (RCTs) were eligible for inclusion if they enrolled healthy participants, employed food-based dietary pattern interventions without energy restriction, and reported NCD biomarker outcomes. NCD biomarkers were included as an outcome if ≥10 trials were available. A systematic search of five electronic databases identified 4008 records. Sixty-eight articles from 59 RCTs reporting lipids, glycemic, and inflammatory biomarkers were included for quantitative syntheses. Risk-of-bias was predominantly categorized as low or having some concerns, and confidence-of-evidence low. Relative to western habitual diet, the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), dietary guidelines-based, plant-based, and low-fat diets reduced low-density lipoprotein cholesterol (mean difference range: −0.29 to −0.17 mmol/L), total cholesterol (−0.36 to −0.24 mmol/L), and apolipoprotein B (−0.11 to −0.07 g/L) (all p < 0.05); the Paleo, plant-based and dietary guidelines-based diets reduced homeostasis model assessment of insulin resistance (−0.95 to −0.35, all p < 0.05). No dietary pattern ranked consistently highest. The Paleo diet received the highest all-outcomes-combined average Surface Under the Cumulative Ranking Curve value (67%), followed by DASH (62%) and Mediterranean diets (57%), whereas western habitual diet was lowest (36%). Our findings were independent of macronutrient composition, highlighting the significance of dietary pattern-level analysis.

Background Aortic intima-media thickness (aIMT) measurement is an established indicator of preclinical atherosclerosis. We aimed to describe the aIMT in infants with congenital heart disease undergoing cardiac surgery over the first year of life and explore its association with cardiopulmonary bypass, growth velocity, and a diagnosis of left heart obstruction. Methods and Results A prospective cohort study measuring mean and maximum aIMT preoperatively, at 3 months, and 1 year of age in neonates with congenital heart disease undergoing cardiac surgery. Twenty-four infants with a median gestation of 39 weeks and a median birth weight of 3184 g were included. Sixteen (67%) infants had left outflow tract obstruction. Gestation correlated inversely with baseline mean aIMT (β=-0.027, P =0.018) and positively with the percentage of increase in mean and maximum aIMT between baseline and 3 months (β=17%, P =0.027 and β=15%, P =0.023). The presence of left outflow obstruction was significantly associated with increasing mean and maximum aIMT between baseline and 1 year (mean aIMT change: β=34%, P =0.017 and maximum aIMT change β=43%, P =0.001). Both subgroups of left heart obstruction and non-left heart obstruction significantly changed over time ( P =0.001 and P <0.001) but trends were not statistically different between both subgroups ( P =0.21). Growth velocity and cardiopulmonary bypass were not associated with baseline or change in aIMT over the first year of life. Conclusions AIMT significantly increased over the first 3 months in our cohort of infants with repaired congenital heart disease. Increasing gestation was associated with decreasing aIMT at 3 months. Growth velocity and cardiopulmonary bypass were not associated with aIMT changes over the first year. Left heart obstruction was associated with a trend toward increased aIMT.

About half of Australian women have a body mass index in the overweight or obese range at the start of pregnancy, with serious consequences including preterm birth, gestational hypertension and diabetes, caesarean section, stillbirth, and childhood obesity. Trials to limit weight gain during pregnancy have had limited success and reducing weight before pregnancy has greater potential to improve outcomes. The PreBabe Pilot study was a randomised controlled pilot trial to assess the feasibility, acceptability and potential weight loss achieved using a commercial online partial meal replacement program, (MR) vs. telephone-based conventional dietary advice, (DA) for pre-conception weight-loss over a 10-week period. Women 18-40 years of age with a BMI ≥ 25 kg/m 2 planning pregnancy within the next 6 to 12 months were included in the study. All participants had three clinic visits with a dietitian and one obstetric consultation. In total, 50 women were enrolled in the study between June 2018 and October 2019-26 in MR and 24 in DA. Study retention at the end of 10 week intervention 81% in the MR arm and 75% in the DA arm. In the-intention-to-treat analysis, women using meal replacements lost on average 5.4 ± 3.1% body weight compared to 2.3 ± 4.2% for women receiving conventional advice ( p = 0.029). Over 80% of women in the MR arm rated the support received as excellent, compared to 39% in the DA arm ( p < 0.001). Women assigned to the MR intervention were more likely to achieve pregnancy within 12 months of the 10 week intervention (57% (12 of 21) women assigned to MR intervention vs. 22% (4 of 18) assigned to the DA group ( p = 0.049) became pregnant). The findings suggest that a weight loss intervention using meal replacements in the preconception period was acceptable and may result in greater weight loss than conventional dietary advice alone.

Background: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk., Methods: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach., Results: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients., Conclusions: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.

Hypertensive disorders of pregnancy, such as pre-eclampsia, are known to be independently associated with the development of premature cardiovascular disease (CVD) in women. In pre-eclampsia, the placenta secretes excess anti-angiogenic factors into the maternal circulation, leading to widespread endothelial damage, and inflammation. This endothelial damage is evidenced to persist beyond the acute illness. However, whether it is permanent and responsible for the elevated rates of premature CVD seen in this at-risk group remains unclear. A systematic review of the available literature with respect to vascular structure and function prior to, during and after a pregnancy complicated by pre-eclampsia was performed. Studies non-invasively assessing vascular structure using carotid intima-media thickness (CIMT), retinal microvasculature caliber, CT coronary angiogram, or coronary calcium scores were included. Vascular function was assessed using brachial flow-mediated dilation (FMD), pulse wave analysis (PWA), and peripheral arterial tonometry (PAT). In total 59 articles were included (13 CIMT, 5 CTCA/Ca score, five retinal microvasculature, 27 FMD, 7 PAT, and 14 PWV/PWA), consisting of prospective and retrospective cohort, and case-control studies. Change in vascular structure was evidenced with significant increases in CIMT by 73-180 μm greater than that of non-affected women. This is tempered by other studies reporting resolution of structural changes postpartum, highlighting the need for further research. Accelerated coronary calcification and plaque deposition was identified, with greater rates of increased calcium scores and subclinical coronary artery disease shown by CTCA in women with a history of pre-eclampsia at 30 years postpartum. Impaired endothelial function was consistently reported prior to, during and immediately after pregnancy as evidenced by differences in FMD of 1.7-12.2% less than non-affected women, an increase in PWV by 13.2-26%, and reduced retinal microvascular caliber and arterial elasticity indices. The evidence was less conclusive for the persistence of long-term endothelial dysfunction. Understanding the underlying mechanistic links between pre-eclampsia and CVD is a key step to identifying targeted therapies aimed at "repairing the endothelium" and attenuating risk. This review has highlighted the need for a greater understanding of vascular structure and function following pre-eclampsia through high quality studies with large sample sizes, particularly in the longer postpartum period when clinical CVD disease starts to manifest., (Copyright © 2019 Kirollos, Skilton, Patel and Arnott.)

Carotid artery atherosclerosis is a complex and multifactorial chronic disease. Our aim was to assess the associations between obesity, fat depots and carotid artery stenosis (CAS) in patients with high cardiovascular (CV) risk., Methods: The study group included 391 patients (F/M: 136/255 pts.; age: 61.8 ± 8 years) scheduled for elective coronary angiography. A comprehensive clinical assessment included a carotid artery and abdominal ultrasound involving the following fat depots: (1) carotid extra-media thickness (EMT) indexed to the body mass index (perivascular adipose tissue [PVAT]), and (2) abdominal visceral and subcutaneous fat., Results: Patients with a ≥50% stenosis of internal carotid artery (ICA) were older (65.9 ± 7 vs 60.3 ± 7 years, p < 0.0001) and had increased PVAT (836 ± 120 vs 779 ± 127 μm, p < 0.01) compared to individuals with <50% internal carotid artery stenosis. None of the CAS parameters were associated with any measures of obesity. Multivariable regression model showed that age (p < 0.0001), PVAT (p < 0.0001) and smoking (p = 0.04) were independently associated with the severity of ICA stenosis., Conclusions: Our study showed that carotid extra-media thickness, an index measure of PVAT, is associated with CAS severity. It is a strong and independent predictor of significant ICA stenosis. None of the obesity measurements revealed associations with carotid atherosclerosis., (Copyright © 2019. Published by Elsevier Inc.)

Background: Cystic fibrosis (CF) is the commonest inherited life-shortening illness in white populations, caused by a mutation in the gene that codes for the cystic fibrosis transmembrane regulator protein (CFTR), which functions as a salt transporter. This mutation mainly affects the airways where excess salt absorption dehydrates the airway lining leading to impaired mucociliary clearance. Consequently, thick, sticky mucus accumulates making the airway prone to chronic infection and progressive inflammation; respiratory failure often ensues. Other complications include malnutrition, diabetes and subfertility.Increased understanding of the condition has allowed pharmaceutical companies to design mutation-specific therapies targeting the underlying molecular defect. CFTR potentiators target mutation classes III and IV and aim to normalise airway surface liquid and mucociliary clearance, which in turn impacts on the chronic infection and inflammation. This is an update of a previously published review., Objectives: To evaluate the effects of CFTR potentiators on clinically important outcomes in children and adults with CF., Search Methods: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles, reviews and online clinical trial registries. Last search: 21 November 2018., Selection Criteria: Randomised controlled trials (RCTs) of parallel design comparing CFTR potentiators to placebo in people with CF. A separate review examines trials combining CFTR potentiators with other mutation-specific therapies., Data Collection and Analysis: The authors independently extracted data, assessed the risk of bias in included trials and used GRADE to assess evidence quality. Trial authors were contacted for additional data., Main Results: We included five RCTs (447 participants with different mutations) lasting from 28 days to 48 weeks, all assessing the CFTR potentiator ivacaftor. The quality of the evidence was moderate to low, mainly due to risk of bias (incomplete outcome data and selective reporting) and imprecision of results, particularly where few individuals experienced adverse events. Trial design was generally well-documented. All trials were industry-sponsored and supported by other non-pharmaceutical funding bodies.F508del (class II) (140 participants)One 16-week trial reported no deaths, or changes in quality of life (QoL) or lung function (either relative or absolute change in forced expiratory volume in one second (FEV1) (moderate-quality evidence). Pulmonary exacerbations and cough were the most reported adverse events in ivacaftor and placebo groups, but there was no difference between groups (low-quality evidence); there was also no difference between groups in participants interrupting or discontinuing treatment (low-quality evidence). Number of days until the first exacerbation was not reported, but there was no difference between groups in how many participants developed pulmonary exacerbations. There was also no difference in weight. Sweat chloride concentration decreased, mean difference (MD) -2.90 mmol/L (95% confidence interval (CI) -5.60 to -0.20).G551D (class III) (238 participants)The 28-day phase 2 trial (19 participants) and two 48-week phase 3 trials (adult trial (167 adults), paediatric trial (52 children)) reported no deaths. QoL scores (respiratory domain) were higher with ivacaftor in the adult trial at 24 weeks, MD 8.10 (95% CI 4.77 to 11.43) and 48 weeks, MD 8.60 (95% CI 5.27 to 11.93 (moderate-quality evidence). The adult trial reported a higher relative change in FEV1 with ivacaftor at 24 weeks, MD 16.90% (95% CI 13.60 to 20.20) and 48 weeks, MD 16.80% (95% CI 13.50 to 20.10); the paediatric trial reported this at 24 weeks, MD 17.4% (P < 0.0001)) (moderate-quality evidence). These trials demonstrated absolute improvements in FEV1 (% predicted) at 24 weeks, MD 10.80% (95% CI 8.91 to 12.69) and 48 weeks, MD 10.44% (95% CI 8.56 to 12.32). The phase 3 trials reported increased cough, odds ratio (OR) 0.57 (95% CI 0.33 to 1.00) and episodes of decreased pulmonary function, OR 0.29 (95% CI 0.10 to 0.82) in the placebo group; ivacaftor led to increased dizziness in adults, OR 10.55 (95% CI 1.32 to 84.47). There was no difference between groups in participants interrupting or discontinuing treatment (low-quality evidence). Fewer participants taking ivacaftor developed serious pulmonary exacerbations; adults taking ivacaftor developed fewer exacerbations (serious or not), OR 0.54 (95% CI 0.29 to 1.01). A higher proportion of participants were exacerbation-free at 24 weeks with ivacaftor (moderate-quality evidence). Ivacaftor led to a greater absolute change from baseline in FEV1 (% predicted) at 24 weeks, MD 10.80% (95% CI 8.91 to 12.69) and 48 weeks, MD 10.44% (95% CI 8.56 to 12.32); weight also increased at 24 weeks, MD 2.37 kg (95% CI 1.68 to 3.06) and 48 weeks, MD 2.75 kg (95% CI 1.74 to 3.75). Sweat chloride concentration decreased at 24 weeks, MD -48.98 mmol/L (95% CI -52.07 to -45.89) and 48 weeks, MD -49.03 mmol/L (95% CI -52.11 to -45.94).R117H (class IV) (69 participants)One 24-week trial reported no deaths. QoL scores (respiratory domain) were higher with ivacaftor at 24 weeks, MD 8.40 (95% CI 2.17 to 14.63), but no relative changes in lung function were reported (moderate-quality evidence). Pulmonary exacerbations and cough were the most reported adverse events in both groups, but there was no difference between groups; there was no difference between groups in participants interrupting or discontinuing treatment (low-quality evidence). Number of days until the first exacerbation was not reported, but there was no difference between groups in how many participants developed pulmonary exacerbations. No changes in absolute change in FEV1 or weight were reported. Sweat chloride concentration decreased, MD -24.00 mmol/L (CI 95% -24.69 to -23.31)., Authors' Conclusions: There is no evidence supporting the use of ivacaftor in people with the F508del mutation. Both G551D phase 3 trials demonstrated a clinically relevant impact of ivacaftor on outcomes at 24 and 48 weeks in adults and children (over six years of age) with CF. The R117H trial demonstrated an improvement in the respiratory QoL score, but no improvement in respiratory function.As new mutation-specific therapies emerge, it is important that trials examine outcomes relevant to people with CF and their families and that adverse events are reported robustly and consistently. Post-market surveillance is essential and ongoing health economic evaluations are required.

Background: Paper-based estimated food diaries are often used in research to collect dietary data, despite this method being burdensome for both participants and researchers. Such food diaries are often time consuming, labour intensive, and rely on participant literacy and therefore may lead to greater rates of under-reporting., Methods: This study assessed the validity of the 'Boden Food Plate', a novel web-based electronic application, compared to a paper-based three-day estimated food diary. Participants were also asked to rate their satisfaction with the new electronic diary. Sixty-seven participants with overweight or obesity completed both the electronic and paper-based diaries at two different time-points., Results: Baseline BMI of participants (mean±standard deviation (SD)) was 30.4±2.9kg/m 2 , body weight was 87.6±13.4kg, and age was 42.3±7.7years. Fifty four percent (n=41) of the cohort were female. Bland Altman plots for total energy, and percentage of total energy intake from fat, carbohydrate, and protein, indicated wide limits of agreement between the two methods of dietary data collection, and in some analyses there were a few cases that did not lie within the 95% confidence intervals. Approximately 70% of participants rated the electronic food diary as easier to use and more fun when compared to the traditional paper-based estimated food diary., Conclusion: Innovative and visual dietary collection applications such as the 'Boden Food Plate' provide an enjoyable and interactive means of measuring nutritional intake in a time efficient manner. Further validation studies incorporating micronutrient analysis and to improve the applications validity are warranted., (Copyright © 2017 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

The aim of this study was to introduce and evaluate a contour segmentation method to extract the interfaces of the intima-media complex in carotid B-mode ultrasound images. The method was applied to assess the temporal variation of intima-media thickness during the cardiac cycle. The main methodological contribution of the proposed approach is the introduction of an augmented dimension to process 2-D images in a 3-D space. The third dimension, which is added to the two spatial dimensions of the image, corresponds to the tentative local thickness of the intima-media complex. The method is based on a dynamic programming scheme that runs in a 3-D space generated with a shape-adapted filter bank. The optimal solution corresponds to a single medial axis representation that fully describes the two anatomical interfaces of the arterial wall. The method is fully automatic and does not require any input from the user. The method was trained on 60 subjects and validated on 184 other subjects from six different cohorts and four different medical centers. The arterial wall was successfully segmented in all analyzed images (average pixel size = 57 ± 20 mm), with average segmentation errors of 47 ± 70 mm for the lumen-intima interface, 55 ± 68 mm for the media-adventitia interface and 66 ± 90 mm for the intima-media thickness. The amplitude of the temporal variations in IMT during the cardiac cycle was significantly higher in the diseased population than in healthy volunteers (106 ± 48 vs. 86 ± 34 mm, p = 0.001). The introduced framework is a promising approach to investigate an emerging functional parameter of the arterial wall by assessing the cyclic compression-decompression pattern of the tissues., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: This study will assess measures of vascular health and inflammation in Aboriginal Australian adults with chronic kidney disease (CKD), and determine if intensive periodontal intervention improves cardiovascular health, progression of renal disease and periodontal health over a 24-month follow-up., Methods: The study will be a randomised controlled trial. All participants will receive the periodontal intervention benefits, with the delayed intervention group receiving periodontal treatment 24 months following baseline. Inclusion criteria include being an Aboriginal Australian, having CKD (a. on dialysis; b. eGFR levels of < 60 mls/min/1.73 m(2) (CKD Stages 3 to 5); c. ACR ≥ 30 mg/mmol irrespective of eGFR (CKD Stages 1 and 2); d. diabetes plus albuminuria (ACR ≥ 3 mg/mmol) irrespective of eGFR), having moderate or severe periodontal disease, having at least 12 teeth, and living in Central Australia for the 2-year study duration. The intervention involves intensive removal of dental plaque biofilms by scaling, root-planing and removal of teeth that cannot be saved. The intervention will occur in three visits; baseline, 3-month and 6-month follow-up. The primary outcome will be changes in carotid intima-media thickness (cIMT). Secondary outcomes will include progression of CKD or death as a consequence of CKD/cardiovascular disease. Progression of CKD will be defined by time to the development of the first of: (1) new development of macroalbuminuria; (2) 30 % loss of baseline eGFR; (3) progression to end stage kidney disease defined by eGFR < 15 mLs/min/1.73 m(2); (4) progression to end stage kidney disease defined by commencement of renal replacement therapy. A sample size of 472 is necessary to detect a difference in cIMT of 0.026 mm (SD 0.09) at the significance criterion of 0.05 and a power of 0.80. Allowing for 20 % attrition, 592 participants are necessary at baseline, rounded to 600 for convenience., Discussion: This will be the first RCT evaluating the effect of periodontal therapy on progression of CKD and cardiovascular disease among Aboriginal patients with CKD. Demonstration of a significant attenuation of CKD progression and cardiovascular disease has the potential to inform clinicians of an important, new and widely available strategy for reducing CKD progression and cardiovascular disease for Australia's most disadvantaged population., Trial Registration: This trial is registered with the Australian New Zealand Clinical Trial Registry ANZCTR12614001183673.

Objective: To describe the reported oral health behaviours and perceptions of Indigenous Australians living in Darwin, Northern Territory and to compare those with estimates for Darwin and Australia derived from the National Survey of Adult Oral Health (NSAOH)., Participants: A total of 181 Indigenous Australians aged 22 years and over living in Darwin, participating in screening for a wider randomised clinical trial, were included., Method: Information on socio-demographic characteristics, oral health status including oral health behaviours and perceptions was collected using a questionnaire. Differences between the Darwin study (DS) participants and Australians in NSAOH were made based on non-overlapping 95% confidence intervals., Results: Almost 72% of DS participants had last seen a dentist over a year earlier, compared to 47% and 39% of NSAOH Darwin and Australian participants, respectively. A higher proportion of DS participants usually visited a dentist because of a problem than NSAOH Darwin and NSAOH Australian participants. A higher proportion of DS participants had avoided or delayed a dental visit because of cost than NSAOH participants. Over three times as many DS participants rated their oral health as fair/poor compared to NSAOH participants. A higher proportion of DS participants had perceived gum disease and one or more symptoms of gum disease than NSAOH participants. A higher proportion of DS participants experienced toothache, felt uncomfortable about appearance of their mouth and avoided eating because of oral problems than NSAOH participants., Conclusions: A higher proportion of Indigenous Australians living in Darwin presented with non-optimal oral health behaviours and perceptions compared with both the Darwin and Australian general populations.

Background: Obstructive sleep apnoea (OSA) is a common and potentially reversible cause of systemic hypertension. The mechanisms whereby OSA leads to hypertension and the effects of treatment on arterial function, however, are not well established. Microvascular arterial endothelial and smooth muscle function was assessed in subjects with OSA before and after treatment with continuous positive airways pressure (CPAP)., Methods: Ten subjects of mean (SE) age 49 (8) years with at least moderately severe OSA had detailed forearm vascular reactivity studies before and after 3 months of CPAP treatment. The systemic circulation was assessed by measuring brachial artery pressure, flow and resistance responses to intra-arterial infusions of acetylcholine (ACh; an endothelium dependent vasodilator), sodium nitroprusside (SNP; an endothelium independent vasodilator), L-NMMA (a nitric oxide (NO) antagonist), and L-arginine (the substrate for NO)., Results: Before CPAP, ACh and SNP infusions increased forearm blood flow in a dose dependent manner (p<0.01). After CPAP, endothelium dependent dilation to ACh was significantly increased (434 (23)% of baseline after CPAP v 278 (20)% before CPAP, p<0.001), whereas SNP induced dilation was unchanged. Resting NO production was higher after CPAP, evidenced by a significantly greater reduction in basal flow by L-NMMA (p=0.05). L-Arginine reversed the effect of L-NMMA in all cases., Conclusion: In patients with OSA, treatment with CPAP improves baseline endothelial NO release and stimulates endothelium dependent vasorelaxation in the systemic circulation. This is a potential mechanism for improving systemic and vascular function in patients with OSA treated with CPAP.

Aim: Cardiovascular disease (CVD) rates are substantially higher among patients with Type 2 diabetes than in the general population. The objective of this study was to identify the determinants of carotid intima media thickness (IMT) in patients with Type 2 diabetes., Methods: We measured the thickness of the intima media layer of the carotid artery, a strong predictor of the risk of future vascular events, in 397 Type 2 diabetic patients drawn from the Fenofibrate Intervention and Event Lowering in Diabetes study, prior to treatment allocation., Results: The mean IMT was 0.78 mm [interquartile range (IQR) 0.23 mm], and the maximum IMT was 1.17 mm (IQR 0.36 mm). By multivariate analysis, age, sex, duration of diabetes, triglycerides, and total cholesterol were independently correlated with IMT, as was urine albumin-creatinine ratio (ACR) (P < 0.001). The effect of ACR on IMT was further examined by tertile. Clinically significant differences in IMT were associated with ACR > 0.65 mg/mmol, approximately one-fifth the standard clinical threshold for microalbuminuria (P < 0.01). Long-term diabetes, independent of other parameters, was associated with a 50% increase in age-related thickening., Conclusions: IMT in people with Type 2 diabetes is independently and continuously related to urine albumin levels and to the duration of diabetes. These results support previous data linking urine albumin measurements within the normal range with increased ischaemic cardiac mortality in the setting of Type 2 diabetes, and strongly suggest that urine albumin levels within this range should trigger a formal evaluation for CVD.

1. Ischaemia-reperfusion (IR) injury is an important contributor to tissue damage and has been shown to be attenuated by preconditioning (PC) in some animal models. A recent report has suggested that the forearm can be used for the study of this phenomenon in humans. We aimed to reproduce and further characterize this model. 2. Healthy young adult volunteers (mean (+/-SEM) age 32+/-6 years) were studied on two occasions. During one visit, IR alone was induced by 10 min of upper arm cuff occlusion, whereas on another occasion a PC stimulus (three 3 min cuff inflations) preceded IR. Endothelial function in the ischaemic arm was assessed by measuring arterial flow-mediated dilatation (FMD) and by calculation of forearm blood flow at baseline and 15 and 60 min after IR. Systemic venous blood was sampled from the non-ischaemic arm at baseline, after PC and at 2, 15 and 30 min after IR to assess neutrophil/leucocyte (CD11b) and platelet (bound glycoprotein IIb/IIIa and fibrinogen) activation, as well as numbers of platelet-leucocyte complexes, which were determined by flow cytometry. Because of a lack of measurable effects, the IR experiment was repeated with 20 min ischaemia in six subjects. 3. Five females and eight males completed the study. Flow-mediated dilatation was significantly impaired 30 min after IR (4.1 vs 6.2% at baseline; P<0.05);however, this was not significantly attenuated by ischaemic PC (FMD reduction at 30 min compared with baseline was 2.1+/-0.5% with IR alone and 2.6+/-1.4% with IR after PC; NS). No significant effect was seen on the number of platelet-leucocyte aggregates or on white cell or platelet activation after IR alone or after IR with PC (P>0.6 for all comparisons). Similar results were obtained in six subjects studied subjected to 20 min ischaemia. 4. In conclusion, in healthy young adults, brief periods of skeletal muscle ischaemia lead to arterial endothelial dysfunction, but no significant platelet or white cell activation. Preconditioning does not attenuate this effect on the endothelium. Further experiments with longer ischaemia times and varying PC stimuli may be necessary to produce measurable effects; however, this may prove difficult in conscious human subjects.

Background: The author carried out a literature review of post-operative pain management in day surgery units., Conclusion: Based on this review, the article makes recommendations for: pre-operative information for patients about their proposed surgery and strategies for pain relief during their stay; a recovery protocol for the administration of intravenous opioids of choice, in titrated doses, by appropriately qualified nurses; and a protocol for the administration of oral analgesia by nurses, from a prescribed list, for patients in pain on the ward.