Search

This study examines the potential utility of using continuous glucose monitoring (CGM) to prescribe an exercise time to target peak hyperglycaemia in people with type 2 diabetes (T2D). The main aim is to test the feasibility of prescribing an individualised daily exercise time, based on the time of CGM-derived peak glucose, for people with T2D. Thirty-five individuals with T2D (HbA1c: 7.2 ± 0.8%; age: 64 ± 7 y; BMI: 29.2 ± 5.2 kg/m2) were recruited and randomised to one of two 14 d exercise interventions: i) ExPeak (daily exercise starting 30 min before peak hyperglycaemia) or placebo active control NonPeak (daily exercise starting 90 min after peak hyperglycaemia). The time of peak hyperglycaemia was determined via a two-week baseline CGM. A CGM, accelerometer, and heart rate monitor were worn during the free-living interventions to objectively measure glycaemic control outcomes, moderate-to-vigorous intensity physical activity (MVPA), and exercise adherence for future translation in a clinical trial. Participation in MVPA increased 26% when an exercise time was prescribed compared to habitual baseline (p < 0.01), with no difference between intervention groups (p > 0.26). The total MVPA increased by 10 min/day during the intervention compared to the baseline (baseline: 23 ± 14 min/d vs. intervention: 33 ± 16 min/d, main effect of time p = 0.03, no interaction). The change in peak blood glucose (mmol/L) was similar between the ExPeak (−0.44 ± 1.6 mmol/L, d = 0.21) and the NonPeak (−0.39 ± 1.5 mmol/L, d = 0.16) intervention groups (p = 0.92). Prescribing an exercise time based on CGM may increase daily participation in physical activity in people with type 2 diabetes; however, further studies are needed to test the long-term impact of this approach.

NEW FINDINGS What is the central question of this study? Is the estrous cycle affected during disuse atrophies and if so, how do estrous cycle changes relate to musculoskeletal outcomes? What is the main finding and its importance? Rodent estrous cycles are altered during disuse atrophy, which corresponds to musculoskeletal outcomes. However, the estrous cycle does not appear changed in Lewis Lung Carcinoma, which corresponded to no differences in muscle size compared to healthy controls. These findings suggest a relationship between estrous cycle and muscle size during atrophic pathologies. ABSTRACT Hyperglycemia can cause disruptions in vascular function, whereas exercise has been shown to restore vascular function. The primary aim of this study is to investigate the effect of performing whole-body resistance exercise, 30-min before, immediately following, or 30- or 60-min after a high carbohydrate meal, on endothelial function, measured by flow-mediated dilation (FMD). Healthy adults will be recruited to this randomized crossover trial to compare the postprandial glycaemic and vascular responses to four different exercise timing conditions and a control: i) C- control, high carbohydrate meal/no exercise, ii) 30Pre- 30 min of resistance exercises (~30% of 1RM [Repetition Maximum]), 30 min before a high carbohydrate meal, iii) IP- 30 min of resistance exercises (~30% of 1RM), immediately following a high carbohydrate meal, iv) 30Post- 30 min of resistance exercises, 30 min after a high carbohydrate meal and v) 60Post- 30 min of resistance exercises, 60 min after a high carbohydrate meal. Measures of metabolic and vascular function will be assessed at baseline and for two hours following the carbohydrate-based breakfast meal.

BACKGROUND LDL particle size and number (LDL-P) are emerging lipid risk factors. Nonsystematic reviews have suggested that diets lower in carbohydrates and higher in fats may result in increased LDL particle size when compared with higher-carbohydrate diets. OBJECTIVES This study aimed to systematically review available evidence and conduct meta-analyses of studies addressing the association of carbohydrate restriction with LDL particle size and LDL-P. METHODS We searched 6 electronic databases on 4 January, 2021 for randomized trials of any length that reported on dietary carbohydrate restriction (intervention) compared with higher carbohydrate intake (control). We calculated standardized mean differences (SMDs) in LDL particle size and LDL-P between the intervention and control groups of eligible studies, and pooled effect sizes using random-effects models. We performed prespecified subgroup analyses and examined the effect of potential explanatory factors. Internal validity and publication bias were assessed using Cochrane's risk-of-bias tool and funnel plots, respectively. Studies that could not be meta-analyzed were summarized qualitatively. RESULTS This review summarizes findings from 38 randomized trials including a total of 1785 participants. Carbohydrate-restricted dietary interventions were associated with an increase in LDL peak particle size (SMD = 0.50; 95% CI: 0.15, 0.86; P

Consuming a bedtime snack is often recommended for people with type 2 diabetes.This systematic review aims to evaluate the evidence from intervention studies to determine whether consuming a bedtime snack improves fasting hyperglycemia and/or overall glycemic control in individuals with type 2 diabetes. Methods: PubMed, Medline (EBSCO), Cochrane Library and CINAHL Plus (EBSCO) databases were searched until July 20 2022. We included prospective studies in people with type 2 diabetes or prediabetes that included the intervention of a bedtime snack, consumed 30 minutes after dinner and 2 hours before bed and reported glycemic outcomes.The systematic review included 16 studies. There was no consistent relationship between consumption of a bedtime snack and improved glycemic control, especially when a no snack control was included. Of the four studies that included the use of corn starch, a low dose seemed to have benefits over high dose corn starch in terms of improved nocturnal and fasting glucose levels.Current advice to consume a bedtime snack is based on a limited number of intervention studies that often do not include a no snack control, nor have used a feasible bedtime snack option that could be translated into every day clinical practice. Further research is needed in type 2 diabetes patients treated with or without insulin.PROSPERO Registration Number: CRD42020182523.

The purpose of this study was to determine whether postmeal walking (PMW, breaking up exercise into short bouts after meals) is an effective and feasible alternative to continuous walking for the management of gestational diabetes. Forty-one women with gestational diabetes were randomised between weeks 28–30 gestation to either standard care (30 minutes continuous exercise) or standard care with PMW (10 minutes of walking after breakfast, lunch, and dinner). Continuous glucose and activity monitors were worn to measure glycaemic control and adherence during 3 days of standard care (baseline) followed by 3 days of postmeal or continuous walking. A linear mixed model analysed the changes from baseline between postmeal and continuous walking, as an average of the 3-day periods. Thirty-two women (PMW n = 17: control n = 15, 33 ± 5 years, body mass index 25 ± 4 kg·m–2) completed the trial. Postprandial and overnight glucose concentrations were similar between PMW and control; both interventions improved from baseline. There was no difference in adherence between groups; however, PMW completed more minutes of prescribed physical activity across baseline and intervention days compared to the continuous walking standard-care group. Preliminary findings from this proof-of-concept study suggest PMW could be a promising alternative to, and work interchangeably with, traditional advice to perform continuous moderate-intensity physical activity in women with gestational diabetes. Novelty: Three 10-minute postmeal walks may be comparable to 30 minutes continuous walking for glucose control in women with gestational diabetes. Accumulating activity in short bouts after meals is a feasible alternate to continuous exercise for women with gestational diabetes.

Maintaining blood glucose within the target range is the primary treatment goal for women with gestational diabetes mellitus (GDM). Foods with low glycaemic loads are recommended in clinical practice; however, the relative importance of other key lifestyle variables is unexplored. This pilot study explored the associations of glycaemic load, carbohydrates and physical activity parameters on blood glucose concentrations in free-living women with GDM. Twenty-nine women (28–30 weeks gestation, 34 ± 4 years) with GDM were enrolled. Continuous glucose monitoring, physical activity (ActivPAL inclinometer) and dietary intake and dietary quality were measured concurrently for 3 days. Pearson correlation analyses determined the association between glucose levels and lifestyle variables. Despite all receiving the same nutrition education, only 55% of women were following a low glycaemic load diet with a large range of carbohydrate intakes (97–267 g/day). However, the glycaemic load did not correlate with 3-hr postprandial glucose (r2 = 0.021, p = 0.56) or 24-h glucose iAUC (r2 = 0.021, p = 0.58). A significant relationship between total stepping time and lower 24-h glucose iAUC (r2 = 0.308, p = 0.02) and nocturnal glucose (r2 = 0.224, p = 0.05) was found. In free-living women with diet-controlled GDM, more physical activity, i.e., steps accumulated across the day, may be a simple and effective strategy for improving maternal blood glucose concentrations.

Clinical practice guidelines on physical activity and diabetes currently stipulate physical activity can be accumulated in bouts of ≥10 minutes to meet recommendations for health benefits. Individuals are also encouraged to interrupt prolonged sitting with brief activity breaks of ∼1 to 5 minutes in duration. Growing research highlights accumulating activity in shorter bouts across the day as a potential strategy to improve glycemic control and to help those who are largely sedentary meet physical activity guidelines. Research has shown favourable glycemic benefits for postprandial glucose and glycated hemoglobin with either 3 short (10 to 15 minutes) or frequent brief (1 to 5 minutes) bouts of activity spread around meals or throughout the day. To date, most studies examining accumulated activity were done with people with type 2 diabetes compared with sedentary conditions, were short term and measured various indices of glycemic control using continuous glucose monitoring. The 7 trials comparing accumulating 3 short bouts to a single bout showed comparable benefits for glycemic control (i.e. fasting glucose, 24 h mean glucose and postprandial hyperglycemia). Furthermore, timing short bouts around meals may improve postprandial glucose and hyperglycemia more than a single bout. It is unknown whether a threshold for the duration of accumulated bouts exists---that is, "how much is enough?" In this narrative review, we focus on the glycemic effects of physical activity accumulated in short or brief bouts for people with prediabetes and diabetes as compared with a single continuous bout. Given that poor adherence to physical activity recommendations and that fewer opportunities exist in modern societies for incidental (nonexercise) physical activity, accumulating activity may be a choice strategy for improving glycemic control in those with and at risk of diabetes.

Summary In type 2 diabetes, liver insulin resistance and excess hepatic glucose production results in elevated fasting glucose. A bedtime snack has been recommended to improve fasting glucose, yet there is little evidence supporting this recommendation. Moreover, the optimal composition of a bedtime snack is unknown. Purpose To determine whether a low-carbohydrate protein-rich bedtime snack (Egg) could reduce fasting plasma glucose levels in people with type 2 diabetes when compared to a high-carbohydrate protein-rich bedtime snack (Yogurt) or a No Bedtime Snack condition. Secondary outcomes included glucose control assessed by continuous glucose monitoring (CGM) and fasting insulin sensitivity markers. Methods Using a randomized crossover design, participants with type 2 diabetes (N = 15) completed three separate isocaloric conditions: i) Egg, ii) Yogurt, and iii) No Bedtime Snack, each lasting three days. CGM was collected throughout and duplicate fasting blood samples were obtained on the morning of day 4 in each condition. Results Fasting plasma glucose (P = 0.04, d = 0.68), insulin (P = 0.04, d = 0.45), and nocturnal glucose (P = 0.02, d = 0.94) were significantly lower, and quantitative insulin sensitivity check index (QUICKI; P = 0.003) was improved, in the Egg compared to the Yogurt bedtime snack. There were no significant differences between either bedtime snack and No Bedtime Snack. Conclusion In the short-term, a low-carbohydrate bedtime snack (Egg) lowered fasting glucose and improved markers of insulin sensitivity when compared to a high-carbohydrate protein-matched bedtime snack (Yogurt). However, consuming a low- or high-carbohydrate bedtime snack did not appear to lower fasting glucose compared to consuming an isocaloric diet with no bedtime snack. Clinical trial registry clinicaltrials.gov ( NCT03207269 ).

The incidence of gestational diabetes mellitus (GDM) is increasing. One in three women require insulin to achieve glycaemic targets in GDM. However, it is unclear whether insulin therapy alone is the most effective treatment for all women in achieving glycaemic control and preventing adverse pregnancy outcomes. Although no oral hypoglycaemic agents are approved for pregnancy in Australia, recent research indicates that metformin is effective in preventing adverse perinatal outcomes and may even have possible benefits in the long term. Furthermore, there appears to be a specific role for both metformin and insulin among the GDM population. Metformin provides an option to offer an individualised approach to treat GDM.

Gestational diabetes mellitus (GDM) is the most common complication of pregnancy and a significant clinical and public health problem with lifelong and intergenerational adverse health consequences for mothers and their offspring. The preconception, early pregnancy, and interconception periods represent opportune windows to engage women in preventive and health promotion interventions. This review provides an overview of findings from observational and intervention studies on the role of diet, physical activity, and weight (change) during these periods in the primary prevention of GDM. Current evidence suggests that supporting women to increase physical activity and achieve appropriate weight gain during early pregnancy and enabling women to optimize their weight and health behaviors prior to and between pregnancies have the potential to reduce rates of GDM. Translation of current evidence into practice requires further development and evaluation of co-designed interventions across community, health service, and policy levels to determine how women can be reached and supported to optimize their health behaviors before, during, and between pregnancies to reduce GDM risk.

We investigated whether substituting the final half within 60-min bouts of exercise with passive warm or cold water immersion would provide similar or greater benefits for cardiometabolic health. Thirty healthy participants were randomized to two of three short-term training interventions in a partial crossover (12 sessions over 14–16 days, 4 week washout): (i) EXS: 60 min cycling 70% maximum heart rate (HRmax), (ii) WWI: 30 min cycling then 30 min warm water (38–40°C) immersion, and/or (iii) CWI: 30 min cycling then 30 min cold water (10–12°C) immersion. Before and after, participants completed a 20 min cycle work trial, V.O2max test, and an Oral Glucose Tolerance Test during which indirect calorimetry was used to measure substrate oxidation and metabolic flexibility (slope of fasting to post-prandial carbohydrate oxidation). Data from twenty two participants (25 ± 5 year, BMI 23 ± 3 kg/m2, Female = 11) were analyzed using a fixed-effects linear mixed model. V.O2max increased more in EXS (interaction p = 0.004) than CWI (95% CI: 1.1, 5.3 mL/kg/min, Cohen’s d = 1.35), but not WWI (CI: −0.4, 3.9 mL/kg/min, d = 0.72). Work trial distance and power increased 383 ± 223 m and 20 ± 6 W, respectively, without differences between interventions (interaction both p > 0.68). WWI lowered post-prandial glucose ∼9% (CI −1.9, −0.5 mmol/L; d = 0.63), with no difference between interventions (interaction p = 0.469). Substituting the second half of exercise with WWI provides similar cardiometabolic health benefits to time matched exercise, however, substituting with CWI does not.

The objective of this study was to test if a low-calorie diet plus interval exercise (LCD+INT) improves adiposopathy, an endocrine dysfunction, when compared with an energy-deficit–matched LCD in obese women. Subjects (age: 48.2 ± 2.4 years, body mass index: 37.8 ± 1.3 kg/m2) were randomized to a 13-day LCD (n = 12; mixed meals of ∼1200 kcal/day) or LCD+INT (n = 12; 12 sessions of 60 min/day alternating 3 min at 50% and 90% peak heart rate). Exercise was estimated to expend 350 kcal per oxygen uptake–heart rate regression analysis and individuals were refed calories expended to match energy availability between groups. Absolute (post – pre caloric intake) and relative (total daily and exercise energy expenditure relative to calorie intake) energy deficits were calculated. Fitness (peak oxygen uptake) and body composition (BodPod; Cosmed USA Inc.) were measured and a 120-min, 75g oral glucose tolerance test was performed at pre- and post-intervention to assess adiposopathy (i.e., ratio of high molecular weight–adiponectin to leptin) and estimate insulin sensitivity. LCD and LCD+INT had similar absolute (P = 0.55) and relative (P = 0.76) energy deficits. LCD and LCD+INT had similar reductions in fat mass (both P < 0.001), despite LCD inducing greater weight loss (P = 0.02) than LCD+INT. Both treatments improved adiposopathy (P = 0.003) and peripheral insulin sensitivity (P = 0.02). Absolute energy deficit correlated to improved adiposopathy (r = –0.41, P = 0.05), and absolute and relative energy deficits were associated with increased insulin sensitivity (r = –0.47, P = 0.02; and r = –0.40, P = 0.05, respectively), independent of body composition changes and increased peak oxygen uptake. Taken together, LCD, with or without INT, improves adiposopathy in relation to insulin sensitivity in obese women, suggesting that a short-term energy deficit is key for reducing risk of type 2 diabetes.

Aim To examine the effect of walking before dinner on 24-h glycemic control in individuals with type 2 diabetes using the standardized multi-site Exercise-Physical Activity and Diabetes Glucose Monitoring (E-PAraDiGM) Protocol. Methods Eighty participants were studied under two conditions (exercise vs. non-exercise control) separated by 72 h in a randomized crossover design. Each condition lasted 2 days during which standardized meals were provided. Exercise consisted of 50 min of treadmill walking at 5.0 km/h before the evening meal, while control involved 50 min of sitting. The primary outcome measure was mean glucose during the 24-h period following exercise (or sitting) measured by continuous glucose monitoring. Results Of the 80 participants who were initially randomized, 73 completed both exercise and control. Sixty-three participants [29 males, 34 females; age = 64 ± 8 years, body mass index = 30.5 ± 6.5 kg/m2 and HbA1c = 51 ± 8 mmol/mol (6.8 ± 0.7%), mean ± SD] complied with the standardized diets and had complete continuous glucose monitoring data. Exercise did not affect mean 24-h glucose compared to control (0.03 mmol/L; 95% CI − 0.17, 0.22, P = 0.778) but individual differences between conditions ranged from − 2.8 to +1.8 mmol/L. Exercise did not affect fasting glucose, postprandial glucose or glucose variability. Glucose concentrations measured by continuous glucose monitoring were reduced during the 50 min of walking in exercise compared to sitting in control (− 1.56 mmol/L; 95% CI − 2.18, − 0.95, p ˂ 0.001). Conclusion Contrary to previous acute exercise studies, 50 min of walking before dinner in the E-PAraDiGM protocol did not affect 24-h glucose profiles. However, highly heterogeneous responses to exercise were observed.

BACKGROUND: The breakfast meal often results in the largest postprandial hyperglycemic excursion in people with type 2 diabetes. OBJECTIVE: Our purpose was to investigate whether restricting carbohydrates at breakfast would be a simple and feasible strategy to reduce daily exposure to postprandial hyperglycemia. DESIGN: Adults with physician-diagnosed type 2 diabetes [n = 23; mean ± SD age: 59 ± 11 y; glycated hemoglobin: 6.7% ± 0.6%; body mass index (kg/m(2)): 31 ± 7] completed two 24-h isocaloric intervention periods in a random order. Participants consumed one of the following breakfasts: 1) a very-low-carbohydrate high-fat breakfast (LCBF

Background Minimally invasive surgery procedures, including stereotactic catheter aspiration and clearance of intracerebral hemorrhage (ICH) with recombinant tissue plasminogen activator hold a promise to improve outcome of supratentorial brain hemorrhage, a morbid and disabling type of stroke. A recently completed Phase III randomized trial showed improved mortality but was neutral on the primary outcome (modified Rankin scale score 0 to 3 at 1 yr). Objective To assess surgical performance and its impact on the extent of ICH evacuation and functional outcomes. Methods Univariate and multivariate models were used to assess the extent of hematoma evacuation efficacy in relation to mRS 0 to 3 outcome and postulated factors related to patient, disease, and protocol adherence in the surgical arm (n = 242) of the MISTIE trial. Results Greater ICH reduction has a higher likelihood of achieving mRS of 0 to 3 with a minimum evacuation threshold of ≤15 mL end of treatment ICH volume or ≥70% volume reduction when controlling for disease severity factors. Mortality benefit was achieved at ≤30 mL end of treatment ICH volume, or >53% volume reduction. Initial hematoma volume, history of hypertension, irregular-shaped hematoma, number of alteplase doses given, surgical protocol deviations, and catheter manipulation problems were significant factors in failing to achieve ≤15 mL goal evacuation. Greater surgeon/site experiences were associated with avoiding poor hematoma evacuation. Conclusion This is the first surgical trial reporting thresholds for reduction of ICH volume correlating with improved mortality and functional outcomes. To realize the benefit of surgery, protocol objectives, surgeon education, technical enhancements, and case selection should be focused on this goal.

Background/Objective: Adventure racing is an ultra-endurance activity that imposes a unique multifaceted stress on the human body. The purpose of this field study was to examine the physiological responses to a 5-day adventure race. Methods: Eight competitors, two teams (1 female each) in the 2012 GODZone adventure race volunteered. Competitors trekked, cycled and paddled ∼326 km in ∼116 hours. Continuous glucose was measured the day before and throughout. Body mass, urinary solutes, and blood pressure and heart rate during resting, standing, and repeated squat-stand conditions, were assessed pre and post. Results: Despite no changes in mean blood glucose levels, there was increased glycemic variability (Standard deviation glucose; Pre: 0.5 ± 0.1 vs Race: 1.0 ± 0.2 mmol/L, p = 0.02) and periods of hypoglycemia (i.e., Min glucose Pre: 4.1 ± 0.3 vs Race: 3.6 ± 0.5 mmol/L, p = 0.05) during the race. After the race, the blood pressure during resting, standing and squat-stand conditions was significantly lower, by 14 ± 14 mmHg, 16 ± 15 mmHg and 18 ± 15 mmHg (all p

Background Low cardiorespiratory fitness (V̇O2peak) is highly associated with chronic disease and mortality from all causes. Whilst exercise training is recommended in health guidelines to improve V̇O2peak, there is considerable inter-individual variability in the V̇O2peak response to the same dose of exercise. Understanding how genetic factors contribute to V̇O2peak training response may improve personalisation of exercise programs. The aim of this study was to identify genetic variants that are associated with the magnitude of V̇O2peak response following exercise training. Methods Participant change in objectively measured V̇O2peak from 18 different interventions was obtained from a multi-centre study (Predict-HIIT). A genome-wide association study was completed (n = 507), and a polygenic predictor score (PPS) was developed using alleles from single nucleotide polymorphisms (SNPs) significantly associated (P –5) with the magnitude of V̇O2peak response. Findings were tested in an independent validation study (n = 39) and compared to previous research. Results No variants at the genome-wide significance level were found after adjusting for key covariates (baseline V̇O2peak, individual study, principal components which were significantly associated with the trait). A Quantile–Quantile plot indicates there was minor inflation in the study. Twelve novel loci showed a trend of association with V̇O2peak response that reached suggestive significance (P –5). The strongest association was found near the membrane associated guanylate kinase, WW and PDZ domain containing 2 (MAGI2) gene (rs6959961, P = 2.61 × 10–7). A PPS created from the 12 lead SNPs was unable to predict V̇O2peak response in a tenfold cross validation, or in an independent (n = 39) validation study (P > 0.1). Significant correlations were found for beta coefficients of variants in the Predict-HIIT (P –4) and the validation study (P –6), indicating that general effects of the loci exist, and that with a higher statistical power, more significant genetic associations may become apparent. Conclusions Ongoing research and validation of current and previous findings is needed to determine if genetics does play a large role in V̇O2peak response variance, and whether genomic predictors for V̇O2peak response trainability can inform evidence-based clinical practice. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR), Trial Id: ACTRN12618000501246, Date Registered: 06/04/2018, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374601&isReview=true.

Introduction et but de l’etude Comparer les objectifs cliniques et la tolerance de la (chimio)radiotherapie chez des patients avec un carcinome epidermoide du canal anal selon l’infection par le virus de l’immunodeficience humaine (VIH). Materiel et methodes Il s’agissait d’une analyse en sous-groupe de la cohorte multicentrique, prospective et retrospective, Anabase, menee par la Federation francaise de cancerologie digestive (FFCD). Les objectifs cliniques incluaient la survie globale, la survie specifique, la survie sans recidive, le controle locoregional, la survie sans colostomie, le taux de reponse a 4–6 mois et la toxicite aigue et tardive severe (de grade 3 ou plus). Les facteurs pronostiques des principaux objectifs cliniques ont ete recherches. Resultats et analyse statistique Entre fevrier 2016 et avril 2020, 1097 patients atteints d’un carcinome epidermoide localise traite par irradiation ont ete inclus dans Anabase. Seuls les 488 patients avec un statut VIH connu ont ete inclus dans cette analyse (86 patients positifs et 402 patients negatifs issus de 50 centres). Le suivi median etait de 35,8 mois. Les caracteristiques tumorales initiales etaient comparables dans les deux groupes (stades T, X2 = 0,32 et N, X2 = 0,54). Les patients VIH-positifs etaient plus jeunes (p Tableau 1 et montrent que les taux de survie globale, controle locoregional et de survie sans colostomie etaient significativement diminues chez les patients infectes par le VIH. Il n’existait pas de difference significative pour la reponse a 4-6 mois, les taux de survie sans recidive et de survie specifique. La tolerance du traitement etait similaire dans les deux groupes (47,7 % de toxicite aigue de grade 3 ou plus chez les patients infectes par le VIH contre 45 % chez les patients non infectes, p = 0,65). Le sexe masculin, le statut OMS ≥ 1 et l’absence de reponse complete a 4–6 mois etaient associes a une survie globale diminuee en analyse uni- et multivariee. Conclusion Les patients infectes par le VIH recevant une (chimio)radiotherapie pour un carcinome epidermoide du canal anal avaient des taux de survie globale et sans colostomie inferieure a ceux des patients non infectes, ainsi qu’un controle locoregional moindre. La toxicite de ce traitement avec les techniques modernes d’irradiation conformationnelle avec modulation d’intensite n’etait pas majoree chez ces patients.

IntroductionThe benefits of physical activity for glycaemic control in type 2 diabetes (T2D) are well-known. However, whether established glycaemic and cardiovascular benefits can be maximised by exercising at a certain time of day is unknown. Given postprandial glucose peaks contribute to worsening glycated haemoglobin (HbA1c) and cardiovascular risk factors, and that exercise immediately lowers blood glucose, prescribing exercise at a specific time of day to attenuate peak hyperglycaemia may improve glycaemic control and reduce the burden of cardiovascular disease in people with T2D.Methods and analysisA single-centre randomised controlled trial will be conducted by the University of Wollongong, Australia. Individuals with T2D (n=70, aged 40–75 years, body mass index (BMI): 27–40 kg/m2) will be recruited and randomly allocated (1:1), stratified for sex and insulin, to one of three groups: (1) exercise at time of peak hyperglycaemia (ExPeak, personalised), (2) exercise not at time of peak hyperglycaemia (NonPeak) or (3) waitlist control (WLC, standard care). The trial will be 5 months, comprising an 8-week intervention and 3-month follow-up. Primary outcome is the change in HbA1c preintervention to postintervention. Secondary outcomes include vascular function (endothelial function and arterial stiffness), metabolic control (blood lipids and inflammation) and body composition (anthropometrics and dual-energy X-ray absorptiometry (DEXA)). Tertiary outcomes will examine adherence.Ethics and disseminationThe joint UOW and ISLHD Ethics Committee approved protocol (2019/ETH09856) prospectively registered at the Australian New Zealand Clinical Trials Registry. Written informed consent will be obtained from all eligible individuals prior to commencement of the trial. Study results will be published as peer-reviewed articles, presented at national/international conferences and media reports.Trial registration numberACTRN12619001049167.

Background A sustained release microparticle formulation of nimodipine (EG-1962) was developed for treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). Objective To assess safety, tolerability, and pharmacokinetics of intracisternal EG-1962 in an open-label, randomized, phase 2 study of up to 12 subjects. Methods Subjects were World Federation of Neurological Surgeons grades 1 to 2, modified Fisher grades 2 to 4, and underwent aneurysm clipping within 48 h of aSAH. EG-1962, containing 600 mg nimodipine, was administered into the basal cisterns. Outcome on the extended Glasgow Outcome Scale (eGOS), pharmacokinetics, delayed cerebral ischemia and infarction, rescue therapy, and safety were evaluated. Results The study was halted when a phase 3 study of intraventricular EG-1962 stopped because that study was unlikely to meet its primary endpoint. Six subjects were randomized (5 EG-1962 and 1 oral nimodipine). After 90-d follow-up, favorable outcome on the eGOS occurred in 1 of 5 EG-1962 and in the single oral nimodipine patient. Four EG-1962 and the oral nimodipine subject had angiographic vasospasm. One EG-1962 subject had delayed cerebral ischemia, and all subjects with angiographic vasospasm received rescue therapy except 1 EG-1962 patient. One subject treated with EG-1962 developed right internal carotid and middle cerebral artery narrowing 5 mo after placement of EG-1962, leading to occlusion and cerebral infarction. Pharmacokinetics showed similar plasma concentrations of nimodipine in both groups. Conclusion Angiographic vasospasm and unfavorable clinical outcome still occurred after placement of EG-1962. Internal carotid artery narrowing and occlusion after placement of EG-1962 in the basal cisterns has not been reported.

Summary Background & aims Postprandial metabolic imbalances are important indicators of later developing cardiovascular disease (CVD). This study investigated the effects of food anthocyanins on vascular and microvascular function, and CVD associated biomarkers following a high fat high energy (HFHE) meal challenge in overweight older adults. Methods Sixteen subjects (13 female, 3 male, mean age 65.9 SD 6.0 and body mass index 30.6 kg/m2 SD 3.9) participated in a crossover, randomized, controlled, double-blind clinical trial (registered under Australian New Zealand Clinical Trials Registry, identifier no. ACTRN12620000437965). Participants consumed a HFHE meal with a 250 mL dose of either intervention (anthocyanins-rich Queen Garnet Plum) or control (apricot) juice. Blood samples and blood pressure measures were collected at baseline, 2 h and 4 h following the HFHE meal. Vascular and microvascular function were evaluated at baseline and 2 h after the HFHE meal. Results Participants had a higher 2 h postprandial flow-mediated dilatation (+1.14%) and a higher microvascular post-occlusive reactive hyperaemia (+0.10 perfusion units per mmHg) when allocated to the anthocyanin compared to the control arm (P = 0.019 and P = 0.049, respectively). C-reactive protein was lower 4 h postprandially in the anthocyanins (1.80 mg/L, IQR 0.90) vs control arm (2.30 mg/L, IQR 1.95) (P = 0.026), accompanied by a trend for lower concentrations of interleukin-6 (P = 0.075). No significant postprandial differences were observed between treatments for blood pressure, triacylglycerol, total cholesterol, serum derivatives of reactive oxidative metabolites, tumor necrosis factor alpha, interleukin-1 beta, or maximum microvascular perfusion following iontophoresis of acetylcholine. Conclusion Fruit-based anthocyanins attenuated the potential postprandial detrimental effects of a HFHE challenge on parameters of vascular and microvascular function, and inflammatory biomarkers in overweight older adults. Anthocyanins may reduce cardiovascular risk associated with endothelial dysfunction and inflammatory responses to a typical high fat ‘Western’ meal. Further studies are required to better elucidate the clinical implications of postprandial biomarkers of CVD.

Arachidonic acid (AA) and docosahexaenoic acid (DHA) are important for neurological development. The aim was to determine the distribution and relative enrichment of AA and DHA among lipoprotein fractions prior to pregnancy, throughout gestation and in the post-partum period. Our hypothesis was that in pregnancy, in contrast to the non-pregnant state, AA and DHA are carried in highest concentration in the very low density lipoprotein (VLDL) fraction secondary to increased gestational liver triglyceride secretion. Two independent prospective, observational cohort studies carried out in Glasgow were combined; one early in pregnancy and one later in pregnancy with post-partum follow up. Across the pregnancy timeline plasma lipoproteins were isolated using sequential ultracentrifugation and lipoprotein fatty acids were extracted and analysed by gas chromatography. High density lipoprotein (HDL) had the highest concentration of AA and DHA compared to other lipoproteins. HDL became progressively enriched in the proportion of triglycerides at 16 weeks of gestation, which peaked at 35 weeks and returned to baseline at 13 weeks postpartum. HDL DHA per HDL-cholesterol and HDL DHA per apoA-I became progressively enriched at 16 weeks of gestation, peaked at 25 weeks and returned to baseline at 13 weeks postpartum, whereas HDL AA (per HDL-C or HDL-apoA-I) did not differ. DHA is carried primarily in HDL rather than VLDL. HDL has anti-oxidant properties that might afford DHA protection against oxidation.

Background Patients who survive aneurysmal subarachnoid hemorrhage (aSAH) are at risk for delayed neurological deficits (DND) and cerebral infarction. In this exploratory cohort comparison analysis, we compared in-hospital outcomes of aSAH patients administered a low-dose intravenous heparin (LDIVH) infusion (12 U/kg/h) vs those administered standard subcutaneous heparin (SQH) prophylaxis for deep vein thrombosis (DVT; 5000 U, 3 × daily). Objective To assess the safety and efficacy of LDIVH in aSAH patients. Methods We retrospectively analyzed 556 consecutive cases of aSAH patients whose aneurysm was secured by clipping or coiling at a single institution over a 10-yr period, including 233 administered the LDIVH protocol and 323 administered the SQH protocol. Radiological and outcome data were compared between the 2 cohorts using multivariable logistic regression and propensity score-based inverse probability of treatment weighting (IPTW). Results The unadjusted rate of cerebral infarction in the LDIVH cohort was half that in SQH cohort (9 vs 18%; P = .004). Multivariable logistic regression showed that patients in the LDIVH cohort were significantly less likely than those in the SQH cohort to have DND (odds ratio (OR) 0.53 [95% CI: 0.33, 0.85]) or cerebral infarction (OR 0.40 [95% CI: 0.23, 0.71]). Analysis following IPTW showed similar results. Rates of hemorrhagic complications, heparin-induced thrombocytopenia and DVT were not different between cohorts. Conclusion This cohort comparison analysis suggests that LDIVH infusion may favorably influence the outcome of patients after aSAH. Prospective studies are required to further assess the benefit of LDIVH infusion in patients with aSAH.

OBJECTIVE Aneurysmal subarachnoid hemorrhage (aSAH) is associated with significant morbidity and mortality. The presence of thick, diffuse subarachnoid blood may portend a worse clinical course and outcome, independently of other known prognostic factors such as age, aneurysm size, and initial clinical grade. METHODS In this post hoc analysis, patients with aSAH undergoing surgical clipping (n = 383) or endovascular coiling (n = 189) were pooled from the placebo arms of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS)–2 and CONSCIOUS-3 randomized, double-blind, placebo-controlled phase 3 studies, respectively. Patients without and with thick, diffuse SAH (≥ 4 mm thick and involving ≥ 3 basal cisterns) on admission CT scans were compared. Clot size was centrally adjudicated. All-cause mortality and vasospasm-related morbidity at 6 weeks and Glasgow Outcome Scale–Extended (GOSE) scores at 12 weeks after aSAH were assessed. The effect of the thick and diffuse cisternal aSAH on vasospasm-related morbidity and mortality, and on poor clinical outcome at 12 weeks, was evaluated using logistic regression models. RESULTS Overall, 294 patients (51.4%) had thick and diffuse aSAH. Compared to patients with less hemorrhage burden, these patients were older (median age 55 vs 50 years) and more often had World Federation of Neurosurgical Societies (WFNS) grade III–V SAH at admission (24.1% vs 16.5%). At 6 weeks, all-cause mortality and vasospasm-related morbidity occurred in 36.1% (95% CI 30.6%–41.8%) of patients with thick, diffuse SAH and in 14.7% (95% CI 10.8%–19.5%) of those without thick, diffuse SAH. Individual event rates were 7.5% versus 2.5% for all-cause death, 19.4% versus 6.8% for new cerebral infarct, 28.2% versus 9.4% for delayed ischemic neurological deficit, and 24.8% versus 10.8% for rescue therapy due to cerebral vasospasm, respectively. Poor clinical outcome (GOSE score ≥ 4) was observed in 32.7% (95% CI 27.3%–38.3%) and 16.2% (95% CI 12.1%–21.1%) of patients with and without thick, diffuse SAH, respectively. CONCLUSIONS In a large, centrally adjudicated population of patients with aSAH, WFNS grade at admission and thick, diffuse SAH independently predicted vasospasm-related morbidity and poor 12-week clinical outcome. Patients with thick, diffuse cisternal SAH may be an important cohort to target in future clinical trials of treatment for vasospasm.

Nimodipine is the only drug approved in the treatment of aneurysmal subarachnoid hemorrhage (aSAH) in many countries. EG-1962, a product developed using the Precisa™ platform, is an extended-release microparticle formulation of nimodipine that can be administered intraventricularly or intracisternally. It was developed to test the hypothesis that delivering higher concentrations of extended-release nimodipine directly to the cerebrospinal fluid would provide superior efficacy compared to systemic administration. A Phase 1/2a multicenter, controlled, randomized, open-label, dose-escalation study determined the maximum tolerated dose and supported the safety and tolerability of EG-1962 in patients with aSAH. EG-1962, 600 mg, was selected for a pivotal, Phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group efficacy, and safety study comparing it to standard of care oral nimodipine in adults with aSAH. Key inclusion criteria are patients with a ruptured saccular aneurysm repaired by clipping or coiling, World Federation of Neurological Surgeons grade 2–4, and modified Fisher score of > 1. Patients must have an external ventricular drain as part of standard of care. Patients are randomized to receive intraventricular investigational product (EG-1962 or NaCl solution) and an oral placebo or oral nimodipine in the approved dose regimen (active control) within 48 h of aSAH. The primary objective is to determine the efficacy of EG-1962 compared to oral nimodipine. The primary endpoint is the proportion of subjects with favorable outcome (6–8) on the Extended Glasgow Outcome Scale assessed 90 days after aSAH. The secondary endpoint is the proportion of subjects with favorable outcome on the Montreal Cognitive Assessment 90 days after aSAH. Data on safety, rescue therapy, delayed cerebral infarction, and health economics will be collected. Trail registration NCT02790632.

The purpose of this study was to examine whether the combination of high-intensity interval training (HIIT) and post-exercise protein supplementation would improve cardiovascular outcomes in individuals with T2D.In a double-blind controlled trial, fifty-three adults with T2D (free of CVD and not on exogenous insulin) were randomized to 12weeks of cardio and resistance-based HIIT (4-10×1min at 90% maximal heart rate) with post-exercise milk, milk-protein, or placebo supplementation, thrice weekly. Before and after, carotid and femoral artery intima media thickness (IMT) and femoral flow profiles were assessed using high-resolution ultrasound. Central and peripheral arterial stiffness were assessed by pulse wave velocity (PWV), and resting and maximal heart rate rates were measured.After 12weeks of HIIT femoral IMT (Pre: 0.84±0.21mm vs. Post: 0.81±0.16mm, p=0.03), carotid-femoral PWV (Pre: 10.1±3.2m/s vs. Post: 8.6±1.8m/s, p0.01) and resting heart rate (Pre: 70.4±10.8bpm vs. Post: 67.8±8.6 bpm, p=0.01) were all significantly lower. There were no differences between nutrition groups (all significant main effects of time) for all outcomes.HIIT reduces femoral IMT, arterial stiffness and resting heart rate in individuals with T2D. The addition of post-exercise milk or protein to HIIT did not have additive effects for improving cardiovascular outcomes in the present study. Taken together, HIIT alone may be an effective means to reduce the burden of cardiovascular complications in T2D.