Carnosine supplementation improves glucose control in adults with pre-diabetes and type 2 diabetes: A randomised controlled trial.

BACKGROUND AND AIMS: Type 2 diabetes (T2DM) is a major cause of morbidity and mortality globally. Carnosine, a naturally occurring dipeptide, has anti-inflammatory, antioxidant, and anti-glycating effects, with preliminary evidence suggesting it may improve important chronic disease risk factors in adults with cardiometabolic conditions. METHODS AND RESULTS: In this randomised controlled trial, 43 adults (30%F) living with prediabetes or T2DM consumed carnosine (2 g) or a matching placebo daily for 14 weeks to evaluate its effect on glucose metabolism assessed via a 2-h 75 g oral glucose tolerance test. Secondary outcomes included body composition analysis by dual energy x-ray absorptiometry (DEXA), calf muscle density by pQCT, and anthropometry. Carnosine supplementation decreased blood glucose at 90 min (-1.31 mmol/L; p = 0.02) and 120 min (-1.60 mmol/L, p = 0.02) and total glucose area under the curve (-3.30 mmol/L; p = 0.04) following an oral glucose tolerance test. There were no additional changes in secondary outcomes. The carnosine group results remained significant before and after adjustment for age, sex, and change in weight (all>0.05), and in further sensitivity analyses accounting for missing data. There were no significant changes in insulin levels. CONCLUSION: This study provides preliminary support for larger trials evaluating carnosine as a potential treatment for prediabetes and the initial stages of T2DM. Likely mechanisms may include changes to hepatic glucose output explaining the observed reduction in blood glucose without changes in insulin secretion following carnosine supplementation.

Patient flow in emergency departments: a comprehensive umbrella review of solutions and challenges across the health system.

BACKGROUND: Globally, emergency departments (EDs) are overcrowded and unable to meet an ever-increasing demand for care. The aim of this study is to comprehensively review and synthesise literature on potential solutions and challenges throughout the entire health system, focusing on ED patient flow. METHODS: An umbrella review was conducted to comprehensively summarise and synthesise the available evidence from multiple research syntheses. A comprehensive search strategy was employed in four databases alongside government or organisational websites in March 2023. Gray literature and reports were also searched. Quality was assessed using the JBI critical appraisal checklist for systematic reviews and research syntheses. We summarised and classified findings using qualitative synthesis, the Population-Capacity-Process (PCP) model, and the input/throughput/output (I/T/O) model of ED patient flow and synthesised intervention outcomes based on the Quadruple Aim framework. RESULTS: The search strategy yielded 1263 articles, of which 39 were included in the umbrella review. Patient flow interventions were categorised into human factors, management-organisation interventions, and infrastructure and mapped to the relevant component of the patient journey from pre-ED to post-ED interventions. Most interventions had mixed or quadruple nonsignificant outcomes. The majority of interventions for enhancing ED patient flow were primarily related to the 'within-ED' phase of the patient journey. Fewer interventions were identified for the 'post-ED' phase (acute inpatient transfer, subacute inpatient transfer, hospital at home, discharge home, or residential care) and the 'pre-ED' phase. The intervention outcomes were aligned with the aim (QAIM), which aims to improve patient care experience, enhance population health, optimise efficiency, and enhance staff satisfaction. CONCLUSIONS: This study found that there was a wide range of interventions used to address patient flow, but the effectiveness of these interventions varied, and most interventions were focused on the ED. Interventions for the remainder of the patient journey were largely neglected. The metrics reported were mainly focused on efficiency measures rather than addressing all quadrants of the quadruple aim. Further research is needed to investigate and enhance the effectiveness of interventions outside the ED in improving ED patient flow. It is essential to develop interventions that relate to all three phases of patient flow: pre-ED, within-ED, and post-ED.

Dietary Total Antioxidant Capacity and Odds of Breast Cancer: A Case-Control Study.

Breast cancer (BC) is the most frequently diagnosed female cancer worldwide. It has been shown that oxidative stress can contribute to cancer development. Therefore, we investigated the association between dietary total antioxidant capacity (TAC) and breast cancer risk in a case-control study. This study was conducted on 136 newly diagnosed breast cancer patients and 272 hospitalized controls in Tehran, Iran. Participant habitual diet was obtained using a 168-item validated food frequency questionnaire. Dietary TAC scores were computed using two different methods: the dietary ferric reducing antioxidant potential (FRAP) method and oxygen radical scavenging capacity (ORAC). The association between dietary TAC and breast cancer risk was estimated by logistic regression. The score of DTAC calculated by ORAC method was associated with lower odds of BC, especially among premenopausal women. However, this association was not significant after controlling potential confounders (ORAC: OR Q4-Q1 = 1.01, 95% CI = 0.42-2.44, p-trend = 0.96). Estimation of DTAC by FRAP method was not associated with the risk of BC (FRAP: OR Q4-Q1 = 1.04, 95% CI = 0.53-2.05, p-trend = 0.8). There were no association detected based on menopausal status. In this study, dietary TAC was not significantly related to the odds of breast cancer.

Liver-expressed antimicrobial peptide 2 is associated with improved pancreatic insulin secretion in adults with overweight and obesity.

AIMS: To examine association of liver-expressed antimicrobial peptide 2 (LEAP2), an endogenous ghrelin antagonist with anorexiant effects, to key cardiometabolic risk factors in people with overweight and obesity. METHODS: In this cross-sectional study, we sought to identify associations between LEAP2 levels and cardiometabolic risk factors, including body composition (dual X-ray absorptiometry), insulin and glucose metabolism (oral and intravenous glucose tolerance tests and hyperinsulinaemic-euglycaemic clamps), plasma lipids and inflammation markers (ELISA and multiplex assays). RESULTS: In 65 participants with overweight or obesity (63.1% male, mean age 31.3 ± 8.5 years), LEAP2 levels were associated with total body fat, but not with body mass index or waist-hip ratio in both univariable and age- and sex-adjusted models (P < 0.05). Higher LEAP2 level was also positively associated with higher insulin secretion in univariable (P = 0.047) and multivariable models adjusted for age, sex and body fat (P = 0.03), but not with fasting glucose levels (P ≥ 0.05). Higher LEAP2 levels were associated insulin resistance (P = 0.07) after adjustment for age and sex, but the association disappeared after an additional adjustment for body fat (P = 0.2). There was an inverse association between LEAP2 levels and nuclear factor kappa-B (NFκB) activity in the peripheral blood mononuclear cells in age-, sex- and body fat-adjusted models (P = 0.04). There were no associations with cardiovascular risk factors (lipids, blood pressure) or other inflammation markers. CONCLUSIONS: These results provide important insights into the association between LEAP2 and cardiometabolic health in a high-risk population of individuals with overweight and obesity. This is a first report of an association between LEAP2 and insulin secretion, insulin sensitivity and NFκB activity. LEAP2 may represent an important potential therapeutic target to promote insulin secretion in people with type 2 diabetes and obesity.

High cereal fibre but not total fibre is associated with a lower risk of type 2 diabetes: Evidence from the Melbourne Collaborative Cohort Study.

AIM: To assess the associations of total dietary fibre and fibre from different food sources (ie, cereal, fruit and vegetables) with the risk of diabetes. MATERIALS AND METHODS: The Melbourne Collaborative Cohort Study enrolled 41 513 participants aged 40 to 69 years from 1990 to 1994. The first and second follow-ups were conducted in 1994 to 1998 and 2003 to 2007, respectively. Self-reported diabetes incidence was recorded at both follow-ups. We analysed data from 39 185 participants, with a mean follow-up of 13.8 years. The relationships between dietary fibre intake (total, fruit, vegetable and cereal fibre) and the incidence of diabetes were assessed using modified Poisson regression, adjusted for dietary, lifestyle, obesity, socioeconomic and other possible confounders. Fibre intake was categorized into quintiles. RESULTS: At total of 1989 incident cases were identified over both follow-up surveys. Total fibre intake was not associated with diabetes risk. Higher intake of cereal fibre (P for trend = 0.003), but not fruit (P for trend = 0.3) and vegetable fibre (P for trend = 0.5), was protective against diabetes. For cereal fibre, quintile 5 versus quintile 1 showed a 25% reduction in diabetes risk (incidence risk ratio [IRR] 0.75, 95% confidence interval [CI] 0.63-0.88). For fruit fibre, only quintile 2 versus quintile 1 showed a 16% risk reduction (IRR 0.84, 95% CI 0.73-0.96). Adjustment for body mass index (BMI) and waist-to-hip ratio eliminated the association and mediation analysis showed that BMI mediated 36% of the relationship between fibre and diabetes. CONCLUSION: Intake of cereal fibre and, to a lesser extent, fruit fibre, may reduce the risk of diabetes, while total fibre showed no association. Our data suggest that specific recommendations regarding dietary fibre intake may be needed to prevent diabetes.

The effects of probiotic and synbiotic supplementation on inflammation, oxidative stress, and circulating adiponectin and leptin concentration in subjects with prediabetes and type 2 diabetes mellitus: a GRADE-assessed systematic review, meta-analysis, and meta-regression of randomized clinical trials.

PURPOSE: Probiotics or synbiotics consumption have been suggested to reduce the risk of cardiovascular disease (CVD) through a decline in inflammation and oxidative stress, however, the results from studies are conflicting. This study filled this knowledge gap by evaluating randomized controlled trials (RCTs) investigating probiotics or synbiotics intake on adipokines, inflammation, and oxidative stress in patients with prediabetes and type-2 diabetes mellitus (T2DM). METHODS: We systematically did search up to March 2022 in PubMed/Medline, Scopus, ISI Web of Science, and Cochrane library. A random-effect model was applied to estimate the weighted mean difference (WMD) and 95% confidence interval (95% CI) for each outcome. RESULTS: A total of 32 RCTs were included in the meta-analysis. This intervention led to a significant decrease in levels of C-reactive protein (CRP) (WMD - 0.62 mg/l; 95% CI - 0.80, - 0.44; p < 0.001), tumor necrosis factor-α (TNF-α) (WMD - 0.27 pg/ml; 95% CI - 0.44, - 0.10; p = 0.002) and malondialdehyde (MDA) (WMD - 0.51 µmol/l; 95% CI - 0.73, - 0.30; p < 0.001), and also a significant increase in levels of glutathione (GSH) (WMD 69.80 µmol/l; 95% CI 33.65, 105.95; p < 0.001), total antioxidant capacity (TAC) (WMD 73.59 mmol/l; 95% CI 33.24, 113.95; p < 0.001) and nitric oxide (NO) (WMD 7.49 µmol/l; 95% CI 3.12, 11.86; p = 0.001), without significant alterations in interleukin-6 (IL-6) and adipokines levels. CONCLUSION: A consumption of probiotics or synbiotics could be a useful intervention to improve cardiometabolic outcomes through a reduced inflammation and oxidative stress in patients with prediabetes and T2DM.

Vitamin D supplementation and exercise for improving physical function, body composition and metabolic health in overweight or obese older adults with vitamin D deficiency: a pilot randomized, double-blind, placebo-controlled trial.

PURPOSE: Vitamin D supplementation may have non-skeletal health benefits and enhance exercise responsiveness, particularly in those with low vitamin D levels. We determined whether, compared with placebo, vitamin D supplementation taken prior to and during a 12-week exercise program improves physical function, body composition or metabolic health, in overweight and obese older adults with vitamin D deficiency. METHODS: Fifty overweight or obese older adults (mean ± SD age: 60 ± 6 years; BMI 30.6 ± 5.7 kg/m2) with vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] < 50 nmol/L) were recruited. Participants were randomly allocated to receive either vitamin D3 (4000 IU/day) or matching placebo for 24 weeks. Between weeks 12 and 24, all participants completed multi-modal exercise three days per week while continuing with vitamin D/placebo. Mean changes in physical function (primary outcome: gait speed), body composition and biochemical parameters at weeks 12 and 24 were compared between groups. RESULTS: Vitamin D supplementation, with or without exercise, had no effect on gait speed. From baseline to week 12, vitamin D supplementation increased serum 25(OH)D levels (placebo: 2.5 ± 14.7 nmol/L; treatment: 43.4 ± 18.4 nmol/L; P < 0.001) and reduced stair climb times (placebo: 0.3 ± 1.0 s; treatment: - 0.2 ± 1.0 s; P = 0.046). From 12 to 24 weeks, vitamin D supplementation combined with exercise decreased waist circumference (placebo: 1.3 ± 7.3 cm; treatment: - 3.0 ± 6.1 cm; P = 0.02) and waist-to-hip ratio (placebo: 0.01 ± 0.05; treatment: - 0.03 ± 0.05; P = 0.01) relative to placebo. Vitamin D supplementation, with or without exercise, had no effect on other physical function, body composition or metabolic health outcomes. CONCLUSION: Vitamin D supplementation had no effect on most physical function, body composition or metabolic health parameters when taken alone, or during exercise, in overweight or obese older adults with vitamin D deficiency. Vitamin D-related improvements in stair climb times and waist circumference suggest that future trials should explore the effects of vitamin D on muscle power, and its effects on body composition when combined with exercise, in populations with moderate or severe vitamin D deficiency.

Disrupting future discounting: a commentary on an underutilised psychological approach for improving adherence to diet and physical activity interventions.

Non-communicable diseases (NCD) such as CVD and type 2 diabetes mellitus are major contributors to the burden of disease. NCD are largely driven by modifiable lifestyle factors including poor diet and insufficient physical activity, and consequently, prevention is a public health priority. Although diet and physical activity levels can be improved via lifestyle interventions, long-term adherence to such interventions remains low, which limits their effectiveness. Thus, it is critical to identify the underlying mechanisms that challenge uptake and adherence to such interventions. The current commentary discusses an important, but underexplored, psychological driver of poor adherence to lifestyle interventions, namely, future discounting, which describes the tendency to prefer smaller, short-term rewards over larger, long-term rewards. For example, in the nutrition domain, future discounting refers to valuing the immediate reward of excessive intake of energy-dense, nutrient-poor, discretionary foods high in salt, sugar, and saturated fat, and insufficient intake of low-energy, nutrient-dense, whole foods such as vegetables. Prominent theoretical models propose that excessive future discounting is a major contributor to the development of unhealthy lifestyle behaviours. Furthermore, a vast body of evidence suggests that future discounting plays a key role in risk of NCD. Thus, the evidence to date supports the idea that future discounting is an important multi-behaviour target for supporting lifestyle behaviour change; however, this approach has been largely neglected in preventive health efforts. Furthermore, this commentary discusses promising techniques (e.g. Episodic Future Thinking) for disrupting future discounting to promote improved adherence to lifestyle interventions aimed at reducing NCD risk.

Estimating the benefits of obesity prevention on productivity: an Australian perspective.

BACKGROUND/OBJECTIVES: Obesity poses one of the biggest public health challenges globally. In addition to the high costs of obesity to the healthcare system, obesity also impacts work productivity. We aimed to estimate the benefits of preventing obesity in terms of years of life, productivity-adjusted life years (PALYs) and associated costs over 10 years. SUBJECTS/METHODS: Dynamic life table models were constructed to estimate years of life and PALYs saved if all new cases of obesity were prevented among Australians aged 20-69 years from 2021 to 2030. Life tables were sex specific and the population was classified into normal weight, overweight and obese. The model simulation was first undertaken assuming currently observed age-specific incidences of obesity, and then repeated assuming all new cases of obesity were reduced by 2 and 5%. The differences in outcomes (years of life, PALYs, and costs) between the two modelled outputs reflected the potential benefits that could be achieved through obesity prevention. All outcomes were discounted by 5% per annum. RESULTS: Over the next 10 years, 132 million years of life and 81 million PALYs would be lived by Australians aged 20-69 years, contributing AU$17.0 trillion to the Australian economy in terms of GDP. A 5% reduction in new cases of obesity led to a gain of 663 years of life and 1229 PALYs, equivalent to AU$262 million in GDP. CONCLUSIONS: Prevention of obesity is projected to result in substantial economic gains due to improved health and productivity. This further emphasises the need for public health prevention strategies to reduce this growing epidemic.

Beneficial effects of probiotic and synbiotic supplementation on some cardiovascular risk factors among individuals with prediabetes and type 2 diabetes mellitus: A grade-assessed systematic review, meta-analysis, and meta-regression of randomized clinical trials.

Previous studies suggested that probiotics/synbiotics administration exerts some beneficial effects on cardiometabolic risk factors. However, the results from trials have been inconsistent. This study aimed to identify the impact of probiotic and synbiotic supplements on cardiovascular health factors in patients with type 2 diabetes mellitus (T2DM) and prediabetes We searched PubMed/MEDLINE, Web of Science, and Scopus up to February 2022 to identify eligible RCTs. Estimating 95 % confidence (CI) and the weighted mean difference (WMD) for weight, body mass index (BMI), waist circumferences (WC), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP), the random-effects model was used. In the current meta-analysis, 54 RCTs were included. With the probiotic/synbiotics intervention, several parameters changed significantly, including weight (WMD: -0.38, 95 % CI: -0.63 to -0.12 Kg), TG (WMD: -19.08, 95 % CI: -27.65 to -10.51 mg/dl), TC (WMD: -10.46, 95 % CI: -15.19 to -5.72 mg/dl), LDL-C (WMD: -4.87, 95 % CI: -7.65 to -2.09 mg/dl), HDL-C (WMD: -2.70, 95 % CI: 1.33-4.07 mg/dl), SBP (WMD: -3.81, 95 % CI: -6.24 to -1.38 mmHg), and DBP (WMD: -2.01, 95 % CI: -3.12 to -0.91 mmHg). In the subgroup analysis, probiotics/synbiotics supplementation resulted in a greater change in lipid profile components in T2DM patients. Weight and BMI reduced only after synbiotic supplementation. We found that the administration of probiotics and synbiotics had beneficial effects on lipid profiles, anthropometric indices, and blood pressure in individuals with T2DM.

Probiotics and synbiotics supplementation improve glycemic control parameters in subjects with prediabetes and type 2 diabetes mellitus: A GRADE-assessed systematic review, meta-analysis, and meta-regression of randomized clinical trials.

Probiotics and synbiotics have been proposed to exhibit an important role in glucose homeostasis and maintain the balance of the gut microbiota. However, clinical trials have shown mixed findings. Therefore, we conducted a systematic review and meta-analysis of all eligible randomized controlled trials (RCTs) examining the effects of probiotics and synbiotics intake on glycemic outcomes among individuals with prediabetes and type 2 diabetes mellitus (T2DM). The PubMed/Medline, Scopus, ISI Web of Science, and Cochrane library were searched up to March 2022 for published RCTs exploring the effectiveness of probiotics and synbiotics compared to control on glycemic outcomes. The random-effects model was applied in order to the estimation of 95 % confidence interval (CI) and the weighted mean difference (WMD) for each endpoint. Meta-analysis of forty-six RCTs (3067 participants) showed that probiotics and synbiotics supplementation significantly reduced fasting plasma glucose (FPG) (weighted mean difference (WMD): - 11.18 mg/dl, 95 % CI: - 13.60, - 8.75, p ˂0.001), fasting insulin serum level (WMD: -1.23 µIU/ml, 95 % CI: -1.76, -0.71, p ˂0.001), hemoglobin A1c (HbA1c) (WMD: -0.35 %, 95 % CI: -0.44, -0.26, p˂0.001), and homeostatic model assessment of insulin resistance (HOMA-IR) (WMD: -0.87, 95 % CI: -1.09, -0.65, p˂0.001). Additionally, probiotics and synbiotics intake resulted in an increase in values of quantitative insulin-sensitivity check index (QUICKI) (WMD: 0.01, 95 % CI: 0.00, 0.01, p˂0.001). However, probiotics and synbiotics consumption did not change glucose values following oral glucose tolerance test (OGTT). Our findings suggest that probiotic and synbiotic intake has favorable effects on glycemic profile in patients with prediabetes and T2DM.

Carnosine as a potential therapeutic for the management of peripheral vascular disease.

AIMS: To evaluate the potential role of carnosine in the management of peripheral vascular disease. DATA SYNTHESIS: Peripheral vascular disease is growing in its burden and impact; however it is currently under researched, and there are a lack of strong, non-invasive therapeutic options for the clinicians. Carnosine is a dipeptide stored particularly in muscle and brain tissue, which exhibits a wide range of physiological activities, which may be beneficial as an adjunct treatment for peripheral vascular disease. Carnosine's strong anti-inflammatory, antioxidant and antiglycating actions may aid in the prevention of plaque formation, through protective actions on the vascular endothelium, and the inhibition of foam cells. Carnosine may also improve angiogenesis, exercise performance and vasodilatory response, while protecting from ischemic tissue injury. CONCLUSIONS: Carnosine may have a role as an adjunct treatment for peripheral vascular disease alongside typical exercise and surgical interventions, and may be used in high risk individuals to aid in the prevention of atherogenesis. CLINICAL RECOMMENDATION: This review identifies a beneficial role for carnosine supplementation in the management of patients with peripheral vascular disease, in conjunction with exercise and revascularization. Carnosine as a supplement is safe, and associated with a host of beneficial effects in peripheral vascular disease and its key risk factors.

The association between major dietary patterns and severe mental disorders symptoms among a large sample of adults living in central Iran: Baseline data of YaHS-TAMYZ cohort study.

BACKGROUND: The diet's role in developing psychological disorders has been considered by researchers in recent years. OBJECTIVE: To examine the association between major dietary patterns and severe mental disorders symptoms in a large sample of adults living in Yazd city, central Iran. METHODS: This cross-sectional study used the baseline data of a population-based cohort study (Yazd Health study: YaHS). Dietary intakes were assessed by a multiple-choice semi-quantitative food frequency questionnaire (FFQ, Yazd nutrition survey called TAMYZ). Psychological assessments were also done by using the depression, anxiety, and stress scale-21 (DASS-21) questionnaire. Major dietary patterns were identified using principal component analysis (PCA). Analysis of covariance (ANCOVA) and logistic regression analyses were used to evaluate the relationship between dietary patterns and mental disorders symptoms. RESULTS: A total of 7574 adults were included in the current analysis. Four major dietary patterns were identified: "Sugar and Fats", "Processed Meats and Fish", "Fruits" and "Vegetables and Red Meat". After adjustment for all confounding variables, participants in the fifth quintile of "Fruits" dietary pattern which was highly correlated with dried fruits, canned fruits, fruit juice, olive, hydrogenated fats and fruits intake, had a lower odds of severe depression (OR=0.61, 95% CI: 0.45-0.81, p for trend=0.057), anxiety (OR=0.64, 95% CI: 0.50-0.80, p for trend=0.007), and stress, (OR=0.45, 95% CI: 0.30-0.68, p for trend=0.081). CONCLUSIONS: The intake of a dietary pattern high in dried fruits, canned fruits, fruit juice, olive, hydrogenated fats, and fruits might be inversely associated with depression, anxiety, and stress symptoms. Future prospective studies are needed to warrant this finding.

Nurses' harm prevention practices during admission of an older person to the hospital: A multi-method qualitative study.

BACKGROUND: Nurses' harm prevention practices during the admission of older persons to hospital have important consequences for patient safety, preventable patient harm and length of hospital stay. Novel solutions are needed to assist nurses to balance complexity, high workload burden and patient safety during admission processes. AIM: Explore the nurses' experiences of harm prevention practices during the admission of an older person to the hospital. DESIGN: A multi-method qualitative study informed by frameworks of behaviour change and human-centred co-design. METHODS: The purposive sample included 44 nurses, 5 clinicians from other disciplines and 3 consumers recruited from five general medicine wards across three hospitals of a large public health service in metropolitan Melbourne, Australia. Data were collected over 12 h of naturalistic observations of nurses during eight patient admissions, and during four participatory human-centred co-design workshops between August 2019 and January 2020. Observation, field notes and workshop artefact data were integrated for qualitative content and thematic analysis. RESULTS: Analysis revealed a 5-step journey map, with a temporal logic, that captured nurses' experiences, as well as the enablers and barriers to harm prevention practices when admitting an older person to the hospital. The consensus was reached on three priority features to assist nurses to implement harm prevention practices when they admit an older person to the hospital: (1) prioritize important care; (2) tailor care to the individual and (3) see the big picture for the patient. CONCLUSION: The novel research approach identified five steps in nurses' activities and harm prevention practices during admission of an older person to the hospital, and key features for a solution to assist nurses to keep patients safe. The findings provide the foundation for further research to develop interventions to assist nurses to manage high workloads during this complex activity.

Global, Regional, and Country-Specific Lifetime Risks of Stroke, 1990 and 2016.

BACKGROUND: The lifetime risk of stroke has been calculated in a limited number of selected populations. We sought to estimate the lifetime risk of stroke at the regional, country, and global level using data from a comprehensive study of the prevalence of major diseases. METHODS: We used the Global Burden of Disease (GBD) Study 2016 estimates of stroke incidence and the competing risks of death from any cause other than stroke to calculate the cumulative lifetime risks of first stroke, ischemic stroke, or hemorrhagic stroke among adults 25 years of age or older. Estimates of the lifetime risks in the years 1990 and 2016 were compared. Countries were categorized into quintiles of the sociodemographic index (SDI) used in the GBD Study, and the risks were compared across quintiles. Comparisons were made with the use of point estimates and uncertainty intervals representing the 2.5th and 97.5th percentiles around the estimate. RESULTS: The estimated global lifetime risk of stroke from the age of 25 years onward was 24.9% (95% uncertainty interval, 23.5 to 26.2); the risk among men was 24.7% (95% uncertainty interval, 23.3 to 26.0), and the risk among women was 25.1% (95% uncertainty interval, 23.7 to 26.5). The risk of ischemic stroke was 18.3%, and the risk of hemorrhagic stroke was 8.2%. In high-SDI, high-middle-SDI, and low-SDI countries, the estimated lifetime risk of stroke was 23.5%, 31.1% (highest risk), and 13.2% (lowest risk), respectively; the 95% uncertainty intervals did not overlap between these categories. The highest estimated lifetime risks of stroke according to GBD region were in East Asia (38.8%), Central Europe (31.7%), and Eastern Europe (31.6%), and the lowest risk was in eastern sub-Saharan Africa (11.8%). The mean global lifetime risk of stroke increased from 22.8% in 1990 to 24.9% in 2016, a relative increase of 8.9% (95% uncertainty interval, 6.2 to 11.5); the competing risk of death from any cause other than stroke was considered in this calculation. CONCLUSIONS: In 2016, the global lifetime risk of stroke from the age of 25 years onward was approximately 25% among both men and women. There was geographic variation in the lifetime risk of stroke, with the highest risks in East Asia, Central Europe, and Eastern Europe. (Funded by the Bill and Melinda Gates Foundation.).

Potentially inappropriate prescribing and its associations with health-related and system-related outcomes in hospitalised older adults: A systematic review and meta-analysis.

AIMS: To synthesise associations of potentially inappropriate prescribing (PIP) with health-related and system-related outcomes in inpatient hospital settings. METHODS: Six electronic databases were searched: Medline Complete, EMBASE, CINAHL, PyscInfo, IPA and Cochrane library. Studies published between 1 January 1991 and 31 January 2021 investigating associations between PIP and health-related and system-related outcomes of older adults in hospital settings, were included. A random effects model was employed using the generic inverse variance method to pool risk estimates. RESULTS: Overall, 63 studies were included. Pooled risk estimates did not show a significant association with all-cause mortality (adjusted odds ratio [AOR] 1.10, 95% confidence interval [CI] 0.90-1.36; adjusted hazard ratio 1.02, 83% CI 0.90-1.16), and hospital readmission (AOR 1.11, 95% CI 0.76-1.63; adjusted hazard ratio 1.02, 95% CI 0.89-1.18). PIP was associated with 91%, 60% and 26% increased odds of adverse drug event-related hospital admissions (AOR 1.91, 95% CI 1.21-3.01), functional decline (AOR 1.60, 95% CI 1.28-2.01), and adverse drug reactions and adverse drug events (AOR 1.26, 95% CI 1.11-1.43), respectively. PIP was associated with falls (2/2 studies). The impact of PIP on emergency department visits, length of stay, and health-related quality of life was inconclusive. Economic cost of PIP reported in 3 studies, comprised various cost estimation methods. CONCLUSIONS: PIP was significantly associated with a range of health-related and system-related outcomes. It is important to optimise older adults' prescriptions to facilitate improved outcomes of care.

Diet scores and prediction of general and abdominal obesity in the Melbourne collaborative cohort study.

OBJECTIVE: To ascertain which of the Alternative Healthy Eating Index (AHEI) 2010, Dietary Inflammatory Index (DII®) and Mediterranean Diet Score (MDS) best predicted BMI and waist-to-hip circumference ratio (WHR). DESIGN: Body size was measured at baseline (1990-1994) and in 2003-2007. Diet was assessed at baseline using a FFQ, along with age, sex, socio-economic status, smoking, alcohol drinking, physical activity and country of birth. Regression coefficients and 95 % CI for the association of baseline dietary scores with follow-up BMI and WHR were generated using multivariable linear regression, adjusting for baseline body size, confounders and energy intake. SETTING: Population-based cohort in Melbourne, Australia. PARTICIPANTS: Included were data from 11 030 men and 16 774 women aged 40-69 years at baseline. RESULTS: Median (IQR) follow-up was 11·6 (10·7-12·8) years. BMI and WHR at follow-up were associated with baseline DII® (Q5 v. Q1 (BMI 0·41, 95 % CI 0·21, 0·61) and WHR 0·009, 95 % CI 0·006, 0·013)) and AHEI (Q5 v. Q1 (BMI -0·51, 95 % CI -0·68, -0·35) and WHR -0·011, 95 % CI -0·013, -0·008)). WHR, but not BMI, at follow-up was associated with baseline MDS (Group 3 most Mediterranean v. G1 (BMI -0·05, 95 % CI -0·23, 0·13) and WHR -0·004, 95 % CI -0·007, -0·001)). Based on Akaike's Information Criterion and Bayesian Information Criterion statistics, AHEI was a stronger predictor of body size than the other diet scores. CONCLUSIONS: Poor quality or pro-inflammatory diets predicted overall and central obesity. The AHEI may provide the best way to assess the obesogenic potential of diet.

Anti-Cancer Effects of Carnosine-A Dipeptide Molecule.

BACKGROUND: Carnosine is a dipeptide molecule (ß-alanyl-l-histidine) with anti-inflammatory, antioxidant, anti-glycation, and chelating properties. It is used in exercise physiology as a food supplement to increase performance; however, in vitro evidence suggests that carnosine may exhibit anti-cancer properties. METHODS: In this study, we investigated the effect of carnosine on breast, ovarian, colon, and leukemic cancer cell proliferation. We further examined U937 promonocytic, human myeloid leukemia cell phenotype, gene expression, and cytokine secretion to determine if these are linked to carnosine's anti-proliferative properties. RESULTS: Carnosine (1) inhibits breast, ovarian, colon, and leukemic cancer cell proliferation; (2) upregulates expression of pro-inflammatory molecules; (3) modulates cytokine secretion; and (4) alters U937 differentiation and phenotype. CONCLUSION: These effects may have implications for a role for carnosine in anti-cancer therapy.

Are Lifestyle Interventions to Reduce Excessive Gestational Weight Gain Cost Effective? A Systematic Review.

PURPOSE OF REVIEW: Lifestyle interventions (such as diet and physical activity) successfully limit excessive gestational weight gain and can reduce some adverse maternal events; however, benefit is variable and cost-effectiveness remains unclear. We aimed to review published cost-effectiveness analyses of lifestyle interventions compared with usual care on clinically relevant outcome measures. Five international and six grey-literature databases were searched from 2007 to 2018. Articles were assessed for quality of reporting. Data were extracted from healthcare and societal perspectives. Costs were adapted to the common currencies of Australia and the United Kingdom by adjusting for resource utilization, healthcare purchase price and changes in costs over time. Included studies were economic analyses of lifestyle interventions aiming to limit weight-gain during pregnancy and/or reduce risk of gestational diabetes, for women with a BMI of 25 or greater in pre- or early-pregnancy. RECENT FINDINGS: Of the 538 articles identified, six were retained for review: one modelling study and five studies in which an economic analysis was performed alongside a randomized-controlled trial. Outcome measures included infant birth-weight, fasting glucose, insulin resistance, gestational weight-gain, infant respiratory distress syndrome, perceived health, cost per case of adverse outcome avoided and quality-adjusted life years (QALYs). Interventions were cost-effective in only one study. Although many studies have investigated the efficacy of lifestyle interventions in pregnancy, few have included cost-effectiveness analyses. Where cost-effectiveness studies were undertaken, results were inconsistent. Secondary meta-analysis, taxonomy and framework research is now required to determine the effective components of lifestyle interventions and to guide future cost-effectiveness analyses.

Vitamin D supplementation increases adipokine concentrations in overweight or obese adults.

PURPOSE: Vitamin D regulates adipokine production in vitro; however, clinical trials have been inconclusive. We conducted secondary analyses of a randomized controlled trial to examine whether vitamin D supplementation improves adipokine concentrations in overweight/obese and vitamin D-deficient adults. METHODS: Sixty-five individuals with a BMI ≥ 25 kg/m2 and 25-hydroxyvitamin D (25(OH)D) ≤ 50 nmol/L were randomized to oral cholecalciferol (100,000 IU single bolus followed by 4,000 IU daily) or matching placebo for 16 weeks. We measured BMI, waist-to-hip ratio, % body fat (dual X-ray absorptiometry), serum 25(OH)D (chemiluminescent immunoassay) and total adiponectin, leptin, resistin, and adipsin concentrations (multiplex assay; flow cytometry). Sun exposure, physical activity, and diet were assessed using questionnaires. RESULTS: Fifty-four participants completed the study (35M/19F; mean age = 31.9 ± 8.5 years; BMI = 30.9 ± 4.4 kg/m2). After 16 weeks, vitamin D supplementation increased 25(OH)D concentrations compared with placebo (57.0 ± 21.3 versus 1.9 ± 15.1 nmol/L, p < 0.001). There were no differences between groups for changes in adiponectin, leptin, resistin, or adipsin in unadjusted analyses (all p > 0.05). After adjustment for baseline values, season, sun exposure, and dietary vitamin D intake, there was a greater increase in adiponectin (ß[95%CI] = 13.7[2.0, 25.5], p = 0.02) and leptin (ß[95%CI] = 22.3[3.8, 40.9], p = 0.02) in the vitamin D group compared with placebo. Results remained significant after additional adjustment for age, sex, and % body fat (p < 0.02). CONCLUSIONS: Vitamin D may increase adiponectin and leptin concentrations in overweight/obese and vitamin D-deficient adults. Further studies are needed to clarify the molecular interactions between vitamin D and adipokines and the clinical implications of these interactions in the context of obesity. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT02112721.