Relationship between blood lead concentration and nutritional status among Malay primary school children in Kuala Lumpur, Malaysia.

A cross-sectional study was conducted to identify the relationship between blood lead concentration and nutritional status among primary school children in Kuala Lumpur. A total of 225 Malay students, 113 male and 112 female, aged 6.3 to 9.8 were selected through a stratified random sampling method. The random blood samples were collected and blood lead concentration was measured by a Graphite Furnace Atomic Absorption Spectrophotometer. The nutrient intake was determined by the 24-hour Dietary Recall method and Food Frequency Questionnaire. An anthropometric assessment was reported according to growth indices (z-scores of weight-for-age, height-for-age, and weight-for-height). The mean blood lead concentration was low (3.4 ± 1.91 ug/dL) and was significantly different between gender. Only 14.7% of the respondents fulfilled the daily energy requirement. The protein and iron intakes were adequate for a majority of the children. However, 34.7% of the total children showed inadequate intake of calcium. The energy, protein, fat and carbohydrate intakes were significantly different by gender, that is, males had better intake than females. Majority of respondents had normal mean z-score of growth indices. Ten percent of the respondents were underweight, 2.8% wasted and 5.4% stunted. Multiple linear regression showed inverse significant relationships between blood lead concentration with children's age (β= -0.647, p<0.001) and per capita income (β=-0.001, p=0.018). There were inverse significant relationships between blood lead concentration with children's age (β=-0.877, p=0.001) and calcium intake (β= -0.011,p=0.014) and positive significant relationship with weight-for-height (β=0.326, p=0.041) among those with inadequate calcium intake. Among children with inadequate energy intake, children's age (β= -0.621, p< 0.001), per capita income (β= -0.001,p=0.025) and protein intake (β= -0.019, p=0.027) were inversely and significantly related with blood lead concentration. In conclusion, nutritional status might affect the children's absorption of lead and further investigation is required for confirmation

Effects of canagliflozin on heart failure outcomes associated with preserved and reduced ejection fraction in type 2 diabetes: results from the CANVAS Program

Patients with type 2 diabetes mellitus are at high risk of developing heart failure (HF).1 Sodium glucose co-transporter 2 (SGLT2) inhibitors have been demonstrated, in large scale trials, to reduce the risk of HF events in patients with type 2 diabetes deemed to be at high risk based on established cardiovascular disease or multiple risk factors.2-4 However, it is unclear whether benefits are experienced across the broad spectrum of HF patients that includes those with preserved (HFpEF) as well as reduced ejection fraction (HFrEF)

Biomarkers in ringed seals reveal recent onset of borealization in the high- compared to the mid-latitude Canadian Arctic

This work resulted from the ARISE project (NE/P006035/1), part of the Changing Arctic Ocean program, funded by the UKRI Natural Environment Research Council (NERC).Warming of the Arctic has resulted in environmental and ecological changes, termed borealization, leading to the northward shift of temperate species. Borealization has occurred across all trophic levels, altering the structure of the food web. The onset and rate of borealization likely varies with latitude, depending on local warming and advection of warmer water into the Arctic. In order to assess latitudinal trends in food web structure in the Arctic, we analyzed stable nitrogen isotopes of specific amino acids alongside bulk stable carbon isotopes in ringed seal muscle tissue from the Canadian Arctic Archipelago (high-Arctic) and Southern Baffin Bay (mid-Arctic) from 1990 to 2016. Our results indicate a shift in food web structure in the high-Arctic that has occurred more recently when compared with the mid-Arctic. Specifically, over the past 25 years, the trophic position of ringed seals from the mid-Arctic was largely constant, whereas the trophic position of ringed seals decreased in the high-Arctic, reaching similar values observed in the mid-Arctic in 2015-2016. This suggests a potential shortening of the food chain length in the high-Arctic, possibly driven by changes in zooplankton communities feeding complexity in association with sea ice decline. This study identifies a temporal offset in the timing of borealization in the Canadian Arctic, resulting in different response of food webs to ecological changes, depending on latitude.Publisher PDFPeer reviewe

Reasons for hospitalizations in patients with type 2 diabetes in the CANVAS programme: A secondary analysis

Aim: To determine the reasons for hospitalizations in the CANagliflozin cardioVascular Assessment Study (CANVAS) programme and the effects of the sodium-glucose co-transporter-2 inhibitor canagliflozin on hospitalization. Materials and Methods: A secondary analysis was performed on the CANVAS programme that included 10 142 participants with type 2 diabetes randomized to canagliflozin or placebo. The primary outcome was the rate of total (first plus all recurrent) all-cause hospitalizations (ACH). Secondary outcomes were total hospitalizations categorized by the Medical Dictionary for Regulatory Activities hierarchy at the system organ class level, reported by investigators at each centre. Outcomes were assessed using negative binomial models. Results: Of the 7115 hospitalizations reported, the most common reasons were cardiac disorders (23.7%), infections and infestations (15.0%), and nervous system disorders (9.0%). The rate of total ACH was lower in the canagliflozin group (n = 5795) compared with the placebo group (n = 4347): 197.9 versus 215.8 participants per 1000 patient-years, respectively (rate ratio [RR] 0.92; 95% confidence interval [CI] 0.86, 0.98). Canagliflozin reduced the rate of total hospitalizations because of cardiac disorders (RR 0.81; 95% CI 0.75, 0.88). There was no significant difference between the canagliflozin and placebo groups in the rates of total hospitalizations because of infections and infestations (RR 0.96; 95% CI 0.86, 1.02) or nervous system disorders (RR 0.96; 95% CI 0.88, 1.05). Conclusions: In the CANVAS programme, the most common reasons for hospitalization were cardiac disorders, infections and infestations, and nervous system disorders. Canagliflozin, compared with placebo, reduced the rate of total ACH

Compound specific isotope analyses of harp seal teeth : tools for trophic ecology reconstruction

This work resulted from the ARISE project (NE/P006035/1 awarded to CM and RJ, and NE/P00623X/1 awarded to SS), part of the Changing Arctic Ocean programme, funded by the UKRI Natural Environment Research Council (NERC).As sentinels of ecosystem health, high trophic level predators integrate information through all levels of the food web. Their tissues can be used to investigate spatiotemporal variability in foraging behaviour, and with the appropriate analytical methods and tools, archived samples can be used to reconstruct past trophic interactions. Harp seal (Pagophilus groenlandicus) teeth collected in the 1990s from the Northwest Atlantic were analysed for bulk stable carbon and nitrogen isotopes (δ13Cbulk and δ15Nbulk), and compound specific stable nitrogen isotopes of amino acids (δ15NAA) for the first time. We developed a fine-scale, annual growth layer group (GLG) dentine sub-sampling method corresponding to their second and third year of life. In accordance with previous diet studies, while there was individual variability in δ15Nbulk, δ13Cbulk, and δ15NAA measurements, we did not detect significant differences in isotopic niche widths between males and females, or between GLGs. Relative trophic position was calculated as the baseline corrected δ15NAA values using trophic (glutamic acid) and source (phenylalanine and glycine) amino acids. Variability was measured between individuals in their relative trophic position, but within individual variability was low, suggesting that they fed at the same trophic level over these 2 years of life. These novel δ15NAA data may therefore suggest individual, specialist harp seal foraging behaviour in sub-adults. Our findings show that compound specific stable isotope signatures of archived, inert predator tissues can be used as tools for the retrospective reconstruction of trophic interactions on broad spatiotemporal scales.PostprintPeer reviewe

Canagliflozin and heart failure in Type 2 diabetes mellitus: results from the CANVAS Program (Canagliflozin Cardiovascular Assessment Study)

BACKGROUND : Canagliflozin is a sodium glucose cotransporter 2 inhibitor that reduces the risk of cardiovascular events. We report the effects on heart failure and cardiovascular death overall, in those with and without a baseline history of heart failure, and in other participant subgroups. METHODS : The CANVAS Program (Canagliflozin Cardiovascular Assessment Study) enrolled 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk. Participants were randomly assigned to canagliflozin or placebo and followed for a mean of 188 weeks. The primary end point for these analyses was adjudicated cardiovascular death or hospitalized heart failure. RESULTS : Participants with a history of heart failure at baseline (14.4%) were more frequently women, white, and hypertensive and had a history of prior cardiovascular disease (all P0.130), except for a possibly reduced absolute rate of events attributable to osmotic diuresis among those with a prior history of heart failure (P=0.03). CONCLUSIONS : In patients with type 2 diabetes mellitus and an elevated risk of cardiovascular disease, canagliflozin reduced the risk of cardiovascular death or hospitalized heart failure across a broad range of different patient subgroups. Benefits may be greater in those with a history of heart failure at baseline. CLINICAL TRIAL REGISTRATION : URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01032629 and NCT01989754

Mediators of the effects of canagliflozin on kidney protection in patients with type 2 diabetes

Canagliflozin reduced kidney disease progression in participants with type 2 diabetes in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program that explored potential mediators of the effects of canagliflozin on kidney outcomes. The percent mediating effect of 18 biomarkers indicative of disease was determined by comparing the hazard ratios for the effect of randomized treatment from an unadjusted model and from a model adjusting for the average post-randomization level of each biomarker. Multivariable analyses assessed the joint effects of biomarkers that mediated most strongly in univariable analyses. The kidney outcome was defined as a composite of 40% estimated glomerular filtration rate decline, end-stage kidney disease, or death due to kidney disease. Nine biomarkers (systolic blood pressure [8.9% of effect explained], urinary albumin:creatinine ratio [UACR; 23.9%], gamma glutamyltransferase [4.1%], hematocrit [51.1%], hemoglobin [41.3%], serum albumin [19.5%], erythrocytes [56.7%], serum urate [35.4%], and urine pH [7.5%]) individually mediated the effect of canagliflozin on the kidney outcome. In a parsimonious multivariable model, erythrocyte concentration, serum urate, and systolic blood pressure maximized cumulative mediation (115%). Mediating effects of UACR, but not other mediators, were highly dependent upon the baseline level of UACR: UACR mediated 42% and 7% of the effect in those with baseline UACR 30 mg/g or more and under 30 mg/g, respectively. The identified mediators support existing hypothesized mechanisms for the prevention of kidney outcomes with sodium glucose co-transporter 2 inhibitors. Thus, the disparity in mediating effects across baseline UACR subgroups suggests that the mechanism for kidney protection with canagliflozin may vary across patient subgroups

Different eGFR decline thresholds and renal effects of cnagliflozin: data from the CANVAS program

BACKGROUND: Traditionally, clinical trials evaluating effects of a new therapy with creatinine-based renal end points use doubling of serum creatinine (equivalent to a 57% eGFR reduction), requiring large sample sizes. METHODS: To assess whether eGFR declines <57% could detect canagliflozin's effects on renal outcomes, we conducted a post hoc study comparing effects of canagliflozin versus placebo on composite renal outcomes using sustained 57%, 50%, 40%, or 30% eGFR reductions in conjunction with ESKD and renal death. Because canagliflozin causes an acute reversible hemodynamic decline in eGFR, we made estimates using all eGFR values as well as estimates that excluded early measures of eGFR influenced by the acute hemodynamic effect. RESULTS: Among the 10,142 participants, 93 (0.9%), 161 (1.6%), 352 (3.5%), and 800 (7.9%) participants recorded renal outcomes on the basis of 57%, 50%, 40%, or 30% eGFR reduction, respectively, during a mean follow-up of 188 weeks. Compared with a 57% eGFR reduction (risk ratio [RR], 0.51; 95% confidence interval [95% CI], 0.34 to 0.77), the effect sizes were progressively attenuated when using 50% (RR, 0.61; 95% CI, 0.45 to 0.83), 40% (RR, 0.70; 95% CI, 0.57 to 0.86), or 30% (RR, 0.81; 95% CI, 0.71 to 0.93) eGFR reductions. In analyses that controlled for the acute hemodynamic fall in eGFR, effect sizes were comparable, regardless of whether a 57%, 50%, 40%, or 30% eGFR reduction was used. Estimated sample sizes for studies on the basis of lesser eGFR reductions were much reduced by controlling for this early hemodynamic effect. CONCLUSIONS: Declines in eGFR <57% may provide robust estimates of canagliflozin's effects on renal outcomes if the analysis controls for the drug's acute hemodynamic effect. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: CANagliflozin cardioVascular Assessment Study (CANVAS), NCT01032629 and CANVAS-R, NCT01989754

Canagliflozin for primary and secondary prevention of cardiovascular events: results from the CANVAS Program (Canagliflozin Cardiovascular Assessment Study)

BACKGROUND : Canagliflozin is a sodium glucose cotransporter 2 inhibitor that significantly reduces the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in patients with type 2 diabetes mellitus and elevated cardiovascular risk. The comparative effects among participants with and without a history of cardiovascular disease (secondary versus primary prevention) were prespecified for evaluation. METHODS : The CANVAS Program (Canagliflozin Cardiovascular Assessment Study) randomly assigned 10 142 participants with type 2 diabetes mellitus to canagliflozin or placebo. The primary prevention cohort comprised individuals ≥50 years of age with ≥2 risk factors for cardiovascular events but with no prior cardiovascular event, and the secondary prevention cohort comprised individuals ≥30 years of age with a prior cardiovascular event. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Secondary outcomes included heart failure hospitalization and a renal composite (40% reduction in estimated glomerular filtration rate, renal replacement therapy, or renal death). RESULTS : Primary prevention participants (N=3486; 34%) were younger (63 versus 64 years of age), were more often female (45% versus 31%), and had a longer duration of diabetes mellitus (14 versus 13 years) compared with secondary prevention participants (N=6656; 66%). The primary end point event rate was higher in the secondary prevention group compared with the primary prevention group (36.9 versus 15.7/1000 patient-years, P<0.001). In the total cohort, the primary end point was reduced with canagliflozin compared with placebo (26.9 versus 31.5/1000 patient-years; hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75-0.97; P<0.001 for noninferiority, P=0.02 for superiority) with no statistical evidence of heterogeneity (interaction P value=0.18) between the primary (HR, 0.98; 95% CI, 0.74-1.30) and secondary prevention (HR, 0.82; 95% CI, 0.72-0.95) cohorts. Renal outcomes (HR, 0.59; 95% CI, 0.44-0.79 versus HR, 0.63; 95% CI, 0.39-1.02; interaction P value=0.73) and heart failure hospitalization (HR, 0.68; 95% CI, 0.51-0.90 versus HR, 0.64; 95% CI, 0.35-1.15; interaction P value=0.91) were similarly reduced in the secondary and primary prevention cohorts, respectively. Lower extremity amputations were similarly increased in the secondary and primary prevention cohorts (HR, 2.07; 95% CI, 1.43-3.00 versus HR, 1.52; 95% CI, 0.70-3.29; interaction P value=0.63). CONCLUSIONS : Patients with type 2 diabetes mellitus and prior cardiovascular events had higher rates of cardiovascular outcomes compared with the primary prevention patients. Canagliflozin reduced cardiovascular and renal outcomes with no statistical evidence of heterogeneity of the treatment effect across the primary and secondary prevention groups. Additional studies will provide further insights into the effects of canagliflozin in these patient populations. CLINICAL TRIAL REGISTRATION : URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01032629 and NCT01989754