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

Effects of canagliflozin on anaemia in patients with type 2 diabetes and chronic kidney disease: a post-hoc analysis from the CREDENCE trial

Background: Sodium-glucose co-transporter 2 inhibitors might enhance erythropoiesis and increase red blood cell mass. We assessed the long-term effects of canagliflozin on anaemia-related outcomes. Methods: In a post-hoc analysis of the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, we included patients with type 2 diabetes and chronic kidney disease who were randomly assigned to treatment with canagliflozin or placebo at 690 sites in 34 countries. We assessed the effects of canagliflozin versus matched placebo on haemoglobin and haematocrit using linear mixed-effects models. The primary outcome of this post-hoc analysis was a composite outcome of investigator-reported anaemia or treatment for anaemia, which was assessed using Kaplan-Meier analysis and Cox regression models. All analyses were done by intention to treat. Findings: Between March 24, 2014, and May 5, 2017, 4401 participants were randomly assigned to receive canagliflozin (100 mg; n=2202) or placebo (n=2199). At baseline, mean haemoglobin concentration was 132·0 g/L (SD 17·7), 1599 (36%) of 4401 participants had anaemia (defined as haemoglobin <130 g/L in men or <120 g/L in women), and 33 (<1%) of 4401 participants used erythropoiesis-stimulating agents. During a median follow-up period of 2·6 years (IQR 2·1–3·1), mean haemoglobin concentration was 7·1 g/L (95% CI 6·4–7·8) higher and haematocrit was 2·4% (2·2–2·6) higher in the canagliflozin group than the placebo group. Overall, 573 of 4401 participants had either an investigator-reported anaemia event or initiation of treatment for anaemia: 358 (8%) of 4401 participants reported anaemia events, 343 (8%) initiated iron preparations, 141 (3%) initiated erythropoiesis-stimulating agents, and 114 (2%) received blood transfusion. The risk of the composite outcome of anaemia events or initiation of treatment for anaemia was lower in the canagliflozin group than the placebo group (hazard ratio 0·65, 95% CI 0·55–0·77; p<0·0001). Compared with the placebo group, participants in the canagliflozin group also had lower risks of anaemia events alone (0·58, 0·47–0·72; p<0·0001), initiation of iron preparations (0·64, 0·52–0·80; p<0·0001), and need for erythropoiesis-stimulating agents (0·65, 0·46–0·91; p=0·012). Interpretation: These data suggest that canagliflozin reduces the risk of anaemia-associated outcomes, including the need for erythropoiesis-stimulating agents, among patients with type 2 diabetes and chronic kidney disease

Contribution of anadromous fish to the diet of European catfish in a large river system

Many anadromous fish species, when migrating from the sea to spawn in fresh waters, can potentially be a valuable prey for larger predatory fish, thereby efficiently linking these two ecosystems. Here, we assess the contribution of anadromous fish to the diet of European catfish (Silurus glanis) in a large river system (Garonne, southwestern France) using stable isotope analysis and allis shad (Alosa alosa) as an example of anadromous fish. Allis shad caught in the Garonne had a very distinct marine delta(13)C value, over 8 per thousand higher after lipid extraction compared to the mean delta(13)C value of all other potential freshwater prey fish. The delta(13)C values of European catfish varied considerably between these two extremes and some individuals were clearly specializing on freshwater prey, whereas others specialized on anadromous fish. The mean contribution of anadromous fish to the entire European catfish population was estimated to be between 53% and 65%, depending on the fractionation factor used for delta(13)C

Potassium homeostasis and management of dyskalemia in kidney diseases: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Potassium disorders are common in patients with kidney disease, particularly in patients with tubular disorders and low glomerular filtration rate. A multidisciplinary group of researchers and clinicians met in October 2018 to identify evidence and address controversies in potassium management. The issues discussed encompassed our latest understanding of the regulation of tubular potassium excretion in health and disease; the relationship of potassium intake to cardiovascular and kidney outcomes, with increasing evidence showing beneficial associations with plant-based diet and data to suggest a paradigm shift from the idea of dietary restriction toward fostering patterns of eating that are associated with better outcomes; the paucity of data on the effect of dietary modification in restoring abnormal serum potassium to the normal range; a novel diagnostic algorithm for hypokalemia that takes into account the ascendency of the clinical context in determining cause, aligning the educational strategy with a practical approach to diagnosis; and therapeutic approaches in managing hyperkalemia when chronic and in the emergency or hospital ward. In sum, we provide here our conference deliberations on potassium homeostasis in health and disease, guidance for evaluation and management of dyskalemias in the context of kidney diseases, and research priorities in each of the above areas

Advanced tools and techniques to add value to soil stabilization practice

The aim of this paper is to demonstrate the advanced tools and techniques used for adding value to the soil stabilization practice. The tools presented involve advanced laboratory tests and modeling using codes and soft computing to evaluate the mechanical behavior of stabilized soils with cement, ranging from short-term to long-term behavior. More precisely, these tools are able to: 1. Predict the mechanical behavior of the stabilized soils over time from data obtained in the early ages saving time in laboratory tests; 2. Predict the mechanical behavior of the stabilized soils over time based on basic parameters of soil type and binder using historical accurate data, avoiding mechanical laboratory tests. 3. Incorporate the serviceability limit state concept in a novel proposal to estimate the design modulus in function of the uniaxial compressive strength and the strain level, making more economic and sustainable geotechnical solutions.This work was supported by FCT—‘‘Fundação para a Ciência e a Tecnologia’’, within ISISE, project UID/ECI/04029/2013 and through the post doctoral Grant fellowship with reference SFRH/BPD/94792/2013. This work was also partly financed by FEDER funds through the Competitivity Factors Operational Programme—COMPETE and by national funds through FCT within the scope of the project POCI-01-0145-FEDER-007633.info:eu-repo/semantics/publishedVersio

Application of Nitrogen and Carbon Stable Isotopes (δ15Ν and δ13C) to Quantify Food Chain Length and Trophic Structure

Increasingly, stable isotope ratios of nitrogen (delta N-15) and carbon (delta C-13) are used to quantify trophic structure, though relatively few studies have tested accuracy of isotopic structural measures. For laboratory-raised and wild-collected plant-invertebrate food chains spanning four trophic levels we estimated nitrogen range (NR) using delta N-15, and carbon range (CR) using delta C-13, which are used to quantify food chain length and breadth of trophic resources respectively. Across a range of known food chain lengths we examined how NR and CR changed within and between food chains. Our isotopic estimates of structure are robust because they were calculated using resampling procedures that propagate variance in sample means through to quantified uncertainty in final estimates. To identify origins of uncertainty in estimates of NR and CR, we additionally examined variation in discrimination (which is change in delta N-15 ordelta C-13 from source to consumer) between trophic levels and among food chains. delta N-15 discrimination showed significant enrichment, while variation in enrichment was species and system specific, ranged broadly (1.4‰ to 3.3‰), and importantly, propagated variation to subsequent estimates of NR. However, NR proved robust to such variation and distinguished food chain length well, though some overlap between longer food chains infers a need for awareness of such limitations. delta C-13 discrimination was inconsistent; generally no change or small significant enrichment was observed. Consequently, estimates of CR changed little with increasing food chain length, showing the potential utility of delta C-13 as a tracer of energy pathways. This study serves as a robust test of isotopic quantification of food chain structure, and given global estimates of aquatic food chains approximate four trophic levels while many food chains include invertebrates, our use of four trophic level plant-invertebrate food chains makes our findings relevant for a majority of ecological systems

Cardiovascular Effects of Canagliflozin in Relation to Renal Function and Albuminuria

Background: People with type 2 diabetes mellitus (T2DM) have elevated cardiovascular (CV) risk, including for hospitalization for heart failure (HHF). Canagliflozin reduced CV and kidney events in patients with T2DM and high CV risk or nephropathy in the CANVAS (CANagliflozin cardioVascular Assessment Study) Program and the CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial. Objectives: The aim of this study was to assess the effects of canagliflozin on CV outcomes according to baseline estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (UACR) in pooled patient-level data from the CANVAS Program and CREDENCE trial. Methods: Canagliflozin effects on CV death or HHF were assessed by baseline eGFR (60 mL/min/1.73 m2) and UACR (300 mg/g). HRs and 95% CIs were estimated by using Cox regression models overall and according to subgroups. Results: A total of 14,543 participants from the CANVAS Program (N = 10,142) and the CREDENCE (N = 4,401) trial were included, with a mean age of 63 years, 35% female, 75% White, 13.2% with baseline eGFR 300 mg/g. Rates of CV death or HHF increased as eGFR declined and/or UACR increased. Canagliflozin significantly reduced CV death or HHF compared with placebo (19.4 vs 28.0 events per 1,000 patient-years; HR: 0.70; 95% CI: 0.62-0.79), with consistent results across eGFR and UACR categories (all P interaction >0.40). Conclusions: Risk of CV death or HHF was higher in those with lower baseline eGFR and/or higher UACR. Canagliflozin consistently reduced CV death or HHF in participants with T2DM and high CV risk or nephropathy regardless of baseline renal function or level of albuminuria. (Canagliflozin Cardiovascular Assessment Study [CANVAS], NCT01032629; A Study of the Effects of Canagliflozin [JNJ-24831754] on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus [CANVAS-R], NCT01989754; and Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy [CREDENCE], NCT02065791

Sex differences in chronic kidney disease prevalence in Asia: a systematic review and meta-analysis

Background Previous reports on the prevalence of chronic kidney disease (CKD) in Asia have suggested important sex disparities but have been inconsistent in nature. We sought to synthesize available sex-disaggregated CKD prevalence data in Asia to quantify sex disparities in the region. Methods We systematically searched MEDLINE and Embase for observational studies involving ≥500 adults who reported sex-disaggregated CKD prevalence data in any of the 26 countries in East, Southeast and South Asia. For each study we calculated the female:male prevalence ratio (PR), with a ratio >1 indicating a higher female prevalence. For each country, log-transformed PRs were pooled using random effects meta-analysis. These were then combined using a fixed effects model, weighting by population size, to estimate a pooled PR for each of East, Southeast and South Asia and Asia overall. Results Sex-disaggregated data were available from 171 cohorts, spanning 15 countries and comprising 2 550 169 females and 2 595 299 males. Most studies (75.4%) came from East Asia (China, Taiwan, Japan and South Korea). Across Asia, CKD prevalence was higher in females {pooled prevalence 13.0% [95% confidence interval (CI) 11.3–14.9]} compared with males [pooled prevalence 12.1% (95% CI 10.3–14.1)], with a pooled PR of 1.07 (95% CI 0.99–1.17). Substantial heterogeneity was observed between countries. The pooled PRs for East, Southeast and South Asia were 1.11 (95% CI 1.02–1.21), 1.09 (0.88–1.36) and 1.03 (0.87–1.22), respectively. Conclusions Current evidence suggests considerable between-country and -region heterogeneity in the female:male PR of CKD. However, there remains a large part of the region where data on sex-specific CKD prevalence are absent or limited. Country-level assessment of the differential burden of CKD in females and males is needed to define locally relevant policies that address the needs of both sexes