Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Flora and vegetation of Cerro El Aguila, Michoacan, Mexico [Flora y vegetaci�n del cerro El �guila, Michoac�n, M�xico]

A list of vascular plants of El �guila hill, the higher mountain located in the municipalities of Lagunillas and Morelia, in the Mexican state of Michoac�n is given. The field work was carried out from 2007 to 2010. The flora comprises 105 families, 343 genera, 633 species, and 42 infraespecific taxa. The most diverse families were Asteraceae (153 species), Fabaceae (53) and Poaceae (34). Genera with the largest species richness were Salvia (17), Stevia (12) and Verbesina (11). Herbs comprise 72.4% of the whole flora. Based in physiognomic features and species abundance, five vegetation types are described. Pinus-Quercus forest and Quercus forest were the most diverse vegetation types ((286 y 383 species, respectively). According to NOM-059-ECOL-2010 five species are included within risk category Under Special Protection (Cedrela dugesii, Cupressus lusitanica, Dahlia scapigera, Gentiana spathacea, and Laelia speciosa), and one more as Endangered (Tilia americana var. mexicana). Efforts to conserve the vegetation and flora in the study area should be developed taking in account the problems derived for land-use changes

Flora and vegetation of Cerro El Aguila, Michoacan, Mexico [Flora y vegetación del cerro El Águila, Michoacán, México]

A list of vascular plants of El Águila hill, the higher mountain located in the municipalities of Lagunillas and Morelia, in the Mexican state of Michoacán is given. The field work was carried out from 2007 to 2010. The flora comprises 105 families, 343 genera, 633 species, and 42 infraespecific taxa. The most diverse families were Asteraceae (153 species), Fabaceae (53) and Poaceae (34). Genera with the largest species richness were Salvia (17), Stevia (12) and Verbesina (11). Herbs comprise 72.4% of the whole flora. Based in physiognomic features and species abundance, five vegetation types are described. Pinus-Quercus forest and Quercus forest were the most diverse vegetation types ((286 y 383 species, respectively). According to NOM-059-ECOL-2010 five species are included within risk category Under Special Protection (Cedrela dugesii, Cupressus lusitanica, Dahlia scapigera, Gentiana spathacea, and Laelia speciosa), and one more as Endangered (Tilia americana var. mexicana). Efforts to conserve the vegetation and flora in the study area should be developed taking in account the problems derived for land-use changes

Detection and uptake of cadmium (Cd), chromium (Cr), lead (Pb) and mercury (Hg) in Ipomoea aquatica Forsk. (Water Spinach) in open canal road, Imus, Cavite

In the Philippines, anthropogenic activities continue to pollute water and landforms. To resolve this, plants have been found to have abilities in extracting and distributing heavy metals to its organs. Ipomoea aquatica Forsk. (water spinach), a semi-aquatic vascular plant has shown potential in the phytoextraction of various heavy metals. This study aims to determine heavy metals present in the soil samples of Open Canal Road, Imus, Cavite; to identify certain heavy metals absorbed by the I. aquatica Forsk. (water spinach); and to determine if the heavy metal concentrations in the soil and plant samples are within permissible levels set by the World Health Organization (WHO). The research procedure included plant identification, water spinach and soil sample preparation, soil analysis, metal analysis using Atomic Absorption Spectroscopy (AAS) and Cold Vapor Technique (CVT), data gathering, and interpretation. From the analysis, high levels of lead were detected from the soil, 18.37 ppm; 4.42 ppm in leaves, 4.25 ppm in stems, and 4.33 ppm in roots of I. aquatica Forsk. (water spinach) samples. Mercury was detected with values of 0.03 ppm in the soil and throughout the plant organs. Cadmium and chromium were not detectable with values less than 0.01 ppm and 0.03 ppm, respectively. In comparison to the set standards of WHO, the levels of heavy metals in the soil and plant were considerably normal. Meanwhile, the amount of lead in the plant organs (roots, stems, leaves) is twice the acceptable level of 2.0 ppm; mercury levels exceeded the standard by 0.01 ppm. Nonetheless, its ability to be a phytoremediating agent for Lead and minimal amounts of Mercury for the canal is still feasible since it is able to translocate significant amounts of heavy metals throughout its plant organs

Knowledge and readiness of filipino physical educators in addressing injuries in physical education settings

In school, there are a lot of lesson, skills and&nbsp; experiences that may took place. It is inevitable to encounter unexpected certainties during class hours, especially during Physical Education classes. There are a lot of unexpected certainties like injuries that may took place, the latter may deprove the students in attaining the knowledge and skills they may acquired during their physical education classes. Moreover, it is the teacher's primary role to keep the students safe from any harm. Thus, this study aimed to assess the knowledge and readiness of Filipino Physical Educators in addressing injuries in Physical Education settings. This mixed-method sequential explanatory research considered twenty (20) physical educators of a state-funded higher education institution were selected for the quantitative phase. Four (4) of them were selected in the qualitative phase via extreme case sampling that measured their demographic profile, knowledge, readiness, and experiences in first aid management. Using the Pearson r test manifests a negative relationship between the variables of this study and the demographic profile of the respondents/participants. As per the&nbsp; results of the quantitative phase and the findings of the qualitataive phase this study delineates that the Physical Educators do have a sufficient level of knowledge and readiness in terms of addressing and responding to unexpected certainties that may took place on their respective physical education classes. Furthermore, it is recommended that Physical Educators must consider a variety of strategies to improve their knowledge and readiness in dealing with injuries. With this, further knowledge and information should be obtained to strengthen and enhance the knowledge and readiness they initially have

Nephrotoxic Metal Mixtures and Preadolescent Kidney Function

Exposure to metals including lead (Pb), cadmium (Cd), and arsenic (As), may impair kidney function as individual toxicants or in mixtures. However, no single medium is ideal to study multiple metals simultaneously. We hypothesized that multi-media biomarkers (MMBs), integrated indices combining information across biomarkers, are informative of adverse kidney function. Levels of Pb, Cd, and As were quantified in blood and urine in 4–6-year-old Mexican children (n = 300) in the PROGRESS longitudinal cohort study. We estimated the mixture effects of these metals, using weighted quantile sum regression (WQS) applied to urine biomarkers (Umix), blood biomarkers (Bmix), and MMBs, on the cystatin C-based estimated glomerular filtration rate (eGFR) and serum cystatin C assessed at 8–10 years of age, adjusted for covariates. Quartile increases in Umix and the MMB mixture were associated with 2.5% (95%CI: 0.1, 5.0) and 3.0% (95%CI: 0.2, 5.7) increased eGFR and −2.6% (95% CI: −5.1%, −0.1%) and −3.3% (95% CI: −6.5%, −0.1%) decreased cystatin C, respectively. Weights indicate that the strongest contributors to the associations with eGFR and serum cystatin C were Cd and Pb, respectively. MMBs detected mixture effects distinct from associations with individual metals or media-type, highlighting the benefits of incorporating information from multiple exposure media in mixtures analyses