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 <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >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 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<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

Collaboration, Connection Reflection: Exploring Public Art in South Africa

Wealth inequality has resulted in neglected people and tattered communities in Cape Town, South Africa. A multitude of organizations are dedicated to improving the lives of people in need. A unique approach to helping people and improving societal dynamics is through collaborative art. Art is a powerful form of expression that can unite people through the process of creation. This project assisted Khulisa Social Solution’s Streetscapes Program in a collaborative process to create a mural. In order to establish trust with the program participants, we generated a mosaic of collected bottle tops. The shared experience of labor afforded more positive relationships that assisted in the development of a representative community art piece

DYNAMIC CORRECTION OF POSTURAL KYPHOSIS

Many American adults in today's society spend extended periods of time hunched over a computer or phone. This hunched position weakens the upper posterior muscles that support the shoulder and neck prompting muscle imbalance. Specifically, the lower trapezius and clavicle flexor muscles become too weak while the pectoral and upper trapezius muscles become too tight leading to the condition known as postural kyphosis or, more commonly, rounded shoulders. Our project aimed to design, build, and test a device able to treat and correct postural kyphosis through sensorimotor training. While the effectiveness of this device was determined through a short-term biomechanical validation processes, we recommend further testing to gather the long-term effects of use

Modification of the existing maximum residue levels for mefentrifluconazole in various commodities

Abstract In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant BASF Agro B.V. Arnhem (NL) Freienbach Branch submitted a request to the competent national authority in Austria to modify the existing maximum residue levels (MRLs) for the active substance mefentrifluconazole in various crops and swine liver and other swine products. The data submitted in support of the request were found to be sufficient to derive MRL proposals. Adequate analytical methods for enforcement are available to control the residues of mefentrifluconazole in the plant commodities under consideration and in animal matrices at the validated limit of quantification (LOQ) of 0.01 mg/kg. New data relevant to the data gaps on storage stability and feeding studies of triazole derivative metabolites (TDMs), that were identified during the peer review of confirmatory data of the TDMs, were submitted in support of the present MRL application. Based on the risk assessment results, EFSA concluded that the short‐term and long‐term intake of residues resulting from the use of mefentrifluconazole according to the reported agricultural practices is unlikely to present a risk to consumer health. EFSA noted a narrow safety margin with regard to acute exposure to mefentrifluconazole residues from the intake of spinaches if residues occur at the level of the proposed MRL. EFSA also performed an indicative risk assessment for the TDMs based on uses of mefentrifluconazole only. The estimated exposure for TDMs did not exceed the toxicological reference values

Evaluation of confirmatory data following the Article 12 MRL review for S‐metolachlor

Abstract The applicant Syngenta Crop Protection AG submitted a request to the competent national authority in Germany to evaluate the confirmatory data that were identified for S‐metolachlor in the framework of the maximum residue level (MRL) review under Article 12 of Regulation (EC) No 396/2005 as not available. To address the data gaps, a new freezer storage stability study for S‐metolachlor in commodities with high acid content was submitted. However, the data gap on storage stability was considered only partially addressed for strawberries because, in the absence of information on the storage time interval of the samples of the residue trials performed on strawberries, no conclusion on the validity of these trials could be drawn. The data gap on the lack of trials to support the good agricultural practice (GAP) on pineapples was not addressed. Consequently, the existing tentative MRLs for strawberries and pineapple cannot be confirmed and EFSA recommends lowering these MRLs to the enforcement limit of quantification (LOQ). Since a new lower LOQ for enforcement in high acid content commodities of 0.01 mg/kg has been validated, it is proposed to change the existing MRL value from 0.05* to 0.01* mg/kg for these two commodities

Modification of the existing maximum residue levels or for flonicamid in kales, Chinese cabbages and kohlrabies

Abstract In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant DLR‐Rheinpfalz submitted a request to the competent national authority in Germany to modify the existing maximum residue levels (MRLs) for the active substance flonicamid in Chinese cabbages, kales and kohlrabies. The data submitted in support of the request were found to be sufficient to derive MRL proposals for the commodities under assessment. Adequate analytical methods for enforcement are available to control the residues of flonicamid, 4‐trifluoromethylnicotinic acid (TFNA) and N‐(4‐trifluoromethylnicotinoyl) glycine (TFNG) (sum expressed as flonicamid) in the commodities under consideration at the validated combined limit of quantification (LOQ) of 0.03 mg/kg and the residues of flonicamid and TFNA‐AM in animal matrices at the validated combined LOQ of 0.02 mg/kg. Based on the risk assessment results, EFSA concluded that the short‐term and long‐term intake of residues resulting from the use of flonicamid according to the reported agricultural practices is unlikely to present a risk to consumer health

Evaluation of confirmatory data following the Article 12 MRL review for fenbuconazole

Abstract The applicant Corteva Agrosciences submitted a request to the competent national authority in Slovenia to evaluate the confirmatory data that were identified for fenbuconazole in the framework of the MRL review under Article 12 of Regulation (EC) No 396/2005 as not available. To address the Article 12 confirmatory data gaps, new residue trials analysing triazole derivative metabolites (TDMs) were submitted on grapefruits, lemons, apples, pears, peaches, cherries and blueberries. Following the assessment of submitted data, EFSA concluded that Article 12 confirmatory data gaps are considered addressed for grapefruits, oranges, lemons, limes, pome fruits, peaches, cherries and blueberries. The calculated livestock dietary burdens indicated that for the individual TDMs, the trigger value of 0.004 mg/kg bw day is not exceed from the intake of apple pomace and citrus dried pulp. The new information provided required the assessment of consumer exposure to TDMs, which identified no consumer intake concerns for the crops under consideration. No data were submitted to address the Article 12 confirmatory data gaps for tree nuts, apricots, plums, table grapes, wine grapes, cranberries, bananas, sweet peppers/bell peppers, cucurbits with edible/inedible peel, peanuts/groundnuts, sunflower seeds and rapeseeds/canola seeds, barley, rye and wheat. For these commodities, the existing EU MRL could be lowered to the enforcement LOQ

Modification of the existing maximum residue level for azoxystrobin in hops

Abstract In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Syngenta Crop Protection AG submitted a request to the competent national authority in Germany to modify the existing maximum residue level (MRL) for the active substance azoxystrobin in hops. The data submitted in support of the request were found to be sufficient to derive an MRL proposal for hops. Adequate analytical methods for enforcement are available to control the residues of azoxystrobin on the commodity under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, noting that an acute risk assessment was not deemed necessary for azoxystrobin, EFSA concluded that the long‐term intake of residues resulting from the use of azoxystrobin according to the reported agricultural practice is unlikely to present a risk to consumer health

Modification of the existing maximum residue levels for metazachlor in leeks and honey

Abstract In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant BASF SE submitted a request to the competent national authority in the Netherlands to modify the existing maximum residue levels (MRLs) for the active substance metazachlor in leeks and honey. The data submitted in support of the request were found to be sufficient to derive MRL proposals. Adequate analytical methods for enforcement are available to control the residues of metazachlor metabolites 479 M04, 479 M08 and 479 M16 in plant matrices and honey at the validated limit of quantification (LOQ) of 0.01 and 0.02 mg/kg for each analyte. Based on the risk assessment results, EFSA concluded that the short‐term and long‐term intake of residues resulting from the use of metazachlor according to the reported agricultural practice is unlikely to present a risk to consumer health

Modification of the existing maximum residue levels for acibenzolar‐S‐methyl in grapes

Abstract In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Syngenta Crop Protection AG submitted a request to the competent national authority in Italy to modify the existing maximum residue levels (MRLs) for the active substance acibenzolar‐S‐methyl in grapes. The data submitted in support of the request were found to be sufficient to derive MRL proposals for table and wine grapes. Adequate analytical methods for enforcement are available to control the residues of acibenzolar‐S‐methyl residues and of the metabolite acibenzolar acid (free and conjugated) in plant matrices at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short‐term and long‐term intake of residues resulting from the use of acibenzolar‐S‐methyl according to the reported agricultural practices is unlikely to present a risk to consumer health