Background In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain.

Severe hypoglycemia was strongly associated with increased risks of a range of adverse clinical outcomes. It is possible that severe hypoglycemia contributes to adverse outcomes, but these analyses indicate that hypoglycemia is just as likely to be a marker of vulnerability to such events. (Funded by Servier and the National Health and Medical Research Council of Australia; ClinicalTrials.gov number, NCT00145925.).

BACKGROUNDObstructive sleep apnea is associated with an increased risk of cardiovascular events; whether treatment with continuous positive airway pressure (CPAP) prevents major cardiovascular events is uncertain. METHODSAfter a 1-week run-in period during which the participants used sham CPAP, we randomly assigned 2717 eligible adults between 45 and 75 years of age who had moderate-tosevere obstructive sleep apnea and coronary or cerebrovascular disease to receive CPAP treatment plus usual care (CPAP group) or usual care alone (usual-care group). The primary composite end point was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack. Secondary end points included other cardiovascular outcomes, health-related quality of life, snoring symptoms, daytime sleepiness, and mood. RESULTSMost of the participants were men who had moderate-to-severe obstructive sleep apnea and minimal sleepiness. In the CPAP group, the mean duration of adherence to CPAP therapy was 3.3 hours per night, and the mean apnea-hypopnea index (the number of apnea or hypopnea events per hour of recording) decreased from 29.0 events per hour at baseline to 3.7 events per hour during follow-up. After a mean follow-up of 3.7 years, a primary end-point event had occurred in 229 participants in the CPAP group (17.0%) and in 207 participants in the usual-care group (15.4%) (hazard ratio with CPAP, 1.10; 95% confidence interval, 0.91 to 1.32; P = 0.34). No significant effect on any individual or other composite cardiovascular end point was observed. CPAP significantly reduced snoring and daytime sleepiness and improved health-related quality of life and mood. 920T h e ne w e ngl a nd jou r na l o f m e dicine O bstructive sleep apnea causes episodic hypoxemia and nocturnal sympathetic nervous system activation 1 and elevates blood pressure 2 and markers of oxidative stress, inflammation, and hypercoagulation. 3,4

In patients in the ICU, there was no significant difference in 90-day mortality between patients resuscitated with 6% HES (130/0.4) or saline. However, more patients who received resuscitation with HES were treated with renal-replacement therapy. (Funded by the National Health and Medical Research Council of Australia and others; CHEST ClinicalTrials.gov number, NCT00935168.).

Among patients with septic shock undergoing mechanical ventilation, a continuous infusion of hydrocortisone did not result in lower 90-day mortality than placebo. (Funded by the National Health and Medical Research Council of Australia and others; ADRENAL ClinicalTrials.gov number, NCT01448109 .).

This review summarises data from four studies including 38,723 participants across six continents.There was clear evidence that SGLT2 inhibitors reduce the risk dialysis, transplantation or death due to kidney disease, as well as a range of other major kidney outcomes, and that these agents also provide protection against acute kidney injury. Additionally, there were definitive, separate benefits at all levels of kidney function, including an approximate 30% proportional risk reduction in the composite kidney outcome in participants with baseline eGFR less than 45 mL/min/1•73m 2 in whom these drugs are mostly not permitted for use. Implications of all the available evidenceThese results provide the strongest evidence yet that SGLT2 inhibitors should be routinely offered to individuals with type 2 diabetes at risk of progressive kidney disease. The clear evidence of renoprotection across the spectrum of kidney function studied to date call into question current restrictions on the use of SGLT2 inhibitors in people with reduced kidney function, and suggest that many more individuals with type 2 diabetes at high risk of kidney failure are likely to benefit from treatment.

clinicaltrials.gov Identifier: NCT01560052.

No abstract