Low-dose versus High-dose Alteplase for Acute Ischemic Stroke

Primary and Secondary outcomes at 3 months

Thrombolytic therapy for Acute Ischemic stroke in lower doses may improve recovery, with simultaneous less haemorrhagic complications. 

The findings of a clinical trial of 3310 patients were randomized in 2 groups: a low-dose intravenous alteplase (0.6 mg per kilogram of body weight) or the standard dose (0.9 mg per kilogram).

The primary objective was to determine whether the low dose would be noninferior to the standard dose with respect to the primary outcome of death or disability at 90 days, which was defined by scores of 2 to 6 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]). Secondary objectives were to determine whether the low dose would be superior to the standard dose with respect to centrally adjudicated symptomatic intracerebral hemorrhage and whether the low dose would be noninferior in an ordinal analysis of modified Rankin scale scores (testing for an improvement in the distribution of scores).

RESULTS

The primary outcome occurred in 855 of 1607 participants (53.2%) in the low-dose group and in 817 of 1599 participants (51.1%) in the standard-dose group (odds ratio, 1.09; 95% confidence interval [CI], 0.95 to 1.25; the upper boundary exceeded the noninferiority margin of 1.14; P=0.51 for noninferiority). Low-dose alteplase was noninferior in the ordinal analysis of modified Rankin scale scores (unadjusted common odds ratio, 1.00; 95% CI, 0.89 to 1.13; P=0.04 for noninferiority). Major symptomatic intracerebral hemorrhage occurred in 1.0% of the participants in the low-dose group and in 2.1% of the participants in the standard-dose group (P=0.01); fatal events occurred within 7 days in 0.5% and 1.5%, respectively (P=0.01). Mortality at 90 days did not differ significantly between the two groups (8.5% and 10.3%, respectively; P=0.07).

CONCLUSION

This trial involving predominantly Asian patients with acute ischemic stroke did not show the noninferiority of low-dose alteplase to standard-dose alteplase with respect to death and disability at 90 days. There were significantly fewer symptomatic intracerebral hemorrhages with low-dose alteplase.

SOURCE: Pubmed, NEJM, ENCHANTED ClinicalTrials.gov number, NCT01422616.)

The 3rd International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) of Feb 2016

Algorithm for Sepsis and Septic Shock identification

SOFA Score

New consensus definitions regarding sepsis and septic shock are proposed from Sepsis-3 consenus in February 2016.

Basic concepts of the new definitions are SOFA Score and Bedside quick SOFA Score (qSOFA). The latter is easily used since it is calculated using Clinical Criteria (decrease in mental status of more than 2 points in Glasgow Coma Scale, systolic blood pressure ≤100 mm Hg, or respiratory rate ≥22/min.).

SOFA Score of more than 2 is associated with in hospital mortality of more than 10%. In cases of septic shock mortality rate exceeds 40%.

SOURCE: JAMA network (http://jama.jamanetwork.com/mobile/article.aspx?articleid=2492881#jsc160002b3)

New Toronto Consensus Guidelines regarding Helicobacter pylori eradication therapy

The new guidelines regarding Helicobacter pylori eradication therapy propose 14-day regimens.

Because of increasing failure of therapy, the consensus group strongly recommended that all H. pylori eradication regimens now be given for 14 days. Recommended first-line strategies include concomitant non-bismuth quadruple therapy (proton pump inhibitor, PPI + amoxicillin + metronidazole + clarithromycin, PAMC), and traditional bismuth quadruple therapy (PPI + bismuth + metronidazole + tetracycline, PBMT). PPI triple therapy (PPI + clarithromycin and either amoxicillin or metronidazole) was restricted to areas with known low clarithromycin resistance or high eradication success with these regimens. Recommended rescue therapies include PBMT and levofloxacin-containing therapy (PPI + amoxicillin + levofloxacin, PAL). Rifabutin regimens should be restricted to patients who fail at least 3 prior options.

SOURCE: American Gastroenterology Association (http://www.gastrojournal.org/article/S0016-5085(16)30108-1/abstract)