2 Minute Medicine Rewind February 22, 2016

Randomized Trial of Stent versus Surgery for Asymptomatic Carotid Stenosis

Extra-cranial carotid artery disease is responsible for 20% of strokes. Literature suggests that carotid artery stenting is an effective alternative to endarterectomy in high risk surgical patients. The ACT I study prospective multicenter trial involving 1453 patients with severe atherosclerotic stenosis of the carotid-artery bifurcation, who were randomly assigned in a 3:1 fashion to stenting versus endarterectomy. The primary end point was the composite of death, stroke or MI during the 30 days after the procedure or ipsilateral stroke 365 days after the procedure. There were no significant differences in baseline demographics between the two groups of patients. Results showed that the primary event rate was 2.8% versus 3.4% in the stenting and endarterectomy groups, with P=0.01 for non-inferiority. Furthermore, the rate of stroke or death within 30 days was 2.9% versus 1.7% with P=0.33. The cumulative 5-year rate of stroke-free survival was 93.1% versus 94.7% in the stenting versus endarterectomy group, with P=0.44. This study suggests that in patient with average risk for surgical complications, stenting was non-inferior to endarterectomy and led to similar rates of complications at the 1 year mark.

Primaquine to reduce transmission of Plasmodium falciparum malaria in Mali: a single-blind, dose-ranging, adaptive randomized phase 2 trial

Literature suggests that addition of primaquine to dihydroartemisinin–piperaquine might reduce transmission of Plasmodium falciparum malaria. This phase 2, single-blinded, study involved 81 patient in Mali and was conducted to evaluate efficacy of primaquine, in addition to standard artemisinin-based combination therapy, in reducing infectivity of P. falciparum. The first stage of the study involved administering either 0.125 mg/kg or 0.5 mg/kg of primaquine and the second stage involved administering 0.25 mg/kg, or 0.0625 mg/kg of primaquine to patients, in addition to weight based 3 day course of dihydroartemisinin–piperaquine. The primary efficacy endpoint was the mean within-person percentage change in mosquito infectivity, measured through membrane-feeding assays, 2 days after primaquine treatment. Results showed that in the 0.25 mg/kg group had a significantly lower within-person infectivity rate at 92.6% (95% CI: 78.3 to 100; P=0.0014) versus 75.0% (95% CI: 45.7 to 100; P=0.014) for the 0.5 mg/kg primaquine group. However, reductions were not significantly different from control for participants assigned to the 0.0625 mg/kg dose group (n=16; 41.9% 95% CI: 1.4 to 82.5; P=0.16) or for the 0.125 mg/kg dose group (n=12; 54.9% 95% CI: 13.4 to 96.3; P=0.096). Furthermore, incidence of adverse events was not statistically different in the groups. In conclusion, this study showed that a single dose of 0.25 mg/kg primaquine, when added to dihydroartemisinin to piperaquine, was efficacious in preventing the transmission of P falciparum malaria.

Association of Body Composition with Survival and Locoregional Control of Radiotherapy-Treated Head and Neck Squamous Cell Carcinoma

Previous studies have established that loss of skeletal muscle (SM), secondary to cachexia, leads to poor outcomes and decreased survival in patients with solid tumors. However, this has not been investigated in patients with head and neck squamous cell carcinoma. Furthermore, there is insufficient data whether weight loss without SM depletion leads to worse outcomes. This single center retrospective study reviewed 190 patients with pathologically proven head and neck squamous cell carcinoma undergoing radiation therapy (RT), and evaluated the role of SM depletion after RT on survival.  The primary outcomes were overall and disease specific survival and locoregional control of disease. SM depletion was evaluated though comparison of pre-RT and post-RT imaging (PET/CT or CT scans). Results indicated that SM depletion was seen in 35.3% (n=67) before RT and in an additional 30.5% (n=58) after RT. SM depletion prior to RT was predictive of reduced overall survival (hazard ratio 1.92; 95% CI: 1.19 to 3.11; P = .007) as was SM depletion post to RT (HR, 2.03; 95% CI: 1.02 to 4.24; P = .04). Furthermore, increased BMI was positively associated with survival (hazard ratio 0.91; 95% CI: 0.87 to 0.96; P < .001). However, weight loss without SM depletion was not predictive of survival. In conclusion, this study showed that SM depletion prior to RT was strongly predictive of mortality but overall weight loss, without SM depletion, was not predictive of mortality.

Cytomegalovirus viral load and mortality after hematopoietic stem cell transplantation in the era of pre-emptive therapy: a retrospective cohort study

CMV viral load in post-transplant patient is often used to guide therapy and yet the association between viremia and clinical endpoints is unclear. This retrospective study evaluated the role of CMV viral load on mortality among 926 patients who underwent allogeneic hematopoietic stem cell transplantation and were CMV seropositive or had a seropositive donor. The primary endpoint was all-cause 1-year mortality, after adjusting for factors such as neutropenia and graft-versus-host disease. Results showed that the overall 1-year mortality was 30.0% (95% CI: 26.9% to 33.0%). A CMV viral load of 250 IU/mL or greater was associated with an increased risk of death in the first 60 days after transplantation, with hazard ratio 19.8, CI: 9.6 to 41.1. Furthermore, this trend persisted for higher CMV viral loads. In conclusion, this study showed that CMV viremia is associated with an increased overall mortality in the post-transplant setting and that viral load correlates well with 1-year mortality.

Pioglitazone after Ischemic Stroke or Transient Ischemic Attack

More than 50% of patients who have had an ischemic stroke or TIA but without a prior diagnosis of diabetes have insulin resistance. It is known that insulin resistance is a major cause of vascular disease, through promotion of hypertension, inflammation, endothelial dysfunction, and platelet reactivity. Insulin-resistance may prove to be a major target for reducing the burden of stroke. This study was a multicenter, double-blinded trial, placebo-controlled trial that randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive pioglitazone, an insulin-sensitizing medication, or placebo. Eligible patients did not have diabetes but were found to have insulin resistance based on the HOMA-IR model. The primary outcome was a first stroke or myocardial infarction. Results showed that the primary outcome occurred in 9.0% (175 of 1939) of patients in the pioglitazone group at the 4.8 year mark versus 11.8% (228 of 1937) patients in the placebo group, (hazard ratio 0.76; 95% CI: 0.62 to 0.93; P = 0.007). However, there was no difference in all-cause mortality between the two groups, hazard ratio 0.93; 95% CI: 0.73 to 1.17; P=0.52). In fact, pioglitazone was associated with weight gain (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture (5.1% vs. 3.2%, P=0.003) compared with placebo. In conclusion, this study showed that pioglitazone was effective in reducing the incidence of stroke and MI in patients with a recent history of ischemic stroke but led to higher incidence of weight gain, edema and fractures.

Image: PD

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