Outcomes for patients with the same disease treated inside and outside of randomized trials: a systematic review and meta-analysis.

BACKGROUND: It is unclear whether participation in a randomized controlled trial (RCT), irrespective of assigned treatment, is harmful or beneficial to participants. We compared outcomes for patients with the same diagnoses who did ("insiders") and did not ("outsiders") enter RCTs, without regard to the specific therapies received for their respective diagnoses. METHODS: By searching the MEDLINE (1966-2010), Embase (1980-2010), CENTRAL (1960-2010) and PsycINFO (1880-2010) databases, we identified 147 studies that reported the health outcomes of "insiders" and a group of parallel or consecutive "outsiders" within the same time period. We prepared a narrative review and, as appropriate, meta-analyses of patients' outcomes. RESULTS: We found no clinically or statistically significant differences in outcomes between "insiders" and "outsiders" in the 23 studies in which the experimental intervention was ineffective (standard mean difference in continuous outcomes -0.03, 95% confidence interval [CI] -0.1 to 0.04) or in the 7 studies in which the experimental intervention was effective and was received by both "insiders" and "outsiders" (mean difference 0.04, 95% CI -0.04 to 0.13). However, in 9 studies in which an effective intervention was received only by "insiders," the "outsiders" experienced significantly worse health outcomes (mean difference -0.36, 95% CI -0.61 to -0.12). INTERPRETATION: We found no evidence to support clinically important overall harm or benefit arising from participation in RCTs. This conclusion refutes earlier claims that trial participants are at increased risk of harm.

The myocardium of fetuses with endocardial fibroelastosis contains fewer B and T lymphocytes than normal control myocardium.

The observation that endocardial fibroelastosis (EFE) can result from an immune response to maternal autoantibody deposition in the fetal myocardium raises the possibility that the fetal immune system may contribute to the pathogenesis of idiopathic EFE and dilated cardiomyopathy (DCM). This study sought to characterize myocardial immune cell presence in fetuses and neonates with idiopathic EFE + DCM, in those with EFE + structural heart disease, and in normal control subjects. Paraffin tissue sections from fetuses identified from the pathology database were stained for B cell, T cell, macrophage, and general hematopoietic cell surface markers. Of the 14 fetuses included in the study, 5 had EFE + DCM, 4 had EFE + structural heart disease, and 5 were normal control fetuses. The EFE + DCM group had fewer B cells than the control group (0.15 vs. 0.44 cells/mm(2); p = 0.005). The EFE + heart disease group had both fewer B cells (0.18 vs. 0.44 cells/mm(2); p = 0.08) and T cells (0.29 vs. 0.80 cells/mm(2); p = 0.04) than the control group. The CD4/CD8 ratio was similar in the EFE + DCM and EFE + heart disease groups (1.0 vs. 0.9; p = 0.17) but higher in the EFE + DCM group than in the control group (0.9 vs. 0.3; p = 0.03). The myocardium of fetuses with EFE contains fewer B and T lymphocytes than normal control fetuses.

Symptoms of disturbed sleep predict major adverse cardiac events after percutaneous coronary intervention.

BACKGROUND: Disturbed sleep is associated with atherosclerosis in native coronary arteries and may be associated with adverse cardiac events after percutaneous coronary intervention (PCI). We sought to determine the association between symptoms of disturbed sleep and adverse cardiovascular events after PCI. METHODS: Outpatients who were stable after successful PCI were assessed for symptoms of disturbed sleep with 10 true/false questions. Follow-up was performed at least 4 years after PCI. The primary outcome was a composite of death, myocardial infarction (MI), and repeated revascularization. RESULTS: Three hundred eighty-eight patients (mean age, 66 ± 11 years) reported on average 3.1 ± 2.1 sleep disturbance symptoms. Follow-up was performed on average 4.4 years after the incident PCI. The primary outcome occurred in 25% of patients. An association was seen between the number of sleep disturbance symptoms and the occurrence of the primary end point. Patients with zero symptoms had a 4-year event rate of 12% compared with a 67% event rate for those with 9 symptoms. On multivariable analysis, sleep symptoms, diabetes mellitus, and the number of diseased coronary vessels were independently associated with the primary end point. Each additional sleep symptom was associated with a hazard ratio (HR) of 1.2 (P = 0.001). The results were driven primarily by the association between symptoms of disturbed sleep and the need for repeated revascularization (repeated PCI HR, 1.9; P = 0.003; coronary artery bypass grafting (CABG) HR, 1.5; P = 0.001). CONCLUSIONS: Symptoms of disturbed sleep were associated with increased risk of long-term adverse cardiovascular outcomes after successful PCI.