The aim of this study was to determine if components of the COPD Assessment Test (CAT), a validated health status impairment instrument, had additional utility in identifying patients at risk for COPD in whom spirometry testing is appropriate. This study was part of the Canadian Obstructive Lung Disease prevalence study. Consenting participants ≥ 40 years of age were identified by random digit dialing. Smoking history, 8-item CAT scores, and post-bronchodilator spirometry were recorded for each. Stepwise logistic regression analysis was used to identify variables related to the presence of airway obstruction and a final logistic model was developed which best predicted COPD in this sample. Of the 801 individuals approached, 532 were included: 51 (9.6%) had COPD, the majority (92%) of whom fit GOLD I or II severity criteria. Items that correlated significantly with a COPD diagnosis included the CAT total score (p = 0.01) and its breathlessness (p < 0.0001) and phlegm (p = 0.001) components. The final logistic model included: age (<55 or ≥55 years), smoking status (current, former, never) and the CAT breathlessness score (ordinal scale 0-5). The area under the receiver-operating characteristic curve for this model was 0.77, sensitivity was 77.6%, specificity was 64.9% and the positive likelihood ratio was 2.21. In summary, the triad of smoking history, age at least 55 years and the presence of exertional breathlessness were key elements of a simple model which had reliable measurement properties when tested in a random population. This may help identify patients at risk for COPD for whom spirometry testing is recommended.

Recently, we identified in two individuals with intellectual disability (ID) different de novo mutations in DEAF1, which encodes a transcription factor with an important role in embryonic development. To ascertain whether these mutations in DEAF1 are causative for the ID phenotype, we performed targeted resequencing of DEAF1 in an additional cohort of over 2,300 individuals with unexplained ID and identified two additional individuals with de novo mutations in this gene. All four individuals had severe ID with severely affected speech development, and three showed severe behavioral problems. DEAF1 is highly expressed in the CNS, especially during early embryonic development. All four mutations were missense mutations affecting the SAND domain of DEAF1. Altered DEAF1 harboring any of the four amino acid changes showed impaired transcriptional regulation of the DEAF1 promoter. Moreover, behavioral studies in mice with a conditional knockout of Deaf1 in the brain showed memory deficits and increased anxiety-like behavior. Our results demonstrate that mutations in DEAF1 cause ID and behavioral problems, most likely as a result of impaired transcriptional regulation by DEAF1.

In this article, the authors reported on four individuals with intellectual disability, severely affected speech development, behavioral problems, and missense mutations affecting the SAND domain of DEAF1. Functional studies showing a loss of function of DEAF1 and behavioral studies in a conditional knockout mouse provided additional support for causality of the DEAF1 mutations in these four reported individuals.

R Raghavan, BS Benzaquen, L Rudski. Timing of bypass surgery in stable patients after acute myocardial infarction. Can J Cardiol 2007;23(12):976-982.OBJECTIVES: To determine the optimal timing for bypass surgery in stable patients after acute myocardial infarction (MI). BACKGROUND: Coronary artery bypass graft surgery (CABG) is a proven treatment for coronary artery disease. Because of the hypothesized risk of hemorrhagic transformation, it had become common practice to wait four to six weeks after MI. Recently, improvements in surgical and perioperative management, as well as an increase in pre-CABG in-hospital waiting times and excess burden on health care resources, have pushed surgeons to operate earlier. The optimal timing for a stable patient to undergo CABG after MI is unclear, because there have been no randomized trials to answer this question. METHODS:The published literature comparing early versus late surgical revascularization procedures in stable post-MI patients was reviewed. RESULTS: No randomized, prospective trials were found; however, several retrospective studies were identified. Most series examining Q wave MIs showed that mortality is higher in the early stages post-MI and progressively decreases with time post-MI. When studies examined non-Q wave MIs separately, there appeared to be less of a mortality difference between early and late surgical revascularization. There was a large disparity between the definitions of early surgery post-MI among the studies, some as early as 6 h and others up to eight days. Factors that increased mortality include abnormal left ventricular function and urgency of surgery, and some studies found risk models helpful to define increased risk after infarction. The possible increased risk of early surgery may be balanced against the potential for improved remodelling, improved quality of life and decreased hospital stay costs. CONCLUSIONS: There is a need for a randomized, prospective trial examining the optimal timing for CABG in stable post-MI patients.