Association of C-reactive protein with bacterial and respiratory syncytial virus-associated pneumonia among children aged <5 years in the PERCH study

Background. Lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of C-reactive protein (CRP) for identifying bacterial pneumonia. We evaluated the sensitivity and specificity of CRP for identifying bacterial vs respiratory syncytial virus (RSV) pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) multicenter case-control study. Methods. We measured serum CRP levels in cases with World Health Organization-defined severe or very severe pneumonia and a subset of community controls. We evaluated the sensitivity and specificity of elevated CRP for "confirmed" bacterial pneumonia (positive blood culture or positive lung aspirate or pleural fluid culture or polymerase chain reaction [PCR]) compared to "RSV pneumonia" (nasopharyngeal/oropharyngeal or induced sputum PCR-positive without confirmed/suspected bacterial pneumonia). Receiver operating characteristic (ROC) curves were constructed to assess the performance of elevated CRP in distinguishing these cases. Results. Among 601 human immunodeficiency virus (HIV)-negative tested controls, 3% had CRP ≥40 mg/L. Among 119 HIVnegative cases with confirmed bacterial pneumonia, 77% had CRP ≥40 mg/L compared with 17% of 556 RSV pneumonia cases. The ROC analysis produced an area under the curve of 0.87, indicating very good discrimination; a cut-point of 37.1 mg/L best discriminated confirmed bacterial pneumonia (sensitivity 77%) from RSV pneumonia (specificity 82%). CRP ≥100 mg/L substantially improved specificity over CRP ≥40 mg/L, though at a loss to sensitivity. Conclusions. Elevated CRP was positively associated with confirmed bacterial pneumonia and negatively associated with RSV pneumonia in PERCH. CRP may be useful for distinguishing bacterial from RSV-associated pneumonia, although its role in discriminating against other respiratory viral-associated pneumonia needs further study

Quantitative methods for tracking cognitive change 3 years after coronary artery bypass surgery: a comparison of on-pump CABG and non-surgical controls

The analysis and interpretation of change in cognitive function test scores after coronary artery bypass grafting (CABG) present considerable statistical challenges. Application of hierarchical linear statistical models can estimate the effects of a surgical intervention on the time course of multiple biomarkers. We use an "analyze then summarize" approach whereby we estimate the intervention effects separately for each cognitive test and then pool them, taking appropriate account of their statistical correlations. The model accounts for dropouts at follow-up, the chance of which may be related to past cognitive score, by implicitly imputing the missing data from individuals' past scores and group patterns. We apply this approach to a study of the effects of CABG on the time course of cognitive function as measured by 16 separate neuropsychological test scores, clustered into 8 cognitive domains. The study includes measurements on 140 CABG patients and 92 nonsurgical controls at baseline, and at 3, 12, and 36 months. Our "analyze then summarize" method allows us to identify differences between the treatment groups in individual tests as well as in aggregate measures. It takes into account the correlation structure of the data and thereby produces more precise results than summarizing before analyzing. The methods used have application to a wide range of intervention studies in which multiple biomarkers are followed over time to quantify health effects. Software to implement the methods in the R statistical package is available from the authors at http://www.biostat.jhsph.edu/sbarry/software/ATSrcode.pdf

Cognitive outcomes 3 years after Coronary Artery Bypass Surgery: a comparison of on-pump CABG and non-surgical controls

&lt;b&gt;Background&lt;/b&gt; &lt;br&gt;Coronary artery bypass grafting has been associated with both early and late postoperative cognitive decline, but interpretation of previous studies has been limited by lack of appropriate control groups. We compared changes in cognitive performance from baseline to 3 years in patients undergoing coronary artery bypass grafting with those of a control group of patients with known risk factors for coronary artery disease but without surgery.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Methods&lt;/b&gt;&lt;/br&gt; &lt;br&gt;Patients undergoing coronary artery bypass grafting (n = 140) and a demographically similar nonsurgical control group with coronary artery disease (n = 92) completed baseline neuropsychological assessment and were followed up prospectively at 3, 12, and 36 months. Cognitive performance was assessed with a battery of neuropsychological tests, measuring the cognitive domains of attention, language, verbal and visual memory, visuospatial, executive function, and psychomotor and motor speed. The statistical analyses were performed in two ways: using data from all tested individuals, and using a model imputing missing observations for individuals lost to follow-up.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Results&lt;/b&gt;&lt;/br&gt; &lt;br&gt;Both the coronary artery bypass grafting and nonsurgical control groups improved from baseline to 1 year, with additional improvement between 1 and 3 years for some cognitive tests. The coronary artery bypass grafting group had statistically significantly greater improvement than the nonsurgical controls for some subtests, and had a comparable longitudinal course for the remainder of the subtests. Both study groups had a trend toward nonsignificant decline at 3 years on some measures, but the overall differences between groups over time were not statistically significant.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Conclusions&lt;/b&gt;&lt;/br&gt; &lt;br&gt;Prospective longitudinal neuropsychological performance of patients with coronary artery bypass grafting did not differ from that of a comparable nonsurgical control group of patients with coronary artery disease at 1 or 3 years after baseline examination. This finding suggests that previously reported late cognitive decline after coronary artery bypass grafting may not be specific to the use of cardiopulmonary bypass, but may also occur in patients with similar risk factors for cardiovascular and cerebrovascular disease.&lt;/br&gt

Is there cognitive decline 1 year after CABG? Comparison with surgical and nonsurgical controls

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; It is widely assumed that decline in cognition after coronary artery bypass grafting (CABG) is related to use of the cardiopulmonary bypass pump. Because most studies have not included comparable control groups, it remains unclear whether postoperative cognitive changes are specific to cardiopulmonary bypass, general aspects of surgery, or vascular pathologies of the aging brain.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; This nonrandomized study included four groups: CABG patients (n = 140); off-pump coronary surgery (n = 72); nonsurgical cardiac controls (NSCC) with diagnosed coronary artery disease but no surgery (n = 99); and heart healthy controls (HHC) with no cardiac risk factors (n = 69). Subjects were evaluated at baseline (preoperatively), 3 months, and 12 months. Eight cognitive domains and a global cognitive score, as well as depressive and subjective symptoms were analyzed.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; At baseline, patients with coronary artery disease (CABG, off-pump, and NSCC) had lower performance than the HHC group in several cognitive domains. By 3 months, all groups had improved. From 3 to 12 months, there were minimal intrasubject changes for all groups. No consistent differences between the CABG and off-pump patients were observed.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Compared with heart healthy controls (HHC), the groups with coronary artery disease had lower cognitive test scores at baseline. There was no evidence that the cognitive test performance of coronary artery bypass grafting (CABG) patients differed from that of control groups with coronary artery disease over a 1-year period. This study emphasizes the need for appropriate control groups for interpreting longitudinal changes in cognitive performance after CABG.&lt;/p&gt