Prevalence and incidence of liver enzyme elevations in a pooled oncology clinical trial cohort.

Few epidemiologic studies describe longitudinal liver chemistry (LC) elevations in cancer patients. A population-based retrospective cohort was identified from 31 Phase 2-3 oncology trials (excluding targeted therapies) conducted from 1985 to 2005 to evaluate background rates of LC elevations in patients (n = 3998) with or without liver metastases. Patients with baseline liver metastases (29% of patients) presented with a 3% prevalence of alanine transaminase (ALT) ≥ 3x upper limits normal (ULN) and 0.2% prevalence of bilirubin ≥ 3xULN. During follow-up, the incidence (per 1000 person-months) of new onset ALT elevations ≥3xULN was 6.1 (95% CI: 4.5, 8.0) and 2.2 (95% CI: 0.9, 4.5) in patients without and with liver metastases, respectively. No new incident cases of ALT and bilirubin elevations suggestive of severe liver injury occurred among those with liver metastases; a single case occurred among those without metastasis. Regardless of the presence of liver metastases, LC elevations were rare in cancer patients during oncology trials, which may be due to enrollment criteria. Our study validates uniform thresholds for detection of LC elevations in oncology studies and serves as an empirical referent point for comparing liver enzyme abnormalities in oncology trials of novel targeted therapies. These data support uniform LC stopping criteria in oncology trials.

The acquisition of abstract words by young infants.

Young infants' learning of words for abstract concepts like 'all gone' and 'eat,' in contrast to their learning of more concrete words like 'apple' and 'shoe,' may follow a relatively protracted developmental course. We examined whether infants know such abstract words. Parents named one of two events shown in side-by-side videos while their 6-16-month-old infants (n=98) watched. On average, infants successfully looked at the named video by 10 months, but not earlier, and infants' looking at the named referent increased robustly at around 14 months. Six-month-olds already understand concrete words in this task (Bergelson & Swingley, 2012). A video-corpus analysis of unscripted mother-infant interaction showed that mothers used the tested abstract words less often in the presence of their referent events than they used concrete words in the presence of their referent objects. We suggest that referential uncertainty in abstract words' teaching conditions may explain the later acquisition of abstract than concrete words, and we discuss the possible role of changes in social-cognitive abilities over the 6-14 month period.