Citations

OBJECTIVE: The US Surgeon General has called for new approaches to close the mental health services gap for the large proportion of US children with significant mental health needs who have not received evaluation or services within the previous 6 to 12 months. In response, investigators sought to develop brief, easily understood, scientifically derived “warning signs” to help parents, teachers, and the lay public to more easily recognize children with unmet mental health needs and bring these children to health care providers' attention for evaluation and possible services. METHOD: Analyses of epidemiologic data sets from >6000 children and parents were conducted to (1) determine the frequency of common but severely impairing symptom profiles, (2) examine symptom profile frequencies according to age and gender, (3) evaluate positive predictive values of symptom profiles relative to Diagnostic and Statistical Manual of Mental Disorders diagnoses, and (4) examine whether children with 1 or more symptom profiles receive mental health services. RESULTS: Symptom-profile frequencies ranged from 0.5% to 2.0%, and 8% of the children had 1 or more symptom profile. Profiles generated moderate-to-high positive predictive values (52.7%–75.4%) for impairing psychiatric diagnoses, but fewer than 25% of children with 1 or more profiles had received services in the previous 6 months. CONCLUSIONS: Scientifically robust symptom profiles that reflect severe but largely untreated mental health problems were identified. Used as “action signs,” these profiles might help increase public awareness about children's mental health needs, facilitate communication and referral for specific children in need of evaluation, and narrow the child mental health services gap.

Purpose The trial objectives were to identify the maximum-tolerated dose (MTD) of first-line gemcitabine plus nab-paclitaxel in metastatic pancreatic adenocarcinoma and to provide efficacy and safety data. Additional objectives were to evaluate positron emission tomography (PET) scan response, secreted protein acidic and rich in cysteine (SPARC), and CA19-9 levels in relation to efficacy. Subsequent preclinical studies investigated the changes involving the pancreatic stroma and drug uptake. Patients and Methods Patients with previously untreated advanced pancreatic cancer were treated with 100, 125, or 150 mg/m 2 nab-paclitaxel followed by gemcitabine 1,000 mg/m 2 on days 1, 8, and 15 every 28 days. In the preclinical study, mice were implanted with human pancreatic cancers and treated with study agents. Results A total of 20, 44, and three patients received nab-paclitaxel at 100, 125, and 150 mg/m 2 , respectively. The MTD was 1,000 mg/m 2 of gemcitabine plus 125 mg/m 2 of nab-paclitaxel once a week for 3 weeks, every 28 days. Dose-limiting toxicities were sepsis and neutropenia. At the MTD, the response rate was 48%, with 12.2 median months of overall survival (OS) and 48% 1-year survival. Improved OS was observed in patients who had a complete metabolic response on [ 18 F]fluorodeoxyglucose PET. Decreases in CA19-9 levels were correlated with increased response rate, progression-free survival, and OS. SPARC in the stroma, but not in the tumor, was correlated with improved survival. In mice with human pancreatic cancer xenografts, nab-paclitaxel alone and in combination with gemcitabine depleted the desmoplastic stroma. The intratumoral concentration of gemcitabine was increased by 2.8-fold in mice receiving nab-paclitaxel plus gemcitabine versus those receiving gemcitabine alone. Conclusion The regimen of nab-paclitaxel plus gemcitabine has tolerable adverse effects with substantial antitumor activity, warranting phase III evaluation.