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Deaths attributable to psychostimulants with abuse potential have increased in the United States (US) in recent years. Methamphetamine use, in particular, has risen sharply. We evaluated the correlation between amphetamine- and methamphetamine-related case exposures reported to the Michigan Poison Center (MiPC) coinciding with psychostimulant age-adjusted mortality rates from the Michigan Department of Health and Human Services (MDHHS).We compared amphetamine and methamphetamine exposures reported to the MiPC from 2012 to 2018, queried from ToxSentryPsychostimulant deaths reported by MDHHS increased from 17 to 165 between 2012 and 2018. The average age-adjusted rate of psychostimulant-involved overdose deaths per 100,000 state residents rose from 0.2 to 1.8. Linear regression of MiPC amphetamine exposure rates with state health department-reported age-adjusted psychostimulant mortality rates yielded a slope of 1.93, SE 0.5,Psychostimulant use and associated deaths in the US are increasing, representing an evolving public health threat. Michigan demonstrates consistency with national trends and data from the MiPC correlates strongly with state-reported age-adjusted psychostimulant mortality rates. Strengthening collaboration between poison centers and state health departments is critical for detection and mitigation efforts and can thereby inform resource allocation.

Objectives: We examined primary care providers' (PCPs') management of attention-deficit/hyperactivity disorder (ADHD) during and following families' participation in two arms of the Children's ADHD Telemental Health Treatment Study. We hypothesized that more intensive treatment during the trial would show an “after-effect” with more assertive PCPs' management during short term follow-up. Methods: We conducted a pragmatic follow-up of PCPs' management of children with ADHD who had been randomized to two service delivery models. In the Direct Service Model, psychiatrists provided six sessions over 22 weeks of pharmacotherapy followed by behavior training. In the Consultation Model, psychiatrists provided a single-session consultation and made treatment recommendations to PCPs who implemented these recommendations at their discretion for 22 weeks. At the end of the trial, referring PCPs for both service delivery models resumed ADHD treatment for 10 weeks. We performed intent-to-treat analysis using all 223 original participants. We applied linear regression models on continuous outcomes, Poisson regression models on count outcomes, and logistic regression models to binary outcomes. Missing data were addressed through imputations. Results: Participants in the Direct Service Model had more ADHD visits than those in the Consultation Model across the full 32 weeks (mean = 7.05 visits vs. 3.36 visits; adjusted rate ratio = 2.1 [1.85–2.38]; p

BACKGROUND: Experimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in persons with autism spectrum disorder. Oxytocin has been administered in clinical practice to many children with autism spectrum disorder. METHODS: We conducted a 24-week, placebo-controlled phase 2 trial of intranasal oxytocin therapy in children and adolescents 3 to 17 years of age with autism spectrum disorder. Participants were randomly assigned in a 1:1 ratio, with stratification according to age and verbal fluency, to receive oxytocin or placebo, administered intranasally, with a total target dose of 48 international units daily. The primary outcome was the least-squares mean change from baseline on the Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW), which includes 13 items (scores range from 0 to 39, with higher scores indicating less social interaction). Secondary outcomes included two additional measures of social function and an abbreviated measure of IQ. RESULTS: Of the 355 children and adolescents who underwent screening, 290 were enrolled. A total of 146 participants were assigned to the oxytocin group and 144 to the placebo group; 139 and 138 participants, respectively, completed both the baseline and at least one postbaseline ABC-mSW assessments and were included in the modified intention-to-treat analyses. The least-squares mean change from baseline in the ABC-mSW score (primary outcome) was −3.7 in the oxytocin group and −3.5 in the placebo group (least-squares mean difference, −0.2; 95% confidence interval, −1.5 to 1.0; P = 0.61). Secondary outcomes generally did not differ between the trial groups. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONS: This placebo-controlled trial of intranasal oxytocin therapy in children and adolescents with autism spectrum disorder showed no significant between-group differences in the least-squares mean change from baseline on measures of social or cognitive functioning over a period of 24 weeks. (Funded by the National Institute of Child Health and Human Development; SOARS-B ClinicalTrials.gov number, NCT01944046.)

OBJECTIVE: Our objective was to determine whether ADHD medication is associated with a decreased risk of unintentional injuries in children and adolescents in the United States across sexes, age groups and injury types. METHODS: We used de-identified inpatient, outpatient, and filled prescription claims data from the Truven Health MarketScan® Research Databases. Individuals were followed from January 1, 2005, date of first ADHD diagnosis or medication prescription, or age 6, whichever occurred last, until December 31, 2014, first healthcare insurance disenrollment, or the first year at which their age was recorded as 19, whichever occurred first. A person was considered on ADHD medication during a given month if a prescription was filled in that month. The outcome was defined as emergency department visits for injuries, including traumatic brain injuries, with unintentional causes. Odds of having the outcome were compared between medicated and un-medicated months at the population-level and in within-individual analyses using logistic regression. RESULTS: Among 1 968 146 individuals diagnosed with ADHD or receiving ADHD medication, 87 154 had at least one event. At the population-level, medication use was associated a lower risk of injuries, both in boys (OR= 0.85; 95% CI: 0.84–0.86) and girls (OR=0.87; 95% CI: 0.85–0.89). Similar results were obtained from within-individual analysis among male (OR= 0.72; 95% CI: 0.70–0.74) and female (OR= 0.72; 95% CI: 0.69–0.75) children, and among male (OR= 0.64; 95% CI: 0.60–0.67) and female (OR= 0.65; 95% CI: 0.60–0.71) adolescents. Similar results were found for traumatic brain injuries. CONCLUSION: ADHD medication use was associated with a reduction of different types of unintentional injuries in children and adolescents of both sexes.

Background Stereotactic radiosurgery (SRS) is a treatment modality that is frequently used as salvage therapy for small nodular recurrent high-grade gliomas (HGG). Due to the infiltrative nature of HGG, it is unclear if this highly focused technique provides a durable local control benefit. Objective To determine how demographic or clinical factors influence the pattern of failure following SRS for recurrent high-grade gliomas. Methods We retrospectively reviewed clinical, radiographic, and follow-up information for 47 consecutive patients receiving SRS for recurrent HGG at our institution between June 2006 and July 2016. All patients initially presented with an HGG (WHO grade III and IV). Following SRS for recurrence, all patients experienced treatment failure, and we evaluated patterns of local, regional, and distant failure in relation to the SRS 50% isodose line. Results Most patients with recurrent HGG developed "in-field" treatment failure following SRS (n = 40; 85%). Higher SRS doses were associated with longer time to failure (hazards ratio = 0.80 per 1 Gy increase; 95% confidence interval 0.67-0.96; P = .016). There was a statistically significant increase in distant versus in-field failure among older patients (P = .035). This effect was independent of bevacizumab use (odds ratio = 0.54, P = 1.0). Conclusion Based on our experience, the majority of treatment failures after SRS for recurrent HGG were "in-field." Older patients, however, presented with more distant failures. Our results indicate that higher SRS doses delivered to a larger area as fractioned or unfractioned regimen may prolong time to failure, especially in the older population.

Background In rapidly changing fields such as the study of drug use, the need for accurate and timely data is paramount to properly inform policy and intervention decisions. Trends in drug use can change rapidly by month, and using study designs with flexible modules could present advantages. Timely data from online panels can inform proactive interventions against emerging trends, leading to a faster public response. However, threats to validity from using online panels must be addressed to create accurate estimates. Objective The objective of this study was to demonstrate a comprehensive methodological approach that optimizes a nonprobability, online opt-in sample to provide timely, accurate national estimates on prevalence of drug use. Methods The Survey of Non-Medical Use of Prescription Drugs Program from the Researched Abuse, Diversion and Addiction Related Surveillance (RADARS) System is an online, cross-sectional survey on drug use in the United States, and several best practices were implemented. To optimize final estimates, two best practices were investigated in detail: exclusion of respondents showing careless or improbable responding patterns and calibration of weights. The approach in this work was to cumulatively implement each method, which improved key estimates during the third quarter 2018 survey launch. Cutoffs for five exclusion criteria were tested. Using a series of benchmarks, average relative bias and changes in bias were calculated for 33 different weighting variable combinations. Results There were 148,274 invitations sent to panelists, with 40,021 who initiated the survey (26.99%). After eligibility assessment, 20.23% (29,998/148,274) of the completed questionnaires were available for analysis. A total of 0.52% (157/29,998) of respondents were excluded based on careless or improbable responses; however, these exclusions had larger impacts on lower volume drugs. Number of exclusions applied were negatively correlated to total dispensing volume by drug (Spearman ρ=–.88, P Conclusions Our study illustrates a new approach to using nonprobability online panels to achieve national prevalence estimates for drug abuse. We were able to overcome challenges with using nonprobability internet samples, including misclassification due to improbable responses. Final drug use and health estimates demonstrated concurrent validity to national probability-based drug use and health surveys. Inclusion of multiple best practices cumulatively improved the estimates generated. This method can bridge the information gap when there is a need for prompt, accurate national data.

Approach-avoidance conflict arises when the drives to pursue reward and avoid harm are incompatible. Previous neuroimaging studies of approach-avoidance conflict have shown large variability in reported neuroanatomical correlates. These prior studies have generally neglected to account for potential sources of variability, such as individual differences in choice preferences and modeling of hemodynamic response during conflict. In the present study, we controlled for these limitations using a hierarchical Bayesian model (HBM). This enabled us to measure participant-specific per-trial estimates of conflict during an approach-avoidance task. We also employed a variable epoch method to identify brain structures specifically sensitive to conflict. In a sample of 28 human participants, we found that only a limited set of brain structures [inferior frontal gyrus (IFG), right dorsolateral prefrontal cortex (dlPFC), and right pre-supplementary motor area (pre-SMA)] are specifically correlated with approach-avoidance conflict. These findings suggest that controlling for previous sources of variability increases the specificity of the neuroanatomical correlates of approach-avoidance conflict.

OBJECTIVE Brain arteriovenous malformations (bAVMs) are rare in pediatric patients but represent the most common cause of hemorrhagic stroke in this population. Pediatric patients demonstrate superior outcomes in comparison with adult patients with similar lesions and presentations. Most studies of clinical outcomes of pediatric bAVMs use the modified Rankin Scale (mRS), despite a lack of validation in pediatric patients. METHODS The authors interviewed the parents of 26 pediatric patients who underwent multimodality bAVM treatment and administered the Pediatric Quality of Life Inventory (PedsQL)—a well-validated tool for pediatric outcomes that quantifies performance in a physical, emotional, social, and school domains. They also reviewed clinical information from the patients' medical charts. Statistical analysis was performed using a log-transformed t-test, the Mann-Whitney exact test, the Kruskal-Wallis test, and Spearman correlation. In addition, the literature was reviewed for prior reports of clinical outcome of pediatric cases of bAVM. RESULTS The average PedsQL health-related quality of life score was 71 ± 24, with an average age at diagnosis of 12.5 years and an average follow-up period of 6.8 years. Seventeen patients (65%) presented with hemorrhage and 4 (15%) with seizures. PedsQL scores correlated strongly and at a statistically significant level (p < 0.001) with mRS, Pediatric Overall Performance Category (POPC), Pediatric Cerebral Performance Category (PCPC), and Glasgow Outcome Scale scores. Multivariate modeling validated special education, corrective devices, and cure status as significant predictors of PedsQL scores. Statistically significant risk factors for undergoing placement of a ventriculoperitoneal shunt included lower Glasgow Coma Scale motor scores on admission (p = 0.042), cerebellar location (p = 0.046), and nidus volume (p = 0.017). Neither treatment modality nor location statistically affected clinical outcomes at follow-up. CONCLUSIONS There have been few studies of long-term clinical outcomes of bAVM in pediatric patients, and previously published studies have used conventional metrics that have been validated in the adult population, such as the mRS. Although these metrics can serve as reasonable surrogates, an accurate understanding of overall health-related quality of life is contingent on utilizing validated toolsets, such as the PedsQL.

BACKGROUND Brain arteriovenous malformations (BAVMs) are a frequent cause of pediatric hemorrhagic stroke, which frequently results in significant morbidity and mortality. OBJECTIVE To analyze the results of multimodality treatment for a consecutive series of pediatric patients with ruptured and unruptured BAVMs at a single institution. METHODS Forty patients

The Children’s Attention-deficit Hyperactivity Disorder (ADHD) Telemental Health Treatment Study (CATTS) tested the hypotheses that children and caregivers who received guideline-based treatment delivered through a hybrid telehealth service delivery model would experience greater improvements in outcomes than children and caregivers receiving treatment via a comparison delivery model. Here, we present caregiver outcomes. 88 primary care providers (PCPs) in seven geographically underserved communities referred 223 children (ages 5.5 − 12.9 years) to the randomized controlled trial. Over 22 weeks, children randomized to the CATTS service delivery model received six sessions of telepsychiatry and six sessions of caregiver behavior management training provided in person by community therapists who were trained and supervised remotely. Children randomized to the comparison Augmented Primary Care (APC) service model received management in primary care augmented by a single telepsychiatry consultation. Caregiver outcomes included changes in distress, as measured by the Patient Health Questionnaire (PHQ-9), Parenting Stress Index (PSI), Caregiver Strain Questionnaire (CSQ) and Family Empowerment Scale (FES). Caregivers completed five assessments. Multilevel mixed effects regression modeling tested for differences between the two service delivery models in caregiver outcomes from baseline to 25 weeks. Compared to caregivers of children in the APC model, caregivers of children in the CATTS service model showed statistically significantly greater improvements on the PHQ-9 (β = -1.41, 95 % CI = [−2.74, −0.08], p

Oscillations of the brain's local field potential (LFP) may coordinate neural ensembles and brain networks. It has been difficult to causally test this model or to translate its implications into treatments, because there are few reliable ways to alter LFP oscillations. We developed a closed-loop analog circuit to enhance brain oscillations by feeding them back into cortex through phase-locked transcranial electrical stimulation. We tested the system in a rhesus macaque with chronically implanted electrode arrays, targeting 8-15 Hz (alpha) oscillations. Ten seconds of stimulation increased alpha oscillatory power for up to 1 second after stimulation offset. In contrast, open-loop stimulation decreased alpha power. There was no effect in the neighboring 15-30 Hz (beta) LFP rhythm or on a neighboring array that did not participate in closed-loop feedback. Analog closed-loop neurostimulation might thus be a useful strategy for altering brain oscillations, both for basic research and the treatment of neuro-psychiatric disease.

Hyperactivity, impulsiveness, and distractibility are common problems in children with autism spectrum disorder (ASD). Extended-release guanfacine is approved for children with attention deficit hyperactivity disorder but not well studied in ASD.In a multisite, randomized clinical trial, extended-release guanfacine was compared with placebo in children with ASD accompanied by hyperactivity, impulsiveness, and distractibility.Sixty-two subjects (boys, N=53; girls, N=9; mean age=8.5 years [SD=2.25]) were randomly assigned to guanfacine (N=30) or placebo (N=32) for 8 weeks. The guanfacine group showed a 43.6% decline in scores on the Aberrant Behavior Checklist-hyperactivity subscale (least squares mean from 34.2 to 19.3) compared with a 13.2% decrease in the placebo group (least squares mean from 34.2 to 29.7; effect size=1.67). The rate of positive response (much improved or very much improved on the Clinical Global Impression-Improvement scale) was 50% (15 of 30) for guanfacine compared with 9.4% (3 of 32) for placebo. A brief cognitive battery tapping working memory and motor planning showed no group differences before or after 8 weeks of treatment. The modal dose of guanfacine at week 8 was 3 mg/day (range: 1-4 mg/day), and the modal dose was 3 mg/day (range: 2-4 mg/day) for placebo. Four guanfacine-treated subjects (13.3%) and four placebo subjects (12.5%) exited the study before week 8. The most common adverse events included drowsiness, fatigue, and decreased appetite. There were no significant changes on ECG in either group. For subjects in the guanfacine group, blood pressure declined in the first 4 weeks, with return nearly to baseline by endpoint (week 8). Pulse rate showed a similar pattern but remained lower than baseline at endpoint.Extended-release guanfacine appears to be safe and effective for reducing hyperactivity, impulsiveness, and distractibility in children with ASD.

Background The design and conclusions of A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) trial are controversial, and its structure limits analysis of patients who could potentially benefit from treatment. Objective To analyze the results of a consecutive series of patients with unruptured brain arteriovenous malformations (BAVMs), including a subgroup analysis of ARUBA-eligible patients. Methods One hundred five patients with unruptured BAVMs were treated over an 8-year period. From this series, 90 adult patients and a subgroup of 61 patients determined to be ARUBA eligible were retrospectively reviewed. A subgroup analysis for Spetzler-Martin grades I/II, III, and IV/V was performed. The modified Rankin Scale was used to assess functional outcome. Results Persistent deficits, modified Rankin Scale score deterioration, and impaired functional outcome occurred less frequently in ARUBA-eligible grade I/II patients compared with grade III to V patients combined (P = .04, P = .04, P = .03, respectively). Twenty-two of 39 patients (56%) unruptured grade I and II BAVMs were treated with surgery without and with preoperative embolization, and all had a modified Rankin Scale score of 0 to 1 at the last follow-up. All patients treated with surgery without and with preoperative embolization had radiographic cure at the last follow-up. Conclusion The results of ARUBA-eligible and unruptured grade I/II patients overall show that excellent outcomes can be obtained in this subgroup of patients, especially with surgical management. Functional outcomes for ARUBA-eligible patients were similar to those of patients who were randomized to medical management in ARUBA. On the basis of these data, in appropriately selected patients, we recommend treatment for low-grade BAVMs.

BackgroundEmbolization before stereotactic radiosurgery (SRS) for brain arteriovenous malformations (BAVMs) is controversial.ObjectiveTo compare clinical and radiographic outcomes in patients undergoing pre-SRS embolization with ethylene copolymer (Onyx) with outcomes in patients undergoing SRS alone.MethodsSeventy consecutive patients with BAVMs who underwent SRS were retrospectively reviewed. Univariate and multivariate analyses were performed to assess the factors associated with radiographic obliteration and complication.ResultsForty-one (59%) patients presented without BAVM rupture and 29 (41%) patients presented with rupture. Pre-SRS embolization was used in 20 patients (28.6%; 7 unruptured and 13 ruptured). Twenty-five of 70 (36%) patients sustained a complication from treatment, including 6 (9%) patients with a post-SRS latency period hemorrhage. Ten (14%) patients had persistent neurological deficits after treatment. Functional outcome (as modified Rankin Scale), complication rate, and radiographic obliteration at last follow-up were not significantly different between embolized and non-embolized groups in both unruptured and ruptured BAVMs. For unruptured BAVMs, 3- and 5-year rates of radiographic obliteration were 23% and 73% for non-embolized patients and 20% and 60% for embolized patients, respectively. For ruptured BAVMs, 3- and 5-year rates of radiographic obliteration were 45% and 72% for non-embolized patients and 53% and 82% for embolized patients, respectively.ConclusionPre-SRS embolization with Onyx was not associated with worse clinical or radiographic outcomes than SRS treatment without embolization. Pre-SRS embolization has a low complication rate and can safely be used to target high-risk BAVM features in carefully selected patients destined for SRS.

Temozolomide (TMZ) is one of the most potent chemotherapy agents for the treatment of glioblastoma. Unfortunately, almost half of glioblastoma tumors are TMZ resistant due to overexpression of methylguanine methyltransferase (MGMT(hi)). Coadministration of O6-benzylguanine (O6BG) can restore TMZ sensitivity, but causes off-target myelosuppression. Here, we conducted a prospective clinical trial to test whether gene therapy to confer O6BG resistance in hematopoietic stem cells (HSCs) improves chemotherapy tolerance and outcome.We enrolled 7 newly diagnosed glioblastoma patients with MGMT(hi) tumors. Patients received autologous gene-modified HSCs following single-agent carmustine administration. After hematopoietic recovery, patients underwent O6BG/TMZ chemotherapy in 28-day cycles. Serial blood samples and tumor images were collected throughout the study. Chemotherapy tolerance was determined by the observed myelosuppression and recovery following each cycle. Patient-specific biomathematical modeling of tumor growth was performed. Progression-free survival (PFS) and overall survival (OS) were also evaluated.Gene therapy permitted a significant increase in the mean number of tolerated O6BG/TMZ cycles (4.4 cycles per patient, P0.05) compared with historical controls without gene therapy (n = 7 patients, 1.7 cycles per patient). One patient tolerated an unprecedented 9 cycles and demonstrated long-term PFS without additional therapy. Overall, we observed a median PFS of 9 (range 3.5-57+) months and OS of 20 (range 13-57+) months. Furthermore, biomathematical modeling revealed markedly delayed tumor growth at lower cumulative TMZ doses in study patients compared with patients that received standard TMZ regimens without O6BG.These data support further development of chemoprotective gene therapy in combination with O6BG and TMZ for the treatment of glioblastoma and potentially other tumors with overexpression of MGMT.Clinicaltrials.gov NCT00669669.R01CA114218, R01AI080326, R01HL098489, P30DK056465, K01DK076973, R01HL074162, R01CA164371, R01NS060752, U54CA143970.

Objective Evaluate determinants of mental health service use among depressed adolescents. Method We assessed mental health services use over the 12 months following screening among 113 adolescents (34 males, 79 females) from an integrated healthcare system who screened positive for depression (Patient Health Questionnaire-9 score ≥11). Youth characteristics (demographics, depression severity, and co-morbidity) and parent characteristics (parent history of depression, parent-report of youth externalizing and internalizing problems) were compared among youth who had received mental health services and those who had not. Multivariate regression was used to evaluate the strongest factors associated with mental health service use. Results Overall, 52% of adolescents who screened positive for depression received mental health service in the year following screening. Higher parent-reported youth internalizing problems (OR 5.37, CI 1.77–16.35), parental history of depression/anxiety (OR 4.12, CI 1.36–12.48) were significant factors associated with mental health service use. Suicidality and functional impairment were not associated with increased mental health services use. Conclusion Parental factors including recognition of the adolescent's internalizing symptoms and parental experience with depression/anxiety are strongly associated with mental health service use for depressed adolescents. This highlights the importance of educating parents about depression and developing systems to actively screen and engage youth in treatment for depression.

Hemangiopericytomas (HPC) are mesenchymal tumors with a propensity towards chronicity and metastasis. This study aimed to reflect a single institution experience with both World Health Organization (WHO) grade II and III HPC. Pathology records from the years 1990-2013 at the University of Washington were searched to identify tumors unequivocally classified as HPC. Electronic chart review was then utilized to collect pertinent patient data. Of the WHO grade II HPC, there were four men and two women (average age 52 years) while the grade III HPC group had eight men and two women (average age 51 years). Sixty-six percent of WHO grade II tumors were located in the middle or posterior fossa as compared to none of the grade III tumors. Survival analysis revealed a significant survival benefit for patients who underwent complete resection (223 months) versus those with subtotal resection (138 months, p0.05). Factors such as age, sex, the use of up-front radiation, and whether the patient had a recurrence did not show statistical significance related to overall survival or progression free survival. Radiation in the form of external beam radiotherapy given at the time of the first recurrence did trend towards improved progression free survival (56 months) compared to those patients who were not radiated (22 months, p=0.09) All patients with radical resection went on to never have a recurrence. Our results indicate that HPC are tumors with limited response to radiation and best treated with aggressive resection. Future studies will determine whether molecular-based therapies may provide added adjuvant benefit.

This article evaluates the additive effects of children's comorbid conditions with attention-deficit/hyperactivity disorder (ADHD) in relation to caregivers' distress, in a clinical trial conducted through telemental health (TMH).The Children's ADHD Telemental Health Treatment Study (CATTS) is examining the effectiveness of treatment delivered via TMH for children with ADHD who are living in underserved communities. The CATTS trial recruited 223 children (μ=9.53±2.06 years) and their caregivers. Diagnoses of ADHD and comorbid oppositional defiant disorder (ODD) and anxiety disorders (ADs) were established with the Child Behavior Checklist and the Computerized Diagnostic Interview Schedule for Children. We took advantage of rich baseline data from the CATTS trial to investigate associations between caregivers' distress and children's comorbid mental health conditions. Caregivers' distress was assessed with the Patient Health Questionnaire-9, Parenting Stress Index, and Caregiver Strain Questionnaire. ANOVAs were used to compare children with ADHD alone with children having one comorbid condition (ODD or ADs) and children having two comorbid conditions (ODD and ADs).Three quarters (75.3%) of participants met criteria for ODD and/or AD comorbid with ADHD: 24.7% had neither comorbidity; 47.5% had ODD or AD; and 27.8% had both ODD and AD comorbidities. The parents of children with multiple comorbid conditions experienced the highest levels of depression, stress, and burden of care.The CATTS sample that was recruited from underserved communities provided evidence of additive effects of child psychiatric comorbidities with caregivers' distress, echoing earlier findings from the Multi-modal Treatment of ADHD (MTA) study that was conducted with a metropolitan sample of youth. Results indicate that caregivers' distress should be addressed in developing treatment models for children with ADHD.http://clinicaltrials.gov/show/NCT00830700 .

To assess the diagnostic yield of a computed tomography urography (CTU) study in patients less than 50 years of age, who have a history of military service, and who are at increased risk of urological cancers secondary to harmful practices and work-related exposures. 137 Consecutive patients who underwent CTU between 2012 and 2013 for new onset of hematuria were included. Initial review of the clinical interpretations of the CTU studies grouped the studies into negative and positive exams for any urological findings. Review of the patients’ medical records and subsequent radiology studies determined microscopic versus gross hematuria at presentation and any findings after their CTU study consistent with a urological malignancy. The positive exams were reviewed by second readers, blinded to the clinical interpretation of the initial CTU studies, who first read the unenhanced images. The readers characterized findings as visible on non-contrast CT alone or they requested contrast-enhanced images. Each urological finding was recorded for each patient. Of the 137 included patients, 84 had micro-hematuria and 53 had gross hematuria. There were a total of 99 negative examinations of the 137 included patients. Contrast was requested 14 times to confirm 11 benign cysts. No findings concerning for malignancy were found by the readers or on subsequent record reviews for each patient. An unenhanced CT may be appropriate to evaluate new onset microscopic, and possibly gross hematuria, in patients younger than 40, even in patients at increased risk of urologic cancer.

Anesthetic protocols that allow quick induction, short processing time, and rapid reversal are necessary for researchers performing minimally invasive procedures (including morphometric measurements or attachment of radiocollars). The objective of this study was to evaluate the effectiveness of medetomidine and butorphanol as a substitute for xylazine in ketamine-based field immobilization protocols for bobcats (Lynx rufus) to reduce recovery and total field times. During 2008 and 2009, 11 bobcats were immobilized with an intramuscular combination of ketamine (10 mg/kg)-xylazine (0.75 mg/kg) (KX) or ketamine (4 mg/kg)-medetomidine (40 mcg/kg)-butorphanol (0.4 mg/kg) (KMB). Time to initial sedation, recumbency, and full anesthesia were recorded postinjection. Time to head up, sternal, standing, full recovery, and total processing times were recorded post-reversal. Throughout anesthesia, heart rate (HR), respiratory rate (RR), rectal temperature (RT), and noninvasive hemoglobin-oxygen saturation (SpO2) were recorded at 5-min intervals. The KX combination had a median time to full anesthesia of 10 min, a median recovery time of 46 min, and a median total processing time of 83 min. Alternatively, the KMB combination had a median time to full anesthesia of 21 min, a median recovery time of 18 min, and a median total processing time of 64 min. The KX protocol produced a median HR of 129 beats/min, RR of 25 breaths/min, RT of 38.3 degrees C, and SpO2 of 93%. The KMB protocol produced a median HR of 97 beats/min, RR of 33 breaths/min, RT of 38.4 degrees C, and SpO2 of 92%. Though both protocols provided safe and reliable sedation, the benefits of using medetomidine and butorphanol to lower ketamine doses and decrease processing time for brief nonsurgical sedation of bobcats in the field are presented.

Comparison of healthcare costs for youth with mild traumatic brain injuries (TBIs) to costs in a matched cohort of children without TBI in the 3 years following injury.This study used a prospective cohort design with 3-year follow-up. Costs were examined using the well-established two-step model and controlling for potential confounding variables.Four-hundred and ninety subjects from a large health maintenance organization, 14 years old or younger, who sustained a mild TBI in 1993, were identified using computerized records. For each youth with mild TBI, three control subjects were selected (n = 1470), matched on age, sex and enrolment at the time of injury.Not applicable.TBI exposure was associated with an increase in the proportion of subjects who had non-zero medical costs in all categories examined and a 75% increase in mean total costs. Presence of psychological distress was also associated with increased proportion of subjects with costs in all categories examined and was associated with an approximate doubling of mean total costs.Mild TBI and psychological distress were each associated with significant increases in healthcare costs in an HMO setting.

To describe the differential completion rates and cost of sequential methods for a survey of adolescents enrolled in a regional health care delivery organization.Four thousand randomly selected enrollees were invited to complete a mailed health survey. Techniques used to boost response included (1) a follow-up mailing, (2) varying the appearance of the survey, (3) reminder calls, and (4) phone calls to obtain parent and child consent and to administer the survey. We evaluated the outcome and costs of these methods.Seven hundred eighty-three enrollees (20%) completed the first mailed survey and 521 completed the second, increasing the overall response rate to 33%. Completion was significantly higher among respondents who received only the plain survey than those receiving only the color survey (P.001). Reminder calls boosted response by 8%. Switching to administration of the survey by phone boosted response by 20% to 61%. The cost per completed survey was $29 for the first mailing, $26 after both mailings, $42 for mailings and reminder calls, and $48 for adding phone surveys.The response to mailings and reminder calls was low and the cost was high, with decreasing yield at each step, although some low-cost techniques were helpful. Results suggest phone surveys may be most effective among similar samples of adolescents.

A complex therapeutic challenge for Alzheimer's disease (AD) is minimizing deleterious aspects of microglial activation while maximizing beneficial actions, including phagocytosis/clearance of amyloid beta (Abeta) peptides. One potential target is selective suppression of microglial prostaglandin E(2) receptor subtype 2 (EP2) function, which influences microglial phagocytosis and elaboration of neurotoxic cytokines. To test this hypothesis, we transplanted bone marrow cells derived from wild-type mice or mice homozygous deficient for EP2 (EP2(-/-)) into lethally irradiated 5-month-old wild-type or APPswe-PS1DeltaE9 double transgenic AD mouse model recipients. We found that cerebral engraftment by bone marrow transplant (BMT)-derived wild-type or EP2(-/-) microglia was more efficient in APPswe-PS1DeltaE9 than in wild-type mice, and APPswe-PS1DeltaE9 mice that received EP2(-/-) BMT had increased cortical microglia compared with APPswe-PS1DeltaE9 mice that received wild-type BMT. We found that myeloablative irradiation followed by bone marrow transplant-derived microglia engraftment, rather than cranial irradiation or BMT alone, was responsible for the approximate one-third reduction in both Abeta plaques and potentially more neurotoxic soluble Abeta species. An additional 25% reduction in cerebral cortical Abeta burden was achieved in mice that received EP2(-/-) BMT compared with mice that received wild-type BMT. Our results provide a foundation for an adult stem cell-based therapy to suppress soluble Abeta peptide and plaque accumulation in the cerebrum of patients with AD.

Objective Although multiple studies of adolescents have examined the association of depression with individual health risk behaviors such as obesity or smoking, this is one of the few studies that examined the association between depression and multiple risk behaviors. Methods A brief mail questionnaire, which screened for age, gender, weight, height, sedentary behaviors, physical activity, perception of general health, functional impairment and depressive symptoms, was completed by a sample of 2291 youth (60.7% response rate) aged 13–17 enrolled in a health care plan. A subset of youth who screened positive on the two-item depression screen and a random sample of those screening negative were approached to participate in a telephone interview with more in-depth information obtained on smoking and at-risk behaviors associated with drug and alcohol use. Results Youth screening positive for high levels of depressive symptoms compared to those with few or no depressive symptoms were significantly more likely to meet criteria for obesity, had a poorer perception of health, spent more time on the computer, got along less well with parents and friends, had more problems completing school work and were more likely to have experimented with smoking and a wide array of behaviors associated with drug and alcohol use. Conclusions Because many adverse health behaviors that develop in adolescence continue into adulthood, the association of depressive symptoms with multiple risk behaviors and poor functioning suggest that early interventions are needed at an individual, school, community and primary care level.

Anxiety disorders are among the most common and functionally impairing mental health disorders to occur in childhood and adolescence. Primary care providers can expect to treat youth who have anxiety disorders frequently, and this article aims to provide the tools necessary to evaluate and manage patients who present with anxiety symptoms during childhood or adolescence. This article discusses the epidemiology of anxiety disorders, including the increased risk of future anxiety disorders and other mental health problems that are associated with having an anxiety disorder in childhood and adolescence. Next, the etiology of anxiety disorders is delineated, including discussion of genetic, cognitive-behavioral, physiological, and ecological explanatory models, and a summary of neurophysiological findings related to childhood and adolescent anxiety. Next, methods and tools are presented for assessment and treatment of anxiety disorders, with a focus on assessment and treatment that can be initiated in a primary care setting. Evidence-based therapy and medication interventions are reviewed. The article includes a focus on developmental differences in symptom presentation, assessment techniques, and treatment strategies, such that a primary care provider will have tools for working with the wide age range in their practices: preschool children through adolescents. We conclude that many effective intervention strategies exist, and their improving availability and ease of use makes it both critical and achievable for children and adolescents with anxiety disorders to be accurately diagnosed and treated with evidence-based medication and therapy.

Purpose: Hypoxia is associated with resistance to radiotherapy and chemotherapy and activates transcription factors that support cell survival and migration. We measured the volume of hypoxic tumor and the maximum level of hypoxia in glioblastoma multiforme before radiotherapy with [18F]fluoromisonidazole positron emission tomography to assess their impact on time to progression (TTP) or survival. Experimental Design: Twenty-two patients were studied before biopsy or between resection and starting radiotherapy. Each had a 20-minute emission scan 2 hours after i.v. injection of 7 mCi of [18F]fluoromisonidazole. Venous blood samples taken during imaging were used to create tissue to blood concentration (T/B) ratios. The volume of tumor with T/B values above 1.2 defined the hypoxic volume (HV). Maximum T/B values (T/Bmax) were determined from the pixel with the highest uptake. Results: Kaplan-Meier plots showed shorter TTP and survival in patients whose tumors contained HVs or tumor T/Bmax ratios greater than the median (P ≤ 0.001). In univariate analyses, greater HV or tumor T/Bmax were associated with shorter TTP or survival (P < 0.002). Multivariate analyses for survival and TTP against the covariates HV (or T/Bmax), magnetic resonance imaging (MRI) T1Gd volume, age, and Karnovsky performance score reached significance only for HV (or T/Bmax; P < 0.03). Conclusions: The volume and intensity of hypoxia in glioblastoma multiforme before radiotherapy are strongly associated with poorer TTP and survival. This type of imaging could be integrated into new treatment strategies to target hypoxia more aggressively in glioblastoma multiforme and could be applied to assess the treatment outcomes.

Pain is a feared component of cancer for a patient. The patient's prior experience with cancer pain will affect how he or she deals with ongoing and acute onset new pain. Radiation therapy has been and continues to be a major component in the management of cancer pain. New technologies are rapidly becoming available that will allow more specific and accurate targeting, while limiting the dose that is received by normal tissues and thus minimizing the potential for tissue toxicity. How new techniques and technologies are incorporated into the management of cancer pain will require a better understanding of the disease process being treated.

This observational study supplements the strong and consistent link found between childhood depression and deficits in interpersonal functioning by examining the relationship between a high versus low score on the Children's Depression Inventory (CDI) and children's emotions when interacting with their best friends. High-CDI and low-CDI target children (n=86) were paired for videotaped game-playing with self-reported best friends. Researchers found that although high-CDI target children were not distinguishable from low-CDI peers in their displays of positive and negative emotion. However, the partners of high-CDI target children displayed significantly more negative emotion during the competitive task and significantly less positive emotion during the cooperative task than did partners of low-CDI target children. In addition, high-CDI target children and their partners reported less enjoyment of their interactions than low-CDI target children and their partners. This combination of findings suggests that depressive symptoms were associated with a relative lack of success achieving an optimal friendship interaction even under highly favorable conditions.

The purpose of this study was to examine the prescribing strategies that telepsychiatrists used to provide pharmacologic treatment in the Children's Attention-Deficit/Hyperactivity Disorder (ADHD) Telemental Health Treatment Study (CATTS).CATTS was a randomized controlled trial that demonstrated the superiority of a telehealth service delivery model for the treatment of ADHD with combined pharmacotherapy and behavior training (n=111), compared with management in primary care augmented with a telepsychiatry consultation (n=112). A diagnosis of ADHD was established with the Computerized Diagnostic Interview Schedule for Children (CDISC), and comorbidity for oppositional defiant disorder (ODD) and anxiety disorders (AD) was established using the CDISC and the Child Behavior Checklist. Telepsychiatrists used the Texas Children's Medication Algorithm Project (TCMAP) for ADHD to guide pharmacotherapy and the treat-to-target model to encourage their assertive medication management to a predetermined goal of 50% reduction in ADHD-related symptoms. We assessed whether telepsychiatrists' decision making about making medication changes was associated with baseline ADHD symptom severity, comorbidity, and attainment of the treat-to-target goal.Telepsychiatrists showed high fidelity (91%) to their chosen algorithms in medication management. At the end of the trial, the CATTS intervention showed 46.0% attainment of the treat-to-target goal compared with 13.6% for the augmented primary care condition, and significantly greater attainment of the goal by comorbidity status for the ADHD with one and ADHD with two comorbidities groups. Telepsychiatrists' were more likely to decide to make medication adjustments for youth with higher baseline ADHD severity and the presence of disorders comorbid with ADHD. Multiple mixed methods regression analyses controlling for baseline ADHD severity and comorbidity status indicated that the telepsychiatrists also based their decision making session to session on attainment of the treat-to-target goal.Telepsychiatry is an effective service delivery model for providing pharmacotherapy for ADHD, and the CATTS telepsychiatrists showed high fidelity to evidence-based protocols.

High-grade (World Health Organization [WHO] Grade II and III) meningiomas constitute a minority of all meningioma cases but are associated with significant morbidity and mortality, due to more aggressive tumor behavior and a tendency to recur despite standard therapy with resection and radiotherapy. They display a higher degree of vascularity than WHO Grade I meningiomas and produce angiogenic and growth factors, including vascular endothelial growth factor (VEGF). Bevacizumab, a humanized monoclonal antibody against VEGF-A, has been used in the treatment of recurrent or progressive meningiomas resistant to standard therapy. We report a patient with a recurrent left frontotemporal meningioma and associated-vision loss who experienced substantial visual field recovery after 3 cycles of bevacizumab. In addition, we provide a review of the literature regarding the efficacy of bevacizumab in the treatment of recurrent meningiomas.

Purpose The purpose of phase 1 was to determine the maximum tolerated dose (MTD) of motexafin gadolinium (MGd) given concurrently with temozolomide (TMZ) and radiation therapy (RT) in patients with newly diagnosed supratentorial glioblastoma multiforme (GBM). Phase 2 determined whether this combination improved overall survival (OS) and progression-free survival (PFS) in GBM recursive partitioning analysis class III to V patients compared to therapies for recently published historical controls. Methods and Materials Dose escalation in phase 1 progressed through 3 cohorts until 2 of 6 patients experienced dose-limiting toxicity or a dose of 5 mg/kg was reached. Once MTD was established, a 1-sided 1-sample log-rank test at significance level of .1 had 85% power to detect a median survival difference (13.69 vs 18.48 months) with 60 deaths over a 12-month accrual period and an additional 18 months of follow-up. OS and PFS were estimated using the Kaplan-Meier method. Results In phase 1, 24 patients were enrolled. The MTD established was 5 mg/kg, given intravenously 5 days a week for the first 10 RT fractions, then 3 times a week for the duration of RT. The 7 patients enrolled in the third dose level and the 94 enrolled in phase 2 received this dose. Of these 101 patients, 87 were eligible and evaluable. Median survival time was 15.6 months (95% confidence interval [CI]: 12.9-17.6 months), not significantly different from that of the historical control ( P =.36). Median PFS was 7.6 months (95% CI: 5.7-9.6 months). One patient (1%) experienced a grade 5 adverse event possibly related to therapy during the concurrent phase, and none experience toxicity during adjuvant TMZ therapy. Conclusions Treatment was well tolerated, but median OS did not reach improvement specified by protocol compared to historical control, indicating that the combination of standard RT with TMZ and MGd did not achieve a significant survival advantage.

Purpose: To identify and illustrate the potential problems with brachytherapy in obese patients. Methods and Materials: Three patients with body mass index greater than 30 were treated with prostate brachytherapy. Transrectal ultrasound (TRUS) was performed using a 6.0-MHz Siemens Sonoline Prima ultrasound machine and a Barzell-Whitmore stepper unit. The patients' weight required use of an accessory table support. Results: Once set up, there was ample room to maneuver, providing that the patient's legs were abducted fully. TRUS imaging of the prostate was unaffected by patients' obesity. The amount of periprostate adipose tissue visualized on TRUS appeared to be no different than that noted in nonobese patients. Similarly, there was no increased distance between the prostate and rectal surface, either on preimplant CT or transverse TRUS. To date, our experience is that the perineal skin to prostate distance was not so great that standard 20-cm applicator needles could not be used. For the 2 sub–350-pound patients who could be imaged on our CT scanner, postimplant target coverage (V100) was 88% and 95%. Conclusions: Standard TRUS and brachytherapy needles are sufficient to implant even the largest patients.

Glioblastoma multiforme is the most aggressive type of primary brain tumor. Glioblastoma growth dynamics vary widely across patients, making it difficult to accurately gauge their response to treatment. We developed a model-based metric of therapy response called Days Gained that accounts for this heterogeneity. Here, we show in 63 newly diagnosed patients with glioblastoma that Days Gained scores from a simple glioblastoma growth model computed at the time of the first postradiotherapy MRI scan are prognostic for time to tumor recurrence and overall patient survival. After radiation treatment, Days Gained also distinguished patients with pseudoprogression from those with true progression. Because Days Gained scores can be easily computed with routinely available clinical imaging devices, this model offers immediate potential to be used in ongoing prospective studies. Cancer Res; 73(10); 2976–86. ©2013 AACR.

OBJECTIVE: To examine predictors of depression persistence after a positive screening test to inform management protocols for screened youth. METHODS: We conducted a cohort study of 444 youth (aged 13–17 years) from a large health care delivery system. Youth with depressive symptoms, based on a 2-item depression screen, were oversampled for the baseline interview. Baseline assessments included the Patient Health Questionnaire 9-item (PHQ-9) depression screen as well as clinical factors that were hypothesized to influence depression persistence (family history of depression, functional impairment, perceived social support, anxiety symptoms, externalizing symptoms, and medical comorbidity). Logistic regression analysis was used to examine factors associated with the persistence of depression at 6 months postbaseline. RESULTS: Of 113 youth with a positive baseline screen (PHQ-9 ≥11), 47% and 35% continued to be positive at 6-week and 6-month follow-up, respectively. After controlling for treatment status, only 2 factors were significantly associated with depression persistence at 6 months: baseline depressive symptom score and continuing to have a positive screen at 6 weeks. For each 1-point increase on the PHQ-9 score at baseline, youth had a 16% increased odds of continuing to be depressed at 6 months (odds ratio: 1.16, 95% confidence interval: 1.01–1.34). Youth who continued to screen positive 6 weeks later had almost 3 times the odds of being depressed at 6 months (odds ratio: 2.89, 95% confidence interval: 1.09–7.61). CONCLUSIONS: Depressive symptom severity at presentation and continued symptoms at 6 weeks postscreening are the strongest predictors of depression persistence. Patients with high depressive symptom scores and continued symptoms at 6 weeks should receive active treatment.

Objective This study examined differences in co-occurring symptoms, psychosocial correlates, health care utilization and functional impairment in youth who screened positive for depression, stratified by whether or not they also self-reported externalizing problems. Methods The AdoleSCent Health Study examined a random sample of youth ages 13–17 enrolled in a health care system. A total of 2291 youth (60.7% of the eligible sample) completed a brief depression screen: the two-item Patient Health Questionnaire. The current analyses focus on a subset of youth ( n =113) who had a follow-up interview and screened positive for possible depression on the Patient Health Questionnaire 9 using a cutoff score of 11 or higher [1]. Youth were categorized as having externalizing behavior if their score was ≥7 on the Pediatric Symptom Checklist (PSC) externalizing scale [2,3]. χ 2 tests and Wilcoxon rank sum tests were used to compare groups. Results Differences between groups included that youth with depression and externalizing symptoms had a higher rate of obesity and had higher self-reported functional impairment than youth with depression symptoms alone. Conclusions Adding screening for externalizing problems to existing recommendations for depression screening may help primary care providers to identify a high-risk depressed group of youth for referral to mental health services.

Summary Increasing age is the most robust predictor of greater malignancy and treatment resistance in human gliomas. However, the adverse association of clinical course with aging is rarely considered in animal glioma models, impeding delineation of the relative importance of organismal versus progenitor cell aging in the genesis of glioma malignancy. To address this limitation, we implanted transformed neural stem/progenitor cells (NSPCs), the presumed cells of glioma origin, from 3- and 18-month-old mice into 3- and 20-month host animals. Transplantation with progenitors from older animals resulted in significantly shorter (P ≤ 0.0001) median survival in both 3-month (37.5 vs. 83 days) and 20-month (38 vs. 67 days) hosts, indicating that age-dependent changes intrinsic to NSPCs rather than host animal age accounted for greater malignancy. Subsequent analyses revealed that increased invasiveness, genomic instability, resistance to therapeutic agents, and tolerance to hypoxic stress accompanied aging in transformed NSPCs. Greater tolerance to hypoxia in older progenitor cells, as evidenced by elevated HIF-1 promoter reporter activity and hypoxia response gene (HRG) expression, mirrors the upregulation of HRGs in cohorts of older vs. younger glioma patients revealed by analysis of gene expression databases, suggesting that differential response to hypoxic stress may underlie age-dependent differences in invasion, genomic instability, and treatment resistance. Our study provides strong evidence that progenitor cell aging is responsible for promoting the hallmarks of age-dependent glioma malignancy and that consideration of progenitor aging will facilitate development of physiologically and clinically relevant animal models of human gliomas.

A cohort design was used to determine the contribution of traumatic brain injury (TBI) and psychiatric illness to health care costs for adolescents and adults in the 3 years following mild or moderate-to-severe TBI compared to a matched cohort without TBI, controlling for confounders. In all, 3756 subjects 15 years or older from a large health maintenance organization database were examined. We identified subjects who sustained a TBI in 1993 (n=939) and selected three control subjects per TBI-exposed subject (n=2817), matched for age, sex, and enrollment at the time of injury. Unadjusted mean costs in 2009-adjusted dollars were compared using Kruskal-Wallis tests and Mann-Whitney U tests, and adjusted mean costs were compared using gamma regression analyses. Average costs were 76% higher in the 3 years after injury for the mild TBI group, and 5.75 times greater for the moderate-to-severe TBI group compared to controls. The presence of psychiatric illness was associated with more than doubling of total costs for both inpatient and outpatient non-mental health care. Gamma regression analyses confirmed significantly higher costs in patients with TBI or psychiatric illness. A significant interaction between moderate-to-severe TBI and psychiatric illness indicated a 3.39 times greater cost among patients with both exposures compared with those exposed to moderate-to-severe TBI without psychiatric illness. TBI and psychiatric illness were each associated with significant increases in health care costs; those with the combination of moderate-to-severe TBI and psychiatric illness had much higher costs than any other group.

Purpose: To compare 3 Tesla (3T) multi-voxel and single-voxel proton MR spectroscopy (MRS), dynamic susceptibility contrast perfusion MRI (DSC), and diffusion-weighted MRI (DWI) for distinguishing recurrent glioma from postradiation injury. Materials and Methods: We reviewed all 3T MRS, DSC and DWI studies performed for suspicion of malignant glioma recurrence between October 2006 and December 2008. Maximum Cho/NAA and Cho/Cr peak-area and peak-height ratios were recorded for both multi-voxel and single-voxel MRS. Maximum cerebral blood volume (CBV) and minimum apparent diffusion coefficient (ADC) were normalized to white matter. Histopathology and clinical-radiologic follow-up served as reference standards. Receiver operating characteristic curves for each parameter were compared. Results: Forty lesions were classified as glioma recurrence (n = 30) or posttreatment effect (n = 10). Diagnostic performance was similar for CBV ratio (AUC = 0.917, P < 0.001), multi-voxel Cho/Cr peak-area (AUC = 0.913, P = 0.002), and multi-voxel Cho/NAA peak-height (AUC = 0.913, P = 0.002), while ADC ratio (AUC = 0.726, P = 0.035) did not appear to perform as well. Single-voxel MRS parameters did not reliably distinguish tumor recurrence from posttreatment effects. Conclusion: A 3T DSC and multi-voxel MRS Cho/Cr peak-area and Cho/NAA peak-height appear to outperform DWI for distinguishing glioma recurrence from posttreatment effects. Single-voxel MRS parameters do not appear to distinguish glioma recurrence from posttreatment effects reliably, and therefore should not be used in place of multi-voxel MRS. J. Magn. Reson. Imaging 2012;35:56-63. © 2011 Wiley Periodicals, Inc.

Background. Data on smoking prevalence from four cross-sectional community-based surveys (1979–1990) are presented for 2,605 adolescents and young adults 12–24 years of age. Methods. The surveys were conducted in two treatment and two control cities in Northern California as part of the Stanford Five-City Project, a multifactor cardiovascular disease prevention study. Results. Over the 12-year study period, prevalence of daily smoking declined in all cities by approximately 50% among 16- to 19- and 20- to 24-year-olds but showed little change among those 12–15 years old. Although the declines were especially large in the two treatment cities and in one control city, the declines in treatment cities were not significantly different from those in control cities. During each period, smoking prevalence escalated most sharply between the ages of 12–15 and 16–19, the period of development when students advanced from junior high to high school. Conclusions. Despite impressive secular declines, it appears that the Five-City Project community intervention, which targeted smoking in adults, did not have a diffusion effect on the tobacco use habits of adolescents.

OBJECTIVE: The purpose of this study was to examine the performance characteristics and validity of the Patient Health Questionnaire-9 Item (PHQ-9) as a screening tool for depression among adolescents. METHODS: The PHQ-9 was completed by 442 youth (aged 13–17 years) who were enrolled in a large health care–delivery system and participated in a study on depression outcomes. Criterion validity and performance characteristics were assessed against an independent structured mental health interview (the Child Diagnostic Interview Schedule [DISC-IV]). Construct validity was tested by examining associations between the PHQ-9 and a self-report measure of functional impairment, as well as parental reports of child psychosocial impairment and internalizing symptoms. RESULTS: A PHQ-9 score of 11 or more had a sensitivity of 89.5% and a specificity of 77.5% for detecting youth who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression on the DISC-IV. Receiver-operator-curve analysis revealed that the PHQ-9 had an area under the curve of 0.88 (95% confidence interval: 0.82–0.94), and the cut point of 11 was optimal for maximizing sensitivity without loss of specificity. Increasing PHQ-9 scores were significantly correlated with increasing levels of functional impairment, as well as parental report of internalizing symptoms and psychosocial problems. CONCLUSIONS: Although the optimal cut point is higher among adolescents, the sensitivity and specificity of the PHQ-9 are similar to those of adult populations. The brief nature and ease of scoring of this instrument make this tool an excellent choice for providers and researchers seeking to implement depression screening in primary care settings.

Glioblastoma multiforme (GBM) is the most malignant form of primary brain tumors known as gliomas. They proliferate and invade extensively and yield short life expectancies despite aggressive treatment. Response to treatment is usually measured in terms of the survival of groups of patients treated similarly, but this statistical approach misses the subgroups that may have responded to or may have been injured by treatment. Such statistics offer scant reassurance to individual patients who have suffered through these treatments. Furthermore, current imaging-based treatment response metrics in individual patients ignore patient-specific differences in tumor growth kinetics, which have been shown to vary widely across patients even within the same histological diagnosis and, unfortunately, these metrics have shown only minimal success in predicting patient outcome. We consider nine newly diagnosed GBM patients receiving diagnostic biopsy followed by standard-of-care external beam radiation therapy (XRT). We present and apply a patient-specific, biologically based mathematical model for glioma growth that quantifies response to XRT in individual patients in vivo. The mathematical model uses net rates of proliferation and migration of malignant tumor cells to characterize the tumor's growth and invasion along with the linear-quadratic model for the response to radiation therapy. Using only routinely available pre-treatment MRIs to inform the patient-specific bio-mathematical model simulations, we find that radiation response in these patients, quantified by both clinical and model-generated measures, could have been predicted prior to treatment with high accuracy. Specifically, we find that the net proliferation rate is correlated with the radiation response parameter (r = 0.89, p = 0.0007), resulting in a predictive relationship that is tested with a leave-one-out cross-validation technique. This relationship predicts the tumor size post-therapy to within inter-observer tumor volume uncertainty. The results of this study suggest that a mathematical model can create a virtual in silico tumor with the same growth kinetics as a particular patient and can not only predict treatment response in individual patients in vivo but also provide a basis for evaluation of response in each patient to any given therapy.

OBJECTIVE: To examine the validity of the Patient Health Questionnaire 2 (PHQ-2), a 2-item depression-screening scale, among adolescents. METHODS: After completing a brief depression screen, 499 youth (aged 13–17 years) who were enrolled in an integrated health care system were invited to participate in a full assessment, including a longer depression-screening scale (Patient Health Questionnaire 9-item depression screen) and a structured mental health interview (Diagnostic Interview Schedule for Children). Eighty-nine percent (n = 444) completed the assessment. Criterion validity and construct validity were tested by examining associations between the PHQ-2 and other measures of depression and functional impairment. RESULTS: A PHQ-2 score of ≥3 had a sensitivity of 74% and specificity of 75% for detecting youth who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for major depression on the Diagnostic Interview Schedule for Children and a sensitivity of 96% and specificity of 82% for detecting youth who met criteria for probable major depression on the Patient Health Questionnaire 9-item depression screen. On receiver operating characteristic analysis, the PHQ-2 had an area under the curve of 0.84 (95% confidence interval: 0.75–0.92), and a cut point of 3 was optimal for maximizing sensitivity without loss of specificity for detecting major depression. Youth with a PHQ-2 score of ≥3 had significantly higher functional-impairment scores and significantly higher scores for parent-reported internalizing problems than youth with scores of CONCLUSIONS: The PHQ-2 has good sensitivity and specificity for detecting major depression. These properties, coupled with the brief nature of the instrument, make this tool promising as a first step for screening for adolescent depression in primary care.

Purpose: To examine the relationships between anterior knee laxity (AKL), genu recurvatum (GR), and general joint laxity (GJL) with sagittal plane energetics in males and females during a drop jump task. Methods: A total of 68 females and 50 males were measured for AKL, GR, and GJL and were instrumented to obtain neuromuscular and biomechanical data on their dominant limb during the initial landing phase of a 45-cm drop jump. Multiple linear regressions determined the extent to which the three joint laxity variables combined to predict hip, knee, and ankle work absorption and stiffness. Associations between joint laxity and joint kinematics, joint kinetics, and muscle activation amplitudes were also investigated to further interpret significant relationships. Results: Higher AKL and GJL and lower GR combined to predict greater knee work absorption (R 2 = 0.210, ? = 0.002) and stiffness (R 2 = 0.127, ? = 0.033) and lower ankle stiffness (R2= 0.115, ? = 0.048) in females. These associations were modulated through greater peak knee extensor moments and flexion angles, lower hamstring activation, and lower ankle extensor moments. In males, joint laxity had little impact on knee energetics, but a significant association was observed between greater GJL and decreased ankle stiffness (R 2 = 0.209, ? = 0.012), a product of both greater peak ankle flexion and decreased ankle extensor moment. Conclusions: Females with greater AKL and GJL and lower GR demonstrated a landing strategy that increased work absorption and stiffness about the knee, whereas females with greater GR demonstrated a landing style that reduced knee work absorption and stiffness. The findings suggest that AKL, GR, and GJL may represent distinct risk factors and support the need to consider more comprehensive laxity profiles as they relate to knee joint function and anterior cruciate ligament injury risk.

Background. Trends in blood pressure, smoking, and cholesterol were examined from 1979–1980 through 1985–1986 in four cities in California by level of education (

Magnetic resonance (MR) diffusion-weighted imaging (DWI), dynamic susceptibility contrast-enhanced perfusion imaging (DSC), and MR spectroscopy (MRS) techniques provide specific physiologic information that may distinguish malignant glioma progression from post-radiation change, yet no single technique is completely reliable. We propose a simple, multiparametric scoring system to improve diagnostic accuracy beyond that of each technique alone. Fifteen subjects with lesions suspicious for glioma progression following radiation therapy who had also undergone 3-tesla DWI, DSC, and MRS studies of the lesion were retrospectively reviewed. Minimum apparent diffusion coefficient (ADC) ratio, maximum regional cerebral blood volume (rCBV) ratio, and maximum MRS choline/creatine (Cho/Cr) and choline/N-acetyl-aspartate (Cho/NAA) metabolic peak-height ratios were quantified within each lesion. Each parameter (ADC ratio, rCBV ratio, and combined Cho/Cr and Cho/NAA ratios) was scored as either glioma progression (one point) or radiation change (zero point) based upon thresholds derived from our own data. For each lesion, the combined parameters yielded a multiparametric score (0 to 3) for prediction of tumor progression or post-radiation change. Optimum thresholds for ADC ratio (1.30), rCBV ratio (2.10), and either combined Cho/Cr (1.29) and Cho/NAA (1.06) yielded diagnostic accuracies of 86.7%, 86.7%, and 84.6%, respectively (p

Depression is common among athletes following sport injury, yet few studies have explored the severity of postinjury depression. Among those studies, only one examined gender differences although women in the general population are more likely than men to experience depression. No research to date has used interviews to assess depression despite their standard use among mental health professionals. In a quasi-experimental design, we used a self-report checklist and a clinical interview to compare depression among male and female athletes at 1 week, 1 month, and 3 months postinjury. Results revealed significant effects of group (injured vs. control) and time (since injury), and these effects were different for the two depression measures. We also explored the sensitivity and specificity of the user-rated checklist in identifying severely depressed athletes compared with the interview. Findings underscore the importance of multimodal approaches and clinical judgment when evaluating athletes' postinjury depression symptoms.

The complex issues associated with barriers to treatment entry for parents who are involved with child welfare has not been well explored. Accessing timely treatment is now critical for these parents since the introduction of the Adoption and Safe Families Act of 1997, limiting the time until a permanency decision is made. Using a longitudinal, qualitative approach, substance-abusing parents from 15 families, their relevant family members, and service providers were interviewed approximately every 3 months over an 18-month period. The experiences of these parents add to our knowledge of the unique barriers this population faces, and expands our understanding of the mechanisms by which certain barriers may delay treatment.