No abstract

Mood and anxiety disorders are the most prevalent psychiatric conditions and are exacerbated by stress. Recent studies have suggested cyclooxygenase-2 (COX-2) inhibition could represent a novel treatment approach or augmentation strategy for affective disorders including anxiety disorders and major depression. We show that traditional COX-2 inhibitors and a newly developed substrate-selective COX-2 inhibitor (SSCI) reduce a variety of stress-induced behavioral pathologies in mice. We found that these behavioral effects were associated with a dampening of neuronal excitability in the basolateral amygdala (BLA) ex vivo and in vivo, and were mediated by small-conductance calcium-activated potassium (SK) channel and CB1 cannabinoid receptor activation. Taken together, these data provide further support for the potential utility of SSCIs, as well as traditional COX-2 inhibitors, as novel treatment approaches for stress-related psychiatric disorders.DOI: http://dx.doi.org/10.7554/eLife.14137.001

Significant differences noted on motor outcomes at the 6-8 month visit were no longer apparent in later visits. Referral to early intervention services is high in both the groups. These findings are important to those caring for infants with CHD because many of these patients may need referral for early intervention.

Background Off‐label drug prescribing is common in pediatric clinical medicine, though the extent and impact of this practice in pediatric oncology has not yet been characterized. Methods We completed a retrospective single‐institution cohort study evaluating prevalence, characteristics, and clinical outcomes of off‐label prescribing of 108 FDA‐approved targeted anticancer drugs in patients < 30 years old treated for cancer from 2007 to 2017. Dosing strategies were adjusted for body size and compared to FDA‐approved adult dosing regimen. A composite toxicity endpoint was defined as a patient having unplanned clinic visits, emergency department visits, or unplanned hospital admissions that were at least possibly related to the off‐label treatment. Results The overall prevalence of off‐label use of targeted therapies was 9.2% (n = 374 patients). The prevalence increased significantly over the study period (P < .0001). Patients treated off‐label were more likely to have neuro‐oncology diagnoses compared to patients not treated off‐label (46% vs 29%; P < .0001). Of the 108 potential agents, 38 (35%) were used by at least one patient. The median starting dose was below the FDA‐approved normalized dose for 44.4% of agents. Fifteen percent of patients had a complete response while receiving off‐label therapy, 38% experienced toxicity as defined, and 13% discontinued off‐label therapy due to toxicity. Conclusions In this real‐world evaluation of prescribing at a large pediatric cancer center, off‐label prescribing of FDA‐approved targeted therapies was common, increasing in prevalence, encompassed a broad sample of targeted agents, and was tolerable. Clinicians commonly start dosing below the equivalent FDA‐approved dose.