A proof-of-concept randomized controlled trial of follow-up mental health care for traumatic injury patients following hospital discharge.

INTRODUCTION: Traumatic injuries account for a huge burden of disease. Many patients develop persistent mental health problems in the months following hospital discharge. This proof-of-concept trial investigated whether Stepped Care comprising follow-up assessment telephone calls and appropriate referral information would lead to better mental health and functioning in traumatic injury patients. METHODS: Patients admitted to the Trauma Service at Royal North Shore Hospital were randomized to either Stepped Care (n = 84) or Treatment as Usual (n = 90). All patients were assessed for anxiety, depression, and posttraumatic stress prior to hospital discharge. Those in Stepped Care received a telephone call at 1-month and 3-months after hospital discharge in which they were administered a brief assessment; patients who reported mental health or pain difficulties were provided with information for local specialists to address their specific problem. All patients were independently assessed by telephone interview 9- months after hospital discharge for posttraumatic stress disorder (PTSD) (primary outcome), as well as for anxiety, depression, disability, and pain. RESULTS: There were 58 (73%) patients that could be contacted at either the 1-month or 3-month assessments. Of those contacted, 28 patients (48% of those contacted) were referred for specialist assistance. There were no differences between treatment arms on PTSD symptoms at follow-up [F1,95 = 0.55, p = 0.46]. At the 9-month assessment, patients in the Stepped Care condition reported significantly less anxiety [F1,95 = 5.07, p = 0.03] and disability [F1,95 = 4.37, p = 0.04] relative to those in Treatment as Usual. At 9 months there was no difference between conditions on depression [F1,95 = 1.03, p = 0.31]. There were no differences between conditions on self-reported pain difficulties. CONCLUSIONS: This proof-of-concept trial suggests that brief screening assessments of traumatic injury patients following hospital discharge, combined with appropriate referral information, may lead to better functional outcomes. Further research is needed with larger sample sizes and greater verification of referral uptake to validate this finding.

Preoperative imaging characteristics predict poor survival and inadequate resection for left-sided pancreatic adenocarcinoma: a multi-institutional analysis.

BACKGROUND: Optimal treatment of pancreatic ductal adenocarcinoma of the neck, body and tail (PDAC-NBT) necessitates R0 surgical resection. Preoperative radiographic identification of patients likely to achieve successful oncologic resection remains difficult. This study seeks to identify preoperative imaging characteristics predictive of non-R0 resections or impaired survival for PDAC-NBT. METHODS: Patients at five high-volume centers who underwent resection for PDAC-NBT were retrospectively analyzed. The most immediate preoperative cross-sectional scan was assessed along with outcome measures of overall survival and margin status. RESULTS: 330 patients were treated between 2001 and 2016. Margin status included 247 R0 (78.2%), 67 R1 (21.2%), and 2 R2 (0.6%). A non-R0 resection predicted worse survival (p = 0.0002). On preoperative imaging, patients with tumors greater than 20 mm, tumor attenuation greater than 70 Hounsfield units, or who demonstrated pancreatic atrophy and/or calcifications also had worse survival (p = 0.010, p = 0.036, p = 0.025 respectively). Patients with tumors interfacing with the splenic artery or vein or extending posteriorly achieved fewer R0 resections (p = 0.0006, p = 0.0004, p = 0.001, respectively). CONCLUSION: Preoperative cross-sectional imaging can identify tumor characteristics associated with poor survival and non-R0 resection. Further investigation is needed to identify the appropriate surgical and treatment modifications necessary to clinically benefit this subset of patients.

Oncoplastic breast conserving surgery is associated with a lower rate of surgical site complications compared to standard breast conserving surgery.

BACKGROUND: Oncoplastic breast conserving surgery (OBCS) integrates plastic surgery techniques in the resection of breast cancer and lowers the rate of re-excision while improving breast cosmesis. The goal of this study is to compare the surgical site complication rate of OBCS with that of standard BCS. METHODS: A single institution chart review evaluated all patients undergoing BCS for treatment of breast cancer. Patients treated from January 2009 to December 2010, prior to adoption of oncoplastic techniques, were identified as the standard surgery (SS) group. Patients treated with OBCS from January 2013 to July 2015 were identified as the oncoplastic surgery (OS) group. All surgical site complications were recorded. RESULTS: Overall, 561 patients were evaluated. The SS group comprised 273 patients compared with 288 patients in the OS group. Surgical site complications occurred in 49 patients (17.9%) in the SS group compared with 23 patients (8.0%) in the OS group (p < 0.001). DISCUSSION: Overall, BCS has a low rate of significant surgical site complications. OBCS has a lower rate of surgical site complications compared to standard BCS.

Estradiol-induced enhancement of fear extinction in female rats: The role of NMDA receptor activation.

Converging cross-species evidence indicates that fear extinction (the laboratory basis of exposure therapy for anxiety disorders) in females is modulated by endogenous and exogenous estradiol. The mechanisms underlying estradiol's influences on fear extinction are largely undefined. However, one likely candidate is the NMDA-receptor (NMDAr), activation of which is necessary for estradiol-mediated enhancements in structural and functional neural plasticity, as well as extinction consolidation in males. Here, we demonstrate that systemic co-administration of the non-competitive NMDAr antagonist, MK801, blocked the enhancement of fear extinction by systemic estradiol in ovariectomized rats. In intact rats, MK801 during diestrus (rising estradiol) prevented the enhancement in extinction recall in rats that received extinction training during proestrus (peak estradiol). Systemic administration of the partial NMDAr agonist D-cycloserine (DCS) prior to extinction training facilitated extinction in ovariectomized rats, mimicking the effects of estradiol. In intact rats, DCS administered on the afternoon of proestrus and the morning of estrus (declining estradiol) facilitated extinction in rats that received extinction training during metestrus (low estradiol). Finally, DCS also facilitated extinction in ovariectomized rats when administered immediately after extinction training. Combined, these findings suggest that endogenous and exogenous estradiol enhance fear extinction via NMDAr-dependent mechanisms. Moreover, these findings raise the possibility that fear extinction deficits during periods of low endogenous estradiol levels can be reversed by increasing NMDAr activation via DCS administration, either well prior to, or immediately after, extinction training.

Effects of systemic estradiol on fear extinction in female rats are dependent on interactions between dose, estrous phase, and endogenous estradiol levels.

Administering estradiol to females during periods of low endogenous estradiol enhances their ability to extinguish fear, the laboratory basis of exposure therapy for anxiety disorders. It has therefore been proposed that estradiol could be a useful adjunct to enhance exposure therapy outcomes. The present study aimed to clarify the boundary conditions under which estradiol could be used for this purpose, by assessing whether the impact of estradiol, administered systemically prior to extinction training, differs depending on dose and estrous phase in adult female rats. Results demonstrated that in rats extinguished during metestrus (naturally low estradiol), a low dose of estradiol reduced freezing during extinction training and augmented extinction recall the following day, whereas a high dose of estradiol had no effect on either extinction training or recall. In rats extinguished during proestrus (naturally high estradiol), a high dose of estradiol impaired extinction recall, whereas a low dose of estradiol had no effect, or impairing effects, on extinction recall in different experiments. A subsequent analysis revealed that estradiol-treated proestrus rats that exhibited impaired extinction recall had significantly higher pre-treatment serum estradiol levels than those that exhibited good extinction recall. Together, these results indicate that systemically administered estradiol interacts with endogenous estradiol to produce an inverted U shaped dose effect on fear extinction, where low and high estradiol levels lead to poor extinction recall, and moderate estradiol levels lead to good extinction recall. These results highlight potential limitations to the use of estradiol as an adjunct to exposure therapy in clinical settings.

Individual differences in fear extinction and anxiety-like behavior.

There is growing appreciation for the substantial individual differences in the acquisition and inhibition of aversive associations, and the insights this might give into identifying individuals particularly vulnerable to stress and psychopathology. We examined whether animals that differed in rate of extinction (i.e., Fast versus Slow) were different in their response to an acute stress in adulthood or following a chronic stress that occurred either early or later in life. We found that Slow Extinguishers had significantly poorer extinction retention than Fast Extinguishers, but an acute stressor did not differentially affect anxiety-like behavior in the two groups. Further, while exposure to chronic stress in adulthood did not impact on the extinction phenotypes or anxiety-like behavior, exposure to chronic stress early in life affected both extinction retention and anxiety-like behavior. These findings have implications for the development of a more nuanced approach to identifying those most at risk of anxiety disorders.