Trauma Resilience and Recovery Program: Addressing Mental Health in Pediatric Trauma Centers.

OBJECTIVE: Approximately 225,000 children sustain injuries requiring hospitalization annually. Posttraumatic stress disorder (PTSD) and depression are prevalent among pediatric patients and caregivers post-injury. Most U.S. trauma centers do not address patients' mental health needs. Better models of care are needed to address emotional recovery. This article describes the engagement and recovery trajectories of pediatric patients enrolled in the Trauma Resilience and Recovery Program (TRRP), a stepped-care model to accelerate emotional recovery following hospitalization. METHODS: TRRP is designed to (a) provide in-hospital education about post-injury emotional recovery and assess child and caregiver distress; (b) track mental health symptoms via a 30-day text-messaging program; (c) complete 30-day PTSD and depression phone screens; and (d) provide evidence-based treatment via telehealth or in-person services or referrals, if needed. All 154 families approached were offered TRRP services, 96% of whom agreed to enroll in TRRP. Most patients were boys (59.8%), and average age was 9.12 years [standard deviation (SD) = 5.42]. Most injuries (45.8%) were sustained from motor vehicle accidents. RESULTS: In hospital, 68.5% of caregivers and 78.3% of children reported clinically significant distress levels. Over 60% of families enrolled in the texting service. TRRP re-engaged 40.1% of families for the 30-day screen, 35.5% of whom reported clinically significant PTSD (M = 13.90, SD = 11.42) and/or depression (M = 13.35, SD = 11.16). Most (76%) patients with clinically significant symptomology agreed to treatment. CONCLUSIONS: Our intervention model was feasible and increased reach to families who needed services. Efforts to improve follow-up engagement are discussed, as are initial successes in implementing this model in other pediatric trauma centers.

Implementation and Utility of an Automated Text Messaging System to Facilitate Symptom Self-Monitoring and Identify Risk for Post-Traumatic Stress Disorder and Depression in Trauma Center Patients.

Background and Introduction: Comprehensive monitoring and follow-up after traumatic injury is important for psychological recovery. However, scalable services to facilitate this are limited. Automated text message-based symptom self-monitoring (SSM) may be a feasible approach. This study examined its implementation and utility in identifying patients at risk for mental health difficulties after traumatic injury.Materials and Methods: Five hundred two patients admitted to a Level I trauma center between June 20, 2016 and July 31, 2017 were offered enrollment in a text message-based SSM service. Patients who enrolled received daily text message prompts over 30 days and most participated in a mental health screening 30 days postbaseline.Results: Approximately 67% of patients enrolled in the service; of these, 58% responded to the text messages, with an average response rate of 53%. Younger patients and those with elevated peritraumatic distress were more likely to enroll. Patients with higher levels of mental health stigma, who were White, or had been in a motor vehicle collision were more likely to enroll and respond to text messages once enrolled. Patients' daily ratings of distress detected clinically elevated 30-day mental health screens with high sensitivity (83%) and specificity (70%).Discussion and Conclusions: Text message-based SSM can be implemented as a clinical service in Level I trauma centers, and patient participation may increase engagement in mental health follow-up. Further, it can inform the use of risk assessments in practice, which can be used to identify patients with poor psychological recovery who require additional screening.

Programmed death 1 immune checkpoint inhibitors.

Programmed death 1 (PD-1) is an immune checkpoint that provides inhibitory signals to the immune system in order to modulate the activity of T cells in peripheral tissues and maintain self-tolerance in the setting of infection and inflammation. In cancer, the immune checkpoints are exploited so that the tumor cells are able to evade the immune system. Immune checkpoint inhibitors are a type of cancer immunotherapy that targets pathways such as PD-1 in order to reinvigorate and enhance the immune response against tumor cells. The US Food and Drug Administration (FDA) has approved 2 PD-1 inhibitors, nivolumab and pembrolizumab, and several others are under investigation. Although PD-1 inhibitors have demonstrated activity in many different types of malignancies, FDA approval has been granted only in melanoma and in non-small cell lung cancer (NSCLC). Identifying biomarkers that can predict response to PD-1 inhibitors is critical to maximizing the benefit of these agents. Future directions for PD-1 inhibitors include investigation of combination therapies, use in malignancies other than melanoma and NSCLC, and refinement of biomarkers.

Caregivers' and Young Children's Emotional Health Needs After Pediatric Traumatic Injury.

Pediatric traumatic injury (PTI) is associated with emotional health difficulties, but most US trauma centers do not adequately address emotional recovery needs. This study aimed to assess families' emotional health needs following PTI and determine how technology could be used to inform early interventions. Individual semi-structured, qualitative interviews were conducted with caregivers of children admitted to a Level I trauma center in the Southeastern United States to understand families' experiences in-hospital and post-discharge. Participants included 20 caregivers of PTI patients under age 12 (M = 6.4 years; 70% male, 45% motor vehicle collision). Thematic analysis was used to analyze data from interviews that were conducted until saturation. Caregivers reported varying emotional needs in hospital and difficulties adjusting after discharge. Families responded enthusiastically to the potential of a technology-enhanced resource for families affected by PTI. A cost-effective, scalable intervention is needed to promote recovery and has potential for widespread pediatric hospital uptake.

Opioid Misuse: An Organizational Response While Managing Cancer-Related Pain.

BACKGROUND: Opioids are commonly prescribed to manage cancer pain. Similar to the general population, patients with cancer are not excluded from the risk for opioid misuse and dependence. This situation can contribute to clinician reluctance to prescribe and manage pain using opioids. OBJECTIVES: The purpose of this article is to provide an overview of how opioid misuse may affect pain management in patients with cancer and to describe a comprehensive cancer center's approach to safely managing cancer pain. METHODS: Based on a literature review, the project team developed a stewardship program. Project components included selecting a validated screening tool for risk of opioid misuse, determining if a history of addiction affects pain management in patients with cancer, and establishing a task force to focus on the opioid crisis and to follow the Joint Commission's revised pain assessment and management standards. FINDINGS: The project established a hospitalwide opioid stewardship program. Through the use of a multidisciplinary, universal precautions approach to assessing misuse in all patients with cancer who are prescribed opioids, healthcare teams can potentially reduce risks associated with misuse while safely managing cancer pain.

Patient Engagement in a Technology-Enhanced, Stepped-Care Intervention to Address the Mental Health Needs of Trauma Center Patients.

BACKGROUND: Annually, post-traumatic stress disorder, depression, or both, develop in the first year after injury in more than 400,000 adults treated in US trauma centers (≥20%). Yet, few trauma centers monitor and address mental health recovery, and there is limited evaluation and high structural variability across existing programs. More research is needed to guide efforts to establish such programs and to inform national standards and recommendations. STUDY DESIGN: This article describes patient engagement in a stepped-care service to address patients' mental health needs. Trauma-activation patients admitted to our Level I trauma center for at least 24 hours were approached before discharge. Patients were provided education in person at the bedside (step 1), symptom monitoring via a 30-day text-messaging tool (step 2), telephone screening approximately 30 days post injury (step 3), and, when appropriate, mental health treatment referrals and treatment (step 4). RESULTS: We approached and educated 1,122 patients (56%) on the floor during a 33-month period. Of these, 1,096 patients (98%) enrolled in our program and agreed to 30-day follow-up mental health screening. We reached 676 patients for the 30-day screen, 243 (36%) of these patients screened positive for post-traumatic stress disorder and/or depression. Most of the 243 patients who graduated to step 4 accepted treatment referrals (68%) or were already receiving services from a provider (7%). Home-based telemental health was preferred by 66% of patients who accepted referrals. CONCLUSIONS: This work demonstrates the feasibility of an evidence-based, technology-enhanced, stepped-care intervention to address the mental health needs of trauma center patients. Strategies to reach a higher percentage of patients in follow-up are needed. We recommend trauma centers test and adopt broad-based approaches to ensure optimal long-term patient outcomes.

Parallel phase Ib studies of two schedules of buparlisib (BKM120) plus carboplatin and paclitaxel (q21 days or q28 days) for patients with advanced solid tumors.

PURPOSE: Phosphatidylinositol-3-kinase I (PI3K) inhibition sensitizes a wide range of cancer cell lines to platinum/taxane-based chemotherapy. This phase I study combines buparlisib, a pan-class 1A PI3K inhibitor, with two schedules of carboplatin and paclitaxel for patients with advanced solid tumors (ClinicalTrials.gov, NCT01297452). METHODS: There were two regimens: Group 1 received carboplatin AUC 5 and paclitaxel 175 mg/m(2), on day 1 of a 21-day cycle with pegfilgrastim support; Group 2 received carboplatin AUC 5 (day 1) and paclitaxel 80 mg/m(2) (days 1, 8, and 15) on a 28-day cycle without growth factor support. In both groups, three dose levels of buparlisib were explored: 50, 80, and 100 mg/day. Primary endpoint was to identify recommended phase II doses of buparlisib in both groups. RESULTS: Thirty subjects enrolled, 16 in Group 1 and 14 in Group 2. The DLTs were elevated alkaline phosphatase (n = 1) and uncomplicated neutropenia (n = 2). The median numbers of cycles were 5 (Group 1) and 6 (Group 2). The MTDs for buparlisib were 100 mg/day in Group 1 and 80 mg/day in Group 2. Among 25 patients with measurable disease, the confirmed objective response rate was 20% (one complete response, four partial responses). Among three patients with known loss of PTEN expression, all derived clinical benefit from treatment. CONCLUSION: The addition of buparlisib to carboplatin + paclitaxel was well tolerated, and preliminary activity was notable against tumors with loss of PTEN expression.

Phase I study of flavopiridol with oxaliplatin and fluorouracil/leucovorin in advanced solid tumors.

PURPOSE: Flavopiridol, a cyclin-dependent kinase inhibitor, has promising clinical activity when combined with chemotherapy. Preclinical data indicate that flavopiridol enhances oxaliplatin- and fluorouracil (5FU)-induced apoptosis in a sequence-dependent manner. EXPERIMENTAL DESIGN: We conducted a phase I trial of flavopiridol + FOLFOX (folinic acid, 5FU, and oxaliplatin) for advanced solid tumors. Flavopiridol was administered every 2 weeks with oxaliplatin before 5FU, based on sequence-dependent growth inhibition. Flavopiridol pharmacokinetics and p53 status were evaluated. RESULTS: Forty-eight patients were treated on study. With dose escalation of oxaliplatin (85 mg/m(2)) and 5FU (2,400 mg/m(2)), dose-limiting toxicities included hyponatremia, thrombocytopenia, and neutropenia. 5FU was subsequently reduced to allow for dose escalation of flavopiridol. Dose-limiting toxicities with escalation of flavopiridol were nausea, vomiting, and neutropenia. The maximum tolerated dose was 70 mg/m(2) flavopiridol, 85 mg/m(2) oxaliplatin, and 1,800 mg/m(2) 5FU continuous infusion over 48 hours. Clinical activity was noted in platinum-refractory germ cell tumors: 3 of 9 (33%) evaluable patients showed a partial response on imaging and 7 of 10 (70%) had a decline in serum tumor markers. Responses were also observed in pancreatic, gastric, and sweat gland tumors. Flavopiridol pharmacokinetics had significant interpatient variability. At the maximum tolerated dose, tumor samples were p53 mutant (>30% positive cells) for responders and p53 wild-type for nonresponders. CONCLUSIONS: Flavopiridol with FOLFOX is a safe and tolerable regimen. Promising clinical activity was seen across tumor types. Encouraging results in the platinum-refractory germ cell tumor population has prompted a phase II trial that is currently open for accrual.

Patients undergoing treatment for pancreatic adenocarcinoma can mount an effective immune response to vaccinations.

BACKGROUND: Immunotherapy has been proposed as a novel treatment for pancreatic cancer. However, patients with pancreatic cancer have been observed to have depressed immune responses, suggesting that immunotherapy might have limited utility in this group of patients. We sought to determine whether patients undergoing postresection or primary medical treatment for pancreatic adenocarcinoma were immunocompetent. METHODS: We enrolled patients with pancreatic adenocarcinoma scheduled for postresection or primary chemotherapy and/or radiation therapy. At the initiation of therapy, the patients had an anergy panel placed and baseline blood work performed. During the first week of treatment, patients received tetanus toxoid (TT), Haemophilus influenzae and Pneumococcus vaccines. Twelve weeks after vaccine administration, IgG titers against the 3 administered vaccines were done, and lymphocyte proliferation assays in response to TT were performed. RESULTS: Eighteen patients were originally enrolled, and 14 patients completed all elements of the trial. Anergy panel responses were obtained for 15 patients who comprised the final study group; both pre- and postvaccination data were available for 14 patients. Nine of 15 patients demonstrated at least a 10-mm induration in response to mumps or Candida antigen (60% response rate, 95% confidence interval (CI) 32-84%). Thirteen of 14 patients demonstrated a > or =3-fold increase in IgG against one or more vaccines (93% response rate, 95% CI 66-100%). Nine of 14 patients (64% response rate, 95% CI 35-87%) demonstrated at least a 3-fold rise of lymphocyte proliferation against TT. CONCLUSIONS: Patients with pancreatic cancer were capable of mounting effective cellular and humoral responses to standard vaccines. These data suggest that immunotherapy for pancreatic cancer may be feasible and merits further investigation.

A phase II study of modified deGramont 5-fluorouracil, leucovorin, and oxaliplatin in previously treated patients with metastatic colorectal cancer.

PURPOSE: To evaluate the toxicity and efficacy of a modified deGramont regimen of 5-fluorouracil (5-FU), leucovorin, and oxaliplatin in patients with advanced colorectal cancer who have progressed on at least one but not more than two prior chemotherapy regimens. PATIENTS AND METHODS: Patients with stage 4 colorectal cancer were treated with oxaliplatin 85 mg/m2 by a 2-hour intravenous infusion, followed by leucovorin 500 mg/m2 by a 2-hour intravenous infusion, followed by 5-FU 400 mg/m2 by bolus injection, followed by 5-FU 2.4 g/m2 administered by a 46-hour continuous infusion. Cycles were administered every 2 weeks. RESULTS: Seventy patients were treated and 68 patients had previously received irinotecan. Eleven percent of patients had a partial response, 33% of CEA-evaluable patients had a > or = 50% drop in their CEA level. The median time to progression was 6.2 months, and the median overall survival was 8.7 months. Toxicity was mild to moderate, as 14% of patients experienced grade 3 or 4 neutropenia and 3% of patients experienced grade 3 neuropathy. CONCLUSION: The modified deGramont regimen of 5-FU, leucovorin, and oxaliplatin is tolerable and is associated with a modest degree of antitumor activity in patients who have progressed on both 5-FU and irinotecan.