Using a Pediatric Bruising Clinical Decision Rule in the Emergency Department

Children in their first year of life are most at risk of child maltreatment. Young children and infants are most at risk of fatality. Seemingly minor injuries are commonly present prior to extreme physical abuse. The most common injury to precede near-fatality and death due to child abuse is bruising that was disregarded or misdiagnosed as accidental. Bruising in children who have not started to cruise or walk is suspicious of non-accidental injury and can be predictive of abuse. The emergency department (ED) at a critical access hospital in rural Alaska does not use an evidence-based tool to assess bruises in pediatric patients. There is a lack of information about how to identify and respond to bruising that indicates further evaluation. The goal of this project is to provide ED nurses with a clinical tool and training that will help them to recognize children and infants who are at high risk for physical abuse The solution is to provide evidence-based, clinical guidance and steps to follow for a pediatric patient with a bruise that may be the result of inflicted injury. The TEN-4-FACESp bruising clinical decision rule (BCDR) is a validated tool that is 96% sensitive and 87% specific for distinguishing accidental and non-accidental bruising in young children. To reach the goal of recognizing and responding to abusive bruising in pediatric patients, an updated protocol for pediatric non-accidental injury using an algorithm has been created. ED nurses will be provided two skills training sessions in the use of a BCDR in the ED. Nurses will determine the next steps and resources if a pediatric patient in the ED has a positive finding on the BCDR. The Stetler Model of Evidence-Based Practice, focusing on how research findings are implemented into clinical practice, is the guiding framework. This project follows a step-by-step guide to applying the evidenced-based, validated BCDR in the ED and adapts new information into practice. The training will improve referral-making and increase communication and teamwork in the multidisciplinary environments and the ED. Success will be measured in the number of ED nurses who receive training. Nurses will recognize bruises that are highly specific to abuse, along with bruising that less specific and more commonly seen in non-abused children. Nurses will recognize that bruising patterns in abused children differ from those in non-abused children. Bridging the gap in knowledge and communication will increase the number of young children who are provided appropriate evaluation for non-accidental injuries

How to Work Collaboratively Within the Health System: Workshop Summary and Facilitator Reflection

Effectiveness in health services research requires development of specific knowledge and skills for working in partnership with health system decision-makers. In an initial effort to frame capacity-building activities for researchers, we designed a workshop on working collaboratively within the health system. The workshop, based on recent research exploring health system experience and perspectives on research collaborations, was trialed at the annual Canadian Health Services and Policy Research (CAHSPR) conference in May 2019. Participants reported positive evaluations of the workshop. However, further efforts should target health services researchers that may not be as motivated to develop skills in collaborative research. Additional attention to equipping researchers with the skills needed to work in partnerships is recommended, including approaches and materials that avoid oversimplification of complex challenges

Potential Biomarkers for Physical Exercise-Induced Brain Health

Physical exercise has long been recognized as an effective and economic strategy to promote brain health in humans. The cellular and structural changes in the brains of exercised animals, including enhancements of neurogenesis and synaptogenesis, dendritic remodeling, and synaptic plasticity, have been considered as the key biological alterations accounting for exercise-elicited benefits to brain health. However, what transduces body movements into the above-mentioned changes remains largely unknown. Emerging theories indicate that physical activity triggers the release of various factors into the circulation from skeletal muscle (neurotrophins, myokines, and cytokines) and/or adipose tissue (adipokines). In this chapter, we review several of these molecules that are potentially implicated in this process, including neurotrophic factors (BDNF, IGF-1, and VEGF), adipokines (adiponectin and irisin), and myokines/cytokines (IL-15). The relationship, either causal or concomitant, between levels of these molecules (particularly in the blood) and brain function after exercise may help to identify biomarkers that can serve as objective indicators to evaluate exercise therapy on diseased or ageing brain. In addition, unmasking biomarkers may be instrumental in elucidating the mechanisms mediating exercise-induced brain health, thereby contributing to novel drug discovery for treatments to maintain brain health

Detection of HPV and the role of p16INK4A overexpression as a surrogate marker for the presence of functional HPV oncoprotein E7 in colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Based on the well-recognized etiological role of human papillomavirus (HPV) in cervical, anogenital and oropharyngeal carcinogenesis, a potential role of HPV in colorectal carcinogenesis has been suggested. For that reason, the aim of the present study was to investigate the presence of HPV DNA in colorectal carcinomas (CRC) and to study overexpression of p16^INK4Aas a marker for the presence of an active HPV oncoprotein E7. These findings were correlated with clinical and pathological prognostic factors of CRC.</p> <p>Methods</p> <p>The presence of HPV was assessed using a multiplex PCR system of 10 non-biotinylated primers. The amplified fragments of HPV positive samples were further analyzed by a highly sensitive, broad spectrum SPF10 PCR and subsequently genotyped using reverse hybridization in a line probe assay.</p> <p>P16^INK4Aprotein expression was investigated in a subset of 90 (30 HPV positive and 60 HPV negative) CRC samples by immunohistochemistry.</p> <p>Results</p> <p>HPV DNA was found in 14.2% of the CRC samples with HPV16 as the most prevalent type. No significant differences in clinical and pathological variables were found between HPV positive and negative CRCs, except for age. HPV positive patients were significantly younger (p = 0.05). There was no significant correlation between the presence of HPV and overexpression of p16^INK4A(p = 0.325).</p> <p>Conclusions</p> <p>In conclusion, the presence of oncogenic HPV DNA in a small cohort of CRC samples may suggest that HPV may be involved in the carcinogenesis of some CRC. However, contrary to what has been observed in head and neck squamous cell cancer and cancer of the uterine cervix, p16^INK4Adoes not seem to be a surrogate marker for an active HPV infection in CRC. Therefore, further functional analyses are necessary to elucidate the role of HPV in CRC.</p

A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART SWOG 1609) in Patients with Nonpancreatic Neuroendocrine Tumors.

PurposeImmune checkpoint blockade has improved outcomes across tumor types; little is known about the efficacy of these agents in rare tumors. We report the results of the (nonpancreatic) neuroendocrine neoplasm cohort of SWOG S1609 dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART).Patients and methodsWe performed a prospective, open-label, multicenter phase II clinical trial of ipilimumab plus nivolumab across multiple rare tumor cohorts, with the (nonpancreatic) neuroendocrine cohort reported here. Response assessment by grade was not prespecified. The primary endpoint was overall response rate [ORR; RECIST v1.1; complete response (CR) and partial response (PR)]; secondary endpoints included progression-free survival (PFS), overall survival (OS), stable disease &gt;6 months, and toxicity.ResultsThirty-two eligible patients received therapy; 18 (56%) had high-grade disease. Most common primary sites were gastrointestinal (47%; N = 15) and lung (19%; N = 6). The overall ORR was 25% [95% confidence interval (CI) 13-64%; CR, 3%, N = 1; PR, 22%, N = 7]. Patients with high-grade neuroendocrine carcinoma had an ORR of 44% (8/18 patients) versus 0% in low/intermediate grade tumors (0/14 patients; P = 0.004). The 6-month PFS was 31% (95% CI, 19%-52%); median OS was 11 months (95% CI, 6-∞). The most common toxicities were hypothyroidism (31%), fatigue (28%), and nausea (28%), with alanine aminotransferase elevation (9%) as the most common grade 3/4 immune-related adverse event, and no grade 5 events.ConclusionsIpilimumab plus nivolumab demonstrated a 44% ORR in patients with nonpancreatic high-grade neuroendocrine carcinoma, with 0% ORR in low/intermediate grade disease