Traumatic brain injury (TBI) is the leading cause of death and disability in children. Many clinical practice guidelines (CPGs) have addressed pediatric TBI in the last decade but significant variability in the use of these guidelines persists. Here, we systematically review CPGs recommendations for pediatric moderate-to-severe TBI, evaluate the quality of CPGs, synthesize the quality of evidence and strength of included recommendations, and identify knowledge gaps. A systematic search was conducted in MEDLINE ^® , Embase, Cochrane CENTRAL, Web of Science, and Web sites of organizations publishing recommendations on pediatric injury care. We included CPGs developed in high-income countries from January 2012 to May 2023, with at least one recommendation targeting pediatric (≤ 19 years old) moderate-to-severe TBI populations. The quality of included clinical practice guidelines was assessed using the AGREE II tool. We synthesized evidence on recommendations using a matrix based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. We identified 15 CPGs of which 9 were rated moderate to high quality using AGREE II. We identified 90 recommendations, of which 40 (45%) were evidence based. Eleven of these were based on moderate to high quality evidence and were graded as moderate or strong by at least one guideline. These included transfer, imaging, intracranial pressure control, and discharge advice. We identified gaps in evidence-based recommendations for red blood cell transfusion, plasma and platelet transfusion, thromboprophylaxis, surgical antimicrobial prophylaxis, early diagnosis of hypopituitarism, and mental health mangement. Many up-to-date CPGs are available, but there is a paucity of evidence to support recommendations, highlighting the urgent need for robust clinical research in this vulnerable population. Our results may be used by clinicians to identify recommendations based on the highest level of evidence, by healthcare administrators to inform guideline implementation in clinical settings, by researchers to identify areas where robust evidence is needed, and by guideline writing groups to inform the updating of existing guidelines or the development of new ones.

Tacrolimus (FK506) is at present the mainstay of immunosuppression for small intestinal transplantation. This study investigates the effects of chronic treatment with varying dosages of tacrolimus on animal well-being, weight gain, intestinal permeability, and the active transport of nutrients as measured by in vitro studies quantifying glucose flux. The effect of acute treatment with high-dose tacrolimus on glucose flux was also investigated. In the chronic studies, juvenile male Lewis rats were given tacrolimus in a dosage of 0.1 mg/kg, 0.5 mg/kg, and 2 mg/kg q. second day by subcutaneous injection for five weeks. In the acute studies, animals were treated with 2 mg/kg given q. 24 hr [mult] 48 hr, 24 hr and 12 hr prior to sacrifice. In the acute treatment groups, tacrolimus caused no change in glucose flux. In the chronically treated animals, FK506 levels were within the clinically relevant range. Chronic treatment with 0.5 and 2 mg/kg caused a significant reduction in weight gain. These same groups of animals had a significant increase in intestinal permeability as measured by absorption of 99Te-DTPA. Glucose flux was affected in all chronically treated groups, with net flux increasing in the jejunum and decreasing in the ileum. These findings show that chronic treatment with low-dose tacrolimus is well tolerated, but in higher doses there are significant effects in intestinal permeability and nutrient uptake, and animal weight gain. We suggest that these changes are due to alterations in intestinal permeability that do not appear to be mediated by an acute drug effect and more likely represent chronic changes, possibly from alterations in gene expression. These findings suggest that further studies regarding the effects of tacrolimus on nutrient transport, intestinal permeability, and the known immunologically related functions of tacrolimus should be done.

BACKGROUND: Tests and treatments that are not supported by evidence and could expose patients to unnecessary harm, referred to here as low-value clinical practices, consume up to 30% of health care resources. Choosing Wisely and other organizations have published lists of clinical practices to be avoided. However, few apply to injury and most are based uniquely on expert consensus. We aimed to identify low-value clinical practices in acute injury care. METHODS: We conducted a scoping review targeting articles, reviews and guidelines that identified low-value clinical practices specific to injury populations. Thirty-six experts rated clinical practices on a five-point Likert scale from clearly low value to clearly beneficial. Clinical practices reported as low value by at least one level I, II, or III study and considered clearly or potentially low-value by at least 75% of experts were retained as candidates for low-value injury care. RESULTS: Of 50,695 citations, 815 studies were included and led to the identification of 150 clinical practices. Of these, 63 were considered candidates for low-value injury care; 33 in the emergency room, 9 in trauma surgery, 15 in the intensive care unit, and 5 in orthopedics. We also identified 87 “gray zone” practices, which did not meet our criteria for low-value care. CONCLUSION: We identified 63 low-value clinical practices in acute injury care that are supported by empirical evidence and expert opinion. Conditional on future research, they represent potential targets for guidelines, overuse metrics and de-implementation interventions. We also identified 87 “gray zone” practices, which may be interesting targets for value-based decision-making. Our study represents an important step toward the deimplementation of low-value clinical practices in injury care. LEVEL OF EVIDENCE: Systematic Review, Level IV.

Road traffic injuries constitute a significant global health burden; the World Health Organization estimates that they result in 1.35 million deaths annually. While most pedestrian injury studies rely predominantly on statistical modelling, this paper argues for a mixed-methods approach combining spatial analysis, environmental scans, and local knowledge for assessing environmental risk factors. Using data from the Nova Scotia Trauma Registry, severe pedestrian injury cases and ten corresponding hotspots were mapped across the Halifax Regional Municipality. Using qualitative observation, quantitative environmental scans, and a socioeconomic deprivation index, we assessed hotspots over three years to identify key social- and built-environmental correlates. Injuries occurred in a range of settings; however, clear patterns were not observed based on land use, age, or socio-economic status (SES) alone. Three hotspots revealed an association between elevated pedestrian injury and a pattern of geographic, environmental, and socio-economic factors: low- to middle-SES housing separated from a roadside attraction by several lanes of traffic, and blind hills/bends. An additional generalized scenario was constructed representing common risk factors across all hotspots. This study is unique in that it moves beyond individual measures (e.g., statistical, environmental scans, or geographic information systems (GIS) mapping) to combine all three methods toward identifying environmental features associated with pedestrian motor vehicle crashes (PMVC).