Level 1 versus level 2 trauma centers in the treatment of traumatic brain injury

OBJECTIVE: Evaluate three phases of traumatic brain injury care between Level 1 and Level 2 trauma centers using The Trauma Quality Improvement Program (TQIP). Use Emergency Medical Services (EMS) evaluations to determine which trauma centers, and procedures are preferentially chosen. Use trauma center level and other hospital metrics to distinguish differences between the courses of treatment and outcomes for traumatic brain injury patients (TBI). Evaluate specific neurosurgical procedures and their outcomes were based on the severity of the injury, length of time to procedure, and which trauma centers treated them. DESIGN: Demographic and trauma center readiness were evaluated using Chi Squared analysis .Independent samples T-test and Mann-Whitney U were used to compare variables such as EMS response time, Glasgow Coma Scale (GCS) , Injury Severity Score (ISS), length of stay. Multinomial logistic regression was used to evaluate specific procedures and outcomes. RESULTS: There were significant differences in gender, race, the number of adult beds, the number of beds in the burn unit, the number of beds in the Intensive Care Unit (ICU) for burn recovery, number of beds available in the ICU for trauma recovery, the number of neurosurgeons available, the number of orthopedic surgeons available, and the number of trauma surgeons available between the trauma centers. Also average total GCS, and component GCS metrics were significantly lower in level 1 than level 2 trauma centers. ISS scores based on Abbreviated Injury Scale (AIS) also showed significantly higher ISS scores for Level 1 centers. Patients admitted to Level 1 trauma centers spent significantly longer with EMS responders than Level 2 centers. Level 1 trauma centers have significantly longer average stays for both single head trauma and multiple head trauma patients respectively. The American College of Surgeons (ACS) level of treatment could be predicted by EMS time and GCS. ISS can significantly predict the length of stay in both level 1 and level 2 centers. When controlled for injury severity there was no significant differences in EMS length of response, length of Emergency Department (ED) stay or total length of stay. Types of procedures conducted can be predicted using ACS level, ISS, and EMS response time. There was no significant difference in the lengths of times to procedures, and the outcomes of such procedures could not be predicted. CONCLUSION: TQIP gives us standardized benchmarking to accurately analyze data across different Level 1 and Level 2 trauma centers. The goal is to characterize the course of treatment for TBI patients and improve quality of care. This study showed us that more severe injuries are preferentially treated at higher level trauma centers with longer transit and hospital stays. However, it also it showed us that for very severe injuries the quality of care, and length of time to surgical intervention is consistent across ACS levels

Infusion techniques for peripheral arterial thrombolysis

BACKGROUND: Acute limb ischaemia usually is caused by a blood clot blocking an artery or a bypass graft. Severe acute ischaemia will lead to irreversible damage to muscles and nerves if blood flow is not restored in a few hours. Once irreversible damage occurs, amputation will be necessary and the condition can be life‐threatening. Infusion of clot‐busting drugs (thrombolysis) is a useful tool in the management of acute limb ischaemia. Fibrinolytic drugs are used to disperse blood clots (thrombi) to clear arterial occlusion and restore blood flow. Thrombolysis is less invasive than surgery. A variety of techniques are used to deliver fibrinolytic agents. This is an update of a review first published in 2004. OBJECTIVES: To compare the effects of infusion techniques during peripheral arterial thrombolysis for treatment of patients with acute limb ischaemia. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries to 20 October 2020. We undertook reference checking to identify additional studies. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing infusion techniques for fibrinolytic agents in the treatment of acute limb ischaemia. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as recommended by Cochrane. We assessed the risk of bias in included trials using the Cochrane 'Risk of bias' tool. We evaluated certainty of evidence using GRADE. For dichotomous outcomes, we calculated the odds ratio (OR) with the corresponding 95% confidence interval (CI). We were not able to carry out meta‐analyses due to clinical heterogeneity, so we have reported the results and performed the comparisons narratively. The main outcomes of interest were amputation‐free survival or limb salvage, amputation, mortality, vessel patency, duration of thrombolysis, and complications such as cerebrovascular accident and major and minor bleeding. MAIN RESULTS: Nine studies with a total of 671 participants are included in this update. Trials covered a variety of infusion techniques, dosage regimens, and adjunctive agents. We grouped trials according to types of techniques assessed (e.g. intravenous and intra‐arterial delivery of the agent, 'high‐' and 'low‐dose' regimens of the agent, continuous infusion and 'forced infusion' of the agent, use of adjunctive antiplatelet agents). We assessed the certainty of evidence as very low to low due to the limited power of individual studies to deliver clinically relevant results, small and heterogeneous study populations, use of different inclusion criteria by each study in terms of severity and duration of ischaemia, considerably different outcome measures between trials, and use of different fibrinolytic agents. This heterogeneity prevented pooling of data in meta‐analyses. No regimen has been shown to confer benefit in terms of amputation‐free survival (at 30 days), amputation, or death. For vessel patency, complete success was more likely with intra‐arterial (IA) than with intravenous (IV) infusion (odds ratio (OR) 13.22, 95% confidence interval (CI) 2.79 to 62.67; 1 study, 40 participants; low‐certainty evidence); radiological failure may be more likely with IV infusion (OR 0.02, 95% CI 0.00 to 0.38; 1 study, 40 participants; low‐certainty evidence). Due to the small numbers involved in each arm and design differences between arms, it is not possible to conclude whether any technique offered any advantage over another. None of the treatment strategies clearly affected complications such as cerebrovascular accident or major bleeding requiring surgery or blood transfusion. Minor bleeding complications were more frequent in systemic (intravenous) therapy compared to intra‐arterial infusion (OR 0.03, 95% CI 0.00 to 0.56; 1 study, 40 participants), and in high‐dose compared to low‐dose therapy (OR 0.11, 95% CI 0.01 to 0.96; 1 study, 63 participants). Limited evidence from individual trials appears to indicate that high‐dose and forced‐infusion regimens reduce the duration of thrombolysis. In one trial, the median duration of infusion was 4 hours (range 0.25 to 46) for the high‐dose group and 20 hours (range 2 to 46) for the low‐dose group. In a second trial, treatment using pulse spray was continued for a median of 120 minutes (range 40 to 310) compared with low‐dose infusion for a median of 25 hours (range 2 to 60). In a third trial, the median duration of therapy was reduced with pulse spray at 195 minutes (range 90 to 1260 minutes) compared to continuous infusion at 1390 minutes (range 300 to 2400 minutes). However, none of the studies individually showed improvement in limb salvage at 30 days nor benefit for the amputation rate related to the technique of drug delivery. Similarly, no studies reported a clear difference in occurrence of cerebrovascular accident or major bleeding. Although 'high‐dose' and 'forced‐infusion' techniques achieved vessel patency in less time than 'low‐dose' infusion, more minor bleeding complications may be associated (OR 0.11, 95% CI 0.01 to 0.96; 1 study, 72 participants; and OR 0.48, 95% CI 0.17 to 1.32; 1 study, 121 participants, respectively). Use of adjunctive platelet glycoprotein IIb/IIIa antagonists did not improve outcomes, and results were limited by inclusion of participants with non‐limb‐threatening ischaemia. AUTHORS' CONCLUSIONS: There is insufficient evidence to show that any thrombolytic regimen provides a benefit over any other in terms of amputation‐free survival, amputation, or 30‐day mortality. The rate of CVA or major bleeding requiring surgery or blood transfusion did not clearly differ between regimens but may occur more frequently in high dose and IV regimens. This evidence was limited and of very low certainty. Minor bleeding may be more common with high‐dose and IV regimens. In this context, thrombolysis may be an acceptable therapy for patients with marginally threatened limbs (Rutherford grade IIa) compared with surgery. Caution is advised for patients who do not have limb‐threatening ischaemia (Rutherford grade I) because of risks of major haemorrhage, cerebrovascular accident, and death from thrombolysis

Antibody Validation and Dual IHC Staining of Glioblastoma Multiforme to Isolate Microglia Cells in Glial Cell Population for Biomarker Identification

https://openworks.mdanderson.org/sumexp23/1068/thumbnail.jp

Implications of genome-wide association studies in cancer therapeutics

Genome wide association studies (GWAS) provide an agnostic approach to identifying potential genetic variants associated with disease susceptibility, prognosis of survival and/or predictive of drug response. Although these techniques are costly and interpretation of study results is challenging, they do allow for a more unbiased interrogation of the entire genome, resulting in the discovery of novel genes and understanding of novel biological associations. This review will focus on the implications of GWAS in cancer therapy, in particular germ-line mutations, including findings from major GWAS which have identified predictive genetic loci for clinical outcome and/or toxicity. Lessons and challenges in cancer GWAS are also discussed, including the need for functional analysis and replication, as well as future perspectives for biological and clinical utility. Given the large heterogeneity in response to cancer therapeutics, novel methods of identifying mechanisms and biology of variable drug response and ultimately treatment individualization will be indispensable

Does Pharmacogenomics Account for Variability in Control of Acute Chemotherapy-Induced Nausea and Vomiting with 5-Hydroxytryptamine Type 3 Receptor Antagonists?

Chemotherapy-induced nausea and vomiting is one of the most concerning adverse drug effects from cytotoxic chemotherapy. Despite appropriate use of antiemetic guidelines, 20–30% of patients experience breakthrough nausea and vomiting secondary to chemotherapy. To assess the variability of 5-hydroxytryptamine type 3 receptor antagonist efficacy caused by genetic variation, a review of the available literature was conducted. From the literature, three sources of pharmacogenomic variability were identified: polymorphisms associated with 5-hydroxytryptamine type 3 receptor subunits, drug metabolism via cytochromes P450, and drug transport in the body. Testing for receptor subunit polymorphisms is not applicable to a clinical setting at this time; however, cytochrome P450 2D6 testing is FDA-approved and widely accessible. Cytochrome P450 2D6 ultrarapid metabolizers and poor metabolizers displayed altered antiemetic efficacy when compared with intermediate metabolizers and extensive metabolizers. We postulate that testing for cytochrome P450 2D6 phenotypes may be the most accessible way to provide individualized antiemetic therapy in the future

Interventions for Adolescent Mental Health: An Overview of Systematic Reviews.

Many mental health disorders emerge in late childhood and early adolescence and contribute to the burden of these disorders among young people and later in life. We systematically reviewed literature published up to December 2015 to identify systematic reviews on mental health interventions in adolescent population. A total of 38 systematic reviews were included. We classified the included reviews into the following categories for reporting the findings: school-based interventions (n = 12); community-based interventions (n = 6); digital platforms (n = 8); and individual-/family-based interventions (n = 12). Evidence from school-based interventions suggests that targeted group-based interventions and cognitive behavioral therapy are effective in reducing depressive symptoms (standard mean difference [SMD]: -.16; 95% confidence interval [CI]: -.26 to -.05) and anxiety (SMD: -.33; 95% CI: -.59 to -.06). School-based suicide prevention programs suggest that classroom-based didactic and experiential programs increase short-term knowledge of suicide (SMD: 1.51; 95% CI: .57-2.45) and knowledge of suicide prevention (SMD: .72; 95% CI: .36-1.07) with no evidence of an effect on suicide-related attitudes or behaviors. Community-based creative activities have some positive effect on behavioral changes, self-confidence, self-esteem, levels of knowledge, and physical activity. Evidence from digital platforms supports Internet-based prevention and treatment programs for anxiety and depression; however, more extensive and rigorous research is warranted to further establish the conditions. Among individual- and family-based interventions, interventions focusing on eating attitudes and behaviors show no impact on body mass index (SMD: -.10; 95% CI: -.45 to .25); Eating Attitude Test (SMD: .01; 95% CI: -.13 to .15); and bulimia (SMD: -.03; 95% CI: -.16 to .10). Exercise is found to be effective in improving self-esteem (SMD: .49; 95% CI: .16-.81) and reducing depression score (SMD: -.66; 95% CI: -1.25 to -.08) with no impact on anxiety scores. Cognitive behavioral therapy compared to waitlist is effective in reducing remission (odds ratio: 7.85; 95% CI: 5.31-11.6). Psychological therapy when compared to antidepressants have comparable effect on remission, dropouts, and depression symptoms. The studies evaluating mental health interventions among adolescents were reported to be very heterogeneous, statistically, in their populations, interventions, and outcomes; hence, meta-analysis could not be conducted in most of the included reviews. Future trials should also focus on standardized interventions and outcomes for synthesizing the exiting body of knowledge. There is a need to report differential effects for gender, age groups, socioeconomic status, and geographic settings since the impact of mental health interventions might vary according to various contextual factors