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Davis et al . extend their previous efforts to use inhibitor-kinase interactions to understand kinase inhibitor selectivity by profiling the binding of 72 kinase inhibitors to 442 human kinase catalytic domains. The data reveal group-specific differences in selectivity and suggest the feasibility of developing reasonably specific inhibitors for most kinases. We tested the interaction of 72 kinase inhibitors with 442 kinases covering >80% of the human catalytic protein kinome. Our data show that, as a class, type II inhibitors are more selective than type I inhibitors, but that there are important exceptions to this trend. The data further illustrate that selective inhibitors have been developed against the majority of kinases targeted by the compounds tested. Analysis of the interaction patterns reveals a class of 'group-selective' inhibitors broadly active against a single subfamily of kinases, but selective outside that subfamily. The data set suggests compounds to use as tools to study kinases for which no dedicated inhibitors exist. It also provides a foundation for further exploring kinase inhibitor biology and toxicity, as well as for studying the structural basis of the observed interaction patterns. Our findings will help to realize the direct enabling potential of genomics for drug development and basic research about cellular signaling.

Road traffic injuries (RTIs) are a growing but neglected global health crisis, requiring effective prevention to promote sustainable safety. Low- and middle-income countries (LMICs) share a disproportionately high burden with 90% of the world's road traffic deaths, and where RTIs are escalating due to rapid urbanization and motorization. Although several studies have assessed the effectiveness of a specific intervention, no systematic reviews have been conducted summarizing the effectiveness of RTI prevention initiatives specifically performed in LMIC settings; this study will help fill this gap. In accordance with PRISMA guidelines we searched the electronic databases MEDLINE, EMBASE, Scopus, Web of Science, TRID, Lilacs, Scielo and Global Health. Articles were eligible if they considered RTI prevention in LMICs by evaluating a prevention-related intervention with outcome measures of crash, RTI, or death. In addition, a reference and citation analysis was conducted as well as a data quality assessment. A qualitative metasummary approach was used for data analysis and effect sizes were calculated to quantify the magnitude of emerging themes. Of the 8560 articles from the literature search, 18 articles from 11 LMICs fit the eligibility and inclusion criteria. Of these studies, four were from Sub-Saharan Africa, ten from Latin America and the Caribbean, one from the Middle East, and three from Asia. Half of the studies focused specifically on legislation, while the others focused on speed control measures, educational interventions, enforcement, road improvement, community programs, or a multifaceted intervention. Legislation was the most common intervention evaluated with the best outcomes when combined with strong enforcement initiatives or as part of a multifaceted approach. Because speed control is crucial to crash and injury prevention, road improvement interventions in LMIC settings should carefully consider how the impact of improvements will affect speed and traffic flow. Further road traffic injury prevention interventions should be performed in LMICs with patient-centered outcomes in order to guide injury prevention in these complex settings.

Triage systems play a vital role in emergency department (ED) operations and can determine how well a given ED serves its local population. We sought to describe ED utilization patterns for different triage levels using the National Hospital Ambulatory Medical Care Survey (NHAMCS) database. We conducted a multi-year secondary analysis of the NHAMCS database from 2009-2011. National visit estimates were made using standard methods in Analytics Software and Solutions (SAS, Cary, NC). We compared patients in the mid-urgency range in regard to ED lengths of stay, hospital admission rates, and numbers of tests and procedures in comparison to lower or higher acuity levels. We analyzed 100,962 emergency visits (representing 402,211,907 emergency visits nationwide). In 2011, patients classified as triage levels 1-3 had a higher number of diagnoses (5.5, 5.6 and 4.2, respectively) when compared to those classified as levels 4 and 5 (1.61 and 1.25). This group also underwent a higher number of procedures (1.0, 0.8 and 0.7, versus 0.4 and 0.4), had a higher ED length of stay (220, 280 and 237, vs. 157 and 135), and admission rates (32.2%, 32.3% and 15.5%, vs. 3.1% and 3.6%). Patients classified as mid-level (3) triage urgency require more resources and have higher indicators of acuity as those in triage levels 4 and 5. These patients' indicators are more similar to those classified as triage levels 1 and 2.

Emergency departments are challenging research settings, where truly informed consent can be difficult to obtain. A deeper understanding of emergency medical patients’ opinions about research is needed. We conducted a systematic review and meta-summary of quantitative and qualitative studies on which values, attitudes, or beliefs of emergent medical research participants influence research participation. We included studies of adults that investigated opinions toward emergency medicine research participation. We excluded studies focused on the association between demographics or consent document features and participation and those focused on non-emergency research. In August 2011, we searched the following databases: MEDLINE, EMBASE, Google Scholar, Scirus, PsycINFO, AgeLine and Global Health. Titles, abstracts and then full manuscripts were independently evaluated by two reviewers. Disagreements were resolved by consensus and adjudicated by a third author. Studies were evaluated for bias using standardised scores. We report themes associated with participation or refusal. Our initial search produced over 1800 articles. A total of 44 articles were extracted for full-manuscript analysis, and 14 were retained based on our eligibility criteria. Among factors favouring participation, altruism and personal health benefit had the highest frequency. Mistrust of researchers, feeling like a ‘guinea pig’ and risk were leading factors favouring refusal. Many studies noted limitations of informed consent processes in emergent conditions. We conclude that highlighting the benefits to the participant and society, mitigating risk and increasing public trust may increase research participation in emergency medical research. New methods for conducting informed consent in such studies are needed.

Background Road traffic injuries (RTIs) are the eighth leading cause of death worldwide, with an estimated 90% of RTIs occurring in low- and middle-income countries (LMICs) like Brazil. There has been minimal research in evaluation of delays in transport of RTI patients to trauma centers in LMICs. The objective of this study is to determine specific causes of delays in prehospital transport of road traffic injury patients to designated trauma centers in Maringá, Brazil. Methods A qualitative method was used based on the Consolidated Criteria for Reporting Qualitative Research (COREQ) approach. Eleven health care providers employed at prehospital or hospital settings were interviewed with questions specific to delays in care for RTI patients. A thematic analysis was conducted. Results Responses to primary causes of delay in treatment to RTI patients fell into the following categories: 1) lack of public education, 2) traffic, 3) insufficient personnel/ambulances, 4) bureaucracy, and 5) poor location of stations. Suggestions for improvement in delays fell into the categories of 1) need for centralized station/avoid traffic, 2) improving public education, 3) Increase personnel, 4) increase ambulances, 5) proper extrication/rapid treatment. Conclusion Our study found varied responses between hospital and SAMU providers regarding specific causes of delay for RTI patients; SAMU providers cited primarily traffic, bureaucracy, and poor location as primary factors while hospital employees focused more on public health aspects. These results mirror prehospital system challenges in other developing countries, but also provide solutions for improvement with better infrastructure and public health campaigns.

Background Injuries represent a significant and growing public health concern in the developing world, yet their impact on patients and the emergency health-care system in the countries of East Africa has received limited attention. This study evaluates the magnitude and scope of injury related disorders in the population presenting to a referral hospital emergency department in northern Tanzania. Methods A retrospective chart review of patients presenting to the emergency department at Kilimanjaro Christian Medical Centre was performed. A standardized data collection form was used for data abstraction from the emergency department logbook and the complete medical record for all injured patients. Patient demographics, mechanism of injury, location, type and outcomes were recorded. Results Ten thousand six hundred twenty-two patients presented to the emergency department for evaluation and treatment during the 7-month study period. One thousand two hundred twenty-four patients (11.5%) had injuries. Males and individuals aged 15 to 44 years were most frequently injured, representing 73.4% and 57.8%, respectively. Road traffic injuries were the most common mechanism of injury, representing 43.9% of injuries. Head injuries (36.5%) and extremity injuries (59.5%) were the most common location of injury. The majority of injured patients, 59.3%, were admitted from the emergency department to the hospital wards, and 5.6%, required admission to an intensive care unit. Death occurred in 5.4% of injured patients. Conclusions These data give a detailed and more robust picture of the patient demographics, mechanisms of injury, types of injury and patient outcomes from similar resource-limited settings.

Older adults in the United States receive a significant amount of care in the emergency department (ED), yet the associations between ED and other types of health care utilization have not been adequately studied in this population. The goals of this study were to examine the relationships between health care use before and after an ED visit among older adults. This retrospective cohort study examined health care use among 308 patients 65 years or older discharged from a university-affiliated ED. Proportional-hazards models were used to assess the relationship between pre-ED health care use (primary care physician [PCP], specialist, ED, and hospital) and risk of return ED visits. Older ED patients in this study had visited other types of providers frequently in the previous year (median number of PCP and specialist visits, 4). Patients who used the ED on 2 or more occasions in the previous year were found to have visited their PCP more often than those without frequent ED use (median number of visits, 7.0 vs 4.0; P < .001). Despite more PCP use in this population, frequent ED use was associated with increased risk of a repeat ED visit (hazard ratio, 2.20; 95% confidence interval, 1.15-4.21), in models adjusted for demographics and health status. Older adults who use the ED are also receiving significant amounts of care from other sources; simply providing additional access to care may not improve outcomes for these vulnerable individuals.

At least half the world's population is infected with Helicobacter pylori, although only 10-20% of carriers develop gastric diseases, ranging from ulcer to MALT-lymphoma and adenocarcinoma (MALT is mucosa-associated lymphoid tissue). The clinical outcome of H pylori infection is determined by a complex interaction of environmental influences and host and microbial virulence factors. H pylori genotypes carrying the babA2 gene, encoding a bacterial adhesin mediating interaction with gastric epithelial cells, have enhanced pathogenicity. Moreover, coexistence of babA2 with other bacterial virulence factors further worsens clinical outcomes. To further elucidate the clinical relevance of babA2-genopositive H pylori strains, Carlo-Frederico Zambon and colleagues analysed the association of babA2 genotypes with gastritis, gastroduodenal ulcer disease, or intestinal metaplasia in 167 infected Italian individuals. The coexistence of babA2 with other potentially disease-related H pylori genes, such as cagA, vacA, or oipA, correlated with clinical outcome. 36% of H pylori strains were babA2(-) genopositive, and abundance of babA2 was associated with the genomic presence of the other potential virulence-factor genes. H pylori strains carrying babA2, cagA, and the vacA genotype s1m1 were associated with the highest risk of developing intestinal metaplasia, whereas this condition was rarely (<10%) associated with strains with a cagA-, babA2-, vacA s2m2 genotype. Whilst the risk of developing more serious gastric lesions increased as the number of virulence factor genes accumulated in a given H pylori strain, there was no indication of any one specific bacterial gene-pattern being associated with a particular clinical disease. WHERE NEXT? Identifying the factors responsible for the enhanced pathogenicity of H pylori leading to development of life-threatening diseases in a subset of infected individuals is a mandatory task for the future. Identification of virulence-associated H pylori genes and investigation of their clinical relevance in large prospective studies will help to define such strains with increased pathogenicity. The value of H pylori genotypes as predictors of disease outcome is limited, because the pathogenic impact of bacterial virulence factors is greatly influenced by coexisting environmental and host factors.

Medical schools must evolve with the changing healthcare landscape and financial pressures. Academic Health Centers have responded to these changes with a novel organizational model known as an integrated service line. Traditional medical school departments often create silos, lack of alignment, and financial burdens. To our knowledge, we were the first medical school to implement an integrated structure combining the tripartite missions of academics, research, and clinical services.  The University of Texas Rio Grande Valley School of Medicine accepted its charter class of 55 medical students in 2016 with a traditional medical school department model. By 2023, it had 154 full-time faculty, 14 departments, a growing clinical practice with 25 ambulatory sites, and no university teaching hospital. Facing changes in the local healthcare landscape, medical school leadership implemented a restructuring of the medical school and its outpatient health system into Integrated Service Units (ISUs) in 2023.  This study aims to (1) describe the institutional steps taken to implement an ISU model across academic, research, and clinical domains of a medical school; and (2) evaluate initial outcome observations in the first one-year post-implementation. Over six months in 2023, the institution successfully implemented its vision of reorganizing the medical school across the academic, research, and clinical care areas. The new structure had seven ISUs: Primary and Community Care, Medicine and Oncology, Surgery Specialty and Musculoskeletal, Neuro and Behavioral Health, Surgery, Medical Education, and Clinical Support Services. This paper delves into the challenges, opportunities, and key lessons learned. Embarking on the ISU transformation led us out of our comfort zones and beyond conventional paradigms.  Preliminary findings across academics, research, and clinical services are presented and support that within the first year, the ISU model has accelerated the ability to accomplish our vision of transforming the health of the Rio Grande Valley. Next steps involve examining the long-term impact of the ISUs on the medical school, residencies, patients, and the health system. Areas of focus include financial success, faculty recruitment and retention, and research impact.