Personal protective equipment for reducing the risk of COVID-19 infection among healthcare workers involved in emergency trauma surgery during the pandemic: An umbrella review protocol

Introduction Many healthcare facilities in low-income and middle-income countries are inadequately resourced and may lack optimal organisation and governance, especially concerning surgical health systems. COVID-19 has the potential to decimate these already strained surgical healthcare services unless health systems take stringent measures to protect healthcare workers (HCWs) from viral exposure and ensure the continuity of specialised care for patients. The objective of this broad evidence synthesis is to identify and summarise the available literature regarding the efficacy of different personal protective equipment (PPE) in reducing the risk of COVID-19 infection in health personnel caring for patients undergoing trauma surgery in low-resource environments. Methods We will conduct several searches in the L·OVE (Living OVerview of Evidence) platform for COVID-19, a system that performs automated regular searches in PubMed, Embase, Cochrane Central Register of Controlled Trials and over 30 other sources. The search results will be presented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. This review will preferentially consider systematic reviews of experimental and quasi-experimental studies, as well as individual studies of such designs, evaluating the effect of different PPE on the risk of COVID-19 infection in HCWs involved in emergency trauma surgery. Critical appraisal of eligible studies for methodological quality will be conducted. Data will be extracted using the standardised data extraction tool in Covidence. Studies will, when possible, be pooled in a statistical meta-analysis using JBI SUMARI. The Grading of Recommendations, Assessment, Development and Evaluation approach for grading the certainty of evidence will be followed and a summary of findings will be created. Ethics and dissemination Ethical approval is not required for this review. The plan for issemination is to publish review findings in a peer-reviewed journal and present findings at high-level conferences that engage the most pertinent stakeholders

An Umbrella Review With Meta-Analysis of Chest Computed Tomography for Diagnosis of COVID-19: Considerations for Trauma Patient Management

BackgroundRT-PCR testing is the standard for diagnosis of COVID-19, although it has its suboptimal sensitivity. Chest computed tomography (CT) has been proposed as an additional tool with diagnostic value, and several reports from primary and secondary studies that assessed its diagnostic accuracy are already available. To inform recommendations and practice regarding the use of chest CT in the in the trauma setting, we sought to identify, appraise, and summarize the available evidence on the diagnostic accuracy of chest CT for diagnosis of COVID-19, and its application in emergency trauma surgery patients; overcoming limitations of previous reports regarding chest CT accuracy and discussing important considerations regarding its role in this setting.MethodsWe conducted an umbrella review using Living Overview of Evidence platform for COVID-19, which performs regular automated searches in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and more than 30 other sources. The review was conducted following the JBI methodology for systematic reviews. The Grading of Recommendations, Assessment, Development, and Evaluation approach for grading the certainty of the evidence is reported (registered in International Prospective Register of Systematic Reviews, CRD42020198267).ResultsThirty studies that fulfilled selection criteria were included; 19 primary studies provided estimates of sensitivity (0.91, 95%CI = [0.88–0.93]) and specificity (0.73, 95%CI = [0.61; 0.82]) of chest CT for COVID-19. No correlation was found between sensitivities and specificities (ρ = 0.22, IC95% [–0.33; 0.66]). Diagnostic odds ratio was estimated at: DOR = 27.5, 95%CI (14.7; 48.5). Evidence for sensitivity estimates was graded as MODERATE, and for specificity estimates it was graded as LOW.ConclusionThe value of chest CT appears to be that of an additional screening tool that can easily detect PCR false negatives, which are reportedly highly frequent. Upon the absence of PCR testing and impossibility to perform RT-PCR in trauma patients, chest CT can serve as a substitute with increased value and easy implementation.Systematic Review Registration[www.crd.york.ac.uk/prospero], identifier [CRD42020198267]

International Neurotrauma Training Based on North-South Collaborations: Results of an Inter-institutional Program in the Era of Global Neurosurgery.

Objective: Shortage of general neurosurgery and specialized neurotrauma care in low resource settings is a critical setback in the national surgical plans of low and middle-income countries (LMIC). Neurotrauma fellowship programs typically exist in high-income countries (HIC), where surgeons who fulfill the requirements for positions regularly stay to practice. Due to this issue, neurosurgery residents and medical students from LMICs do not have regular access to this kind of specialized training and knowledge-hubs. The objective of this paper is to present the results of a recently established neurotrauma fellowship program for neurosurgeons of LMICs in the framework of global neurosurgery collaborations, including the involvement of specialized parallel education for neurosurgery residents and medical students. Methods: The Global Neurotrauma Fellowship (GNTF) program was inaugurated in 2015 by a multi-institutional collaboration between a HIC and an LMIC. The course organizers designed it to be a 12-month program based on adapted neurotrauma international competencies with the academic support of the Barrow Neurological Institute at Phoenix Children's Hospital and Meditech Foundation in Colombia. Since 2018, additional support from the UK, National Institute of Health Research (NIHR) Global Health Research in Neurotrauma Project from the University of Cambridge enhanced the infrastructure of the program, adding a research component in global neurosurgery and system science. Results: Eight fellows from Brazil, Venezuela, Cuba, Pakistan, and Colombia have been trained and certified via the fellowship program. The integration of international competencies and exposure to different systems of care in high-income and low-income environments creates a unique environment for training within a global neurosurgery framework. Additionally, 18 residents (Venezuela, Colombia, Ecuador, Peru, Cuba, Germany, Spain, and the USA), and ten medical students (the United Kingdom, USA, Australia, and Colombia) have also participated in elective rotations of neurotrauma and critical care during the time of the fellowship program, as well as in research projects as part of an established global surgery initiative. Conclusion: We have shown that it is possible to establish a neurotrauma fellowship program in an LMIC based on the structure of HIC formal training programs. Adaptation of the international competencies focusing on neurotrauma care in low resource settings and maintaining international mentoring and academic support will allow the participants to return to practice in their home-based countries

A consensus statement for trauma surgery capacity building in Latin America.

Funder: Gates Cambridge Trust; doi: http://dx.doi.org/10.13039/501100005370BACKGROUND: Trauma is a significant public health problem in Latin America (LA), contributing to substantial death and disability in the region. Several LA countries have implemented trauma registries and injury surveillance systems. However, the region lacks an integrated trauma system. The consensus conference's goal was to integrate existing LA trauma data collection efforts into a regional trauma program and encourage the use of the data to inform health policy. METHODS: We created a consensus group of 25 experts in trauma and emergency care with previous data collection and injury surveillance experience in the LA. region. Experts participated in a consensus conference to discuss the state of trauma data collection in LA. We utilized the Delphi method to build consensus around strategic steps for trauma data management in the region. Consensus was defined as the agreement of ≥ 70% among the expert panel. RESULTS: The consensus conference determined that action was necessary from academic bodies, scientific societies, and ministries of health to encourage a culture of collection and use of health data in trauma. The panel developed a set of recommendations for these groups to encourage the development and use of robust trauma information systems in LA. Consensus was achieved in one Delphi round. CONCLUSIONS: The expert group successfully reached a consensus on recommendations to key stakeholders in trauma information systems in LA. These recommendations may be used to encourage capacity building in trauma research and trauma health policy in the region

Severe Pediatric TBI Management in a Middle-Income Country and a High-Income Country: A Comparative Assessment of Two Centers.

Background: Traumatic brain injury (TBI) is a global public health issue with over 10 million deaths or hospitalizations each year. However, access to specialized care is dependent on institutional resources and public health policy. Phoenix Children's Hospital USA (PCH) and the Neiva University Hospital, Colombia (NUH) compared the management and outcomes of pediatric patients with severe TBI over 5 years to establish differences between outcomes of patients managed in countries of varying resources availability. Methods: We conducted a retrospective review of individuals between 0 and 17 years of age, with a diagnosis of severe TBI and admitted to PCH and NUH between 2010 and 2015. Data collected included Glasgow coma scores, intensive care unit monitoring, and Glasgow outcome scores. Pearson Chi-square, Fisher exact, T-test, or Wilcoxon-rank sum test was used to compare outcomes. Results: One hundred and one subjects met the inclusion criteria. NUH employed intracranial pressure monitoring less frequently than PCH (p = 0.000), but surgical decompression and subdural evacuation were higher at PCH (p = 0.031 and p = 0.003). Mortality rates were similar between the institutions (15% PCH, 17% NUH) as were functional outcomes (52% PCH, 54% NUH). Conclusions: Differences between centers included time to specialized care and utilization of monitoring. No significant differences were evidenced in survival and the overall functional outcomes

A consensus statement for trauma surgery capacity building in Latin America

Background Trauma is a significant public health problem in Latin America (LA), contributing to substantial death and disability in the region. Several LA countries have implemented trauma registries and injury surveillance systems. However, the region lacks an integrated trauma system. The consensus conference’s goal was to integrate existing LA trauma data collection efforts into a regional trauma program and encourage the use of the data to inform health policy. Methods We created a consensus group of 25 experts in trauma and emergency care with previous data collection and injury surveillance experience in the LA. region. Experts participated in a consensus conference to discuss the state of trauma data collection in LA. We utilized the Delphi method to build consensus around strategic steps for trauma data management in the region. Consensus was defined as the agreement of ≥ 70% among the expert panel. Results The consensus conference determined that action was necessary from academic bodies, scientific societies, and ministries of health to encourage a culture of collection and use of health data in trauma. The panel developed a set of recommendations for these groups to encourage the development and use of robust trauma information systems in LA. Consensus was achieved in one Delphi round. Conclusions The expert group successfully reached a consensus on recommendations to key stakeholders in trauma information systems in LA. These recommendations may be used to encourage capacity building in trauma research and trauma health policy in the region

Neurosurgical Randomized Trials in Low- and Middle-Income Countries

BACKGROUND The setting of a randomized trial can determine whether its findings are generalizable and can therefore apply to different settings. The contribution of low- and middle-income countries (LMICs) to neurosurgical randomized trials has not been systematically described before. OBJECTIVE To perform a systematic analysis of design characteristics and methodology, funding source, and interventions studied between trials led by and/or conducted in high-income countries (HICs) vs LMICs. METHODS From January 2003 to July 2016, English-language trials with >5 patients assessing any one neurosurgical procedure against another procedure, nonsurgical treatment, or no treatment were retrieved from MEDLINE, Scopus, and Cochrane Library. Income classification for each country was assessed using the World Bank Atlas method. RESULTS A total of 73.3% of the 397 studies that met inclusion criteria were led by HICs, whereas 26.7% were led by LMICs. Of the 106 LMIC-led studies, 71 were led by China. If China is excluded, only 8.8% were led by LMICs. HIC-led trials enrolled a median of 92 patients vs a median of 65 patients in LMIC-led trials. HIC-led trials enrolled from 7.6 sites vs 1.8 sites in LMIC-led studies. Over half of LMIC-led trials were institutionally funded (54.7%). The majority of both HIC- and LMIC-led trials evaluated spinal neurosurgery, 68% and 71.7%, respectively. CONCLUSION We have established that there is a substantial disparity between HICs and LMICs in the number of published neurosurgical trials. A concerted effort to invest in research capacity building in LMICs is an essential step towards ensuring context- and resource-specific high-quality evidence is generated

Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus

Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P&lt;5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights.</p

Sequence data and association statistics from 12,940 type 2 diabetes cases and controls

To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1–5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (>80% of low-frequency coding variants in ~82 K Europeans via the exome chip, and ~90% of low-frequency non-coding variants in ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes