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© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Traumatic brain injury (TBI) is increasingly recognised as being responsible for a substantial proportion of the global burden of disease. Neurosurgical interventions are an important aspect of care for patients with TBI, but there is little epidemiological data available on this patient population. We aimed to characterise differences in casemix, management, and mortality of patients receiving emergency neurosurgery for TBI across different levels of human development. Methods: We did a prospective observational cohort study of consecutive patients with TBI undergoing emergency neurosurgery, in a convenience sample of hospitals identified by open invitation, through international and regional scientific societies and meetings, individual contacts, and social media. Patients receiving emergency neurosurgery for TBI in each hospital's 30-day study period were all eligible for inclusion, with the exception of patients undergoing insertion of an intracranial pressure monitor only, ventriculostomy placement only, or a procedure for drainage of a chronic subdural haematoma. The primary outcome was mortality at 14 days postoperatively (or last point of observation if the patient was discharged before this time point). Countries were stratified according to their Human Development Index (HDI)—a composite of life expectancy, education, and income measures—into very high HDI, high HDI, medium HDI, and low HDI tiers. Mixed effects logistic regression was used to examine the effect of HDI on mortality while accounting for and quantifying between-hospital and between-country variation. Findings: Our study included 1635 records from 159 hospitals in 57 countries, collected between Nov 1, 2018, and Jan 31, 2020. 328 (20%) records were from countries in the very high HDI tier, 539 (33%) from countries in the high HDI tier, 614 (38%) from countries in the medium HDI tier, and 154 (9%) from countries in the low HDI tier. The median age was 35 years (IQR 24–51), with the oldest patients in the very high HDI tier (median 54 years, IQR 34–69) and the youngest in the low HDI tier (median 28 years, IQR 20–38). The most common procedures were elevation of a depressed skull fracture in the low HDI tier (69 [45%]), evacuation of a supratentorial extradural haematoma in the medium HDI tier (189 [31%]) and high HDI tier (173 [32%]), and evacuation of a supratentorial acute subdural haematoma in the very high HDI tier (155 [47%]). Median time from injury to surgery was 13 h (IQR 6–32). Overall mortality was 18% (299 of 1635). After adjustment for casemix, the odds of mortality were greater in the medium HDI tier (odds ratio [OR] 2·84, 95% CI 1·55–5·2) and high HDI tier (2·26, 1·23–4·15), but not the low HDI tier (1·66, 0·61–4·46), relative to the very high HDI tier. There was significant between-hospital variation in mortality (median OR 2·04, 95% CI 1·17–2·49). Interpretation: Patients receiving emergency neurosurgery for TBI differed considerably in their admission characteristics and management across human development settings. Level of human development was associated with mortality. Substantial opportunities to improve care globally were identified, including reducing delays to surgery. Between-hospital variation in mortality suggests changes at an institutional level could influence outcome and comparative effectiveness research could identify best practices. Funding: National Institute for Health Research Global Health Research Group.

Impaired cerebrovascular reactivity has emerged as an important associate with poor long-term outcome after moderate/severe traumatic brain injury (TBI). However, our understanding of what drives or modulates the degree of impaired cerebrovascular function remains poor. Age and biological sex remain important modifiers of cerebrovascular function in health and disease, yet their impact on cerebrovascular reactivity after TBI remains unclear. The aim of this study was to explore subgroup responses based on age and biological sex on cerebral physiology. Data from 283 TBI patients from the CAnadian High Resolution TBI (CAHR-TBI) Research Collaborative were evaluated. Cerebrovascular reactivity was determined using high-frequency cerebral physiology for the derivation of three intracranial pressure (ICP)-based indices: 1) pressure reactivity index (PRx)-correlation between ICP and mean arterial pressure (MAP); 2) pulse amplitude index (PAx)-correlation between pulse amplitude of ICP (AMP) and MAP; and 3) RAC-correlation between AMP and cerebral perfusion pressure (CPP). Insult burden (% time above clinically defined thresholds) were calculated for these indices. These cerebral physiology indices were studied for their relationship with age via linear regression, age trichotomization (< 40, 40 - 60, > 60), and decades of age (< 30, 30-39, 40-49, 50-59, 60-69, > 69) schemes. Similarly, differences based on biological sex were assessed. A statistically significant positive linear correlation was found between PAx, RAC, and age. In corollary, a statistically significant relationship was found between increasing age on trichotomized and decades of age analysis with PAx and RAC measures. PRx failed to demonstrate such relationships to advancing age. There was no clear difference in cerebrovascular reactivity profiles between biological sex categories. These findings suggest that AMP-based cerebrovascular reactivity indices may be better positioned to detect impairment in TBI patients with advancing age. Further investigation into the utility of PAx and RAC is required, as they may prove useful for certain subgroups of patients.

Background: Critical illness with COVID-19 is associated with increased delirium duration and severity, and delirium is associated with poor health outcomes. The pathophysiology of delirium in this population is not well understood but neuroinflammation is hypothesized to play a key role. Objective: To evaluate the relationship between biomarkers of systemic inflammation and delirium in critically ill patients with COVID-19. Design: Observational retrospective data extraction study from March 1, 2020 – June 7, 2020. Biomarker levels and delirium occurrence were assessed up to the first 14 days in the intensive care unit (ICU). Setting: Two large, urban, academic referral hospitals in Indianapolis, IN Patients: Two hundred thirty-five patients admitted to the ICU with a positive SARS-Co-V2 PCR test Methods and Main Results: A total of 235 consecutive patients admitted to the ICU were included in the analysis. The cohort had a mean age of 58.6 years (SD: 15.4), 43.4% were female, 45.9% were African American, with median Acute Physiology and Chronic Evaluation-II score of 18.0 (IQR: 13.0 -15.0). Delirium occurred in 176 (79.1%). Increased levels of C-Reactive Protein (CRP) were associated with increased odds of delirium and coma (OR: 1.27, 95% CI: 1.08, 1.49, p=0.004). Increased levels of D-dimer were not associated with increased odds of delirium/coma (OR: 0.94, 95% CI 0.76, 1.16, p=0.574). Increased levels of ferritin (OR: 1.04, 95% CI 0.84, 1.29, p=0.717) and lactate dehydrogenase (LDH) were also not associated with increased odds of delirium/coma (OR: 0.86, 95% CI 0.70, 1.06, p=0.149). Elevated levels of creatine kinase (CK) levels were associated with lower odds of delirium/coma (OR: 0.71 95% CI 0.52, 0.97, p=0.033). Conclusion: Increased levels of biomarkers of inflammation and thrombosis were associated with greater odds of delirium and coma. Further studies are needed to validate these results in a larger population. “This project was funded, in part, with support from the NIH NHLBI Short-Term Training Program in Biomedical Sciences Grantfunded, in part by T35HL110854 from the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”

INTRODUCTION: Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) are glioneuronal tumors of early childhood. Surgical resection is usually sufficient to cure these benign tumors. The presence of metastatic seeding is rare and has been reported as an adverse prognostic factor. We present 2 cases of young children with recurrent metastatic DIA/DIG to describe their presentation, therapeutic management and outcome and to highlight the importance of molecular characterization of these rare tumors to guide adjuvant therapy. CASES DESCRIPTION: The first patient developed metastatic recurrence after initial gross total resection (GTR) of a localized DIG. The disseminated relapse was treated with monthly carboplatin and vincristine (CB/VCR). Complete response was achieved after 15 cycles and the patient has remained in continuous complete remission for 5 years. Post hoc molecular analysis of the tumor revealed a BRAF-RDX fusion. The second patient presented with a disseminated intraventricular relapse following an incomplete resection of a DIA associated with a SPECC1L-NTRK2 fusion. The patient received 2 cycles of CB/VCR with minimal response and was then switched to Larotrectinib leading to a very good partial response (VGPR) 3 months into therapy and has remained on treatment since then with significant clinical improvement. DISCUSSION/ CONCLUSION: In our 2 cases, metastatic recurrence was responsive to adjuvant therapy leading to complete response with conventional chemotherapy in the first one and to VGPR with NTRK inhibitor in the second patient. Early molecular characterization of these benign tumors is critical in case of incomplete resection or metastatic seeding to widen therapeutic options and maximize chance of cure. Response with NTRK inhibitor appears rapid and significant but the total duration of treatment and sustainability of response after discontinuation remain unknown.

Coral recruitment and juvenile growth are essential processes for coral population maintenance and recovery. A growing body of research has evaluated the influence of reef microstructure on coral settlement and post-settlement survival, showing that physical refugia enhance recruitment. These studies have evaluated coral recruit morality from competition with macroalgae and indirect predation by grazing organisms, but the impact of direct predation by corallivorous piscine species on juvenile corals and how this interacts with reef microstructure is relatively unknown. This study examined whether refugia provided by micro-crevices enhance juvenile coral survival from corallivory. Juvenile corals from two different functional groups, the slow-growing massive Porites lobata and fast-growing branching Pocillopora damicornis, with average nubbin sizes of 1.4 cm × 0.3 cm and 0.5 cm × 1.0 cm (diameter × height), respectively, were attached to experimental tiles using small (1.44 cm3) and large (8.0 cm3) crevice sizes and were monitored for 29 d on a forereef in Palau. Full crevices (four sided) enhanced coral survival compared to exposed microhabitats in both coral taxa, but crevice size did not alter survival rates. Corallivores targeted recruits within crevices regardless of crevice size; dominant predators included small triggerfish (Balistidae), butterflyfish (Chaetodon), and wrasse (Cheilinus). Overall, Pocillopora suffered much higher rates of mortality than Porites. All Pocillopora were consumed by day 8 of the experiment, but mortality was significantly delayed in full crevices compared to exposed and partial crevice (three sided) microhabitats. In contrast, Por. lobata located in all microhabitats survived the entire experiment up to 29 d, with high survival in full (>90%) and partial crevices (70%), but only 28% survival in exposed microhabitats. These findings show the importance of crevices as spatial refugia from predators for juvenile corals and highlight the importance of structural complexity for juvenile coral growth and survival that enhances reef recovery.

BACKGROUND Fructose, which is a sweetener with a low glycemic index, has been shown to elevate postprandial triglyceride compared with glucose. There are limited data on the effect of fructose in a solid mixed meal containing starch and protein. OBJECTIVE We determined the effects of sucrose, fructose, and sucralose on triglyceride, glucose, and insulin in an acute study in healthy, overweight, and obese individuals. DESIGN The study had a randomized crossover design. Twenty-seven participants with a mean age of 44 y and a mean body mass index (in kg/m(2)) of 26 completed the study. Fructose (52 g), sucrose (65 g), and sucralose (0.1 g) were delivered as sweet-taste-balanced muffins with a total fat load (66 g). Blood samples were taken at baseline and every 30 min for 4-h glucose, triglyceride, and insulin concentrations, and the area under the curve (AUC) and the incremental area under the curve (iAUC) were analyzed. RESULTS No significant difference was shown between the 3 sweeteners for triglyceride and glucose concentrations and the AUC. The glucose iAUC was lower for fructose than for sucrose and sucralose (P < 0.05). Insulin concentrations differed significantly by the type of muffin (P = 0.001), the interaction of time by type of muffin (P = 0.035), the AUC (P < 0.001), and the iAUC (P < 0.001). Fructose had a significantly lower insulin response than that of either sucrose (P-treatment = 0.006) or sucralose (P-treatment = 0.041). CONCLUSIONS Fructose, at a moderate dose, did not significantly elevate triglyceride compared with sucrose or sucralose and lowered the glucose iAUC. These results indicate that these sweeteners, at an equivalent sweetness, can be used in normal solid meals. Fructose showed a lower insulin response, which may be beneficial in the long term in individuals at risk of type 2 diabetes. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12615000279527.

Background Deer are an important wildlife species in both the Republic of Ireland and Northern Ireland having colonised most regions across the island of Ireland. In comparison to cattle and sheep which represent the main farmed ruminant species on the island, there is a lack of data concerning their exposure, as measured by the presence of antibodies, to important viral pathogens of ruminants. A study was therefore undertaken to investigate the seroprevalence of wild deer to four viruses, namely bovine viral diarrhoea virus (BVDV), bovine herpesvirus-1 (BoHV-1), Schmallenberg virus (SBV) and bluetongue virus (BTV). Results Two panels of sera were assembled; Panel 1 comprised 259 samples (202 collected in the Republic of Ireland and 57 in Northern Ireland) between 2013 and 2015, while Panel 2 comprised 131 samples collected in the Republic of Ireland between 2014 and 2015. Overall sika deer (Cervus nippon) were sampled most commonly (54.8%), followed by fallow deer (Dama dama) (35.3%), with red deer (Cervus elaphus) (4.3%) and hybrid species (0.3%) sampled less frequently, with the species not being recorded for the remaining 5.3% of deer sampled. Age was not recorded for 96 of the 390 deer sampled. 196 of the remainder were adults, while 68 and 30 were yearlings and calves, respectively. Using commercially available enzyme-linked immunosorbent assays, true prevalence and 95% confidence intervals were calculated as 9.9%, (6.8-13.0% CI), SBV; 1.5% (0.1-3.0% CI), BoHV-1; 0.0%, 0-1.7% CI), BVDV; and 0.0%, (0.01-0.10% CI), BTV. Conclusions The results indicate a very low seroprevalence for both BVDV and BoHV-1 in the wild deer tested within the study and, are consistent with a very low prevalence in Ireland. While serological cross-reaction with cervid herpesviruses cannot be excluded, the results in both cases suggest that the presence of these viruses in deer is not a significant risk to their control and eradication from the cattle population. This is important given the ongoing programme to eradicate BVDV in Ireland and deliberations on a national eradication programme for BoHV-1. The SBV results show consistency with those reported from cattle and sheep on the island of Ireland, while the BTV results are consistent with this virus remaining exotic to Ireland. The results provide a baseline against which future surveys of either wild or farmed/captive deer populations can be compared.

Effective management of occupational health and safety ( OHS) continues to pose a challenge to many organisations. While significant advancement has occurred in knowledge about traditional workplace risks, organisational and labour market changes have created new risks, psychosocial risks are more prevalent, and the trend towards the adoption of OHS management systems has produced only mixed results. These issues are the focus of this review of recent developments in workplace health and safety. We argue there is a need for organisations to refocus systematically on a collaborative approach to identifying and controlling workplace risks, and on improving the integration of OHS into broader systems and every day management to better meet existing and future OHS challenges.

Objectives To give an overview on the use and prevalence of clinical pathways. Design Cross-sectional descriptive study. Study participants European Pathway Association (E-P-A) contact persons in 23 countries. Results Clinical pathways, also known as critical pathways or integrated care pathways, have been used in health care for 20 years. Although clinical pathways are well established, little information exists on their use and dissemination around the world. The E-P-A has performed their first international survey on the use and dissemination of clinical pathways in 23 countries. At present, pathways are used with a minority of patients, mainly in acute hospital trusts. Our survey showed that clinical pathways were predominantly viewed as a multidisciplinary tool to improve the quality and efficiency of evidence-based care. Pathways were also used as a communication tool between professionals to manage and standardize outcome-oriented care. Conclusions There is a future for the use of clinical pathways, but there is a need for international benchmarking and knowledge sharing with regard to their development, implementation and evaluation.

The growing popularity of occupational safety and health management systems in Australia has stimulated critical debate about their effectiveness. This paper asks whether the performance of such systems lives up to expectations. Making use of a research review and an extensive interviewing programme, the paper draws several conclusions. First, it observes that the definitional requirements for an occupational safety and health management system have been watered down, making it more likely that organisations can claim to have a system, but less likely that it will be effective. Second, a review of empirical research reinforces the view that systems can improve health and safety outcomes, but only if they meet strict conditions concerning senior management commitment, effective workforce involvement and programme integration. Third, several barriers to successful implementation are identified, including the failure to meet essential success factors, the inappropriate application of audit tools to ensure compliance, and their problematic application in certain sectors such as small business, contractors, and the part-time and temporary workforce. The paper concludes that occupational safety and health management systems can live up to their promise, but often fail to do so because of inadequate implementation or application in hostile environments.

Importance Hemorrhage into the brain of term newborns often results in major injury and lifelong disability. The clinical epidemiology of neonatal hemorrhagic stroke (NHS) remains undefined, hindering the development of strategies to improve outcomes. Objective To characterize the incidence, types, presentations, associated factors, and outcomes of neonatal hemorrhagic stroke. Design, Setting, and Participants Population-based, nested case-control study. The Alberta Perinatal Stroke Project, a provincial registry, ascertained NHS cases using exhaustive diagnostic code searching (1992-2010, >2500 medical record reviews). Prospective cases were captured through the Calgary Pediatric Stroke Program (2007-2014). Participants included term neonates with magnetic resonance imaging–confirmed NHS including primary and secondary intracerebral hemorrhage, hemorrhagic transformation of ischemic injury, and presumed perinatal hemorrhagic stroke. Control infants with common data were recruited from a population-based study (4 to 1 ratio). Main Outcomes and Measures Infants with NHS underwent structured medical record review using data-capture forms and blinded scoring of neuroimaging. Clinical risk factor common data elements were explored using logistic regression. Provincial live births were obtained from Statistics Canada. Outcomes were extrapolated to the Pediatric Stroke Outcome Measure. Results We identified 86 cases: 51 infants (59%) with NHS, of which 32 (67%) were idiopathic, 30 (35%) were hemorrhagic transformation of primary ischemic injuries (14 with neonatal cerebral sinovenous thrombosis, 11 with hypoxic ischemic encephalopathy, and 5 with neonatal arterial ischemic stroke), and 5 were presumed perinatal hemorrhagic stroke. Sixty-two percent were male. Incidence of pure NHS was 1 in 9500 live births and 1 in 6300 for all forms. Most presented in the first week of life with seizures and encephalopathy. Acute neurosurgical intervention was rare (3 of 86 total cases; 3.5%). Temporal lobe was the most common NHS location (16 of 51 pure NHS cases; 31%). A primary cause was evident in 19 of the 51 cases of non–hemorrhagic transformation NHS (37%). Idiopathic NHS was independently associated with lower maternal age (odds ratio [OR], 0.87; 95% CI, 0.78-0.94), primiparity (OR, 2.98; 95% CI, 1.18-7.50), prior spontaneous abortion (OR, 0.11; 95% CI, 0.02-0.53), difficult fetal transition (bradycardia [OR, 15.0; 95% CI, 2.19-101.9] and low Apgar [OR, 14.3; 95% CI, 2.77-73.5]), and small for gestational age (OR, 14.3; 95% CI, 1.62-126.1). Follow-up of 50 cases at a median of 37 months demonstrated poor neurological outcomes in 21 patients (44%). Conclusions and Relevance Neonatal hemorrhagic stroke is more common than previously reported, occurring in at least 1 in 6300 live births. Etiologies are approximately equally distributed between idiopathic, secondary, and hemorrhagic transformation. Clinical associations do not suggest a common mechanism or predictability of NHS. Recurrence is rare. Outcomes are often poor, mandating attention to prevention and rehabilitation.