Asylum seeker’s ‘brain death’ shows failure of care and of democracy

The news that Hamid Kehazaei, a 24-year-old Iranian asylum seeker detained on Manus Island, has been diagnosed as brain dead following his transfer to the Mater Hospital in Brisbane is a tragedy. That it is a tragedy for this young man and his family is unquestionable – but the extent of this tragedy may be much more pervasive than we realise. If the emerging details of his case are correct, Kehazaei developed septicaemia as a complication of cellulitis (skin and soft-tissue infection) arising from a cut in his foot. This, in itself, is disturbing. Severe infection can result in brain death – either from infection of the brain itself (meningitis, encephalitis or brain abscess), or from brain injury due to a lack of oxygen resulting from cardiac arrest (as appears to be the case here), or from reduced blood supply to the brain. Yet it is very uncommon, especially in a young, previously healthy man. Such a case could occur in Australia and has been described in 2012 in young Indigenous adults in Central Australia. Nevertheless, severe sepsis resulting from a foot infection is preventable. And a case like this occurring in an Australian national would raise serious questions about the appropriateness of the antibiotics used and the timeliness of care. Most cases of brain death result from traumatic brain injury, stroke or lack of oxygen to the brain following asphyxia, near-drowning, or prolonged cardiopulmonary resuscitation. What happened to Hamid Kehazaei raises concerns about the adequacy of care provided to him during initial treatment, including wound care and antibiotics, and how soon he was transferred to expert medical care, first to Port Moresby and subsequently to Brisbane. If this young man became ill and had his brain die while seeking asylum in Australia and while in our care, then we must examine the details of his case and ask ourselves not only whether it was preventable but whether our policies and processes actually contributed to his death

The Impact of a Standardized Pre-visit Laboratory Testing Panel in the Internal Medicine Outpatient Clinic: a Controlled “On-Off” Trial

Background: In several settings, a shorter time to diagnosis has been shown to lead to improved clinical outcomes. The implementation of a rapid laboratory testing allows for a pre-visit testing in the outpatient clinic, meaning that test results are available during the first outpatient visit. Objective: To determine whether the pre-visit laboratory testing leads to a shorter time to diagnosis in the general internal medicine outpatient clinic. Design: An “on-off” trial, allocating subjects to one of two treatment arms in consecutive alternating blocks. Participants: All new referrals to the internal medicine outpatient clinic of a university hospital were included, excluding second opinions. A total of 595 patients were eligible; one person declined to participate, leaving data from 594 patients for analysis. Intervention: In the intervention group, patients had a standardized pre-visit laboratory testing before the first visit. Main Measures: The primary outcome was the time to diagnosis. Secondary outcomes were the correctness of the preliminary diagnosis on the first day, health care utilization, and patient and physician satisfaction. Key Results: There was no difference in time to diagnosis between the two groups (median 35 days vs 35 days; hazard ratio 1.03 [0.87–1.22]; p =.71). The pre-visit testing group had higher proportions of both correct preliminary diagnoses on day 1 (24% vs 14%; p =.003) and diagnostic workups being completed on day 1 (10% vs 3%; p <.001). The intervention group had more laboratory tests done (50.0 [interquartile range (IQR) 39.0–69.0] vs 43.0 [IQR 31.0–68.5]; p <.001). Otherwise, there were no differences between the groups. Conclusions: Pre-visit testing did not lead to a shorter overall time to diagnosis. However, a greater proportion of patients had a correct diagnosis on the first day. Further studies should focus on customizing pre-visit laboratory panels, to improve their efficacy. Trial Registration: NL500

Protocol of the Healthy Brain Study: An accessible resource for understanding the human brain and how it dynamically and individually operates in its bio-social context

The endeavor to understand the human brain has seen more progress in the last few decades than in the previous two millennia. Still, our understanding of how the human brain relates to behavior in the real world and how this link is modulated by biological, social, and environmental factors is limited. To address this, we designed the Healthy Brain Study (HBS), an interdisciplinary, longitudinal, cohort study based on multidimensional, dynamic assessments in both the laboratory and the real world. Here, we describe the rationale and design of the currently ongoing HBS. The HBS is examining a population-based sample of 1,000 healthy participants (age 30-39) who are thoroughly studied across an entire year. Data are collected through cognitive, affective, behavioral, and physiological testing, neuroimaging, bio-sampling, questionnaires, ecological momentary assessment, and real-world assessments using wearable devices. These data will become an accessible resource for the scientific community enabling the next step in understanding the human brain and how it dynamically and individually operates in its bio-social context. An access procedure to the collected data and bio-samples is in place and published on https://www.healthybrainstudy.nl/en/data-and-methods. https://www.trialregister.nl/trial/795

Protocol of the Healthy Brain Study: An accessible resource for understanding the human brain and how it dynamically and individually operates in its bio-social context

The endeavor to understand the human brain has seen more progress in the last few decades than in the previous two millennia. Still, our understanding of how the human brain relates to behavior in the real world and how this link is modulated by biological, social, and environmental factors is limited. To address this, we designed the Healthy Brain Study (HBS), an interdisciplinary, longitudinal, cohort study based on multidimensional, dynamic assessments in both the laboratory and the real world. Here, we describe the rationale and design of the currently ongoing HBS. The HBS is examining a population-based sample of 1,000 healthy participants (age 30-39) who are thoroughly studied across an entire year. Data are collected through cognitive, affective, behavioral, and physiological testing, neuroimaging, bio-sampling, questionnaires, ecological momentary assessment, and real-world assessments using wearable devices. These data will become an accessible resource for the scientific community enabling the next step in understanding the human brain and how it dynamically and individually operates in its bio-social context. An access procedure to the collected data and bio-samples is in place and published on https://www.healthybrainstudy.nl/en/data-and-methods/access. Trail registration: https://www.trialregister.nl/trial/7955

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease