Preventable trauma deaths in the Western Cape of South Africa: A consensus-based panel review.

Injury causes 4.4 million deaths worldwide annually. 90% of all injury-related deaths occur in low-and-middle income countries. Findings from expert-led trauma death reviews can inform strategies to reduce trauma deaths. A cohort of trauma decedents was identified from an on-going study in the Western Cape Province of South Africa. For each case, demographics, injury characteristics, time and location of death and postmortem findings were collected. An expert multidisciplinary panel of reviewed each case, determined preventability and made recommendations for improvement. Analysis of preventable and non-preventable cases was performed using Chi-square, Fisher's exact, and Wilcoxon signed rank tests. A rapid qualitative analysis of recommendations was conducted and descriptively summarized. 138 deaths (48 deceased-on-scene and 90 pre- or in-hospital deaths) were presented to 23 panelists. Overall, 46 (33%) of deaths reviewed were considered preventable or potentially preventable. Of all pre- and in-hospital deaths, late deaths (>24 hours) were more frequently preventable (22, 56%) and due to multi-organ failure and sepsis, compared to early deaths (≤24 hours) with 32 (63%) that were non-preventable and due to central nervous system injury and haemorrhage. 45% of pre and in-hospital deaths were preventable or potentially preventable. The expert panel recommended strengthening community based primary prevention strategies for reducing interpersonal violence alongside health system improvements to facilitate high quality care. For the health system the panel's key recommendations included improving team-based care, adherence to trauma protocols, timely access to radiology, trauma specialists, operative and critical care.

IUD Insertion Under Conscious Sedation: Patient Characteristics with Clinical Decisions.

STUDY OBJECTIVE: Uptake of intrauterine devices (IUDs) in the adolescent population may be limited by anxiety and pain anticipated during the insertion procedure. Our institution offers conscious sedation for IUD insertion to mitigate this concern. The objective of this study was to identify characteristics and outcomes of teens choosing between two types of conscious sedation for insertion of a levonorgestrel IUD. METHODS: This was a single-site, retrospective cohort study over a one year period, reviewing the electronic medical records of patients who had undergone an attempted IUD insertion using conscious sedation. Conscious sedation included nitrous gas (termed "light" sedation) or intravenous midazolam and fentanyl (termed "moderate" sedation). Patient demographic characteristics and medical and gynecological histories were analyzed. RESULTS: There were 69 attempted IUD insertions during the study period. Most patients (75.36%) were placed under light sedation, and 92.75% were successfully inserted. The only significant factor associated with choice in the type of conscious sedation was previous sexual activity, which increased the odds by 10.0 that the patient would choose light sedation (95% CI, 1.23-81.34; P = 0.031). Differences between other factors (age, history of sexual assault, tampon use, and gender identity) were not statistically significant between successful and failed insertions. CONCLUSION: In conclusion, history of sexual activity significantly differed between patients in our cohort who selected light sedation over moderate sedation. No other factors influenced the choice in sedative or success of IUD insertion. Knowing the characteristics of patients who choose nitrous versus intravenous sedation, and how it relates to successful insertion, may help guide pre-procedural counseling for patients regarding sedation for IUD insertion.

Developmental regulation of zinc homeostasis in differentiating oligodendrocytes.

Oligodendrocytes develop through sequential stages and understanding pathways regulating their differentiation remains an important area of investigation. Zinc is required for the function of enzymes, proteins and transcription factors, including those important in myelination and mitosis. Our previous studies using the ratiometric zinc sensor chromis-1 demonstrated a reduction in intracellular free zinc concentrations in mature MBP+ oligodendrocytes compared with earlier stages (Bourassa et al., 2018). We performed a more detailed developmental study to better understand the temporal course of zinc homeostasis across the oligodendrocyte lineage. Using chromis-1, we found a transient increase in free zinc after O4+,O1- pre-oligodendrocytes were switched from proliferation medium into terminal differentiation medium. To gather other evidence for dynamic regulation of free zinc during oligodendrocyte development, qPCR was used to evaluate mRNA expression of major zinc storage proteins metallothioneins (MTs) and metal regulatory transcription factor 1 (MTF1), which controls expression of MTs. MT1, MT2 and MTF1 mRNAs were increased several fold in mature oligodendrocytes compared to oligodendrocytes in proliferation medium. To assess the depth of the zinc buffer, we assayed zinc release from intracellular stores using the oxidizing thiol reagent 2,2'-dithiodipyridine (DTDP). Exposure to DTDP resulted in âˆ¼ 100% increase in free zinc in pre-oligodendrocytes but, paradoxically more modest âˆ¼ 60% increase in mature oligodendrocytes despite increased expression of MTs. These results suggest that zinc homeostasis is regulated during oligodendrocyte development, that oligodendrocytes are a useful model for studying zinc homeostasis in the central nervous system, and that regulation of zinc homeostasis may be important in oligodendrocyte differentiation.

Seeking and reaching emergency care: A cross sectional household survey across two Liberian counties.

The overwhelming burden of morbidity and mortality from injury and medical conditions requiring acute care are borne by low- and middle-income countries lacking accessible, quality care systems. Current evidence suggests the lack of prehospital care systems likely contributes to this disproportionate burden. As an initial step in a longitudinal, collaborative effort to strengthen the chain of survival for emergency conditions in Liberia, baseline attitudes and behaviors in accessing and utilizing emergency care were characterized. A multistage, proportional, cluster sampling frame was employed to conduct a cross-sectional, community-based survey of 800 households across rural Lofa County and the greater capital (Monrovia) metropolitan area. The primary outcome was facility-based utilization of emergency care within the 12 months prior to survey administration. 43.9% of individuals surveyed reported a visit to an emergency unit in the last year. Multivariable logistic regression revealed increased adjusted odds of facility-based emergency care utilization in households that were low-income, non-English-speaking, lacking electricity, or had a non-durable roof. Among these individuals, 23.6% had sought care from a community health worker, family/friend, clinic, pharmacy, or traditional healer prior. The majority of persons seeking care do so without ambulance services. 34.8% of all households have called a community member for a medical emergency, but 88.9% of survey respondents report no first aid training and cite barriers to rendering aid. This represents the first household survey to assess the perceptions and utilization of emergency care in Liberia. Formal pre-hospital care provision is limited and substantial barriers to emergency care access exist. First aid training and acceptance is lacking, despite frequent reliance on community-based aid during emergencies.

Copper induces neuron-sparing, ferredoxin 1-independent astrocyte toxicity mediated by oxidative stress.

Copper is an essential enzyme cofactor in oxidative metabolism, anti-oxidant defenses, and neurotransmitter synthesis. However, intracellular copper, when improperly buffered, can also lead to cell death. Given the growing interest in the use of copper in the presence of the ionophore elesclomol (CuES) for the treatment of gliomas, we investigated the effect of this compound on the surround parenchyma-namely neurons and astrocytes in vitro. Here, we show that astrocytes were highly sensitive to CuES toxicity while neurons were surprisingly resistant, a vulnerability profile that is opposite of what has been described for zinc and other toxins. Bolstering these findings, a human astrocytic cell line was similarly sensitive to CuES. Modifications of cellular metabolic pathways implicated in cuproptosis, a form of copper-regulated cell death, such as inhibition of mitochondrial respiration or knock-down of ferredoxin 1 (FDX1), did not block CuES toxicity to astrocytes. CuES toxicity was also unaffected by inhibitors of apoptosis, necrosis or ferroptosis. However, we did detect the presence of lipid peroxidation products in CuES-treated astrocytes, indicating that oxidative stress is a mediator of CuES-induced glial toxicity. Indeed, treatment with anti-oxidants mitigated CuES-induced cell death in astrocytes indicating that oxidative stress is a mediator of CuES-induced glial toxicity. Lastly, prior induction of metallothioneins 1 and 2 in astrocytes with zinc plus pyrithione was strikingly protective against CuES toxicity. As neurons express high levels of metallothioneins basally, these results may partially account for their resistance to CuES toxicity. These results demonstrate a unique toxic response to copper in glial cells which contrasts with the cell selectivity profile of zinc, another biologically relevant metal.

Developmental regulation of zinc homeostasis in differentiating oligodendrocytes.

Oligodendrocytes develop through well characterized stages and understanding pathways regulating their differentiation remains an active area of investigation. Zinc is required for the function of many enzymes, proteins and transcription factors, including those important in myelination and mitosis. Our previous studies using the ratiometric zinc sensor chromis-1 demonstrated a reduction in intracellular free zinc concentrations in mature oligodendrocytes compared with earlier stages (Bourassa et al., 2018). We performed a more detailed developmental study to better understand the temporal course of zinc homeostasis across the oligodendrocyte lineage. Using chromis-1, we found a transient increase in free zinc after developing oligodendrocytes were switched into differentiation medium. To gather other evidence for dynamic regulation of free zinc during oligodendrocyte development, qPCR was used to evaluate mRNA expression of the major zinc storage proteins metallothioneins (MTs), and metal regulatory transcription factor 1 (MTF-1) which controls expression of MTs. MT-1, MT-2 and MTF1 mRNAs were all increased several fold in mature oligodendrocytes compared to developing oligodendrocytes. To assess the depth of the zinc buffer, we assayed zinc release from intracellular stores using the oxidizing thiol reagent 2,2'-dithiodipyridine (DTDP). Exposure to DTDP resulted in a ∼100% increase in free zinc in developing oligodendrocytes but, paradoxically more modest ∼60% increase in mature oligodendrocytes despite the increased expression of MTs. These results suggest that zinc homeostasis is regulated during oligodendrocyte development, that oligodendrocytes are a useful model for studying zinc homeostasis in the central nervous system, and that regulation of zinc homeostasis may be important in oligodendrocyte differentiation.

GluA1-Shank3 interaction decreases in response to chronic neuronal depolarization.

Interactions between AMPA receptors and synaptic scaffolding proteins are key regulators of synaptic receptor density and, thereby, synapse strength. Shank3 is one such scaffolding protein with high clinical relevance, as genetic variants and deletions of this protein have been linked to autism spectrum disorder. Shank3 acts as a master regulator of the postsynaptic density of glutamatergic synapses, interacting with ionotropic and metabotropic glutamate receptors and cytoskeletal elements to modulate synaptic structure. Notably, Shank3 has been shown to interact directly with the AMPAR subunit GluA1, and Shank3 knockout animals show deficits in AMPAR-mediated synaptic transmission. In this study, we sought to characterize the stability of GluA1-Shank3 interaction in response to chronic stimuli using a highly sensitive and specific proximity ligation assay. We found that GluA1-Shank3 interactions decrease in response to prolonged neuronal depolarization induced by elevated extracellular potassium, and that this reduced interaction is blocked by NMDA receptor antagonism. These results firmly establish the close interaction of GluA1 and Shank3 in cortical neurons in vitro, and that this select interaction is subject to modulation by depolarization.

Defining measures of emergency care access in low-income and middle-income countries: a scoping review.

BACKGROUND: Over 50% of annual deaths in low-income and middle-income countries (LMICs) could be averted through access to high-quality emergency care. OBJECTIVES: We performed a scoping review of the literature that described at least one measure of emergency care access in LMICs in order to understand relevant barriers to emergency care systems. ELIGIBILITY CRITERIA: English language studies published between 1 January 1990 and 30 December 2020, with one or more discrete measure(s) of access to emergency health services in LMICs described. SOURCE OF EVIDENCE: PubMed, Embase, Web of Science, CINAHL and the grey literature. CHARTING METHODS: A structured data extraction tool was used to identify and classify the number of 'unique' measures, and the number of times each unique measure was studied in the literature ('total' measures). Measures of access were categorised by access type, defined by Thomas and Penchansky, with further categorisation according to the 'Three Delay' model of seeking, reaching and receiving care, and the WHO's Emergency Care Systems Framework (ECSF). RESULTS: A total of 3103 articles were screened. 75 met full study inclusion. Articles were uniformly descriptive (n=75, 100%). 137 discrete measures of access were reported. Unique measures of accommodation (n=42, 30.7%) and availability (n=40, 29.2%) were most common. Measures of seeking, reaching and receiving care were 22 (16.0%), 46 (33.6%) and 69 (50.4%), respectively. According to the ECSF slightly more measures focused on prehospital care-inclusive of care at the scene and through transport to a facility (n=76, 55.4%) as compared with facility-based care (n=57, 41.6%). CONCLUSIONS: Numerous measures of emergency care access are described in the literature, but many measures are overaddressed. Development of a core set of access measures with associated minimum standards are necessary to aid in ensuring universal access to high-quality emergency care in all settings.

Neurodevelopmental Consequences of Dietary Zinc Deficiency: A Status Report.

Zinc is a tightly regulated trace mineral element playing critical roles in growth, immunity, neurodevelopment, and synaptic and hormonal signaling. Although severe dietary zinc deficiency is relatively uncommon in the United States, dietary zinc deficiency is a substantial public health concern in low- and middle-income countries. Zinc status may be a key determinant of neurodevelopmental processes. Indeed, limited cohort studies have shown that serum zinc is lower in people diagnosed with autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and depression. These observations have sparked multiple studies investigating the mechanisms underlying zinc status and neurodevelopmental outcomes. Animal models of perinatal and adult dietary zinc restriction yield distinct behavioral phenotypes reminiscent of features of ASD, ADHD, and depression, including increased anxiety and immobility, repetitive behaviors, and altered social behaviors. At the cellular and molecular level, zinc has demonstrated roles in neurogenesis, regulation of cellular redox status, transcription factor trafficking, synaptogenesis, and the regulation of synaptic architecture via the Shank family of scaffolding proteins. Although mechanistic questions remain, the current evidence suggests that zinc status is important for adequate neuronal development and may be a yet overlooked factor in the pathogenesis of several psychiatric conditions. This review aims to summarize current knowledge of the role of zinc in the neurophysiology of the perinatal period, the many cellular targets of zinc in the developing brain, and the potential consequences of alterations in zinc homeostasis in early life.

Intracellular zinc signaling influences NMDA receptor function by enhancing the interaction of ZnT1 with GluN2A.

Zinc, loaded into glutamate-containing presynaptic vesicles and released into the synapse in an activity-dependent manner, modulates neurotransmission through its actions on postsynaptic targets, prominently via high-affinity inhibition of GluN2A-containing NMDA receptors. Recently, we identified a postsynaptic transport mechanism that regulates endogenous zinc inhibition of NMDARs. In this new model of zinc regulation, the postsynaptic transporter ZnT1 mediates zinc inhibition of NMDARs by binding to GluN2A. Through this interaction, ZnT1, a transporter that moves zinc from the cytoplasm to the extracellular domain, generates a zinc microdomain that modulates NMDAR-mediated neurotransmission. As ZnT1 expression is transcriptionally driven by the metal-responsive transcription factor 1 (MTF-1), we found that intracellular zinc strongly drives MTF-1 in cortical neurons in vitro and increases the number of GluN2A-ZnT1 interactions, thereby enhancing tonic zinc inhibition of NMDAR-mediated currents. Importantly, this effect is absent when the interaction between GluN2A and ZnT1 is disrupted by a cell-permeable peptide. These results suggest that zinc-regulated gene expression can dynamically regulate NMDAR-mediated synaptic processes.

A Global Review of Provisions on Emergency Care in National Constitutions.

National constitutions are important tools for the realization of the right to health, and constitutional law linking health and human rights has been associated with improved access to health resources. Meanwhile, emergency care is a lifesaving service delivery platform with the potential to address much of the death and disability in low- and middle-income countries (LMICs). Yet even where services exist, access to emergency care may be systematically limited for vulnerable populations, except where laws explicitly protect the right to emergency care. We therefore sought to catalog and describe constitutional provisions related to emergency care. Through a comprehensive review of 195 national constitutions, we searched provisions for terms related to emergency care and performed qualitative framework analysis on these provisions. Eleven provisions met inclusion criteria, representing ten LMICs with constitutions written since 1996. While seven of the eleven provisions guarantee access to emergency care to all people, three narrow this guarantee to citizens only. Only three constitutions address the affordability of emergency care. While these constitutional provisions represent an important step toward the legal guarantee of access to emergency care for all people, further attention must be paid to the impact of such laws and regulation on the accessibility of emergency care and its related reduction of death and disability globally.

Correction: Deaths in Immigration and Customs Enforcement (ICE) detention: FY2018-2020.

[This corrects the article DOI: 10.3934/publichealth.2021006.].

Characteristics of Deaths Among Individuals in US Immigration and Customs Enforcement Detention Facilities, 2011-2018.

Importance: Concerns have been raised that substandard medical care has contributed to deaths in US Immigration and Customs Enforcement (ICE) detention facilities. After each in-custody death, ICE produces detainee death reviews, which describe the circumstances of the death and determine whether ICE Performance-Based National Detention Standards (PBNDS) were violated. Objective: To describe factors associated with deaths in ICE detention facilities. Design, Setting, and Participants: This case series used data extracted from detainee death reviews of deaths among individuals detained in ICE facilities for whom these reviews were available from January 2011 to December 2018. Exposures: All individuals were in the custody of ICE at the time of death. Main Outcomes and Measures: Data including demographic information, medical histories, recorded medical data, and reported violations of PBNDS were systematically extracted and summarized. Results: Among 71 individuals who died in an ICE detention facility during the study period, detainee death reviews were available for 55 (77.5%). Most were male (47 [85.5%]), and the mean (SD) age at death was 42.7 (11.5) years. Individuals resided in the US for a mean (SD) of 15.8 (13.2) years before detention and were in ICE custody for a median of 39 days (interquartile range, 9-76 days) before death. Most had low burdens of preexisting disease, with 18 (32.7%) having a Charlson Comorbidity Index score of 0 and 15 (27.3%) having a score of 1 or 2. A total of 47 deaths (85.5%) were attributed to medical causes and 8 (14.5%) to suicide. Markedly abnormal vital signs were documented in the death reviews before 29 of 47 deaths from medical causes (61.7%), and 21 of these 29 deaths (72.4%) were preceded by abnormal vital signs during 2 or more encounters with ICE personnel before death or terminal hospital transfer. Overall, 43 detainee death reviews (78.2%) identified PBNDS violations related to medical care, with a mean (SD) of 3.2 (3.0) deficiencies per detainee death review. Conclusions and Relevance: In this case series, deaths in ICE detention facilities from 2011 to 2018 occurred primarily among young men with low burdens of preexisting disease. Markedly abnormal vital signs preceded death or hospital transfer for most nonsuicide deaths. The PBNDS were violated in most detainee death reviews. These results suggest that additional oversight and external evaluation of practices related to medical and psychiatric care within ICE facilities are needed.

A randomized controlled trial investigating the impact of maternal dietary supplementation with pomegranate juice on brain injury in infants with IUGR.

Animal studies have demonstrated the therapeutic potential of polyphenol-rich pomegranate juice. We recently reported altered white matter microstructure and functional connectivity in the infant brain following in utero pomegranate juice exposure in pregnancies with intrauterine growth restriction (IUGR). This double-blind exploratory randomized controlled trial further investigates the impact of maternal pomegranate juice intake on brain structure and injury in a second cohort of IUGR pregnancies diagnosed at 24-34 weeks' gestation. Ninety-nine mothers and their eligible fetuses (n = 103) were recruited from Brigham and Women's Hospital and randomly assigned to 8 oz pomegranate (n = 56) or placebo (n = 47) juice to be consumed daily from enrollment to delivery. A subset of participants underwent fetal echocardiogram after 2 weeks on juice with no evidence of ductal constriction. 57 infants (n = 26 pomegranate, n = 31 placebo) underwent term-equivalent MRI for assessment of brain injury, volumes and white matter diffusion. No significant group differences were found in brain volumes or white matter microstructure; however, infants whose mothers consumed pomegranate juice demonstrated lower risk for brain injury, including any white or cortical grey matter injury compared to placebo. These preliminary findings suggest pomegranate juice may be a safe in utero neuroprotectant in pregnancies with known IUGR warranting continued investigation.Clinical trial registration: NCT04394910, https://clinicaltrials.gov/ct2/show/NCT04394910 , Registered May 20, 2020, initial participant enrollment January 16, 2016.

Deaths in Immigration and Customs Enforcement (ICE) detention: FY2018-2020.

BACKGROUND: Many civil liberties organizations have raised concerns that substandard medical care in United States Immigration and Customs Enforcement (ICE) detention facilities have led to preventable deaths. The 2018 Department of Homeland Security Appropriations Bill required ICE to make public all reports regarding in-custody deaths within 90 days beginning in Fiscal Year (FY) 2018. Accordingly, ICE has released death reports following each in-custody death since April of 2018. This study describes characteristics of deaths among individuals in ICE detention following the FY2018 mandate. METHODS: Data was extracted from death reports published by ICE following the FY2018 mandate. Causes of death were categorized as suicide or medical, and medical deaths as COVID-19-related or not. Characteristics were compared between medical and suicide deaths, and among medical deaths between COVID-19-related and non-COVID-19-related deaths. Additionally, death rates per person-year and per 100,000 admissions were calculated for FY2018, 2019, and 2020 using methods from prior work evaluating deaths among detained immigrants in the United States. RESULTS: Since April 2018, 35 individuals have died in ICE detention. The death rate per 100,000 admissions in ICE detention was 2.303 in FY2018, 1.499 in FY2019, and 10.833 in FY2020. Suicide by hanging was identified as the cause of death in 9 (25.7%), and medical causes in the remaining 26 (74.3%). Among 26 deaths attributable to medical causes, 8 (30.8%) were attributed to COVID-19, representing 72.7% of 11 deaths occurring since April 2020. CONCLUSIONS: The death rate among individuals in ICE detention is increasing amidst the COVID-19 pandemic. Potentially preventable causes of death including COVID-19 and suicide contribute to at least half of recent deaths. Findings suggest that individuals detained by ICE may benefit from improved psychiatric care and prevention measures to combat suicide, as well as increased infection control efforts to reduce mortality associated with COVID-19.

Mapping factors associated with deaths in immigration detention in the United States, 2011-2018: A thematic analysis.

Background: Climate change, poverty, and violence increasingly drive migration to the United States. United States Immigration and Customs Enforcement (ICE) detain some individuals while awaiting determination of immigration status or potential deportation. Over the last two decades, more than 200 individuals died in ICE detention. In this study, we aim to identify systemic issues related to deaths of individuals in ICE detention to potentially mitigate further harm. Methods: The ICE Office of Detention Oversight conducts investigations after each death in detention, producing a report called a "Detainee Death Review". To identify systemic issues in these deaths, we used thematic analysis to review 55 Detainee Death Reviews available between 2011 and 2018. Findings: We identified 3 major themes of pervasive issues-Detainee Not Patient, System Over Patient, and Grossly Substandard Care- and 11 subthemes. Subthemes of culture of shortcuts, delays in care, and poor care delivered were present in the vast majority of cases. Subthemes bias and discrimination, language injustice, falsification of and inconsistencies between records and reports, willful indifference, security over health, communication breakdown, inadequate resources, failure of protective mechanisms, missing/ignoring red flags, and failure of emergency response were also prominent. Interpretation: This study identified underlying systems issues within the medical care provided in ICE detention. While there are issues with language services, discrimination, and inadequate response to medical emergencies, the greatest issue is the lack of independent, external review. Greater transparency is required, so that adherence to basic standards of care for individuals in ICE detention can be better evaluated. Funding: Haas Jr. Fund and the University of Southern California's Equity Research Institute.