Etiology of hospital mortality in children living in low- and middle-income countries: a systematic review and meta-analysis.

In 2019, 80% of the 7.4 million global child deaths occurred in low- and middle-income countries (LMICs). Global and regional estimates of cause of hospital death and admission in LMIC children are needed to guide global and local priority setting and resource allocation but are currently lacking. The study objective was to estimate global and regional prevalence for common causes of pediatric hospital mortality and admission in LMICs. We performed a systematic review and meta-analysis to identify LMIC observational studies published January 1, 2005-February 26, 2021. Eligible studies included: a general pediatric admission population, a cause of admission or death, and total admissions. We excluded studies with data before 2,000 or without a full text. Two authors independently screened and extracted data. We performed methodological assessment using domains adapted from the Quality in Prognosis Studies tool. Data were pooled using random-effects models where possible. We reported prevalence as a proportion of cause of death or admission per 1,000 admissions with 95% confidence intervals (95% CI). Our search identified 29,637 texts. After duplicate removal and screening, we analyzed 253 studies representing 21.8 million pediatric hospitalizations in 59 LMICs. All-cause pediatric hospital mortality was 4.1% [95% CI 3.4%-4.7%]. The most common causes of mortality (deaths/1,000 admissions) were infectious [12 (95% CI 9-14)]; respiratory [9 (95% CI 5-13)]; and gastrointestinal [9 (95% CI 6-11)]. Common causes of admission (cases/1,000 admissions) were respiratory [255 (95% CI 231-280)]; infectious [214 (95% CI 193-234)]; and gastrointestinal [166 (95% CI 143-190)]. We observed regional variation in estimates. Pediatric hospital mortality remains high in LMICs. Global child health efforts must include measures to reduce hospital mortality including basic emergency and critical care services tailored to the local disease burden. Resources are urgently needed to promote equity in child health research, support researchers, and collect high-quality data in LMICs to further guide priority setting and resource allocation.

Fever of Unknown Origin: A Case Report of Hepatic Phlegmon in an Immunocompetent Patient.

Methicillin-resistant Staphylococcus aureus (MRSA) hepatic phlegmon is a rare cause of fever of unknown origin (FUO) in an immunocompetent patient from a high-income country (HIC). MRSA hepatic phlegmon is typically linked to protein malnutrition and chronic gastrointestinal infections in low- to middle-income countries while immunodeficiencies such as chronic granulomatous disease (CGD) are a more common cause in a HIC. Clinical manifestations of hepatic phlegmon can be vague and nonspecific making a complete FUO workup critical during evaluation. We report a case of MRSA hepatic phlegmon in an immunocompetent patient with a nonspecific history and physical exam findings. A 14-year-old male presented with an 11-day history of fever with mild bilateral upper quadrant abdominal pain. The patient also has mild upper quadrant pain with palpation. The patient was diagnosed with a hepatic phlegmon on abdominal ultrasound and computed tomography (CT) of the abdomen. He was started on antibiotics and Interventional Radiology placed drains into the phlegmon and performed vancomycin drain washes. Inflammatory markers were initially elevated and trended down with interventions. The patient did well with treatment and was back to baseline during outpatient follow-up with the Infectious Disease team. This case illustrates the importance of a complete workup in patients with FUO.

Younger and Rural Children are More Likely to be Hospitalized for SARS-CoV-2 Infections.

Purpose: To identify characteristics of SARS-CoV-2 infection that are associated with hospitalization in children initially evaluated in a Pediatric Emergency Department (ED). Methods: We identified cases of SARS-CoV-2 positive patients seen in the Arkansas Children's Hospital (ACH) ED or hospitalized between May 27, 2020, and April 28, 2022 using ICD-10 codes within the Pediatric Hospital Information System (PHIS) Database. We compared infection waves for differences in patient characteristics, and used logistic regressions to examine which characteristics led to a higher chance of hospitalization. Findings: We included 681 pre-Delta cases, 673 Delta cases, and 970 Omicron cases. Almost 17% of patients were admitted to the hospital. Compared to Omicron infected children, pre-Delta and Delta infected children were twice as likely to be hospitalized (OR=2.2 and 2.0, respectively; p<0.0001). Infants less than 1 year of age were >3 times as likely to be hospitalized than children ages 5-14 years regardless of wave (OR=3.42; 95%CI=2.36-4.94). Rural children were almost 3 times as likely than urban children to be hospitalized across all waves (OR=2.73; 95%CI=1.97-3.78). Finally, those with a complex condition had nearly a 15-fold increase in odds of admission (OR=14.6; 95%CI=10.6-20.0). Conclusions: Children diagnosed during the pre-Delta or Delta waves were more likely to be hospitalized than those diagnosed during the Omicron wave. Younger and rural patients were more likely to be hospitalized regardless of wave. We suspect lower vaccination rates and larger distances from medical care influenced higher hospitalization rates.

Beyond the average: An updated framework for understanding the relationship between cell growth, DNA replication, and division in a bacterial system.

Our understanding of the bacterial cell cycle is framed largely by population-based experiments that focus on the behavior of idealized average cells. Most famously, the contributions of Cooper and Helmstetter help to contextualize the phenomenon of overlapping replication cycles observed in rapidly growing bacteria. Despite the undeniable value of these approaches, their necessary reliance on the behavior of idealized average cells masks the stochasticity inherent in single-cell growth and physiology and limits their mechanistic value. To bridge this gap, we propose an updated and agnostic framework, informed by extant single-cell data, that quantitatively accounts for stochastic variations in single-cell dynamics and the impact of medium composition on cell growth and cell cycle progression. In this framework, stochastic timers sensitive to medium composition impact the relationship between cell cycle events, accounting for observed differences in the relationship between cell cycle events in slow- and fast-growing cells. We conclude with a roadmap for potential application of this framework to longstanding open questions in the bacterial cell cycle field.

Fournier's Gangrene: A Rare Infectious Entity in an Adolescent with Type II Diabetes.

Fournier's gangrene is a rapidly progressive necrotizing fasciitis of the perineum and external genital organs that is uncommon in the pediatric age group. We present a case report of a 17-year-old obese male with comorbidities of type II diabetes, hypertension, and tobacco use, who presented to the hospital with vague systemic symptoms and pain in the gluteal area. On examination, he was febrile and had erythema and induration of his left scrotum, perineum, and gluteal region. Imaging obtained due to rapid progression of symptoms was consistent with a diagnosis of Fournier's gangrene. He was managed with broad-spectrum antibiotics, aggressive surgical debridement, and a diverting colostomy. This case brings to light to a classically adult diagnosis that should be considered in adolescents, especially given the rising numbers of risk factors in this population, such as diabetes, obesity, and smoking.

Demographic and clinical characteristics of pediatric COVID-19 in Arkansas: March-December 2020.

The COVID-19 pandemic reached the United States in early 2020 and spread rapidly across the country. This retrospective study describes the demographic and clinical characteristics of 308 children presenting to an Arkansas Children's emergency department (ED) or admitted to an Arkansas Children's hospital with COVID-19 in the first 10 months of the COVID-19 pandemic, prior to the emergence of clinically significant variants and available vaccinations. Adolescents aged 13 and older represented the largest proportion of this population. The most common presenting symptoms were fever, gastrointestinal symptoms, and upper respiratory symptoms. Patients with multisystem inflammatory syndrome in children (MIS-C) had a longer length of stay (LOS) than patients with acute COVID-19. Children from urban zip codes had lower odds of admission but were more likely to be readmitted after discharge. Nearly twenty percent of the study population incidentally tested positive for COVID-19. Despite lower mortality in children with COVID than in adults, morbidity and resource utilization are significant. With many Arkansas children living in rural areas and therefore far from pediatric hospitals, community hospitals should be prepared to evaluate children presenting with COVID-19 and to determine which children warrant transport to pediatric-specific facilities.

The Burden of Critical Illness in Hospitalized Children in Low- and Middle-Income Countries: Protocol for a Systematic Review and Meta-Analysis.

Background: The majority of childhood deaths occur in low- and middle-income countries (LMICs). Many of these deaths are avoidable with basic critical care interventions. Quantifying the burden of pediatric critical illness in LMICs is essential for targeting interventions to reduce childhood mortality. Objective: To determine the burden of hospitalization and mortality associated with acute pediatric critical illness in LMICs through a systematic review and meta-analysis of the literature. Data Sources and Search Strategy: We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, and LILACS using MeSH terms and keywords. Results will be limited to infants or children (ages >28 days to 12 years) hospitalized in LMICs and publications in English, Spanish, or French. Publications with non-original data (e.g., comments, editorials, letters, notes, conference materials) will be excluded. Study Selection: We will include observational studies published since January 1, 2005, that meet all eligibility criteria and for which a full text can be located. Data Extraction: Data extraction will include information related to study characteristics, hospital characteristics, underlying population characteristics, patient population characteristics, and outcomes. Data Synthesis: We will extract and report data on study, hospital, and patient characteristics; outcomes; and risk of bias. We will report the causes of admission and mortality by region, country income level, and age. We will report or calculate the case fatality rate (CFR) for each diagnosis when data allow. Conclusions: By understanding the burden of pediatric critical illness in LMICs, we can advocate for resources and inform resource allocation and investment decisions to improve the management and outcomes of children with acute pediatric critical illness in LMICs.

Why Are So Many Indigenous Peoples Dying and No One Is Paying Attention? Depressive Symptoms and "Loss of Loved Ones" as a Result and Driver of Health Disparities.

Indigenous peoples have not only experienced a devastating rate of historical loss of lives, they are more likely to experience mortality disparities. The purpose of this article is to examine Indigenous women's lived experiences of grief and loss in two Southeastern tribes and the relationship between depressive symptoms and recent loss of a loved one. Our exploratory sequential mixed-methods research was informed by the Indigenous based Framework of Historical Oppression, Resilience, and Transcendence (FHORT). We summarized key qualitative themes from ethnographic data from 287 female participants across the two tribes, collected through focus groups, family interviews, and individual interviews. We then quantitatively examined how these themes predicted depressive outcomes among 127 respondents. Specifically, we examined associations between depressive symptoms and components of historical oppression-historical loss, loss of lives, and the presence of PTSD symptoms-along with resilience and transcendence.

Cannabis and End-of-Life Care: A Snapshot of Hospice Planning and Experiences Among Illinois Medical Cannabis Patients With A Terminal Diagnosis.

INTRODUCTION: Between 2013 and 2019, Illinois limited cannabis access to certified patients enrolled in the Illinois Medical Cannabis Program (IMCP). In 2016, the state instituted a fast-track pathway for terminal patients. The benefits of medicinal cannabis (MC) have clear implications for patients near end-of-life (EOL). However, little is known about how terminal patients engage medical cannabis relative to supportive care. METHODS: Anonymous cross-sectional survey data were collected from 342 terminal patients who were already enrolled in (n = 19) or planning to enroll (n = 323) in hospice for EOL care. Logistic regression models compare patients in the sample on hospice planning vs. hospice enrollment, use of palliative care vs. hospice care, and use standard care vs non-hospice palliative care. RESULTS: In our sample, cancer patients (OR = 0.21 (0.11), p < .01), and those who used the fast-track application into the IMCP (OR = 0.11 (0.06), p < .001) were less likely to be enrolled in hospice. Compared to patients in palliative care, hospice patients were less likely to report cancer as their qualifying condition (OR = 0.16 (0.11), p < .01), or entered the IMCP via the fast-track (OR = 0.23 (0.15), p < .05). DISCUSSION: Given low hospice enrollment in a fairly large EOL sample, cannabis use may operate as an alternative to supportive forms of care like hospice and palliation. Clinicians should initiate conversations about cannabis use with their patients while also engaging EOL Care planning discussions as an essential part of the general care plan.

Survey of Occupational and Environmental Exposure Monitoring Solutions.

INTRODUCTION: Service members are exposed to ambient airborne pollutants that have been linked to adverse health effects; however, capabilities to identify and characterize exposures across multi-domain operations are currently lacking. Occupational and environmental exposure monitoring is problematic because there is not a single simple solution, and current technological limitations suggest that simultaneous deployment of multiple devices may be the most effective near-term strategy. MATERIALS AND METHODS: A broad industry scan of wearable, handheld, or portable occupational and environmental exposure monitoring devices was conducted, and subject matter experts were interviewed about the state of the field. RESULTS: This survey identified limitations including the inability to detect multiple analytes or analyte classes, size and weight, and detection limits, but multiple implementation strategies could be employed to meet a variety of combat needs. Device types could be layered, or specific device types could be deployed in acute toxic exposure environments such as dense urban population centers or subterranean spaces. CONCLUSIONS: Evolving technologies and data management strategies may advance personal exposure monitoring in the future. These new devices and methods will likely supplant current technologies, while still using the programmatic and data framework established with early implementation of current commercial off the shelf devices.

Community-Engaged and Culturally Relevant Research to Develop Behavioral Health Interventions with American Indians and Alaska Natives.

American Indians and Alaska Natives experience pervasive mental, behavioral, and physical health disparities, yet access to culturally relevant and evidenced-based programs (EBPs) are severely limited. The purpose of this research is to describe the process of conducting a rigorous and culturally sensitive research approach, which was used to inform the development of a family-based substance abuse and violence prevention program that promotes resilience. The focus of this article is on the process of this development, rather than the intervention itself. We utilize a convergent mixed-methods design with distinct tribes in the Southeast that included 436 research participants across individual, family, and focus group interviews, field notes and existing data, and a quantitative survey (n = 127). This community-engaged, culturally sensitive, and rigorous research methodology provides a road-map for developing culturally relevant interventions.

Enamide Prodrugs of Acetyl Phosphonate Deoxy-d-xylulose-5-phosphate Synthase Inhibitors as Potent Antibacterial Agents.

To fight the growing threat of antibiotic resistance, new antibiotics are required that target essential bacterial processes other than protein, DNA/RNA, and cell wall synthesis, which constitute the majority of currently used antibiotics. 1-Deoxy-d-xylulose-5-phosphate (DXP) synthase is a vital enzyme in bacterial central metabolism, feeding into the de novo synthesis of thiamine diphosphate, pyridoxal phosphate, and essential isoprenoid precursors isopentenyl diphosphate and dimethylallyl diphosphate. While potent and selective inhibitors of DXP synthase in vitro activity have been discovered, their antibacterial activity is modest. To improve the antibacterial activity of selective alkyl acetylphosphonate (alkylAP) inhibitors of DXP synthase, we synthesized peptidic enamide prodrugs of alkylAPs inspired by the natural product dehydrophos, a prodrug of methyl acetylphosphonate. This prodrug strategy achieves dramatic increases in activity against Gram-negative pathogens for two alkylAPs, butyl acetylphosphonate and homopropargyl acetylphosphonate, decreasing minimum inhibitory concentrations against Escherichia coli by 33- and nearly 2000-fold, respectively. Antimicrobial studies and LC-MS/MS analysis of alkylAP-treated E. coli establish that the increased potency of prodrugs is due to increased accumulation of alkylAP inhibitors of DXP synthase via transport of the prodrug through the OppA peptide permease and subsequent amide hydrolysis. This work demonstrates the promise of targeting DXP synthase for the development of novel antibacterial agents.

It's okay to talk about death: Exploring the end-of-life wishes of healthy young adults.

Young adults (N = 80) participated in advance care planning (ACP) as part of a death and dying course and submitted reflection papers on their experiences. These papers were analyzed using directed qualitative content analysis methods. Among the findings, participants almost exclusively chose a parent or other family member as a Health Care Agent. Twenty-five percent expressed concern about placing burden on their agent, but felt their advance directives (AD) would ease that burden. For many, previous experiences with death helped shape their wishes. This research has practice implications for recruiting more healthy young adults in completing their AD.

Preparing to Die Behind Bars: The Journey of Male Inmates With Terminal Health Conditions.

The prison population is graying as more individuals are receiving longer sentences without opportunities for parole or release for health-related reasons. While research has expanded on end-of-life care in and out of prison settings, to date there has been little research conducted on how inmates experience dying behind bars. Through collecting data during observation of facilitated advance care planning sessions, this qualitative study revealed four main themes: (1) losing a piece of everything, (2) not sure what to feel, (3) where will I die, and (4) finding purpose in the midst of purposelessness. These themes characterize the central issues discussed by inmates as they considered death behind bars. As we seek to improve health care in prison settings, this study provides insight into how inmates view their dying process.

Growth medium-dependent antimicrobial activity of early stage MEP pathway inhibitors.

The in vivo microenvironment of bacterial pathogens is often characterized by nutrient limitation. Consequently, conventional rich in vitro culture conditions used widely to evaluate antibacterial agents are often poorly predictive of in vivo activity, especially for agents targeting metabolic pathways. In one such pathway, the methylerythritol phosphate (MEP) pathway, which is essential for production of isoprenoids in bacterial pathogens, relatively little is known about the influence of growth environment on antibacterial properties of inhibitors targeting enzymes in this pathway. The early steps of the MEP pathway are catalyzed by 1-deoxy-d-xylulose 5-phosphate (DXP) synthase and reductoisomerase (IspC). The in vitro antibacterial efficacy of the DXP synthase inhibitor butylacetylphosphonate (BAP) was recently reported to be strongly dependent upon growth medium, with high potency observed under nutrient limitation and exceedingly weak activity in nutrient-rich conditions. In contrast, the well-known IspC inhibitor fosmidomycin has potent antibacterial activity in nutrient-rich conditions, but to date, its efficacy had not been explored under more relevant nutrient-limited conditions. The goal of this work was to thoroughly characterize the effects of BAP and fosmidomycin on bacterial cells under varied growth conditions. In this work, we show that activities of both inhibitors, alone and in combination, are strongly dependent upon growth medium, with differences in cellular uptake contributing to variance in potency of both agents. Fosmidomycin is dissimilar to BAP in that it displays relatively weaker activity in nutrient-limited compared to nutrient-rich conditions. Interestingly, while it has been generally accepted that fosmidomycin activity depends upon expression of the GlpT transporter, our results indicate for the first time that fosmidomycin can enter cells by an alternative mechanism under nutrient limitation. Finally, we show that the potency and relationship of the BAP-fosmidomycin combination also depends upon the growth medium, revealing a striking loss of BAP-fosmidomycin synergy under nutrient limitation. This change in BAP-fosmidomycin relationship suggests a shift in the metabolic and/or regulatory networks surrounding DXP accompanying the change in growth medium, the understanding of which could significantly impact targeting strategies against this pathway. More generally, our findings emphasize the importance of considering physiologically relevant growth conditions for predicting the antibacterial potential MEP pathway inhibitors and for studies of their intracellular targets.

Living a Life Full of Pain: Older Pain Clinic Patients' Experience of Living With Chronic Low Back Pain.

Chronic low back pain (CLBP) is older adults' most common pain complaint and is associated with many physical and psychosocial consequences, which have been quantitatively examined. However, little research has qualitatively examined the experience itself of CLBP in later life. Study objective was to understand older adults' lived CLBP experience. Guided by van Manen's phenomenological method, 21 pain clinic patients aged 66 to 83 completed semistructured interviews. Under the main theme "living a life full of pain," results are reflected in four existential subthemes: (a) Corporeality: The pain is relentless and constantly monitored, (b) Temporality: To live with pain is to live by pacing day and night, (c) Relationality: Pain creates limits that can be tested or obeyed, and (d) Spatiality: Manipulating the space around me to accommodate the pain. Findings improve understanding of the patient experience of late life CLBP and highlights the importance of empathy and patient-centeredness when treating older adults.

Not So Golden After All: The Complexities of Chronic Low Back Pain in Older Adulthood.

Background and Objectives: The study objective was to understand how Chronic low back pain (CLBP) impacts key aging concepts such as retirement, housing, health, and independence. Research Design and Methods: Twenty-one pain clinic patients (66-83 years old) with CLBP engaged in 23 in-depth semistructured interviews, which were audio-recorded and transcribed verbatim. Guided by van Manen's phenomenological method, researchers used line-by-line thematic coding to analyze data through an iterative process. Results: Participants' accounts illustrate the interplay between aging and living with CLBP. Under the larger theme "Not so golden after all," results are reflected in five subthemes: (a) Falling apart; (b) Pain stigmatizes aging; (c) Hurting slowly, aging quickly; (d) Pain threatens independence; (e) The reality of unrealized futures. Discussion and Implications: This study improves our understanding of how CLBP complicates growing older with regard to tarnished retirements and stigmatization. Findings highlight the importance of coordinated care and recognition of pain-related loss.

"It has changed my whole life": The systemic implications of chronic low back pain among older adults.

Chronic low back pain (CLBP) is the most common pain complaint among older adults. Despite its prevalence, very little research has qualitatively examined the diverse consequences of living with CLBP in later life. As part of a larger study aiming to understand the experience of CLBP among older adults, the objective of this manuscript is to understand how older adults experience CLBP and its impacts on the functioning of older adults. Guided by van Manen's phenomenological method, 23 semi-structured interviews with 21 pain clinic patients aged 66-83 were conducted. Through an iterative process assisted by NVivo 11 software, researchers used line-by-line thematic coding to identify main impacts of CLBP. Under the main theme "It has changed my whole life," results are reflected in six subthemes: (a) Pain damages sense of self; (b) trapped in a body that doesn't work anymore; (c) me, my partner, and my pain; (d) pain complicates family relationships; (e) painfully employed; and (f) feeling socially and recreationally repressed. This study improves our understanding of older pain clinic patients' experience of living with debilitating CLBP and offers direction for social work intervention in the context of multidisciplinary pain management.

Agency behind bars: Advance care planning with aging and dying offenders.

Aging and terminally ill individuals in U.S. prisons are increasing, making critical the need for appropriate end-of-life (EOL) care and advance care planning (ACP). Applying Bandura's agentic perspective, the authors examined 20 aging/dying offenders' EOL preferences and ACP. Findings include 6 themes: decisions in the shadow of the past, what works best for me, feeling blessed, what is really going on, can anyone be trusted, and turning agency over to someone else. This study provides critical information that will assist professionals who work with dying offenders, as it presents a vivid illustration of their dying process.