Introduction of Hydroxyurea Therapy to a Cohort of Sickle Cell Patients in Northern Haiti.

Although the prevalence of sickle cell anemia is high in Haiti, treatment with hydroxyurea (HU) is uncommon. HU therapy was started at a hospital in Northern Haiti for children and young adults who had presented with complications of their disease. The patients were followed in clinic for their response to therapy and the principal outcome was hospitalization for complications. There was a 70% decrease in the rate of hospitalization in the cohort with no significant complications or deaths during the study period. Treatment with HU is a proven therapy that reduces the morbidity associated with sickle cell anemia and efforts should be made to assure access and affordability in regions with a high prevalence.

Methylene Blue for Refractory Shock in Children: A Systematic Review and Survey Practice Analysis.

OBJECTIVES: Shock refractory to fluid and catecholamine therapy has significant morbidity and mortality in children. The use of methylene blue to treat refractory shock in children is not well described. We aim to collect and summarize the literature and define physicians' practice patterns regarding the use of methylene blue to treat shock in children. DESIGN: We conducted a systematic search of MEDLINE, Embase, PubMed, Web of Science, Cochrane for studies involving the use of methylene blue for catecholamine-refractory shock from database inception to 2019. Collected studies were analyzed qualitatively. To describe practice patterns of methylene blue use, we electronically distributed a survey to U.S.-based pediatric critical care physicians. We assessed physician knowledge and experience with methylene blue. Survey responses were quantitatively and qualitatively evaluated. SETTING: Pediatric critical and cardiac care units. PATIENTS OR SUBJECTS: Patients less than or equal to 25 years old with refractory shock treated with methylene blue. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-thousand two-hundred ninety-three abstracts met search criteria, 139 articles underwent full-text review, and 24 studies were included. Studies investigated refractory shock induced by a variety of etiologies and found that methylene blue was generally safe and increased mean arterial blood pressure. There is overall lack of studies, low number of study patients, and low quality of studies identified. Our survey had a 22.5% response rate, representing 125 institutions. Similar proportions of physicians reported using (40%) or never even considering (43%) methylene blue for shock. The most common reasons for not using methylene blue were unfamiliarity with this drug, its proper dosing, and lack of evidentiary support. CONCLUSIONS: Methylene blue appears safe and may benefit children with refractory shock. There is a stark divide in familiarity and practice patterns regarding its use among physicians. Studies to formally assess safety and efficacy of methylene blue in treating pediatric shock are warranted.

Developing Pediatric Critical Care in Kenya.

OBJECTIVE: To describe efforts to improve the care of critically ill children in a tertiary care public hospital in a resource-limited setting. DESIGN: Descriptive. SETTING: Pediatric wards at the Kenyatta National Hospital in Nairobi, Kenya. PATIENTS: Critically ill children admitted to the hospital. INTERVENTIONS: A graduated approach to improving critical care capacity in a resource-limited setting. MEASUREMENTS AND MAIN RESULTS: Pediatric mortality was tracked in the adult ICU and PICU following the engagement of a pediatric intensivist and creation of a critical care team. Mortality declined from 76.2% to 37.5% in the first 2 years of the new PICU. CONCLUSIONS: Caring for critically ill children in resource-limited setting presents many challenges. The stepwise approach described here has led to a nearly 50% reduction in mortality among critically ill children at Kenyatta National Hospital. It is a viable strategy to begin to address the disproportionate number of critically ill and injured children in resource-limited setting.

Diphtheria in Children in Northern Haiti.

Infection with Corynebacterium diphtheriae persists in Haiti. Twenty-six children with clinically severe respiratory diphtheria presented to a hospital in northern Haiti during a 3-year period beginning in early 2015. The mortality rate was 50%. Partial or absent vaccinations as well as delayed and limited care contributed to mortality. This cohort offer insights into the multiple challenges involved in preventing and caring for children with diphtheria in resource-limited settings.

A regional cohort study of the treatment of critically ill children with bronchiolitis.

OBJECTIVE: To describe the treatment practices in critically ill children with RSV bronchiolitis across four regional PICUs in the northeastern United States, and to determine the factors associated with increased ICU length of stay in this population. METHODS: We conducted a retrospective cohort study of children who were admitted with RSV bronchiolitis between July 2009 and July 2011 to the PICUs of Connecticut Children's Medical Center, Yale-New Haven Children's Hospital, Maria Fareri Children's Hospital, and Baystate Children's Hospital. Data were collected regarding clinical characteristics and intensive care course among these hospitals. RESULTS: During the study period, 323 children were admitted to one of the four ICUs with RSV bronchiolitis. Despite similar mortality risk scores among ICUs, there was considerable variation in the use of therapies, particularly intubation and mechanical ventilation, in which there was greater than a 3.5-fold increased risk of intubation between sites with the highest and lowest frequency of intubation (odds ratio: 3.8; 95% confidence interval: 2.2-6.4). Albuterol was the most commonly used respiratory treatment, followed by chest physiotherapy, high-flow nasal cannula, and hypertonic saline. Longer stays in the ICU were associated with more frequent use of therapies, specifically invasive mechanical ventilation, inhaled corticosteroids, intrapulmonary percussive ventilation, and chest physiotherapy. CONCLUSIONS: Even within a close geographic region, there is significant variation in the treatment provided to critically ill children with RSV bronchiolitis. None of these treatments were associated with shorter durations of hospitalization in this population and some, such as mechanical ventilation, were associated with longer ICU lengths of stay.

Risk Factors for Delayed Enteral Nutrition in Critically Ill Children.

OBJECTIVE: Delayed enteral nutrition, defined as enteral nutrition started 48 hours or more after admission to the PICU, is associated with an inability to achieve full enteral nutrition and worse outcomes in critically ill children. We reviewed nutritional practices in six medical-surgical PICUs and determined risk factors associated with delayed enteral nutrition in critically ill children. DESIGN: Retrospective cross-sectional study using medical records as source of data. SETTING: Six medical-surgical PICUs in northeastern United States. PATIENTS: Children less than 21 years old admitted to the PICU for 72 hours or more excluding those awaiting or recovering from abdominal surgery. MEASUREMENTS AND MAIN RESULTS: A total of 444 children with a median age of 4.0 years were included in the study. Enteral nutrition was started at a median time of 20 hours after admission to the PICU. There was no significant difference in time to start enteral nutrition among the PICUs. Of those included, 88 children (19.8%) had delayed enteral nutrition. Risk factors associated with delayed enteral nutrition were noninvasive (odds ratio, 3.37; 95% CI, 1.69-6.72) and invasive positive-pressure ventilation (odds ratio, 2.06; 95% CI, 1.15-3.69), severity of illness (odds ratio for every 0.1 increase in pediatric index of mortality 2 score, 1.39; 95% CI, 1.14-1.71), procedures (odds ratio, 3.33; 95% CI, 1.67-6.64), and gastrointestinal disturbances (odds ratio, 2.05; 95% CI, 1.14-3.68) within 48 hours after admission to the PICU. Delayed enteral nutrition was associated with failure to reach full enteral nutrition while in the PICU (odds ratio, 4.09; 95% CI, 1.97-8.53). Nutrition consults were obtained in less than half of the cases, and none of the PICUs used tools to assure the adequacy of energy and protein nutrition. CONCLUSIONS: Institutions in this study initiated enteral nutrition for a high percentage of patients by 48 hours of admission. Noninvasive positive-pressure ventilation was most strongly associated with delay enteral nutrition. A better understanding of these risk factors and assessments of nutritional requirements should be explored in future prospective studies.

Procedural sedation for MRI in children with ADHD.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood, affecting 5-8% of children. It has been observed that these children have poor sedation experiences; however, to date there is minimal research on procedural sedation in this population. AIM: To examine whether children with ADHD required larger doses of propofol for magnetic resonance imaging (MRI) sedation. METHODS: The hospital's administrative billing database was used to identify all billing codes for MRI brain scans (with and without contrast) in children aged between 5 and 12 years over the preceding 5.5 years. The hospital's electronic medical record database provided baseline demographics. The sedation record was reviewed for propofol dose, psychostimulant use, and prescribed dose. All children received a standard weight-based dose of midazolam prior to receiving the necessary amount of propofol. Primary outcome was the dose of propofol administered (mg·kg(-1) ) to achieve adequate sedation. RESULTS: A total of 258 procedures met the inclusion criteria. The sample was 52% male, 74% White, 7.8% Black, 7.8% Hispanic, 4.3% Asian, and 6.2% other. ADHD was documented for 49 procedures with a prevalence of 18.5%. Patients with ADHD were older, more likely to be male, Hispanic, or to report race as 'Refused/Unknown'. Indications for MRI for patients with ADHD varied significantly, with 'Behavioral' and 'Neurocutaneous' being significantly overrepresented in the ADHD group. The average sedative dose for all patients was 2.8 mg·kg(-1) (95% CI 2.62-2.94). Sedative dose was similar among children with and without ADHD diagnosis. CONCLUSIONS: Our study illustrates that children with ADHD do not have higher sedative requirements to achieve a successful brain MRI.

Corticosteroid therapy in critically ill pediatric asthmatic patients.

OBJECTIVES: IV corticosteroids are routinely prescribed to treat critically ill children with asthma. However, no specific dosing recommendations have been made for children admitted to the PICU. We aim to determine current asthma corticosteroid dosing preferences in PICUs within North America. DESIGN: Cross-sectional, self-administered survey. SETTING: North American PICUs. SUBJECTS: Pediatric intensivists working in the United States and Canada. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 104 intensivists completed the survey. Of these, 70% worked in the United States, 67% attended in PICUs with at most 20 beds, and 79% had more than 10 years of PICU experience. The majority of asthmatics were admitted to PICUs based on clinical asthma examination/score or because the patient was receiving continuous albuterol. IV methylprednisolone is prescribed by a large majority of intensivists (96%). Of those who prescribe methylprednisolone, 66% use a starting dose of 4 mg/kg/d, whereas 31% use a starting dose of 2 mg/kg/d, and only 3% use 1 mg/kg/d. The large majority of respondents (85%) use "clinical experience" as their rationale for their preferred dosage. In multivariate logistic regression analysis, only knowledge of the National Heart, Lung, and Blood Institute guidelines was an independent predictor of prescribing an initial corticosteroid dose of 4 mg/kg/d (odds ratio, 3.69 [95% CI, 1.26-10.80]; p = 0.017). Country of practice, years of experience, and PICU size were not associated with corticosteroid dosing preference. CONCLUSIONS: Most intensivists administer methylprednisolone to critically ill asthmatics at doses 2 to 4 times higher than recommended by the National Heart, Lung, and Blood Institute guidelines for hospitalized asthmatic children. The rationale for these decisions is likely multifactorial, but in the absence of evidence-based data, most of them cite clinical experience as their deciding factor. Future research is needed to determine the most appropriate corticosteroid dosage in this critically ill patient population.

Antibiotics and antimicrobial resistance in the COVID-19 era: Perspective from resource-limited settings.

The dissemination of COVID-19 around the globe has been followed by an increased consumption of antibiotics. This is related to the concern for bacterial superinfection in COVID-19 patients. The identification of bacterial pathogens is challenging in low and middle income countries (LMIC), as there are no readily-available and cost-effective clinical or biological markers that can effectively discriminate between bacterial and viral infections. Fortunately, faced with the threat of COVID-19 spread, there has been a growing awareness of the importance of antimicrobial stewardship programs, as well as infection prevention and control measures that could help reduce the microbial load and hence circulation of pathogens, with a reduction in dissemination of antimicrobial resistance. These measures should be improved particularly in developing countries. Studies need to be conducted to evaluate the worldwide evolution of antimicrobial resistance during the COVID-19 pandemic, because pathogens do not respect borders. This issue takes on even greater importance in developing countries, where data on resistance patterns are scarce, conditions for infectious pathogen transmission are optimal, and treatment resources are suboptimal.

Angiopoietin Level Trajectories in Toddlers With Severe Sepsis and Septic Shock and Their Effect on Capillary Endothelium.

OBJECTIVE: Angiopoietins are postulated diagnostic biomarkers in children and adults with severe sepsis and septic shock. The diagnostic value of angiopoietins in children less than 5 years old has not been established, nor has their effect on permeability in the capillary microvasculature. We aim to determine if levels of angiopoietin-1 or -2 (angpt-1, -2) are diagnostic for severe sepsis/shock in young children and whether they affect the permeability of cultured human dermal microvascular endothelial cells (HDMEC). DESIGN: Prospective observational study of children < 5 years old. Patients were classified as non-systemic inflammatory response syndrome (SIRS), SIRS/sepsis and severe sepsis/septic shock. SETTING: Tertiary care pediatric hospitals. PATIENTS: Critically ill children. INTERVENTIONS: None. MEASUREMENTS: Plasma angpt-1 and -2 levels were measured with enzyme-linked immunoassays. Expression of angpt-2 in endothelial cells was assessed with quantitative polymerase chain reaction. Permeability changes in cultured HDMECs were assessed with transendothelial electrical resistance measurements. RESULTS: Angpt-1 levels were significantly higher in younger children compared with levels found in previous study of older children across disease severity (all P < 0.001). Angpt-2 was significantly higher in this cohort with severe sepsis/septic shock compared with children without SIRS and SIRS/sepsis (all P < 0.003). Angpt-2/1 ratio was also elevated in children with severe sepsis/septic shock but an order of magnitude less than older children (P < 0.02, P = 0.002). Angpt-1 and -2 did not affect basal HDMEC permeability or modulate leak in isolation or in the presence of tumor necrosis factor (TNF). CONCLUSIONS: Angpt-2 levels and the angpt-2/1 ratio are appropriate diagnostic biomarkers of severe sepsis/septic shock in children less than 5 years old. Neither angpt-1 nor -2 affects basal HDMEC permeability alone or modulates TNF induced capillary leak.

Tight junction structure, function, and assessment in the critically ill: a systematic review.

BACKGROUND: Epithelial and endothelial barrier integrity, essential for homeostasis, is maintained by cellular boarder structures known as tight junctions (TJs). In critical illness, TJs may become disrupted, resulting in barrier dysfunction manifesting as capillary leak, pulmonary edema, gut bacterial translocation, and multiple organ failure. We aim to provide a clinically focused overview of TJ structure and function and systematically review and analyze all studies assessing markers of endothelial and epithelial TJ breakdown correlated with clinical outcomes in critically ill humans. METHODS: We systematically searched MEDLINE, EMBASE, and PubMed. Additional articles were identified by targeted searches. We included studies that looked at the relationship between biomarkers of endothelial or epithelial TJ structure or function and critical illness. Results were qualitatively analyzed due to sample size and heterogeneity. RESULTS: A total of 5297 abstracts met search criteria, of which 150 articles met requirements for full text review. Of these, 30 studies met inclusion criteria. Fifteen of the 30 reports investigated proteins of endothelial tight junctions and 15 investigated epithelial TJ markers, exclusively in the gastrointestinal epithelium. No studies investigated TJ-derived proteins in primary cardiac or pulmonary pathology. CONCLUSIONS: TJ integrity is essential for homeostasis. We identified multiple studies that indicate TJs are disrupted by critical illness. These studies highlight the significance of barrier disruption across many critical disease states and correlate TJ-associated markers to clinically relevant outcomes. Further study on the role of multiple tissue-specific claudins, particularly in the setting of respiratory or cardiac failure, may lead to diagnostic and therapeutic advances. SYSTEMATIC REVIEW REGISTRATION: This systematic review is registered in the PROSPERO database: CRD42017074546 .

Decompensated hyperglycemic hyperosmolarity without significant ketoacidosis in the adolescent and young adult population.

AIM: To identify patients aged 10-30 years with probable hyperglycemic hyperosmolar syndrome (HHS), to describe demographic and clinical profiles, and to attempt to assess risk factors for poor outcomes. STUDY DESIGN: Retrospective cohort study (medical records review). SETTING: A 944-bed tertiary care teaching and research hospital and a 425-bed affiliated facility. PATIENTS: 10-30 year-old patients with a primary or secondary discharge diagnosis of HHS or diabetic ketoacidosis (DKA). Patients with a serum glucose >600 mg/dl in the absence of significant ketoacidosis (possible HHS) were profiled. Further stratification based on measured or calculated serum osmolarity >320 mOsm/kg (probable HHS) was undertaken. INTERVENTIONS: Patients received treatment for hyperglycemic crises, consisting primarily of fluids, electrolyte replacement and insulin. MEASUREMENTS AND MAIN RESULTS: Of the 629 admissions, 10 with a diagnosis of HHS and 33 with a diagnosis of DKA met the initial study criteria for HHS. 60% were African Americans and 89% were new-onset diabetics. From this group, 20 admissions had serum osmolarity > or =320 mOsm/kg. Fisher's exact test and Pearson coefficients were used to examine associations between risk factor and poor outcomes and correlations between admission data and length of hospital stay, respectively. Serious complications occurred in four patients (including two deaths, 10% mortality) and were limited to those with unreversed shock over the first 24 hours of admission and who received <40 ml/kg of intravenous fluids over the first 6 hours of treatment. CONCLUSIONS: HHS was underdiagnosed in this population and occurred disproportionately in African Americans. Serious complications occurred exclusively in those with unreversed shock and inadequate fluid resuscitation.

Clinical Progress in the Management of Tetralogy of Fallot in the Dominican Republic: A Case Series.

BACKGROUND: Definitive surgical interventions for Dominican children with congenital heart disease, like those of other low- and middle-income countries, have been historically limited. METHODS: We undertook review of a case series focusing on the surgical correction of complex forms of tetralogy of Fallot at a single center, CEDIMAT Centro Cardiovascular, in the Dominican Republic, over a 30-month period. RESULTS: According to our criteria, 43 cases were determined to be complex tetralogy of Fallot repairs from the two-year period. Besides tetralogy of Fallot, the cohort had an additional 55 anatomic anomalies that had to be addressed at the time of surgery. Median age at the time of surgery was notably 30 months, and an average of 42 months elapsed from the time of diagnosis to the time of surgery for this group. Only 33% of the cases reviewed had no hypercyanotic crises before repair. Median time to extubation for this group of patients was one day, with a three-day median length of stay in the intensive care setting. CONCLUSIONS: Our study importantly captures the present experience of a surgical congenital heart program that has recently transitioned from a traditional "mission model" to a now self-sustaining local practice. Both the number and the complexity of the lesions corrected in this caseload represent an advance from the level of care previously provided to children in the Dominican Republic.

Predictors of mortality in a paediatric intensive care unit in Kigali, Rwanda.

BACKGROUND: The enormous burden of critical illness in resource-limited settings has led to a growing interest in paediatric critical care in these regions. However, published data on the practice of critical care and patient outcomes in these settings are scant. OBJECTIVE: This study sought to identify risk factors associated with mortality in the newly established Paediatric Intensive Care Unit (PICU) at Kigali University Teaching Hospital (KUTH) in Rwanda and test the predictive ability of a newly devised mortality risk score, the modified PRISM (MP) score. METHODS: All admissions to the PICU at KUTH from October 2012 to October 2014 were included. Demographic and physiological data on each patient were gathered and each was assigned a MP score. This prospective cross-sectional study examined the association between the characteristics and physiological status of these patients and mortality. Using logistic regression, factors associated with mortality in the PICU were analysed. RESULTS: A total of 213 children were admitted to the PICU during the study period. Three patients were excluded because of missing data. Of this total, 59% were male, 25% were neonates and nearly 60% were moderately to severely malnourished. The overall mortality rate was 50%. On bivariate analysis, factors associated with increased mortality were male sex, use of vasoactive medications, a MP score ≥ 5, a discharge diagnosis of septic shock, and malnutrition on admission. On multivariate analysis, only the use of vasoactive drugs [odds ratio (OR) 12.24, 95% confidence interval (CI) 4.4-35.4, p < 0.001] and MP score ≥ 5 (OR 16.1, CI 6.3-40.8, p < 0.001) were associated with mortality. CONCLUSION: The observed mortality rate was in the range reported in other resource-limited settings. The initial attempt to create and implement a risk of mortality tool for this setting determined a score that could identify those patients at higher risk of mortality. In PICUs in resource-limited settings, the gathering of data and use of severity of illness tools could improve care in a number of ways.