Feasibility trial for the management of severe acute malnutrition in older children with sickle cell anemia in Nigeria.

Children with sickle cell anemia (SCA) living in Nigeria are at an increased risk of malnutrition, which contributes to increased morbidity and mortality. However, evidence-based guidelines for managing malnutrition in children with SCA are lacking. To address this gap, we conducted a multicenter, randomized controlled feasibility trial to assess the feasibility and safety of treating children with SCA aged from 5 to 12 years and having uncomplicated severe acute malnutrition (body mass index z score of <-3.0). Children with SCA and uncomplicated severe acute malnutrition were randomly allocated to receive supplemental ready-to-use therapeutic food (RUTF) with or without moderate-dose hydroxyurea therapy (20 mg/kg per day). Over a 6-month enrollment period, 3190 children aged from 5 to 12 years with SCA were evaluated for eligibility, and 110 of 111 children who were eligible were enrolled. During the 12-week trial, no participants withdrew or missed visits. One participant died of unrelated causes. Adherence was high for hydroxyurea (94%, based on pill counts) and RUTF (100%, based on the number of empty sachets returned). No refeeding syndrome event or hydroxyurea-related myelosuppression occurred. At the end of the trial, the mean change in body mass index z score was 0.49 (standard deviation = 0.53), and 39% of participants improved their body mass index z score to ≥-3.0. Our findings demonstrate the feasibility, safety, and potential of outpatient treatment for uncomplicated severe acute malnutrition in children with SCA aged from 5 to 12 years in a low-resource setting. However, RUTF sharing with household and community members potentially confounded the response to malnutrition treatment. This trial was registered at clinicaltrials.gov as #NCT03634488.

Financial stress as a mediator of the association between maternal childhood adversity and infant birth weight, gestational age, and NICU admission.

BACKGROUND: To examine whether financial stress during pregnancy mediates the association between maternal exposure to adverse childhood experiences (ACEs) and three birth outcomes (i.e., gestational age, birth weight, and admission to the neonatal intensive care unit [NICU]). METHODS: Data were obtained from a prospective cohort study of pregnant women and their infants in Florida and North Carolina. Mothers (n = 531; Mage at delivery = 29.8 years; 38% Black; 22% Hispanic) self-reported their exposure to childhood adversity and financial stress during pregnancy. Data on infant gestational age at birth, birth weight, and admission to the NICU were obtained from medical records within 7 days of delivery. Mediation analysis was used to test study hypotheses, adjusting for study cohort, maternal race, ethnicity, body mass index, and tobacco use during pregnancy. RESULTS: There was evidence of an indirect association between maternal exposure to childhood adversity and infant gestational age at birth (b = -0.03, 95% CI = -0.06 - -0.01) and infant birth weight (b = -8.85, 95% CI = -18.60 - -1.28) such that higher maternal ACE score was associated with earlier gestational age and lower infant birth weight through increases in financial distress during pregnancy. There was no evidence of an indirect association between maternal exposure to childhood adversity and infant NICU admission (b = 0.01, 95% CI = -0.02-0.08). CONCLUSIONS: Findings demonstrate one pathway linking maternal childhood adversity to a potentially preterm birth or shorter gestational age, in addition to low birth weight at delivery, and present an opportunity for targeted intervention to support expecting mothers who face financial stress.

Emergency cricothyrotomy in morbid obesity: comparing the bougie-guided and traditional techniques in a live animal model.

BACKGROUND: Cricothyrotomy is a rare, time sensitive procedure that is more challenging to perform when anatomical landmarks are not easily palpated before the initial incision. There is a paucity of literature describing the optimal technique for cricothyrotomy in patients with impalpable airway structures, such as in morbid obesity. In this study, we used a live sheep model of morbid obesity to compare the effectiveness of two common cricothyrotomy techniques. METHODS: We randomly assigned emergency medicine residents to perform one of two cricothyrotomy techniques on a live anesthetized sheep. To simulate the anterior soft tissue neck thickness of an adult with morbid obesity we injected 120 mL of a mixture of autologous blood and saline into the anterior neck of the sheep. The traditional technique (as described in the New England Journal Video titled "Cricothyroidotomy") used a Shiley tracheostomy tube and no bougie, and the bougie-guided technique used a bougie and a standard endotracheal tube. The primary outcome was the total procedure time; the secondary outcome was first attempt success. RESULTS: 23 residents were included, 11 assigned to the bougie-guided technique and 12 to the traditional technique. After injection of blood and saline, the median depth from skin to cricothyroid membrane was 3.0 cm (IQR 2.5-3.4 cm). The median time for the bougie technique was 118 s (IQR 77-200 s) compared to 183 s (IQR 134-270 s) for the traditional technique (median difference 62 s, 95% CI 10-144 s). Success on the first attempt occurred in 7/11 (64%) in the bougie group and 6/12 (50%) in the traditional technique group. CONCLUSION: In this study, which simulated morbid obesity on a living animal model complete with active hemorrhage and time pressure caused by extubation before the procedure, the bougie-guided technique was faster than the traditional technique using a tracheostomy tube without a bougie.

Breath carbonyl levels in a human population of seven hundred participants.

Oxidative stress is associated with numerous health conditions and disorders, and aldehydes are known biomarkers of oxidative stress that can be non-invasively measured in exhaled human breath. Few studies report breath aldehyde levels in human populations, and none claim participant numbers in the hundreds or more. Further, the breath community must first define the existing aldehyde concentration variance in a normal population to understand when these levels are significantly perturbed by exogenous stressors or health conditions. In this study, we collected breath samples from 692 participants and quantified C4-C10 straight chain aldehyde levels. C9 aldehyde was the most abundant in breath, followed by C6. C4 and C5 appear to have bimodal distributions. Post hoc, we mined our dataset for other breath carbonyls captured by our assay, which involves elution of breath samples onto a solid phase extraction cartridge, derivatization and liquid chromatography-quadrupole time of flight mass spectrometry (LC-qTOF). We found a total of 21 additional derivatized compounds. Using self-reported demographic factors from our participants, we found no correlation between these breath carbonyls and age, gender, body mass index (BMI), ethnicity or smoking habit (tobacco and marijuana). This work was preceded by a small confounders study, which was intended to refine our breath collection procedure. We found that breath aldehyde levels can be affected by participants' using scented hygiene products such as lotions and mouthwashes, while collecting consecutive breath samples, rinsing the mouth with water, and filtering inspired air did not have an effect. Using these parameters to guide our sampling, subjects were instructed to avoid the prior conditions to provide a breath sample for our study.

Defying Occam's Razor: Colonic Luminal Endometriosis in an Adolescent With Crohn's Disease.

Abdominal pain is a common symptom in Crohn's disease, presumably associated with mucosal inflammation and/or luminal stenosis. However, pain is not specific to Crohn's disease, and other etiologies should be considered, particularly gynecologic pathology in an adolescent female. We present an unusual case of endometrial tissue found in the colonic polyp of an adolescent with known Crohn's disease and abdominal pain. Histologic analysis differentiated endometriosis from active inflammation secondary to Crohn's disease. Endometriosis and Crohn's disease are both classified as chronic inflammatory disorders. It remains unclear whether overlapping etiological factors exist for the two disorders. There is a paucity of data on comanagement of endometriosis and inflammatory bowel disease, especially in adolescents. Given the finding of endometriosis in the colonic polyp was unanticipated, this case also reinforces the merits of endoscopic staging of disease whenever significant changes in therapy are considered.

Utility of plain abdominal radiography in adult ED patients with suspected constipation.

BACKGROUND: Abdominal radiographs are often obtained in ED patients with suspected constipation, although their utility in adults is not well understood. We sought to compare ED management when an abdominal radiograph is and is not obtained. METHODS: We performed a retrospective chart review study of adult ED patients with a chief complaint of constipation from 2010 through 2016. Trained abstractors recorded radiologic tests ordered, treatments received, and final diagnosis. We determined the physician interpretation of the abdominal radiograph and its use in clinical decision making. RESULTS: Of 1142 eligible patients, 481 (42%) patients underwent abdominal radiography. Stool burden rated moderate or large was observed in 271 patients (46%). Sixteen patients (3%) were diagnosed with small bowel obstruction; 15/16 of these patients had high risk features such as old age, complex surgical history, history of small bowel obstruction, abdominal malignancy, or presented with vomiting or inability to pass flatus. Of the 197 patients with no or mild stool burden or normal radiograph, 109 (55%) were diagnosed with constipation and 89 (45%) received constipation treatment in the ED. Conversely, of the 271 patients with moderate or greater stool burden, 114 (42%) received no treatment for constipation in the ED and 104 (38%) were prescribed no discharge medications for constipation; 77 of these 271 patients (28%) were diagnosed with something other than constipation. CONCLUSION: Plain abdominal radiography did not appear to significantly affect the ED management of patients presenting with constipation; it was common for patients to receive treatment that was in direct opposition to radiographic findings. Though a small number of patients had concerning diagnoses identified on plain radiography, the history and physical examination should have sufficiently excluded simple constipation, prompting an alternate diagnostic approach. Fecal loading on radiography does not preclude a more serious diagnosis. In conclusion, abdominal radiography appears to have low value in patients with constipation.

Identifying Emergency Department Patients at Low Risk for a Variceal Source of Upper Gastrointestinal Hemorrhage.

BACKGROUND: Assessing the likelihood of a variceal versus nonvariceal source of upper gastrointestinal bleeding (UGIB) guides therapy, but can be difficult to determine on clinical grounds. The objective of this study was to determine if there are easily ascertainable clinical and laboratory findings that can identify a patient as low risk for a variceal source of hemorrhage. METHODS: This was a retrospective cohort study of adult ED patients with UGIB between January 2008 and December 2014 who had upper endoscopy performed during hospitalization. Clinical and laboratory data were abstracted from the medical record. The source of the UGIB was defined as variceal or nonvariceal based on endoscopic reports. Binary recursive partitioning was utilized to create a clinical decision rule. The rule was internally validated and test characteristics were calculated with 1,000 bootstrap replications. RESULTS: A total of 719 patients were identified; mean age was 55 years and 61% were male. There were 71 (10%) patients with a variceal UGIB identified on endoscopy. Binary recursive partitioning yielded a two-step decision rule (platelet count > 200 × 109 /L and an international normalized ratio [INR] < 1.3), which identified patients who were low risk for a variceal source of hemorrhage. For the bootstrapped samples, the rule performed with 97% sensitivity (95% confidence interval [CI] = 91%-100%) and 49% specificity (95% CI = 44%-53%). CONCLUSION: Although this derivation study must be externally validated before widespread use, patients presenting to the ED with an acute UGIB with platelet count of >200 × 109 /L and an INR of <1.3 may be at very low risk for a variceal source of their upper gastrointestinal hemorrhage.

The Bougie and First-Pass Success in the Emergency Department.

STUDY OBJECTIVE: The bougie may improve first-pass intubation success in operating room patients. We seek to determine whether bougie use is associated with emergency department (ED) first-pass intubation success. METHODS: We studied consecutive adult ED intubations at an urban, academic medical center during 2013. Intubation events were identified by motion-activated video recording. We determined the association between bougie use and first-pass intubation success, adjusting for neuromuscular blockade, video laryngoscopy, abnormal airway anatomy, and whether the patient was placed in the sniffing position or the head was lifted off the bed during intubation. RESULTS: Intubation with a Macintosh blade was attempted in 543 cases; a bougie was used on the majority of initial attempts (80%; n=435). First-pass success was greater with than without bougie use (95% versus 86%; absolute difference 9% [95% confidence interval {CI} 2% to 16%]). The median first-attempt duration was higher with than without bougie (40 versus 27 seconds; difference 14 seconds [95% CI 11 to 16 seconds]). Bougie use was independently associated with greater first-pass success (adjusted odds ratio 2.83 [95% CI 1.35 to 5.92]). CONCLUSION: Bougie was associated with increased first-pass intubation success. Bougie use may be helpful in ED intubation.

Randomized clinical trial of propofol versus alfentanil for moderate procedural sedation in the emergency department.

STUDY OBJECTIVE: To compare the frequency of airway and respiratory adverse events leading to an intervention between moderate sedation using alfentanil or propofol. METHODS: We performed a randomized clinical trial in which adults undergoing moderate sedation in the ED received either alfentanil or propofol. Our primary outcome was the frequency of airway and respiratory adverse events leading to an intervention. Other outcomes included sedation depth, efficacy, sedation time, patient satisfaction, pain, and satisfaction. RESULTS: 108 subjects completed the trial: 52 receiving alfentanil and 56 receiving propofol. Airway or respiratory adverse events leading to an intervention were similar between the two groups: 23% for alfentanil and 20% for propofol (p=0.657). There were no serious adverse events in any group. Secondary outcomes were notably different in the rate of reported pain (48% for alfentanil, 13% for propofol) and recall (75% for alfentanil, 23% for propofol) and similar in the rate of satisfaction with the procedure (87% for alfentanil, 84% for propofol). CONCLUSION: We found a similar frequency of airway and respiratory adverse events leading to intervention between alfentanil and propofol used for moderate procedural sedation. Both agents appear safe for moderate procedural sedation.

Endotracheal Intubation with the King Laryngeal Tube™ In Situ Using Video Laryngoscopy and a Bougie: A Retrospective Case Series and Cadaveric Crossover Study.

BACKGROUND: Removal of a functioning King laryngeal tube (LT) prior to establishing a definitive airway increases the risk of a "can't intubate, can't oxygenate" scenario. We previously described a technique utilizing video laryngoscopy (VL) and a bougie to intubate around a well-seated King LT with the balloons deflated; if necessary, the balloons can be rapidly re-inflated and ventilation resumed. OBJECTIVE: Our objective is to provide preliminary validation of this technique. METHODS: Emergency physicians performed all orotracheal intubations in this two-part study. Part 1 consisted of a historical analysis of VL recordings from emergency department (ED) patients intubated with the King LT in place over a two-year period at our institution. In Part 2, we analyzed VL recordings from paired attempts at intubating a cadaver, first with a King LT in place and then with the device removed, with each physician serving as his or her own control. The primary outcome for all analyses was first-pass success. RESULTS: There were 11 VL recordings of ED patients intubated with the King LT in place (Part 1) and 11 pairs of cadaveric VL recordings (Part 2). The first-pass success rate was 100% in both parts. In Part 1, the median time to intubation was 43 s (interquartile range [IQR] 36-60 s). In Part 2, the median time to intubation was 23 s (IQR 18-35 s) with the King LT in place and 17 s (IQR 14-18 s) with the King LT removed. CONCLUSIONS: Emergency physicians successfully intubated on the first attempt with the King LT in situ. The technique described in this proof-of-concept study seems promising and merits further validation.

Cladribine inhibits a diltiazem-induced increase in red blood cell purine nucleotide concentrations in a zebrafish model.

Minimizing drug interactions is paramount to improving the efficacy and tolerability of cancer therapy. The zebrafish represents an innovative cancer model due to highly conserved genetics and inherent capacity for high-throughput chemical screening. This pilot study extends the utility of the zebrafish to a preclinical model for pharmacodynamics by examining the interaction of the nucleoside analogue, cladribine with the calcium channel blocker, diltiazem. Cladribine (0.7-3.5 mM) and/or diltiazem (2.4 mM), was injected intraperitoneally into adult zebrafish and red blood cell (RBC) lysates were assayed by HPLC for levels of purine nucleotides (e.g. ATP), potential biomarkers of cardiovascular health. Diltiazem increased RBC ATP concentrations, which were inhibited by co-injection of cladribine. These results suggest a novel drug interaction and highlight the feasibility of the zebrafish as an in vivo model for pharmacodynamic studies.