Association Between Treatments and Short-Term Biochemical Improvements and Clinical Outcomes in Post-Severe Acute Respiratory Syndrome Coronavirus-2 Inflammatory Syndrome.

OBJECTIVES: To 1) analyze the short-term biochemical improvements and clinical outcomes following treatment of children with post-severe acute respiratory syndrome coronavirus-2 inflammatory syndrome (multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2) admitted to U.K. PICUs and 2) collate current treatment guidance from U.K. PICUs. DESIGN: Multicenter observational study. SETTING: Twenty-one U.K. PICUs. PATIENTS: Children (< 18 yr) admitted to U.K. PICUs between April 1, 2020, and May 10, 2020, fulfilling the U.K. case definition of pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Routinely collected, deidentified data were analyzed. Propensity score and linear mixed effects models were used to analyze the effect of steroids, IV immunoglobulin, and biologic agents on changes in C-reactive protein, platelet counts, and lymphocyte counts over the course of PICU stay. Treatment recommendations from U.K. clinical guidelines were analyzed. Over the 6-week study period, 59 of 78 children (76%) received IV immunoglobulin, 57 of 78 (73%) steroids, and 18 of 78 (24%) a biologic agent. We found no evidence of a difference in response in clinical markers of inflammation between patients with multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 who were treated with IV immunoglobulin, steroids, or biologics, compared with those who were not. By the end of the study period, most patients had received immunomodulation. The 12 patients who did not receive any immunomodulators had similar decrease in inflammatory markers as those treated. Of the 14 guidelines analyzed, the use of IV immunoglobulin, steroids, and biologics was universally recommended. CONCLUSIONS: We were unable to identify any short-term benefit from any of the treatments, or treatment combinations, administered. Despite a lack of evidence, treatment guidelines for multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 have become very similar in advising step-wise treatments. Retaining clinical equipoise regarding treatment will allow clinicians to enroll children in robust clinical trials to determine the optimal treatment for this novel important condition.

Distance-Learning Initiatives Targeting Non-physician Anesthesia Providers in Low-Resource Environments.

PURPOSE OF REVIEW: "Distance-learning" encompasses a variety of didactics, from self-directed online learning to focused courses and programs. Despite increasing internet availability, focused distance-learning courses are rarely practiced in low- or middle-income countries, particularly among non-physician anesthetists. This review aims to discuss the availability, significance, and challenges of distance-learning programs for non-physician anesthesia providers in low-resource settings. RECENT FINDINGS: Task shifting and sharing in anesthesia remains essential in low-resource settings to meet the demand of surgical need. Distance-learning may be the ideal option in these settings, as it can be used to train the individual at their workplace even in remote areas. Different models and techniques are described. Success depends on the course design, communication strategies, handling of technical issues, and support mechanisms. SUMMARY: Distance-learning should be an essential part of training and in-service support for non-physician anesthetists. Global advocates of safe, effective anesthesia services need to support the development and delivery of distance-learning courses.

Acute Kidney Injury in Pediatric Inflammatory Multisystem Syndrome Temporally Associated With Severe Acute Respiratory Syndrome Coronavirus-2 Pandemic: Experience From PICUs Across United Kingdom.

OBJECTIVES: To study the prevalence, evolution, and clinical factors associated with acute kidney injury in children admitted to PICUs with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. DESIGN: Multicenter observational study. SETTING: Fifteen PICUs across the United Kingdom. PATIENTS: Patients admitted to United Kingdom PICUs with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 between March 14, 2020, and May 20, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Deidentified data collected as part of routine clinical care were analyzed. All children were diagnosed and staged for acute kidney injury based on the level of serum creatinine above the upper limit of reference interval values according to published guidance. Severe acute kidney injury was defined as stage 2/3 acute kidney injury. Uni- and multivariable analyses were performed to study the association between demographic data, clinical features, markers of inflammation and cardiac injury, and severe acute kidney injury. Over the study period, 116 patients with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 were admitted to 15 United Kingdom PICUs. Any-stage acute kidney injury occurred in 48 of 116 patients (41.4%) and severe acute kidney injury in 32 of 116 (27.6%) patients, which was mostly evident at admission (24/32, 75%). In univariable analysis, body mass index, hyperferritinemia, high C-reactive protein, Pediatric Index of Mortality 3 score, vasoactive medication, and invasive mechanical ventilation were associated with severe acute kidney injury. In multivariable logistic regression, hyperferritinemia was associated with severe acute kidney injury (compared with nonsevere acute kidney injury; adjusted odds ratio 1.04; 95% CI, 1.01-1.08; p = 0.04). Severe acute kidney injury was associated with longer PICU stay (median 5 days [interquartile range, 4-7 d] vs 3 days [interquartile range, 1.5-5 d]; p < 0.001) and increased duration of invasive mechanical ventilation (median 4 days [interquartile range, 2-6 d] vs 2 days [interquartile range, 1-3 d]; p = 0.04). CONCLUSIONS: Severe acute kidney injury occurred in just over a quarter of children admitted to United Kingdom PICUs with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. Hyperferritinemia was significantly associated with severe acute kidney injury. Severe acute kidney injury was associated with increased duration of stay and ventilation. Although short-term outcomes for acute kidney injury in pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 appear good, long-term outcomes are unknown.

Intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: a multicentre observational study.

BACKGROUND: In April, 2020, clinicians in the UK observed a cluster of children with unexplained inflammation requiring admission to paediatric intensive care units (PICUs). We aimed to describe the clinical characteristics, course, management, and outcomes of patients admitted to PICUs with this condition, which is now known as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). METHODS: We did a multicentre observational study of children (aged <18 years), admitted to PICUs in the UK between April 1 and May 10, 2020, fulfilling the case definition of PIMS-TS published by the Royal College of Paediatrics and Child Health. We analysed routinely collected, de-identified data, including demographic details, presenting clinical features, underlying comorbidities, laboratory markers, echocardiographic findings, interventions, treatments, and outcomes; serology information was collected if available. PICU admission rates of PIMS-TS were compared with historical trends of PICU admissions for four similar inflammatory conditions (Kawasaki disease, toxic shock syndrome, haemophagocytic lymphohistiocytosis, and macrophage activation syndrome). FINDINGS: 78 cases of PIMS-TS were reported by 21 of 23 PICUs in the UK. Historical data for similar inflammatory conditions showed a mean of one (95% CI 0·85-1·22) admission per week, compared to an average of 14 admissions per week for PIMS-TS and a peak of 32 admissions per week during the study period. The median age of patients was 11 years (IQR 8-14). Male patients (52 [67%] of 78) and those from ethnic minority backgrounds (61 [78%] of 78) were over-represented. Fever (78 [100%] patients), shock (68 [87%]), abdominal pain (48 [62%]), vomiting (49 [63%]), and diarrhoea (50 [64%]) were common presenting features. Longitudinal data over the first 4 days of admission showed a serial reduction in C-reactive protein (from a median of 264 mg/L on day 1 to 96 mg/L on day 4), D-dimer (4030 µg/L to 1659 µg/L), and ferritin (1042 µg/L to 757 µg/L), whereas the lymphocyte count increased to more than 1·0 × 109 cells per L by day 3 and troponin increased over the 4 days (from a median of 157 ng/mL to 358 ng/mL). 36 (46%) of 78 patients were invasively ventilated and 65 (83%) needed vasoactive infusions; 57 (73%) received steroids, 59 (76%) received intravenous immunoglobulin, and 17 (22%) received biologic therapies. 28 (36%) had evidence of coronary artery abnormalities (18 aneurysms and ten echogenicity). Three children needed extracorporeal membrane oxygenation, and two children died. INTERPRETATION: During the study period, the rate of PICU admissions for PIMS-TS was at least 11-fold higher than historical trends for similar inflammatory conditions. Clinical presentations and treatments varied. Coronary artery aneurysms appear to be an important complication. Although immediate survival is high, the long-term outcomes of children with PIMS-TS are unknown. FUNDING: None.

A Distance Blended Learning Program to Upgrade the Clinical Competence of District Non-doctor Anesthesia Providers in Nepal.

BACKGROUND: Across Nepal, anesthesia at a district level is provided mostly by non-doctor anesthesia providers (anesthesia assistants-AAs). Nepal's Government recognized the need to sustain competence with continuous professional development and to upgrade 6-month trained working AAs to professional equivalence with the new national standard of 12-month training. As they are essential district health workers and AA clinical training sites are full, an innovative distance blended learning, competency-based, upgrade 1-year course was developed and conducted in 2014-2017 for two batches. METHODS: The course content was developed over 18 months by a team of Nepali and overseas AA training experts. The 1-year course started with a refresher course, continued with tablet-based 12-month self-learning modules and clinical case logs, regular educational mentor communication, midcourse 2-week contact time in an AA training site, regular text messaging and ended with clinical examination and multiple-choice questions. Tablet content included 168 new case studies, pre- and posttests, video lectures, matching exercises and a resource library. All module work and logged clinical cases were uploaded centrally, where clinical mentors were able to review work. Clinical skills were upgraded, as needed, through direct clinical contact midway through the course. Quantitative and qualitative course assessments were included. RESULTS: Fourteen working AAs in first batch and eight working AAs in second batch from district, zonal and mission hospitals across Nepal were enrolled. All remained working at their hospitals throughout the course, and there were no significant tablet problems inhibiting course completion. Twenty-one AAs completed all modules successfully with time required for module completion averaging 19.2 h (range 11.2-32). One AA left the course after 3 months with a personal problem. Subjectively, AAs felt that the obstetric and pediatric modules were more difficult; lowest marks were objectively seen in the airway module. Clinical mentors averaged 8.2 h mentoring review work per module with direct student communication of 2.9 h per module per month. Participants logged a total of 5473 clinical cases, ranging between 50 and 788 cases each. Complications were recorded; outcomes were good. Challenges were the national IT infrastructure making data synchronization difficult and the lack of clinical exposure at some AA's hospitals. Nineteen AAs attended the final examination, and all passed. Two AAs withdrew before the final examination period due to personal and logistic reasons. CONCLUSION: This is the first use of distance blended learning to upgrade district health workers in Nepal and perhaps for non-doctor anesthesia providers globally. Key success factors were motivated students, cultural and contextualized clinical content, good educational mentoring relationships with regular communication, central IT and motivational support, and face-to-face midcourse clinical contact time.

Tablet e-Logbooks: Four Thousand Clinical Cases and Complications e-Logged by 14 Nondoctor Anesthesia Providers in Nepal.

BACKGROUND: To meet the need for essential surgery across rural Nepal, anesthesia at district level is delivered by nondoctor anesthetists. They require support to maintain confidence and competence, and upgraded professional registration to secure their status. To meet these needs, a distance-blended learning course was pioneered and delivered. A core course requirement was to log all clinical cases; these were logged on a new e-logbook. METHODS: Fourteen nondoctor anesthesia providers working in 12 different districts across Nepal were enrolled in the 1-year course. The course is based on self-completion on a tablet loaded with new learning modules, a resource library, and a case logbook. Continuous educational mentoring was provided by anesthesiologists by phone and email. The logbook included preanesthesia assessment and interventions, American Society of Anesthesiologists (ASA) grading, types of cases and anesthesia given, monitors used, complications, outcomes and free text remarks. Cases were uploaded monthly to a database, and mentors reviewed all logbook entries. RESULTS: The 14 nondoctor anesthesia providers were widely distributed across the country in district, zonal, community, and mission hospitals, and had different levels of clinical experience and caseloads. Logbooks and uploads were regularly completed without difficulty; 1% cases were entered incompletely with no case details provided. A total of 4143 cases were recorded. Annual caseload per nondoctor anesthesia provider ranged from 50 to 788, the majority of which were under spinal anesthesia; 34% of the total cases were cesarean deliveries, of which 99% received spinal anesthesia. Fifty gastrointestinal laparotomies (1% total) were recorded. Ninety-one percent of cases were ASA I, 0.8% ASA III/IV. Pulse oximetry was used in 98% of cases. Complications were recorded in 6% of cases; the most common were circulation problems (69%) including hypotension and occasional bradycardia after spinal anesthesia. Airway complications were usually under ketamine anesthesia requiring basic airway maneuvers; 4 difficult intubations were recorded under general anesthesia. Anesthesia outcomes were good with overall mortality of 0.1% (total 4 cases). Causes of death included severe preeclampsia, sepsis postlaparotomy, and patients with multiorgan failure for minor procedure. CONCLUSIONS: The tablet-based electronic anesthesia logbook was successfully used to record cases, complications, and outcomes across rural Nepal. The nondoctor anesthesia providers had trust and confidence in recording outcomes. It remains to be tested whether an e-logbook would be routinely completed outside of a specific training course. Such a logbook could be incorporated into all continuous professional development programs for rural nondoctor anesthetists.

Focal Segmental Glomerulosclerosis in a Patient with Ambiguous Genitalia: A Diagnostic Dilemma.

INTRODUCTION: The renal condition referred to as focal segmental glomerulosclerosis (FSGS) presents a diagnostic dilemma for the clinician. It encompasses and displays a nonspecific histologic appearance on a kidney biopsy specimen, rather than a unique disease entity. This characteristic of FSGS often makes treatment decisions and prognostication difficult. A 34-year-old man, who was born with ambiguous genitalia, had received a diagnosis of FSGS in young adulthood and now had advanced kidney disease. He underwent genetic testing to determine whether a genetic disorder was underlying his kidney disease and to ascertain his risk of FSGS recurrence if he were to receive a kidney transplant. The literature pertaining to genetic causes of FSGS is reviewed. We present here a diagnostic dilemma that clinicians face when confronted by a case of FSGS for which the underlying cause is unclear.

Characteristics of patients diagnosed with renal vein thrombosis and glomerulopathy: a case series.

BACKGROUND: Few contemporary studies have evaluated the clinical characteristics of patients with biopsy-proven glomerulopathy diagnosed with renal vein thrombosis (RVT). METHODS: Retrospective case series study within an integrated health system in a 12-year period (January 1, 2000 through December 31, 2011) investigating clinical characteristics of all adult patients who underwent native or transplant kidney biopsy and also had a diagnosis of RVT. Patient characteristics, diagnostic studies, and outcomes were evaluated. RESULTS: Among 3763 eligible patients, 17 had imaging confirmed RVT. Of these, 15 had membranous nephropathy (idiopathic or secondary to autoimmune disease). Although the biopsy population included primary and secondary glomerular disease patients, all 17 RVT patients had severe nephrotic syndrome and profound hypoalbuminemia with mean (SD) of albumin: 1.5 g/dL (0.66). CONCLUSION: Clinically significant RVT in patients with glomerulopathy appears to be a rather rare entity, occurring predominantly in patients with severe nephrotic syndrome due to idiopathic membranous nephropathy and membranous nephropathy secondary to autoimmune disease.

High variability of mitochondrial gene order among fungi.

From their origin as an early alpha proteobacterial endosymbiont to their current state as cellular organelles, large-scale genomic reorganization has taken place in the mitochondria of all main eukaryotic lineages. So far, most studies have focused on plant and animal mitochondrial (mt) genomes (mtDNA), but fungi provide new opportunities to study highly differentiated mtDNAs. Here, we analyzed 38 complete fungal mt genomes to investigate the evolution of mtDNA gene order among fungi. In particular, we looked for evidence of nonhomologous intrachromosomal recombination and investigated the dynamics of gene rearrangements. We investigated the effect that introns, intronic open reading frames (ORFs), and repeats may have on gene order. Additionally, we asked whether the distribution of transfer RNAs (tRNAs) evolves independently to that of mt protein-coding genes. We found that fungal mt genomes display remarkable variation between and within the major fungal phyla in terms of gene order, genome size, composition of intergenic regions, and presence of repeats, introns, and associated ORFs. Our results support previous evidence for the presence of mt recombination in all fungal phyla, a process conspicuously lacking in most Metazoa. Overall, the patterns of rearrangements may be explained by the combined influences of recombination (i.e., most likely nonhomologous and intrachromosomal), accumulated repeats, especially at intergenic regions, and to a lesser extent, mobile element dynamics.

Evaluation and comparison of parental needs, stressors, and coping strategies in a pediatric intensive care unit.

OBJECTIVE: To evaluate and compare the needs, stressors, and coping strategies of mothers and fathers in a pediatric intensive care unit, and to advance the development of the COMPASS questionnaire for examining parent experiences. DESIGN: Prospective cohort study using a modified version of a pilot questionnaire, incorporating a series of 58 questions based on a visual analog scale in three categories of needs, stressors, and coping strategies. SETTING: Tertiary pediatric intensive care unit, Southampton University Hospitals, Southampton, UK. SUBJECTS: A total of 182 parents (91 mothers and 91 fathers) of children admitted to the pediatric intensive care unit. INTERVENTIONS: Collection and analysis of needs, stressors, and coping strategies scores. MEASUREMENTS AND MAIN RESULTS: Both parents identified the need for honest, open, timely, and understandable information, with access to their child as paramount. Parents found feelings of uncertainty and helplessness to be particularly stressful. The main coping strategies employed by parents were related to trust, assurance, and believing in positive outcomes. The particular needs and stressors of mothers and fathers were found to be similar. There were, however, some statistically significant differences in stressors: mothers had higher stress scores regarding how their child looked, not being able to care for them, witnessing procedures, and on leaving their child as compared with fathers. There were no statistically significant differences in coping mechanisms between the sexes. CONCLUSIONS: Acute parental experiences can be documented using the COMPASS questionnaire. This study highlights the principal needs, stressors, and coping strategies of parents of children in the pediatric intensive care unit. The experiences of mothers and fathers are similar, but we identify some differences in stressors between the sexes.

The value of high-resolution manometry in the assessment of the resting characteristics of the lower esophageal sphincter.

INTRODUCTION: High-resolution manometry (HRM) is faster and easier to perform than conventional water perfused manometry. There is general acceptance of its usefulness in evaluating upper esophageal sphincter and esophageal body. There has been less emphasis on the use of HRM to evaluate the lower esophageal sphincter (LES) resting pressure and length, both factors important in LES barrier function. The aim of this study was to compare the resting characteristics of the LES determined by HRM and conventional manometry in the same patients. METHODS: We performed both HRM and conventional manometry including a slow motorized pull-through technique in 55 patients with foregut symptoms. The characteristics of the LES analyzed were: resting pressure, total length, and abdominal length. Four available modes of HRM analysis were used to assess resting characteristics of the LES: spatiotemporal mode using both abrupt color change and isobaric contour, line tracing, and pressure profile. The values obtained from these four HRM modes were then compared to the conventional manometry measurements. RESULTS: High-resolution manometry and conventional manometry did not differ in their measurement of LES resting pressure. LES overall and abdominal length were consistently overestimated by HRM. A variability up to 4 cm in overall length was observed and was greatest in patients with hiatal hernia (1.8 vs. 0.9 cm, p = 0.027). CONCLUSION: The current construction of the catheter and software analysis used in high-resolution manometry do not allow precise measurement of LES length. Errors in the identification of the upper border of the sphincter may compromise accurate positioning of a pH probe.

A penetrating injury with a cocktail stick resulting in a spreading infection with Streptococcus milleri.

This case deals with a penetrating injury with a cocktail stick sustained to the right foot in a 72-year-old woman. Despite being discharged from the Accident and Emergency Department on empirical oral antibiotic therapy, she went on to develop a severe cellulitis, necessitating admission for intravenous antibiotics, multiple debridement procedures under general anaesthesia and eventual split thickness skin grafting to repair areas of necrosis. This case raises a number of important issues, including the potential hazards of apparently so trivial an injury with a common household item, the absence of any benefit of plain radiography in these injuries and the need for exploration and debridement early in the management, in the face of a refractory response to empirical antibiotics.

Model for optical forward scattering by nonspherical raindrops.

We describe a numerical model for the interaction of light with large raindrops using realistic nonspherical drop shapes. We apply geometrical optics and a Monte Carlo technique to perform ray traces through the drops. We solve the problem of diffraction independently by approximating the drops with area-equivalent ellipsoids. Scattering patterns are obtained for different polarizations of the incident light. They exhibit varying degrees of asymmetry and depolarization that can be linked to the distortion and thus the size of the drops. The model is extended to give a simplified long-path integration.