Standard-Volume Plasma Exchange Improves Outcomes in Patients With Acute Liver Failure: A Randomized Controlled Trial.

BACKGROUND: High volume plasma-exchange (HVPE) improves survival in patients with acute liver failure (ALF), but apprehension regarding volume overload and worsening of cerebral edema remain. METHODS: In an open-label randomized controlled trial, 40 consecutive patients of ALF were randomized 1:1 to either standard medical treatment (SMT) or SMT with standard-volume plasma-exchange (SVPE). SVPE was performed using centrifugal apheresis [target volume of 1.5 to 2.0 plasma volumes per session] until desired response was achieved. Cerebral edema was assessed by brain imaging. Results were analyzed in an intention-to-treat analysis. Primary outcome was 21-day transplant-free survival. The levels of cytokines, damage-associated molecular patterns (DAMPs) and endotoxins were analyzed at baseline and day 5. RESULTS: ALF patients [aged 31.5 ± 12.2 years, 60% male, 78% viral, 83% hyperacute, 70% with SIRS were included. At day 5, SVPE [mean sessions 2.15 ± 1.42, median plasma volume replaced 5.049 L] compared to SMT alone, resulted in higher lactate clearance (p = .02), amelioration of SIRS (84% vs. 26%; P = .02), reduction in ammonia levels [(221.5 ± 96.9) vs.(439 ± 385.6) µg/dl, P = .02) and SOFA scores [9.9(±3.3) vs. 14.6(±4.8); P = .001]. There were no treatment related deaths. SVPE was associated with a higher 21-day transplant free-survival [75% vs. 45%; P = .04, HR 0.30, 95%CI 0.01-0.88]. A significant decrease in levels of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines along with a decrease in endotoxin and DAMPs was seen with SVPE. CONCLUSION: In ALF patients with cerebral edema, SVPE is safe and effective and improves survival possibly by a reduction in cytokine storm and ammonia. CLINICALTRIAL: gov (identifier: NCT02718079).

Diagnostic ability of a smart phone app (injured tooth) in diagnosing traumatic injuries to the teeth - a multicentre analysis.

BACKGROUND: Dental trauma is not uncommon. The initial management provided at the time of injury is critical in predicting prognosis. However, initial management depends on correct diagnosis. Recently an App named 'Injured Tooth' was made available to diagnose traumatic injuries to the teeth and supporting structures. AIM: To test the diagnostic ability of the Injured Tooth App compared with the conventional method of diagnosing traumatic injuries to the teeth. DESIGN: A cross-sectional study was conducted at three different centres with 176 patients aged 0-15 years, having 201 injured teeth. Diagnosis of the injured teeth in these children at every centre was done independently by one experienced faculty using the traditional method and by a student using the Injured Tooth App. RESULTS: Injured Tooth App gave a correct diagnosis for 197 teeth included in the study. Statistical analysis showed that there was good agreement (Kappa = 0.973) between the diagnosis given by the App and the experienced faculty. CONCLUSIONS: The study found that the diagnosis given by the Injured Tooth App was in good agreement with the diagnosis given by an experienced faculty. Hence, the App can be successfully used by dental students to arrive at diagnosis.

Qualitative evaluation of the contribution of CanMEDS roles in the development of area of focused competence diplomas.

Background: While many Area of Focused Competency (AFC) Diplomas are available to those who have completed Pediatric residency training, it is not known which competencies are enhanced within each AFC discipline. Our objective was to determine which CanMEDS roles were targeted by existing AFCs available to those who have completed Pediatric residency training and identify gaps within CanMEDs roles that may be fulfilled by the development of new AFCs. Methods: A qualitative study was undertaken using document analysis methodology to compare CanMEDS competencies across AFCs available to those with Royal College examination eligibility or certification in Pediatrics. RCPSC Competency Training Requirements documents were used to compare and contrast the competencies in each AFC with competencies established in Pediatric residency training. Key and Enabling Competencies were compared for each CanMEDS role to identify differences. Results: Ten AFCs were identified with eligibility requirements including Royal College examination eligibility or certification in Pediatrics. All 10 AFCs included at least one new Medical Expert competency, for a total of 42 unique competencies in this role across all AFCs. The Scholar role had only 10 new competencies across seven AFCs, while only one AFC added a single unique competency in the Collaborator role. Conclusions: The majority of new competencies contributed by AFCs lie within the CanMEDS role of Medical Expert. The Scholar and Collaborator roles have the least differences when comparing competencies of existing AFCs to those competencies established in Pediatric residency training. Developing additional AFCs that offer advanced skills in these roles may help close this gap within the discipline of Pediatrics.

Contexte: Bien que de nombreux diplômes de domaines de compétence ciblée (DCC) soient accessibles aux personnes ayant terminé leur résidence en pédiatrie, nous ne savons pas quelles sont les compétences qui sont approfondies dans chaque discipline de DCC. Notre objectif était de déterminer les rôles CanMEDS visés par les DCC actuellement accessibles aux personnes ayant terminé leur résidence en pédiatrie et de repérer les lacunes dans les rôles CanMEDS qui pourraient être comblées par l'élaboration de nouveaux DCC. Méthodes: Nous avons réalisé une étude qualitative au moyen d'analyse de documents pour comparer les compétences CanMEDS dans les DCC ouverts aux personnes admissibles à l'examen du Collège royal ou ayant une certification en pédiatrie. Les documents sur les exigences de formation du CRMCC ont été utilisés pour comparer les compétences de chaque DCC et les compétences visées dans le cadre de la formation postdoctorale en pédiatrie. Les compétences clés et les compétences habilitantes ont été comparées pour chaque rôle CanMEDS afin de repérer les différences. Résultats: Nous avons trouvé 10 DCC dont les conditions d'admissibilité comprennent l'admissibilité à l'examen du Collège royal ou la certification en pédiatrie. Chacun de ces 10 DCC comprenait au moins une nouvelle compétence d'expert médical et un total de 42 nouvelles compétences propres à ce rôle ont été répertoriées pour l'ensemble des DCC. Pour le rôle d'érudit, nous n'avons trouvé que 10 nouvelles compétences dans sept programmes de DCC, et pour celui de collaborateur, il n'y a qu'une nouvelle compétence dans un programme de DCC. Conclusions: La majorité des nouvelles compétences développées dans les DCC relèvent du rôle CanMEDS d'expert médical. Les rôles d'érudit et de collaborateur présentent le moins de différences lorsqu'on compare les compétences ciblées dans les DCC existants et celles visées dans le cadre de la formation postdoctorale en pédiatrie. La création de DCC supplémentaires permettant l'acquisition de compétences plus poussées dans ces rôles pourrait contribuer à combler cette carence au sein de la discipline de la pédiatrie.

Secondary impacts of the COVID-19 pandemic at a tertiary children's hospital in Canada: a mixed-methods study.

OBJECTIVES: Decisions to pause all non-essential paediatric hospital activities during the initial phase of the COVID-19 pandemic may have led to significant delays, deferrals and disruptions in medical care. This study explores clinical cases where the care of children was perceived by hospital clinicians to have been negatively impacted because of the changes in healthcare delivery attributing to the restrictions placed resulting from the COVID-19 pandemic. DESIGN AND SETTING: This study used a mixed-methods approach using the following: (1) a quantitative analysis of overall descriptive hospital activity between May and August 2020, and utilisation of data during the study period was performed, and (2) a qualitative multiple-case study design with descriptive thematic analysis of clinician-reported consequences of the COVID-19 pandemic on care provided at a tertiary children's hospital. RESULTS: Hospital-level utilisation and activity patterns revealed a substantial change to hospital activity including an initial reduction in emergency department attendance by 38% and an increase in ambulatory virtual care from 4% before COVID-19 to 67% between May and August 2020. Two hundred and twelve clinicians reported a total of 116 unique cases. Themes including (1) timeliness of care, (2) disruption of patient-centred care, (3) new pressures in the provision of safe and efficient care and (4) inequity in the experience of the COVID-19 pandemic emerged, each impacting patients, their families and healthcare providers. CONCLUSION: Being aware of the breadth of the impact of the COVID-19 pandemic across all of the identified themes is important to enable the delivery of timely, safe, high-quality, family-centred paediatric care moving forward.

Molecular characterization of Chinese hamster cells mutants affected in adenosine kinase and showing novel genetic and biochemical characteristics.

BACKGROUND: Two isoforms of the enzyme adenosine kinase (AdK), which differ at their N-terminal ends, are found in mammalian cells. However, there is no information available regarding the unique functional aspects or regulation of these isoforms. RESULTS: We show that the two AdK isoforms differ only in their first exons and the promoter regions; hence they arise via differential splicing of their first exons with the other exons common to both isoforms. The expression of these isoforms also varied greatly in different rat tissues and cell lines with some tissues expressing both isoforms and others expressing only one of the isoforms. To gain insights into cellular functions of these isoforms, mutants resistant to toxic adenosine analogs formycin A and tubercidin were selected from Chinese hamster (CH) cell lines expressing either one or both isoforms. The AdK activity in most of these mutants was reduced to <5% of wild-type cells and they also showed large differences in the expression of the two isoforms. Thus, the genetic alterations in these mutants likely affected both regulatory and structural regions of AdK. We have characterized the molecular alterations in a number of these mutants. One of these mutants lacking AdK activity was affected in the conserved NxxE motif thereby providing evidence that this motif involved in the binding of Mg2+ and phosphate ions is essential for AdK function. Another mutant, FomR-4, exhibiting increased resistance to only C-adenosine analogs and whose resistance was expressed dominantly in cell-hybrids contained a single mutation leading to Ser191Phe alteration in AdK. We demonstrate that this mutation in AdK is sufficient to confer the novel genetic and biochemical characteristics of this mutant. The unusual genetic and biochemical characteristics of the FomR-4 mutant suggest that AdK in this mutant might be complexed with the enzyme AMP-kinase. Several other AdK mutants were altered in surface residues that likely affect its binding to the adenosine analogs and its interaction with other cellular proteins. CONCLUSIONS: These AdK mutants provide important insights as well as novel tools for understanding the cellular functions of the two isoforms and their regulation in mammalian cells.

The Secondary Consequences of the COVID-19 Pandemic in Hospital Pediatrics.

BACKGROUND AND OBJECTIVES: The coronavirus disease (COVID-19) pandemic has broad implications for children and families. Particular attention has been paid to delays in accessing timely pediatric care leading to unintended morbidity. In this study, we aim to describe the broader spectrum of unintended negative consequences for pediatric patients and families due to recent health care and societal changes. METHODS: All full-time doctors, dentists, and nurse practitioners working at a tertiary care children's hospital in Canada were surveyed every 2 weeks throughout the initial phase of the COVID-19 pandemic to identify clinical cases in which they perceived a negative outcome associated with hospital or societal changes as a result of the COVID-19 pandemic. Analysis followed a qualitative case series methodology using a narrative synthesis approach to determine similarities and associated themes. RESULTS: One hundred and forty-one clinicians, representing 26 hospital divisions, reported 57 unique cases in the first 6 weeks of the study. Thematic analysis of the first 50 reported cases was used to identify 6 primary themes focusing on health care quality domains as described by the Agency for Healthcare Research and Quality (safe, effective, patient-centered, timely, efficient, and equitable care). CONCLUSIONS: In this preliminary case analysis, we describe the broad social and clinical impact of COVID-19 on hospitalized pediatric patients and their families. These themes highlight the unintended consequence on families, siblings, disease diagnosis, and hospital-based care provision. Recognition and understanding of the broad implications of the COVID-19 pandemic are necessary as we strive to deliver safe, high-quality, family-centered pediatric care in this new era.

Trainee Principal Investigator Could Improve Recruitment in Trauma Trials: Review of Literature and Experience From a Trauma Center.

INTRODUCTION: Recruitment of patients to participate in randomized control trials (RCT) is a challenging task, especially for trauma trials in which the identification and recruitment are time-limited. Multiple strategies have been tried to improve the participation of doctors and the recruitment of patients. The aim was to study the effect of a trainee principal investigator (TPI) on the efficacy of recruitment for a multicenter hip fracture RCT. METHODS: A retrospective study comparing the number of junior doctors participating in the WHiTE 8 COPAL RCT and patients recruited before and after the introduction of formal TPI role at a major trauma center in the UK. Data was collected for nine months "before" (Nov 2018-July 2019) and six months "after" (Sept 2019-Feb 2020) the role of TPI was assigned. RESULTS: From November 2018 to February 2020, a total of 292 patients were eligible for recruitment into this trial, out of which 196 (67.12 %) were successfully recruited. Excluding the research team, there were seven junior doctors actively recruiting in the "before period" in comparison with 10 in the "after period." Significantly more patients were recruited by junior doctors after a TPI was assigned. Overall, more percentage of eligible patients were recruited into the trial after a TPI was assigned, and this was statistically significant. CONCLUSION: The allocation of a formal TPI significantly improved the recruitment of patients in a national RCT. TPI can work alongside the principal investigator and research team to be a valuable link person coordinating and engaging local trainees to take part in trials.

In vitro propagation, encapsulation, and genetic fidelity analysis of Terminalia arjuna: a cardioprotective medicinal tree.

The present study described an improved and reproducible in vitro regeneration system for Terminalia arjuna using nodal segment explants obtained from a mature plant. Shoot tips excised from in vitro proliferated shoots were encapsulated in 3 % sodium alginate and 100 mM CaCl2[Symbol: see text]2H2O for the development of synthetic seeds which may be applicable in short-term storage and germplasm exchange of elite genotype. Shoot multiplication was significantly influenced by a number of factors, namely types and concentrations of plant growth regulators, medium composition, repeated transfer of mother explants, subculturing of in vitro regenerated shoot clumps, agar concentrations, and temperature. Maximum numbers of shoots (16.50 ± 3.67) were observed on modified Murashige and Skoog (MMS) medium containing 0.5 mg l(-1) of benzylaminopurine (BAP) and 0.1 mg l(-1) of naphthalene acetic acid (NAA). To shortening the regeneration pathway, rooting of micropropagated shoots under in vitro condition was excluded and an experiment on ex vitro rooting was conducted and it was observed that the highest percentage of shoots rooted ex vitro when treated with indole-3-butyric acid (IBA, 250 mg l(-1)) + 2-naphthoxy acetic acid (NOA, 250 mg l(-1)) for 5 min. The well-developed ex vitro rooted shoots were acclimatized successfully in soilrite under greenhouse conditions with 80 % survival of plants. Randomly amplified polymorphic DNA (RAPD) analysis confirmed that all the regenerated plants were genetically identical to the mother plant, suggesting the absence of detectable genetic variation in the regenerated plantlets. To the best of our knowledge, this is the first report on synthetic seed production as well as ex vitro rooting and genetic fidelity assessment of micropropagated shoots of T. arjuna.