title: Similarity relations of DNA and RNA polymerases investigated by the principal component analysis of amino acid sequences

text: The principal component analysis based on the physicochemical properties of amino acid residues is applied to DNA and RNA polymerases to assign the sequence motifs for the polymerization activities of these proteins. After the reconfirmation of the sequence motifs of families A and B of DNA polymerases indicated previously, it elucidates the sequence motifs for the polymerization activity of DNA polymerase III (family C) by the similarity to the polymerization center of multimeric DNA dependent RNA polymerases. This identification proceeds to clarify the sequence motifs for polymerization activities of primases; eukaryotic and archaebacterial primases carry motifs similar to those of family C, while the motifs of eubacterial primase fall into the category of the motifs in family B DNA polymerases such as α, δ, ϵ and II. This finding means that DNA dependent RNA polymerases are also divided into groups corresponding to three families, A, B and C, because the monomeric DNA dependent RNA polymerases in phages are reconfirmed to carry sequence motifs similar to those of family A DNA polymerases. Furthermore, the three families of polymerization motifs are found to fall within the variation range of polymerization motifs displayed by many RNA dependent RNA polymerases, suggesting a close evolutionary relation between them. The sequence motifs for polymerization activities of reverse transcriptase and telomerase seem to be the intermediate between family A DNA polymerase and some RNA dependent RNA polymerases, e.g., from Leviviridae. On the contrary, the sequence fragments similar to the nucleotidyltransferase superfamily including DNA polymerase β are not found in any RNA dependent RNA polymerase, suggesting their other lineage of polymerization motifs.


Estimation of COVID-19 burden in Egypt


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title: Regional Lung Perfusion as Determined by Electrical Impedance Tomography in Comparison With Electron Beam CT Imaging

text: The aim of the experiments was to check the feasibility of pulmonary perfusion imaging by functional electrical impedance tomography (EIT) and to compare the EIT findings with electron beam computed tomography (EBCT) scans. In three pigs, a Swan-Ganz catheter was positioned in a pulmonary artery branch and hypertonic saline solution or a radiographic contrast agent were administered as boli through the distal or proximal openings of the catheter. During the administration through the proximal opening, the balloon at the tip of the catheter was either deflated or inflated. The latter case represented a perfusion defect. The series of EIT scans of the momentary distribution of electrical impedance within the chest were obtained during each saline bolus administration at a rate of 13/s. EBCT scans were acquired at a rate of 3.3/s during bolus administrations of the radiopaque contrast material under the same steady-state conditions. The EIT data were used to generate local time-impedance curves and functional EIT images showing the perfusion of a small lung region, both lungs with a perfusion defect and complete both lungs during bolus administration through the distal and proximal catheter opening with an inflated or deflated balloon, respectively. The results indicate that EIT imaging of lung perfusion is feasible when an electrical impedance contrast agent is used.


title: Reassortment Networks and the Evolution of Pandemic H1N1 Swine-Origin Influenza

text: Prior research developed Reassortment Networks to reconstruct the evolution of segmented viruses under both reassortment and mutation. We report their application to the swine-origin pandemic H1N1 virus (S-OIV). A database of all influenza A viruses, for which complete genome sequences were available in Genbank by October 2009, was created and dynamic programming was used to compute distances between all corresponding segments. A reassortment network was created to obtain the minimum cost evolutionary paths from all viruses to the exemplar S-OIV A/California/04/2009. This analysis took 35 hours on the Cray Extreme Multithreading (XMT) supercomputer, which has special hardware to permit efficient parallelization. Six specific H1N1/H1N2 bottleneck viruses were identified that almost always lie on minimum cost paths to S-OIV. We conjecture that these viruses are crucial to S-OIV evolution and worthy of careful study from a molecular biology viewpoint. In phylogenetics, ancestors are typically medians that have no functional constraints. In our method, ancestors are not inferred, but rather chosen from previously observed viruses along a path of mutation and reassortment leading to the target virus. This specificity and functional constraint render our results actionable for further experiments in vitro and in vivo.


title: System for Infectious Disease Information Sharing and Analysis: Design and Evaluation

text: Motivated by the importance of infectious disease informatics (IDI) and the challenges to IDI system development and data sharing, we design and implement BioPortal, a Web-based IDI system that integrates cross-jurisdictional data to support information sharing, analysis, and visualization in public health. In this paper, we discuss general challenges in IDI, describe BioPortal's architecture and functionalities, and highlight encouraging evaluation results obtained from a controlled experiment that focused on analysis accuracy, task performance efficiency, user information satisfaction, system usability, usefulness, and ease of use.


title: Design and Control of a Mechatronic Tracheostomy Tube for Automated Tracheal Suctioning

text: Goal: Mechanical ventilation is required to aid patients with breathing difficulty to breathe more comfortably. A tracheostomy tube inserted through an opening in the patient neck into the trachea is connected to a ventilator for suctioning. Currently, nurses spend millions of person-hours yearly to perform this task. To save significant person-hours, an automated mechatronic tracheostomy system is needed. This system allows for relieving nurses and other carers from the millions of person-hours spent yearly on tracheal suctioning. In addition, it will result in huge healthcare cost savings. Methods: We introduce a novel mechatronic tracheostomy system including the development of a long suction catheter, automatic suctioning mechanisms, and relevant control approaches to perform tracheal suctioning automatically. To stop the catheter at a desired position, two approaches are introduced: 1) Based on the known travel length of the catheter tip; 2) Based on a new sensing device integrated at the catheter tip. It is known that backlash nonlinearity between the suction catheter and its conduit as well as in the gear system of the actuator are unavoidable. They cause difficulties to control the exact position of the catheter tip. For the former case, we develop an approximate model of backlash and a direct inverse scheme to enhance the system performances. The scheme does not require any complex inversions of the backlash model and allows easy implementations. For the latter case, a new sensing device integrated into the suction catheter tip is developed and backlash compensation controls are avoided. Results: Automated suctioning validations are successfully carried out on the proposed experimental system. Comparisons and discussions are also introduced. Significance: The results demonstrate a significant contribution and potential benefits to the mechanical ventilation areas.


title: Automatic Control of Arterial Carbon Dioxide Tension in Mechanically Ventilated Patients

text: This paper presents a method of controlling the arterial carbon dioxide tension of patients receiving mechanical ventilation. Controlling of the CO(2) tension is achieved by regulating the ventilator initiated breath frequency and also volume per breath.


title: Temporal and Spatial Monitoring and Prediction of Epidemic Outbreaks

text: This paper introduces a nonlinear dynamic model to study spatial and temporal dynamics of epidemics of susceptible-infected-removed type. It involves modeling the respective collections of epidemic states and syndromic observations as random finite sets. Each epidemic state consists of the number of infected individuals in an isolated population system and the corresponding partially known parameters of the epidemic model. The infectious disease could spread between population systems with known probabilities based on prior knowledge of ecological and biological features of the environment. The problem is then formulated in the context of Bayesian framework and estimated via a probability hypothesis density filter. Each population system under surveillance is assumed to be homogenous and fixed, with daily reports on the number of infected people available for monitoring and prediction. When model parameters are partially known, results of numerical studies indicate that the proposed approach can help early prediction of the epidemic in terms of peak and duration.


title: Characterization and Use of a Fiber Optic Sensor Based on PAH/SiO(2) Film for Humidity Sensing in Ventilator Care Equipment

text: Objective: To develop a compact probe that can be used to monitor humidity in ventilator care equipment. A mesoporous film of alternate layers of Poly(allylamine hydrochloride) (PAH) and silica (SiO2) nanoparticles (bilayers), deposited onto an optical fibre was used. The sensing film behaves as a Fabry-Perot cavity of low-finesse where the absorption of water vapour changes the optical thickness and produces a change in reflection proportional to humidity. Methods: The mesoporous film was deposited upon the cleaved tip of an optical fibre using the layer-by-layer method. The sensor was calibrated in a bench model against a commercially available capacitive sensor. The sensitivity and response time were assessed in the range from 5 % relative humidity (RH) to 95%RH for different numbers of bilayers up to a maximum of nine. Results: The sensitivity increases with the number of bilayers deposited; sensitivity of 2.28 mV/%RH was obtained for nine bilayers. The time constant of the response was 1.13 s ± 0.30 s which is faster than the commercial device (measured as 158 s). After calibration, the optical fibre humidity sensor was utilised in a bench top study employing a mechanical ventilator. The fast response time enabled changes in humidity in individual breaths to be resolved. Conclusion: Optical fibre sensors have the potential to be used to monitor breath to breath humidity during ventilator care. Significance: Control of humidity is an essential part of critical respiratory care and the developed sensor provides a sensitive, compact and fast method of humidity monitoring.


title: A Strategic Plan for Strengthening America’s Families: A Brief from the Coalition of Behavioral Science Organizations

text: Despite significant progress in research on the treatment and prevention of psychological, behavioral, and health problems, the translation of this knowledge into population-wide benefit remains limited. This paper reviews the state of America’s children and families, highlighting the influence of stressful contextual and social conditions on child and family well-being and the concentration of disadvantage in numerous neighborhoods and communities throughout the nation. It then briefly reviews the progress that has been made in pinpointing policies that can reduce stressful contextual conditions such as poverty, discrimination, and the marketing of unhealthful foods and substances. It also describes numerous family and school interventions that have proven benefit in preventing psychological and behavioral problems as diverse as tobacco, alcohol, and other drug use; depression; antisocial behavior; academic failure; obesity prevention; and early childbearing. We argue that progress in translating existing knowledge into widespread benefit will require a nationwide effort to intervene comprehensively in neighborhoods and communities of concentrated disadvantage. We present a strategic plan for how such an effort could be organized. The first step in this organizing would be the creation of a broad and diverse coalition of organizations concerned with advancing public health and well-being. Such a coalition could increase public support both for the policies needed to focus on these disadvantaged areas and the research needed to incrementally improve our ability to help these areas.


title: Defining trained immunity and its role in health and disease

text: Immune memory is a defining feature of the acquired immune system, but activation of the innate immune system can also result in enhanced responsiveness to subsequent triggers. This process has been termed ‘trained immunity’, a de facto innate immune memory. Research in the past decade has pointed to the broad benefits of trained immunity for host defence but has also suggested potentially detrimental outcomes in immune-mediated and chronic inflammatory diseases. Here we define ‘trained immunity’ as a biological process and discuss the innate stimuli and the epigenetic and metabolic reprogramming events that shape the induction of trained immunity.


title: The SENIEUR protocol and the efficacy of hepatitis B vaccination in healthy elderly persons by age, gender, and vaccine route

text: BACKGROUND: Reduced response to hepatitis B vaccines is associated with aging, confounding and comorbid conditions, as well as inadvertent subcutaneous (SC) inoculation. We hypothesized that the antibody and T cell-mediated immune responses (T-CMI) of elderly adults to a vaccine intended for intramuscular (IM) administration would be attenuated when deposited into SC fat, independent of confounding conditions. RESULTS: Fifty-two healthy, community dwelling elderly adults (65–82 years), seronegative for HBV, were enrolled in the SENIEUR protocol as a strictly healthy population. These seniors were randomized to receive a licensed alum-adjuvanted recombinant HBV vaccine either SC or IM, with the inoculum site verified by imaging. The response rates, defined as hepatitis B surface antibodies (HBsAb) ≥10 IU/L, were significantly lower in the elderly than in young adults, a group of 12, healthy, 21–34-year-old volunteers. Moreover, elderly participants who received the vaccine IM were significantly more likely to be responders than those immunized SC (54% versus 16%, p = 0.008). The low seroconversion rate in the IM group progressively declined with increasing age, and responders had significantly lower HBsAb titers and limited isotype responses. Moreover, T-CMI (proliferation and cytokine production) were significantly reduced in both percentage of responders and intensity of the response for both Th1 and Th2 subsets in the elderly. CONCLUSIONS: Our data demonstrate the blunted immunogenicity of SC inoculation as measured by peak titers and response rates. Further, the qualitative and quantitative deficits in B- and T-CMI responses to primary alum adjuvanted protein antigens persisted even in strictly healthy elderly populations with verified IM placement compared to younger populations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04162223. Registered 14 November 2019. Retrospectively registered.


title: A Single-Copy IS5-Like Transposon in the Genome of a Bdelloid Rotifer

text: In the course of sequencing telomeric chromosomal regions of the bdelloid rotifer Adineta vaga, we encountered an unusual DNA transposon. Unlike other bdelloid and, more generally, eukaryotic transposable elements (TEs), it exhibits similarity to prokaryotic insertion sequences (ISs). Phylogenetic analysis indicates that this transposon, named IS5_Av, is related to the ISL2 group of the IS5 family of bacterial IS elements. Despite the apparent intactness of the single open reading frame coding for a DDE transposase and the perfect identity of its 213-bp terminal inverted repeats (TIRs), the element is present in only one copy per diploid genome. It does not exhibit any detectable levels of transcription, so that its transposase gene appears to be silent in the bdelloid host. Although horizontal transfers of TEs between kingdoms are not known to happen in nature, it appears likely that IS5_Av underwent integration into the A. vaga genome relatively recently, but was not successful in adapting to the new host and failed to increase in copy number. Alternatively, it might be the only known member of a novel eukaryotic DNA TE superfamily which is so rare that its other members, if any, have not yet been identified in eukaryotic genomes sequenced to date.


title: Alternative Regimens of Neuraminidase Inhibitors for Therapy of Hospitalized Adults with Influenza: A Systematic Review of Randomized Controlled Trials

text: INTRODUCTION: Influenza in hospitalized intensive care unit (ICU) patients with respiratory failure is associated with 25% mortality, despite timely oseltamivir treatment. A systematic review of randomized controlled trials (RCTs) was conducted to evaluate the efficacy and safety of alternative neuraminidase inhibitor (NAI) regimens compared to standard of care in patients hospitalized for H1N1, H3N2, or B influenza. METHODS: The Cochrane collaboration searching methods were followed in Cochrane Library, PubMed, and Web of Science databases (2009–2019). Eligibility criteria were RCTs comparing different regimens of NAIs in hospitalized patients (at least 1 year old) for clinically diagnosed influenza (H1N1, H3N2, or B). Pre-defined endpoints were time to clinical resolution (TTCR), overall mortality, hospital discharge, viral clearance, drug-related adverse events (AEs), and serious adverse events. RESULTS: Seven trials (1579 patients) were included. Two trials compared two regimens of oral oseltamivir therapy, and one trial compared two regimens of intravenous zanamivir therapy vs oral oseltamivir therapy. Four trials focused on intravenous peramivir therapy: two trials compared two different regimens and two trials compared two different regimens vs oral oseltamivir therapy. Overall, the different regimens were well tolerated, with no significant differences in AEs; nonetheless non-significant differences were reported among different regimens regarding TTCR, mortality, and viral clearance. CONCLUSION: Higher compared to standard doses of NAIs or systemic peramivir therapy compared to oral oseltamivir therapy did not demonstrate benefit. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12325-020-01347-5) contains supplementary material, which is available to authorized users.


title: Toxigenic type D Pasteurella multocida in New South Wales pig herds—prevalence and factors associated with infection

text: Between March and July 1987, a study was undertaken to determine the prevalence of and factors associated with toxigenic type D Pasteurella multocida infection in New South Wales pig herds. Toxigenic type D P. multocida was isolated from the nasal cavities of pigs in one (2%) of 50 randomly selected herds. Toxigenic isolates were also recovered from 2 (8%) of a separate group of 25 herds that had purchased pigs from a known infected piggery in South Australia (herd SA). Snout abnormalities were present in 9.4%, 3.2% and 1.8% of grower pigs in the 3 affected herds. Isolation of toxigenic P. multocida was significantly associated (p < 0.0001) with the occurrence of clinically affected pigs in the herd. Purchase of at least 5 pigs from herd SA was associated with an elevated risk (p < 0.05) of isolation of toxigenic P. multocida.


title: Investigations of an enteric infection of cockatoos caused by an enterovirus‐like agent

text: An enteric infection in cockatoos associated with a 30nm diameter enterovirus‐like agent seen in faeces and intestinal epithelial cells is described. The disease is characterised by intractable, profuse, mucoid diarrhoea, weight loss, dehydration and death. Lesions in the intestine consist of villous atrophy, villous fusion, enterocyte hyperplasia and, in some cases, chronic inflammation. Affected birds so far examined have concurrent psittacine beak and feather disease.


title: Characteristics and prognosis of hospital‐treated obstructive bronchitis in children aged less than two years

text: In a prospective study 101 children aged less than 2 years (median age 10 months), were examined the first time they were admitted to a paediatric ward for asthmatic symptoms. Two‐thirds were boys and 58 had parents or siblings with allergic symptoms. During winter‐spring, respiratory syncytial (RS) virus was verified in 50% of children. Other viral agents were adenovirus, parainfluenza 3, coxsackie B 2, ECHO 6 and rotavirus. At the acute stage, 54% of the children displayed changes on pulmonary X‐ray. The total IgE value was + 2 SD score units in 14 children. At reinvestigation after 3–4.5 years, when the children were aged 3.3–6.3 years, 53% were free from asthmatic symptoms; the median age for the last episode was 2 years. A total of 33% had mild asthma, 8% moderate and 6% severe asthma. The factors which correlated significantly with persistent asthma were: (1) The need for daily medication for at least 6 months. (2) A young age in conjunction with the first wheezing episode and on the first admission to a paediatric ward because of asthmatic symptoms. (3) Other past or present atopic symptoms. Heredity, tobacco smoking at home, having a furry pet, RS virus infection, or high total IgE at the time of the first admission did not correlate significantly with the persistence of asthma 3–4.5 years later. The results emphasize the good overall prognosis of wheezing in early childhood, even when the wheezing is severe enough to lead to inpatient treatment.


UNEXPECTED ISOLATION OF A NEWCASTLE DISEASE VIRUS


The decade of the midwife!


The Elements of Data Sharing


title: ω-3 vs. ω-6 lipid emulsions exert differential influence on neutrophils in septic shock patients: impact on plasma fatty acids and lipid mediator generation

text: OBJECTIVE: To compare the effects of a conventional ω-6 lipid infusion and a fish oil based (ω-3) lipid infusion for parenteral nutrition on neutrophil function, lipid mediators, and plasma free fatty acids. DESIGN AND SETTING: Open-label, randomized, pilot study in a university hospital medical intensive care unit and experimental laboratory. PATIENTS AND PARTICIPANTS: Ten patients with septic shock and eight healthy controls. INTERVENTIONS: Patients (five per group) requiring parenteral nutrition received intravenously either a ω-3 or a ω-6 lipid emulsion for a 10-day period. MEASUREMENTS AND RESULTS: At baseline levels of plasma free fatty acids were elevated several-fold, including high concentrations of the ω-6 lipid precursor arachidonic acid (AA). Neutrophils isolated from septic patients displayed markedly reduced responsiveness to ex vivo stimulation, including lipid mediator generation [leukotrienes (LT), PAF], respiratory burst, and phosphoinositide hydrolysis signaling. Under the ω-6 lipid infusion regimen abnormalities in plasma free fatty acids and impairment of neutrophil functions persisted or worsened. In contrast, a rapid switch in the plasma free fatty acid fraction to predominance of the ω-3 acids eicosapentaenoic acid and docosahexaenoic acid over AA occurred in response to ω-3 lipid infusion. LTB(5), in addition to LTB(4), appeared upon neutrophil stimulation originating from these patients, and neutrophil function was significantly improved in the ω-3 lipid group. CONCLUSIONS: ω-3 vs. ω-6 lipid emulsions differentially influence the plasma free fatty acid profile with impact on neutrophil functions. Lipid-based parenteral nutrition in septic patients may thus exert profound influence on sequelae and status of immunocompetence and inflammation. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00134-003-1900-2.


title: Modeling the helicase domain of Brome mosaic virus 1a replicase

text: Brome mosaic virus (BMV) is a representative member of positive-strand RNA viruses. The 1a replicase from BMV is a membrane protein of unknown structure with a methyltransferase N-terminal domain and a putative helicase activity in the C-terminal domain. In order to make a functional prediction of the helicase activity of the BMV 1a C-terminal domain, we have built a model of its structure. The use of fold recognition servers hinted at two different superfamilies of helicases [superfamily 1 (SF1) and superfamily 2 (SF2)] as putative templates for the C-terminal fragment of BMV 1a. A structural model of BMV 1a in SF2 was obtained by means of a fold recognition server (3D-PSSM). On the other hand, we used the helicase motifs described in the literature to construct a model of the structure of the BMV 1a C-terminal domain as a member of the SF1. The biological functionality and statistic potentials were used to discriminate between the two models. The results illustrate that the use of sequence profiles and patterns helps modeling. Accordingly, the C-terminal domain of BMV 1a is a potential member of the SF1 of helicases, and it can be modeled with the structure of a member of the UvrD family of helicases. The helicase mechanism was corroborated by the model and this supports the hypothesis that BMV 1a should have helicase activity.


title: Nurses transforming systems of care: The bicentennial of Florence Nightingale's legacy

text: Lessons from Florence Nightingale are just as relevant today as they were more than 150 years ago. Learn how nurse leaders can follow her lead and embrace the importance of nurturing highly motivated nurses who are critical thinkers.


title: Efficacy and safety of ultra-low dose 0.005% estriol vaginal gel for the treatment of vulvovaginal atrophy in postmenopausal women with early breast cancer treated with nonsteroidal aromatase inhibitors: a phase II, randomized, double-blind, placebo-controlled trial

text: OBJECTIVE: To assess the efficacy and safety of ultra-low dose 0.005% estriol vaginal gel in women with breast cancer receiving nonsteroidal aromatase inhibitors (NSAIs) and experiencing treatment-related vulvovaginal symptoms and signs. METHODS: Women with hormone receptor-positive early breast cancer receiving NSAIs were randomized to either estriol vaginal gel or placebo for 12 weeks. Vaginal maturation, vaginal pH, and total and individual scores of symptoms and signs of vulvovaginal atrophy were assessed at baseline and at weeks 3 and 12; sexual functioning was also evaluated using the Female Sexual Functioning Index (FSFI) questionnaire, as well as circulating estrogens, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). RESULTS: Sixty-one women with a mean age of 59 years were included: 50 received 0.005% estriol vaginal gel and 11 received placebo. Active treatment significantly improved maturation value and pH, vaginal dryness and global scores of symptoms and signs. Active treatment also increased the total FSFI score and all the FSFI domains, with the exception of pain. Small oscillations were observed in FSH and LH, which remained within the postmenopausal range. Estriol levels increased initially and normalized by week 12, and estradiol and estrone remained mostly undetectable throughout the study. CONCLUSIONS: Ultra-low dose 0.005% estriol vaginal gel showed efficacy in improving the symptoms and signs of vulvovaginal atrophy. These results, together with minimal oscillations in hormonal levels throughout the treatment, support the use of ultra-low dose 0.005% estriol vaginal gel as a treatment option for vulvovaginal atrophy in women with breast cancer receiving NSAIs with an indication for treatment with vaginal estrogens.


title: Telemedicine Home-Based Cardiac Rehabilitation: A CASE SERIES

text: In this case series report, we review 2 patients who were among the first to participate in the Henry Ford telemedicine home-based cardiac rehabilitation (TM-HBCR) program. These patients had barriers to full participation in a facility-based cardiac rehabilitation (CR) program due to return to work and access to transportation. However, they were willing and able to participate in the TM-HBCR program. DISCUSSION: The two cases discussed herein are examples of individuals who likely would not have fully participated in CR if the only option available was a facility-based program. While HBCR is not an option for all patients, it does address several barriers that are known to limit participation in facility-based CR for some individuals. SUMMARY: Technology has made it possible to provide the key components of a facility-based CR program through a TM-HBCR model using a secure connection to the patients via their personal mobile device.


title: Effects of NT-814, a dual neurokinin 1 and 3 receptor antagonist, on vasomotor symptoms in postmenopausal women: a placebo-controlled, randomized trial

text: OBJECTIVES: To evaluate the safety, pharmacokinetics, and preliminary efficacy of NT-814, a dual neurokinin 1,3 antagonist, in postmenopausal women with vasomotor symptoms (hot flashes). METHODS: We completed a double-blind, randomized, placebo-controlled trial in three US clinical research units in 76 postmenopausal women with moderate/severe hot flashes. Participants were randomized to 14 days of once-daily NT-814 or placebo within each of four sequential dose cohorts; 50, 100, 150, and 300 mg. Participants completed diaries of hot flash frequency and severity and waking due to night sweats before (baseline) and during treatment. RESULTS: All prespecified efficacy parameters (24-h hot flash frequency and severity, frequency of waking due to night sweats) decreased in all groups (including placebo). Mean reduction from baseline at week 2 in moderate/severe hot flash frequency was 37% in the placebo group and, respectively, 24% (P = 0.048 vs placebo), 59% (P = 0.155), 84% (P < 0.001) and 66% (P = 0.022) in the 50 mg, 100 mg, 150 mg, and 300 mg NT-814 groups; in waking due to night sweats reduction was 20% (P = 0.059), 55% (P = 0.135), 81% (P < 0.001), and 63% (P = 0.031) in the NT-814 groups and 32% in the placebo group. The improvement with NT-814 ≥150 mg was also evident in the first week of treatment. The most common treatment-related adverse events were mild somnolence and headache, more frequently in the 300 mg group. Safety monitoring identified no concerns. CONCLUSIONS: Once-daily NT-814 (≥150 mg/d) resulted in a rapid, marked improvement in hot flashes and waking due to night sweats. No safety concerns were identified. Doses up to 300 mg were well tolerated.


Electroconvulsive Therapy During COVID-19: An Essential Medical Procedure-Maintaining Service Viability and Accessibility.


title: The association between hormone therapy and sarcopenia in postmenopausal women: the Korea National Health and Nutrition Examination Survey, 2008-2011

text: OBJECTIVE: Menopausal transition contributes to sarcopenia, but the effects of hormone therapy (HT) on sarcopenia in postmenopausal women have not been determined. This study assessed the effect of HT on sarcopenia in postmenopausal women. METHODS: The present study included 4,254 postmenopausal women who participated in the Korea National Health and Nutritional Examination Surveys from 2008 to 2011. Appendicular skeletal muscle mass divided by weight (ASM/Wt) and the prevalence of sarcopenia were analyzed in groups of women stratified by duration of HT use. RESULTS: ASM/Wt was higher and the prevalence of sarcopenia was lower in participants with a history of prolonged (≥13 mo) HT use than in participants with a shorter duration of HT use or no HT use. After adjusting for multiple confounding factors, prolonged use of HT remained significantly associated with estimated mean ASM/Wt and the prevalence of sarcopenia (odds ratio: 0.60; 95% confidence interval: 0.41-0.88; P = 0.01). In addition, the prevalence of sarcopenia was linearly associated with history of hypertension, duration of hypertension, physical activity, and duration of HT use. Subgroup analysis showed that the association between duration of HT use and the prevalence of sarcopenia was maintained in younger (<65 y old) and leaner (body mass index <25 kg/m(2)) postmenopausal women. CONCLUSIONS: The present study showed that the prolonged use of HT was associated with high muscle mass and a low prevalence of sarcopenia in postmenopausal women.


Double-Edged Spike: Are SARS-CoV-2 Serologic Tests Safe Right Now?


Desperate times call for temperate measures: practicing infectious diseases during a novel pandemic


title: Knowledge, awareness and practices towards seasonal influenza and its vaccine: implications for future vaccination campaigns in Jordan

text: BACKGROUND. Influenza is an underestimated contributor to morbidity and mortality. Population knowledge regarding influenza and its vaccination has a key role in enhancing vaccination coverage. OBJECTIVES. This study aimed to identify the gaps of knowledge among Jordanian population towards influenza and its vaccine, and to identify the major determinants of accepting seasonal influenza vaccine in adults and children in Jordan. METHODS. This was a cross-sectional study that enrolled 941 randomly selected adults in Amman, Jordan. A four-section questionnaire was used which included questions about the sociodemographic characteristics, knowledge about influenza and the factors that affect seasonal influenza vaccine acceptance and refusal. RESULTS. Only 47.3% of the participants were considered knowledgeable. About half of the participants (51.9%) correctly identified the main influenza preventative measures. Lack of knowledge about the important role of seasonal influenza vaccine in disease prevention was observed. Low vaccination rate (20% of adults) was reported. The most critical barrier against vaccination in adults and children was the concern about the safety and the efficacy of the vaccine, while the most important predictors for future vaccination in adults and children were physician recommendation and government role. In children, the inclusion of the vaccine within the national immunization program was an important determinant of vaccine acceptance. CONCLUSION. Formulating new strategies to improve the population’s level of knowledge, assuring the population about the safety and the efficacy of the vaccine and the inclusion of the vaccine within the national immunization program are the essential factors to enhance vaccination coverage in Jordan.


title: Compliance in teenagers with coeliac disease—a Swedish follow‐up study

text: A group of 47 children with coeliac disease, born between 1973 and 1978 in the Swedish county of Västmanland, participated in a controlled questionnaire study. Health, self‐esteem, knowledge of the disease and dietary compliance were investigated. The children with coeliac disease were otherwise just as healthy as the control children. Growth and self‐esteem were normal. Good knowledge of coeliac disease and dietary treatment was found in 87% of children and dietary compliance was 81%. Girls and younger children (12–14 years) were more compliant than boys and older children (15–17 years). Compliance correlated positively to knowledge.


title: Mixed Infection Is Common in Children with Respiratory Adenovirus Infection

text: ABSTRACT. The presence of concomitant viral or bacterial infection was evaluated in 20 patients hospitalized for adenovirus infection of the middle or lower airways by using new serological methods for detection of both antigens and antibodies. Adenovirus infection was identified by measurement of antibodies with complement fixation test or by direct detection of viral antigen in nasopharyngeal aspirates. Mixed infection was present in 11 (55%) of the 20 patients. Viral coinfection was demonstrated in five (25%) and bacterial in nine (45%) patients. Bacterial coinfection was common, 67%, in children with an infection focus, pneumonia or acute otitis media, but rare, 13%, in those without it. Seroconversion to nontypable Haemophilus influenzae was indicated in six children; four of them were infants, four had pneumonia and three acute otitis media. Pneumococcal infection was indicated in two patients with pneumonia, both aged over two years. Chlamydia trachomatis was involved in one case. The results indicate that bacterial coinfection is common in respiratory adenovirus infection affecting lower airways, especially if pneumonia is present.


title: Multiple sclerosis in the Faroe Islands

text: Detailed questionnaires were completed in 1978–79 by 23 of the 28 then known resident Faroese multiple sclerosis (MS) patients and 127 controls. These controls were divided into 69 Group A (patient sibs and other relatives), 37 Group B (matched neighbor controls, their spouses and sibs, plus patient's spouse), and 21 Group C (distant matched controls, spouses, relatives living where MS patients never resided and British troops were not encamped during the war). No differences between cases and controls were found for education, occupation, types of residence, bathing, sanitary or drinking facilities, and nature of house construction or heating. Detailed dietary histories, available for half the subjects, revealed no difference, cases versus controls, for four age periods between age 0 and 30 years, and for 16 specified foodstuffs. Animal exposures showed overall no consistent differences by location or type of animal. There was a tendency to greater exposure to British troops during the war for cases versus Groups A and B, but this did not attain statistical significance. Vaccinations for smallpox, tetanus and diphtheria were less common in the MS; no difference was found for other vaccinations. Except for a relative deficit in the cases for rubella and (insignificantly) for measles, mumps and chicken pox, reported illnesses were equally common among all groups. Operations, hospitalizations and injuries did not differentiate the groups, nor did age at menarche for women. Neurologic symptoms were significantly more common in the cases than in the controls.


title: Endemism in Tasmanian cool temperate rainforest: alternative hypotheses

text: Endemism in Tasmanian cool temperate rainforest: alternative hypotheseS. Evidence is presented which suggests that hypotheses presented by Kirkpatrick & Brown relating to endemic species in Tasmania are either invalid or of limited importance for woody rainforest species. In their place three hypotheses are presented to account for the presence of endemic species in Tasmanian cool temperate rainforest on the basis of the fossil record and the distribution of species which are closely related to the endemics. The first two hypotheses relate to the presence of the endemic species in the general Tasmanian region. They are: 1.. Some species evolved in southeastern Australia during the Tertiary in response to the changing climate. Some of the ancestral species still occur in temperate rainforest at lower latitudes in Australia. 2.. Some species have remained essentially unchanged in Tasmania during the Tertiary and Quaternary climatic changes. The third hypothesis relates to the restriction of these cool temperate rainforest species to Tasmania: 1.. Post‐glacial climatic changes (especially a decrease in rainfall) and the human influence (especially land clearing and fire) may have combined to eliminate some cool temperate rainforest species from mainland Australia.


title: Derivation and dispersal of Acacia (Leguminosae), with particular reference to Australia, and the recognition of Senegalia and Racosperma

text: The morphology of seedlings, leaves, flowers and inflorescences, anatomy of the pod, the occurrence of extra‐floral nectaries, free amino acids of the seeds, flavonoid compounds in heartwoods, cyanogenic compounds and porate, colporate and extraporate pollen, and susceptibility to rusts, all indicate that three genera, Acacia Miller, Senegalia Raf. and Racosperma Martius, should be recognized. These correspond to currently accepted subgenera of Acacia. The size of these more narrowly circumscribed genera is in keeping with the size of genera of other tribes of low diversity in Leguminosae. Acacia and Senegalia arose independently from the Ingeae, with Racosperma being derived from Senegalia. Section Filicinae is more advanced than section Senegalia of Senegalia, and sections Racosperma and Pukhella, both with at least some species with bipinnate foliage, are the most advanced of Racosperma, while the other sections Pleurinervia and Lycopodiifolia have only phyllodinous species. Long‐range dispersal of Racosperma from the Australian region has occurred, but the broad pattern of distribution is interpreted in terms of plate tectonics. Racosperma was present in Australia in the late Cretaceous but did not become widespread until the general drying of the continent in the Miocene. The flora of SW Australia has been isolated from the rest of the continent by climatic barriers since the late Tertiary and has a high proportion of endemic species. Barriers to plant migration in the east have operated only intermittently and there is no area comparable in endemism to the southwest.


title: Prospective, randomized, single-blinded, multi-center phase II trial of two HER2 peptide vaccines, GP2 and AE37, in breast cancer patients to prevent recurrence

text: PURPOSE: AE37 and GP2 are HER2 derived peptide vaccines. AE37 primarily elicits a CD4+ response while GP2 elicits a CD8+ response against the HER2 antigen. These peptides were tested in a large randomized trial to assess their ability to prevent recurrence in HER2 expressing breast cancer patients. The primary analyses found no difference in 5-year overall disease-free survival (DFS) but possible benefit in subgroups. Here, we present the final landmark analysis. METHODS: In this 4-arm, prospective, randomized, single-blinded, multi-center phase II trial, disease-free node positive and high-risk node negative breast cancer patients enrolled after standard of care therapy. Six monthly inoculations of vaccine (VG) vs. control (CG) were given as the primary vaccine series with 4 boosters at 6-month intervals. Demographic, safety, immunologic, and DFS data were evaluated. RESULTS: 456 patients were enrolled; 154 patients in the VG and 147 in CG for AE37, 89 patients in the VG and 91 in CG for GP2. The AE37 arm had no difference in DFS as compared to CG, but pre-specified exploratory subgroup analyses showed a trend towards benefit in advanced stage (p = 0.132, HR 0.573 CI 0.275–1.193), HER2 under-expression (p = 0.181, HR 0.756 CI 0.499–1.145), and triple-negative breast cancer (p = 0.266, HR 0.443 CI 0.114–1.717). In patients with both HER2 under-expression and advanced stage, there was significant benefit in the VG (p = 0.039, HR 0.375 CI 0.142–0.988) as compared to CG. The GP2 arm had no significant difference in DFS as compared to CG, but on subgroup analysis, HER2 positive patients had no recurrences with a trend toward improved DFS (p = 0.052) in VG as compared to CG. CONCLUSIONS: This phase II trial reveals that AE37 and GP2 are safe and possibly associated with improved clinical outcomes of DFS in certain subgroups of breast cancer patients. With these findings, further evaluations are warranted of AE37 and GP2 vaccines given in combination and/or separately for specific subsets of breast cancer patients based on their disease biology.


title: Vitamin B and Vitamin C Affect DNA Methylation and Amino Acid Metabolism in Mycobacterium bovis BCG

text: Vitamins are essential nutrients and key cofactors of enzymes that regulate cellular metabolism, and also activate the immune system. Recent studies have shown that vitamin B1 (V(B)(1)) and vitamin C (Vc) can inhibit Mycobacterium tuberculosis growth, but the precise mechanism is still not well understood. In the present study, we have used RNA-sequencing (RNA-seq), liquid chromatography coupled to mass spectrometry (LC-MS) and single-molecule real-time (SMRT) sequencing to analyze the transcriptional, metabolic and methylation profiles of Mycobacterium bovis BCG when treated with V(B)(1) and Vc. Our results show that, after vitamin treatment, variant metabolites were mainly clustered in pathways related to amino acid metabolism. Treatment with both vitamins significantly up-regulated the gene encoding cysteine synthase A. Additionally, only BCG that was treated with V(C) showed m4c modifications. Genes harboring this methylation were up-regulated, suggesting that m4c methylation can promote gene transcription to some extent. Overall, this study contributes to the understanding of the effects of V(B)(1) and V(C), and suggests that these vitamins constitute potential anti-tuberculosis drugs.


title: Management in der Behandlung von Patienten nach Einsatz biologischer Agenzien

text: The risk of terrorist attacks with weapons of mass destruction like biological agents is increasing. Biological agents can be disseminated as aerosols or by contaminating food and beverages. The multitude of agents and the different pathways of transmission cause very different clinical presentations. Natural infections with potential biological agents in Germany are rare and in most cases imported from endemic areas abroad. It is crucial to include these diseases in the spectrum of differential diagnosis. Local and state health departments have to be notified as early as possible in dubious cases. Public health management can be efficient only, if there is high reporting discipline and all epidemic measures are well coordinated.


title: Chloroquine and bafilomycin A mimic lysosomal storage disorders and impair mTORC1 signalling

text: Autophagy is dependent upon lysosomes, which fuse with the autophagosome to complete the autophagic process and whose acidic interior permits the activity of their intraluminal degradative enzymes. Chloroquine (CQ) and bafilomycin A1 (BafA) each cause alkalinisation of the lumen and thus impair lysosomal function, although by distinct mechanisms. CQ diffuses into lysosomes and undergoes protonation, while BafA inhibits the ability of the vacuolar type H(+)-ATPase (v-ATPase) to transfer protons into the lysosome. In the present study, we examine the impact of CQ and BafA on the activity of mammalian target of rapamycin complex 1 (mTORC1), inhibition of which is an early step in promoting autophagy. We find each compound inhibits mTORC1 signalling, without affecting levels of protein components of the mTORC1 signalling pathway. Furthermore, these effects are not related to these agents’ capacity to inhibit autophagy or the reduction in amino acid supply from lysosomal proteolysis. Instead, our data indicate that the reduction in mTORC1 signalling appears to be due to the accumulation of lysosomal storage material. However, there are differences in responses to these agents, for instance, in their abilities to up-regulate direct targets of transcription factor EB (TFEB), a substrate of mTORC1 that drives transcription of many lysosomal and autophagy-related genes. Nonetheless, our data imply that widely used agents that alkalinise intralysosomal pH are mimetics of acute lysosomal storage disorders (LSDs) and emphasise the importance of considering the result of CQ and BafA on mTORC1 signalling when interpreting the effects of these agents on cellular physiology.


title: Preparing undergraduate students for clinical work in a complex environment: evaluation of an e-learning module on physiotherapy in the intensive care unit

text: BACKGROUND: Intensive Care Units (ICUs) are daunting environments for physiotherapy (PT) students performing clinical rotations. To prepare students for this environment, a newly developed, evidence-based e-learning module was designed and implemented in the undergraduate curriculum. The aim of this study was to investigate whether e-learning is a feasible method in preparing PT students for clinical work in complex ICU environments, as perceived by students and experts. METHODS: A mixed methods proof of concept study was undertaken. Participants were final-year students of an international curriculum, and experts from didactic and clinical fields. An e-learning module consisting of 7 separate chapters based on the latest scientific evidence and clinical expertise was developed, piloted and incorporated into the undergraduate curriculum as a compulsory course to be completed prior to clinical ICU rotations. Data were collected through 3 focus group meetings and 5 semi-structured interviews; these meetings and interviews were audio recorded, transcribed verbatim and analyzed. RESULTS: The study sample comprised of 14 students and 5 experts. Thematic analysis revealed three themes: expected competencies of PT students in ICU, feeling prepared for ICU clinical work and dealing with local variety. The e-learning module enabled students to anticipate clinical situations and PT tasks in the ICU. Higher level clinical reasoning skills, handling of lines and wires and dealing with out-of-textbook situations could not be achieved with the e-learning module alone. CONCLUSIONS: An e-learning module can sufficiently prepare PT students for their clinical tasks in the ICU, as long as it is integrated with, or closely connected to, the students’ clinical placement.


title: General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections

text: In critical illness, homeostatic corrections representing the culmination of hundreds of millions of years of evolution, are modulated by the activated glucocorticoid receptor alpha (GRα) and are associated with an enormous bioenergetic and metabolic cost. Appreciation of how homeostatic corrections work and how they evolved provides a conceptual framework to understand the complex pathobiology of critical illness. Emerging literature place the activated GRα at the center of all phases of disease development and resolution, including activation and re-enforcement of innate immunity, downregulation of pro-inflammatory transcription factors, and restoration of anatomy and function. By the time critically ill patients necessitate vital organ support for survival, they have reached near exhaustion or exhaustion of neuroendocrine homeostatic compensation, cell bio-energetic and adaptation functions, and reserves of vital micronutrients. We review how critical illness-related corticosteroid insufficiency, mitochondrial dysfunction/damage, and hypovitaminosis collectively interact to accelerate an anti-homeostatic active process of natural selection. Importantly, the allostatic overload imposed by these homeostatic corrections impacts negatively on both acute and long-term morbidity and mortality. Since the bioenergetic and metabolic reserves to support homeostatic corrections are time-limited, early interventions should be directed at increasing GRα and mitochondria number and function. Present understanding of the activated GC-GRα's role in immunomodulation and disease resolution should be taken into account when re-evaluating how to administer glucocorticoid treatment and co-interventions to improve cellular responsiveness. The activated GRα interdependence with functional mitochondria and three vitamin reserves (B1, C, and D) provides a rationale for co-interventions that include prolonged glucocorticoid treatment in association with rapid correction of hypovitaminosis.


Mitteilungen des GRC


Mitteilungen der agswn


title: Nebenwirkungen neuer onkologischer Immuntherapien

text: Systemic treatment with immune checkpoint inhibitors (ICI) has revolutionized the treatment of hematological and oncological diseases in recent years. The mechanism of action hinges on enhancing the natural ability of the immune system to eliminate malignant cells. The most important substances in this arena include inhibitors of PD‑1, PD-L1 and CTLA‑4. As a consequence, the spectrum of treatment-associated adverse reactions is shifting away from classical cytotoxic effects (e.g. pancytopenia and polyneuropathy) towards novel entities of immune-mediated complex diseases. These so-called immune-related adverse events (irAEs) can involve any organ system and mimic known classical autoimmune conditions. Timely recognition of irAEs is the key for rapid initiation of a suitable treatment and is especially challenging in the clinical routine as it requires an intensive interdisciplinary management. Nephrologists are particularly confronted with this kind of problem due to the highly interdisciplinary nature of their work. This article summarizes the broad spectrum of currently known renal and more frequently occuring non-renal forms of irAEs and aims to prime the reader on diagnostic and therapeutic options.


title: A Mathematical Framework for Predicting Lifestyles of Viral Pathogens

text: Despite being similar in structure, functioning, and size, viral pathogens enjoy very different, usually well-defined ways of life. They occupy their hosts for a few days (influenza), for a few weeks (measles), or even lifelong (HCV), which manifests in acute or chronic infections. The various transmission routes (airborne, via direct physical contact, etc.), degrees of infectiousness (referring to the viral load required for transmission), antigenic variation/immune escape and virulence define further aspects of pathogenic lifestyles. To survive, pathogens must infect new hosts; the success determines their fitness. Infection happens with a certain likelihood during contact of hosts, where contact can also be mediated by vectors. Besides structural aspects of the host-contact network, three parameters appear to be key: the contact rate and the infectiousness during contact, which encode the mode of transmission, and third the immunity of susceptible hosts. On these grounds, what can be said about the reproductive success of viral pathogens? This is the biological question addressed in this paper. The answer extends earlier results of the author and makes explicit connection to another basic work on the evolution of pathogens. A mathematical framework is presented that models intra- and inter-host dynamics in a minimalistic but unified fashion covering a broad spectrum of viral pathogens, including those that cause flu-like infections, childhood diseases, and sexually transmitted infections. These pathogens turn out as local maxima of numerically simulated fitness landscapes. The models involve differential and integral equations, agent-based simulation, networks, and probability.


Mitteilungen der DGINA


title: Toward minimal bacterial cells: evolution vs. design

text: Recent technical and conceptual advances in the biological sciences opened the possibility of the construction of newly designed cells. In this paper we review the state of the art of cell engineering in the context of genome research, paying particular attention to what we can learn on naturally reduced genomes from either symbiotic or free living bacteria. Different minimal hypothetically viable cells can be defined on the basis of several computational and experimental approaches. Projects aiming at simplifying living cells converge with efforts to make synthetic genomes for minimal cells. The panorama of this particular view of synthetic biology lead us to consider the use of defined minimal cells to be applied in biomedical, bioremediation, or bioenergy application by taking advantage of existing naturally minimized cells.


The curious case of COVID-19 in children


The distress of Iranian adults during the Covid-19 pandemic – More distressed than the Chinese and with different predictors


title: Bacterial insertion sequences: their genomic impact and diversity

text: Insertion sequences (ISs), arguably the smallest and most numerous autonomous transposable elements (TEs), are important players in shaping their host genomes. This review focuses on prokaryotic ISs. We discuss IS distribution and impact on genome evolution. We also examine their effects on gene expression, especially their role in activating neighbouring genes, a phenomenon of particular importance in the recent upsurge of bacterial antibiotic resistance. We explain how ISs are identified and classified into families by a combination of characteristics including their transposases (Tpases), their overall genetic organisation and the accessory genes which some ISs carry. We then describe the organisation of autonomous and nonautonomous IS‐related elements. This is used to illustrate the growing recognition that the boundaries between different types of mobile element are becoming increasingly difficult to define as more are being identified. We review the known Tpase types, their different catalytic activities used in cleaving and rejoining DNA strands during transposition, their organisation into functional domains and the role of this in regulation. Finally, we consider examples of prokaryotic IS domestication. In a more speculative section, we discuss the necessity of constructing more quantitative dynamic models to fully appreciate the continuing impact of TEs on prokaryotic populations.


title: Candidemia following solid organ transplantation in the era of antifungal prophylaxis: the Australian experience

text: Abstract: Solid organ transplant (SOT) recipients have high rates of invasive fungal infections, with Candida species the most commonly isolated fungi. The aim of this study was to identify differences between incidence rates, risk factors, clinical presentations, and outcomes of candidemia in SOT recipients and non‐SOT patients. Data from the multicenter prospective Australian Candidaemia Study were examined. From August 2001 to July 2004, 24 episodes (2.2%; 24/1068) of candidemia were identified in SOT recipients. During this period, the numbers of transplanted organs included liver (n=455), kidney (n=1605), single lung (n=57), bilateral lung (n=183), heart and lung (n=18), heart (n=157), and pancreas (n=62). The overall annual estimated incidence of candidemia in SOT recipients was higher (3 per 1000 transplant admissions) than in non‐SOT patients (incidence 0.21 per 1000 admissions; P<0.001). The incidence and timing of candidemia post transplant was influenced by the transplanted organ type, with the majority of episodes (n=14, 54%) occurring >6 months after renal transplantation. Risk factors for candidemia in the month preceding diagnosis were similar to non‐SOT recipients except for corticosteroid therapy (P<0.001). Antifungal prophylaxis did not select for more resistant or non‐albicans Candida species in the SOT group. The 30‐day all‐cause mortality was similar to non‐SOT patients with candidemia and remains high at 21%. All deaths in SOT recipients occurred early (within 5 days of diagnosis), underlining a need for better diagnostic tests, targeted prevention, and early treatment strategies.


title: New ethnicities online: reflexive racialisation and the internet

text: In this article we analyse the emergence of Internet activity addressing the experiences of young people in two British communities: South Asian and Chinese. We focus on two web sites: http://www.barficulture.com and http://www.britishbornchinese.org.uk, drawing on interviews with site editors, content analysis of the discussion forums, and E‐mail exchanges with site users. Our analysis of these two web sites shows how collective identities still matter, being redefined rather than erased by online interaction. We understand the site content through the notion of reflexive racialisation. We use this term to modify the stress given to individualisation in accounts of reflexive modernisation. In addition we question the allocation of racialised meaning from above implied by the concept of racialisation. Internet discussion forums can act as witnesses to social inequalities and through sharing experiences of racism and marginalisation, an oppositional social perspective may develop. The online exchanges have had offline consequences: social gatherings, charitable donations and campaigns against adverse media representations. These web sites have begun to change the terms of engagement between these ethnic groups and the wider society, and they have considerable potential to develop new forms of social action.


title: Immunoglobulin G, A, and M Light Chain Ratios in some Humoral Immunological Disorders

text: The total kappa/lambda immunoglobulin light chain ratio and the kappa/lambda ratios within each of the serum immunoglobulin classes G. A. and M were measured in thirteen patients with humoral immunological disorders. Of those patients, eight had common variable immunodeficiency whereas live patients had other forms of humoral immunological deficiencies. Eleven patients had abnormal antibody response in vivo. All but three of the thirteen patients had clearly abnormal light chain ratios in one or more of the immunoglobulin classes. We conclude that humoral immunological disorders, usually characterized by abnormal heavy chain production and a disturbed antibody response, may frequently have a concomitant abnormal synthesis of the light chains resulting in an abnormal kappa/lambda light chain ratio.


title: Interferon‐α Production and Tissue Localization of Interferon‐α/β Producing Cells after Intradermal Administration of Aujeszky's Disease Virus–Infected Cells in Pigs

text: Intradermal administration of glutaraldehyde–fixed Aujeszky's disease virus (ADV) infected autologous or allogeneic cells resulted in the induction of an interferon(IFN)–α/β response in pigs. Using a sensitive dissociation–enhanced lanthanide fluoroimmunoassay (DELFIA), IFN–α/β was detected in blood at 8 and 24 h after injection of ADV–infected cells. In parallel, by means of in situ hybridization, IFN–α/β mRNA containing cells were demonstrated in regional lymph nodes. Occasional IFN–α/β mRNA positive cells were also seen in injected dermal areas, but not in contralateral lymph nodes, spleen, bone marrow, blood or liver. The ability of leucocytes in whole blood cultures to produce IFN–α/β upon stimulation by ADV was markedly diminished 3–7 days after intradermal injection of ADV–infected cells. In contrast, cultures of purified peripheral blood mononuclear cells (PBMC) had intact IFN–α/β responses. Further, serum from ADV–injected pigs inhibited the in vitro ADV–induced IFN‐α/β responses in PBMC from control pigs, most likely due to the demonstrated presence of anti–ADV antibodies. We suggest that the IFN‐α/β producing cells in lymph nodes may participate in the development of antiviral immunity and could be equivalent to Natural IFN–α/β producing (NIP) cells.


title: Apneic Oxygenation for Emergency Intubations in the Pediatric Emergency Department—A Quality Improvement Initiative

text: INTRODUCTION: Emergency airway management of critically ill children in the Emergency Department (ED) is associated with the risk of intubation-related desaturation, which can be minimized by apneic oxygenation. We evaluated the use of apneic oxygenation in the pediatric ED and reported a quality improvement initiative to incorporate apneic oxygenation as a routine standard of care during rapid sequence intubations (RSIs). METHODS: A baseline period from June 2016 to April 2017 highlighted the practice gaps. Quality improvement interventions were subsequently developed and implemented as a care bundle consisting of a pre-intubation checklist, placing reminders and additional oxygen source in resuscitation bays, incorporating into the responsibilities of the airway doctor and the airway nurse (copiloting), education during airway workshops and simulation training for doctors and nurses, as well as enhancing documentation of the intubation process. We monitored a post-intervention observation period from May 2017 to April 2018 for the effectiveness of the care bundle. RESULTS: Apneic oxygenation was not performed in all 22 RSIs during the baseline period. Among 25 RSIs in the post-intervention observation period, providers performed apneic oxygenation in 17 (68%) cases. There was no significant difference in the utilization of apneic oxygenation among emergency physicians and pediatric anesthetists performing RSIs in the pediatric ED. CONCLUSIONS: We successfully implemented a care bundle targeted at incorporating apneic oxygenation as a routine standard of care during emergency intubations performed in ED. This method could be adopted by other pediatric EDs to improve airway management in critically ill children.


title: Schedule-based Family-centered Rounds: A Novel Approach to Achieve High Nursing Attendance and Participation

text: INTRODUCTION: Bedside nurse (RN) presence during family-centered rounds (FCR) enhances communication and collaboration for safer, higher-quality care.1–3 At our institution, RN participation in FCR was variable and lower than desired. The content discussed at each bedside during rounds was inconsistent, contributing to the irregular achievement of established FCR checklist items. METHODS: Using a scheduling tool with a prioritization algorithm and set time allotment/patient, we implemented schedule-based family-centered rounds (SBFCR) on a pediatric acute care unit. Primary outcome metrics included RN attendance and participation. We tracked rounding checklist compliance, parent presence on rounds, and adherence to the schedule. Surveys provided information on provider and family satisfaction. Perceived impact on teaching was the balancing measure because the structure discouraged spending extra time at the cost of team tardiness for the next patient. RESULTS: We created a schedule for 95% workweek days, with the rounding order kept for 93%. Mean RN attendance increased from 69% to 87% and participation increased from 48% to 80% with SBFCR (P < 0.001 for each). FCR checklist compliance increased from 60% to 94% (P < 0.001). Families felt more informed and able to attend; their presence at rounds rose from 66% to 85% (P < 0.001). Most faculty and trainees felt SBFCR was efficient and observed increased teaching with SBFCR. CONCLUSIONS: SBFCR provides an organizational framework for increased RN attendance and participation as well as greater family presence during rounds. The system elevated provider satisfaction with rounding without degrading the perceived educational experience.


title: Key Drivers in Reducing Hospital-acquired Pressure Injury at a Quaternary Children’s Hospital

text: INTRODUCTION: Despite being a participating Solutions for Patient Safety (SPS) children’s hospital and having attempted implementation of the SPS hospital-acquired pressure injuries (HAPIs) prevention bundle, our hospital remained at a HAPI rate that was 3 times the mean for SPS participating children’s hospitals. This performance led to the launch of an enterprise-wide HAPI reduction initiative in our organization. The purpose of this article is to describe the improvement initiative, the key drivers, and the resulting decrease in the SPS-reportable HAPI rate. METHODS: We designed a hospital-wide HAPI reduction initiative with actions grouped into 3 key driver areas: standardization, data transparency, and accountability. We paused all individual hospital unit-based HAPI reduction initiatives. We calculated the rate of SPS-reportable HAPIs per 1,000 patient days during both the pre- and postimplementation phases and compared mean rates using a 2-sided t test assuming unequal variances. RESULTS: The mean SPS-reportable HAPI rate for the preimplementation phase was 0.3489, and the postimplementation phase was 0.0609. The difference in rates was statistically significant (P < 0.00032). This result equates to an 82.5% reduction in HAPI rate. CONCLUSIONS: Having an institutional pause and retooled initiative to reduce HAPI with key drivers in the areas of standardization, data transparency, and accountability had a statistically significant reduction in our organization’s SPS-reportable HAPI rate.


title: Retrospective Review of the Safety and Efficacy of Virtual Reality in a Pediatric Hospital

text: INTRODUCTION: Virtual reality (VR) is an emerging tool for anxiety and fear reduction in pediatric patients. VR use is facilitated by Certified Child Life Specialists (CCLS) at pediatric hospitals. The primary aim of this study was to retrospectively review the safety of VR by analyzing adverse events after the utilization of VR under CCLS supervision. Secondary objectives were to characterize the efficacy of VR in enhancing patient cooperation, describe the integration of VR into Child Life services, and identify interventions that accompanied VR. METHODS: The Stanford Chariot Program developed VR applications, customized VR interfaces, and patient head straps, and distributed these to CCLS. Chart review analyzed VR utilization through CCLS patient notes. Inclusion criteria were all patients ages 6 to 18-years-old who received a Child Life intervention. RESULTS: From June 2017 to July 2018, 31 CCLS saw 8,098 patients, 3,696 of which met age criteria with pre- and post-intervention cooperation data. Two hundred thirteen patients received VR with an accompanying intervention, while 34 patients received only VR. Adverse events were rare, and included increased anxiety (3.8%, n=8), dizziness (0.5%, n=1), and nausea (0.5%, n=1). Patients were more likely to be cooperative after receiving VR (99.5%, n=212) compared to pre-intervention (96.7%, n=206, p=0.041). VR use was most common in the perioperative setting (60%, n=128), followed by outpatient clinics (15%, n=32). CONCLUSION: VR is safe in pediatric patients with appropriate hardware, software, and patient selection. Side effects were rare and self-limited. VR appears to be associated with improvements in cooperation.


title: A Three-part Quality Improvement Initiative to Increase Patient Satisfaction and Reduce Appointment Time

text: INTRODUCTION: PediPlace, a busy pediatric not-for-profit clinic in Lewisville, Tex., struggles with prolonged patient wait times. This quality improvement (QI) project aimed to reduce appointment lengths and improve the patient experience. METHODS: PediPlace introduced 3 interventions: improved patient tracking to measure timing on the electronic health record interface, elimination of script repetition between medical assistants and providers, and patient art kits. RESULTS: From over 2,000 surveys indicated that patients were more satisfied; the percentage of negative survey comments decreased from 20% in 2017 and 2018 to under 10% in 2019. The overall rating of the clinic rose from 3.8 to 4.75 (on a scale of 1–5) after QI interventions as well. The number of patients not checked out declined from 49 errors in October–December 2018 to 25 errors in January–March 2019, indicating that this part of the initiative was initially successful. However, subsequent months experienced higher error rates. Analysis of over 20,000 appointments from June 2018 to July 2019 showed that appointment length did not change after interventions. CONCLUSIONS: There was no difference in appointment lengths between Hispanic/Latino patients and other patients, and an encouraging finding that suggests PediPlace providers are effective bilingual communicators. Furthermore, anecdotal evidence indicated that the art kits were positively received. The interventions appeared to improve the patient experience but did not impact appointment length. PediPlace plans to continue QI initiatives in the future.


title: Establishing Standardized Documentation for Anaphylaxis Treatment in a Tertiary Care Pediatric Allergy Clinic

text: INTRODUCTION: Anaphylaxis is a potentially life-threatening allergic reaction. Common allergy clinic procedures, including oral food challenges and subcutaneous immunotherapy, carry a risk of anaphylaxis, the treatment for which is epinephrine. Our goal was to develop a standardized process for the management and documentation of allergic reactions that occur in a tertiary care pediatric allergy clinic. METHODS: This was a single institution quality improvement pilot study. A multidisciplinary team from the allergy department designed, implemented, and studied the use of a standardized form for the documentation and treatment of allergic reactions within the clinic. RESULTS: A standardized form was developed based on evidence-based guidelines for the management of allergic reactions and included space for documentation. Both clinic providers and staff approved the form. One year after the introduction, we reached 100% adherence for the use of the form in visits during which a patient experienced a severe allergic reaction requiring epinephrine. Two patients required transfer to the emergency room; the quality improvement form was utilized in these cases to document treatment and assist with the hand-off to emergency room personnel before transfer. CONCLUSIONS: We successfully implemented a standardized form for the treatment and documentation of anaphylaxis within our allergy clinic. The next steps focus on further integrating this form into the electronic medical record, determining compliance with evidence-based management of anaphylaxis, and formally assessing the use of the form as a handoff tool in the event of patient transfer.


title: Pediatric Clinician Comfort Discussing Diagnostic Errors for Improving Patient Safety: A Survey

text: INTRODUCTION: Meaningful conversations about diagnostic errors require safety cultures where clinicians are comfortable discussing errors openly. However, clinician comfort discussing diagnostic errors publicly and barriers to these discussions remain unexplored. We compared clinicians’ comfort discussing diagnostic errors to other medical errors and identified barriers to open discussion. METHODS: Pediatric clinicians at 4 hospitals were surveyed between May and June 2018. The survey assessed respondents’ comfort discussing medical errors (with varying degrees of system versus individual clinician responsibility) during morbidity and mortality conferences and privately with peers. Respondents reported the most significant barriers to discussing diagnostic errors publicly. Poststratification weighting accounted for nonresponse bias; the Benjamini–Hochberg adjustment was applied to control for false discovery (significance set at P < 0.018). RESULTS: Clinicians (n = 838; response rate 22.6%) were significantly less comfortable discussing all error types during morbidity and mortality conferences than privately (P < 0.004) and significantly less comfortable discussing diagnostic errors compared with other medical errors (P < 0.018). Comfort did not differ by clinician type or years in practice; clinicians at one institution were significantly less comfortable discussing diagnostic errors compared with peers at other institutions. The most frequently cited barriers to discussing diagnostic errors publicly included feeling like a bad clinician, loss of reputation, and peer judgment of knowledge base and decision-making. CONCLUSIONS: Clinicians are more uncomfortable discussing diagnostic errors than other types of medical errors. The most frequent barriers involve the public perception of clinical performance. Addressing this aspect of safety culture may improve clinician participation in efforts to reduce harm from diagnostic errors.


title: Decreasing Usage of Lights and Sirens in an Urban Environment: A Quality Improvement Project

text: INTRODUCTION: The risk of lights and sirens use in emergency medical services has been well documented. Our critical care transport team performs over 1,800 interfacility nonemergency medical services transports annually into a dense urban environment. Historically, we have utilized lights and sirens to navigate traffic patterns. The use exceeded industry standards. This quality improvement project was undertaken to decrease the use of lights and sirens. METHODS/RESULTS: The baseline use of lights and sirens in 2011 was 76% en route and 73% on return to the facility. We revised the internal policy guiding the appropriate usage of lights and sirens. In 2012, without an improvement in usage, a use justification process was implemented. By 2013, the use of lights and sirens was still high en route, but had decreased to 53% on the return trip. In 2014, we added accountability measures requiring justification, with a subsequent drop in 2015 to 14% en route and 13% on return. In the following 3 years, the transport teams have sustained lights and sirens use to 20% or below. CONCLUSIONS: This quality improvement initiative impacted team behavior and decreased the use of lights and sirens over 5 years, with sustained improvement at or below 20%. This improvement was accomplished through ongoing evaluation, education, data gathering, and open communication. There was no negative impact on patient outcomes during this time. Lights and sirens continue to be used when indicated.


title: ED RAPID: A Novel Children’s Hospital Direct Admission Process Utilizing the Emergency Department

text: INTRODUCTION: Direct hospital admission of children without evaluation in the emergency department (ED) is common, but few guidelines exist to maximize safety by assessing patient stability. This report describes a novel approach to support patient safety. METHODS: An interdisciplinary children’s hospital team developed a brief ED-based evaluation process called the ED Rapid Assessment of Patients Intended for Inpatient Disposition (ED RAPID). It entails a brief evaluation of vital signs and clinical stability by the ED attending physician and nurse. Children deemed stable are admitted to inpatient wards, whereas those requiring immediate intervention undergo full ED evaluation and disposition. We assessed outcomes for all children evaluated through this process from March 2013 through February 2015. RESULTS: During the study period, we identified 715 patients undergoing ED RAPID evaluation. Of these, we directly admitted 691 (96.4%) to the hospital ward after ED RAPID evaluation; median ED treatment time was 4.0 minutes. We transitioned 24 (3.4%) to full ED evaluation, 14 (2.0%) because a ward bed was unavailable, and 10 (1.4%) for clinical reasons identified in the evaluation. We admitted four of the 10 stopped (40% of stops, 0.6% of total) to an intensive care unit, and 6 (60% of stops, 0.8% of total) to the hospital ward after ED care. Eight children (1.1%) admitted to the hospital ward after ED RAPID evaluation required a transfer to an intensive care unit within 12 hours. CONCLUSION: The ED RAPID evaluation process for children directly admitted to the hospital was feasible and effective in this setting.


title: AutoPEWS: Automating Pediatric Early Warning Score Calculation Improves Accuracy Without Sacrificing Predictive Ability

text: INTRODUCTION: Pediatric early warning scores (PEWS) identify hospitalized children at risk for deterioration. Manual calculation is prone to human error. Electronic health records (EHRs) enable automated calculation, removing human error. This study’s objective was to compare the accuracy of automated EHR-based PEWS calculation (AutoPEWS) to manual calculation and evaluate the non-inferiority of AutoPEWS in predicting deterioration. METHODS: We performed a retrospective cohort study inclusive of non-intensive care unit inpatients at a freestanding children’s hospital over 4.5 months in Fall 2018. AutoPEWS mapped the historical manual PEWS scoring rubric to frequently used EHR documentation. We determined accuracy by comparing the expected respiratory subset score based on the current respiratory rate to the actual respiratory score of AutoPEWS and the manual PEWS. The agreement was determined using kappa statistics. We used predicted probabilities from a generalized linear mixed model to calculate areas under the curve for each combination of scores (AutoPEWS, manual) and deterioration outcome (rapid response team activation, unplanned intensive care unit transfer, critical deterioration event). We compared the adjusted difference in areas under the curves between the scores. Non-inferiority was defined as a difference of <0.05. RESULTS: There were 23,514 total PEWS representative of 5,384 patients. AutoPEWS respiratory scores were 99.97% accurate, while the manual PEWS respiratory scores were 86% accurate. AutoPEWS were higher overall than the manual PEWS (mean 0.65 versus 0.34). They showed a fair-to-good agreement (weighted kappa 0.42). Non-inferiority of AutoPEWS compared with the manual PEWS was demonstrated for all deterioration outcomes. CONCLUSIONS: Automation of PEWS calculation improved accuracy without sacrificing predictive ability.


title: Economic Evaluation: Onsite HSV PCR Capabilities for Pediatric Care

text: OBJECTIVE: Herpes simplex virus (HSV) encephalitis has an overall mortality rate of 11%–29% with treatment. Although rare, HSV encephalitis is frequently tested for and empirically treated, especially in the neonatal population. HSV infection can be diagnosed with polymerase chain reaction (PCR) testing, although this frequently requires sending samples to reference laboratories. The inherent delay in results may lead to prolonging empiric treatment and hospital stay, resulting in increased costs. This study investigates whether onsite HSV PCR testing decreases hospitalization duration, acyclovir treatment duration, and financial cost on an institution. PROJECT DESIGN: This single-center project utilized the IHI model for improvement to evaluate third-party HSV PCR processing versus an implemented onsite PCR-based meningitis–encephalitis panel for HSV central nervous system evaluation. The primary outcome was hospital cost differential with secondary outcomes, including duration of acyclovir administration and time to result. RESULTS: We identified 96 children age 0–18 from 2010 to 2016, 74 patients utilizing offsite third-party testing, and 22 patients utilizing onsite. We observed a per-patient cost savings of $428 ($618.43–$190.43, P = 0.029) upon the implementation of onsite testing. The mean duration of acyclovir therapy decreased from 3.7 to 0.26 days per patient (P < 0.001). Time to result decreased from 4.6 to 0.13 days (P < 0.001). CONCLUSIONS: Acquisition of real-time local HSV PCR capabilities significantly decreased time to result and empiric medication use while significantly reducing hospital costs in a military treatment facility.


title: Decreasing Chronic Lung Disease Associated with Bubble CPAP Technology: Experience at Five Years

text: INTRODUCTION: Bubble continuous positive airway pressure (bCPAP) is associated with a decreased risk for chronic lung disease (CLD) in preterm neonates. This report examined the effectiveness of adopting bCPAP to reduce respiratory complications and medication usage in a community hospital NICU. METHODS: The efficacy of bCPAP was assessed by retrospective examination and comparison of 45 neonates who received bCPAP and 87 neonates who received conventional ventilation only. Data on medication usage were also collected and analyzed. RESULTS: After introduction of the bCPAP protocol, the median number of days on oxygen decreased in the bCPAP group compared with the conventional ventilation only group (median = 33 days, IQR = 7.5–66 vs median = 0, IQR = 0–0; P < 0.001). The exposure to conventional ventilation decreased in the bCPAP group compared with the conventional ventilation only group (median = 18 days, IQR = 5–42.5 vs median = 0, IQR = 0–7; P < 0.001). Postimplementation of bCPAP revealed decreases in CLD from 26 (30%) in the conventional ventilation only group to 2 (4%) in the bCPAP group (P = 0.002); there was also a significant decrease in the use of sedative medications in the bCPAP group compared with the conventional ventilation only group (mean = 5.20 doses, SD = 31.97 vs mean = 1.43, SD = 9.98; P < 0.001). CONCLUSION: The use of bCPAP results in significant decreases in the use of conventional ventilation, the risk for CLD, and the need for sedative medication.


title: A Quality Improvement Intervention Bundle to Reduce 30-Day Pediatric Readmissions

text: INTRODUCTION: Pediatric hospital readmissions can represent gaps in care quality between discharge and follow-up, including social factors not typically addressed by hospitals. This study aimed to reduce the 30-day pediatric readmission rate on 2 general pediatric services through an intervention to enhance care spanning the hospital stay, discharge, and follow-up process. METHODS: A multidisciplinary team developed an intervention bundle based on a needs assessment and evidence-based models of transitional care. The intervention included pre-discharge planning with a transition coordinator, screening and intervention for adverse social determinants of health (SDH), medication reconciliation after discharge, communication with the primary care provider, access to a hospital-based transition clinic, and access to a 24-hour direct telephone line staffed by hospital attending pediatricians. These were implemented sequentially from October 2013 to February 2017. The primary outcome was the readmission rate within 30 days of index discharge. The length of stay was a balancing measure. RESULTS: During the intervention, the included services discharged 4,853 children. The pre-implementation readmission rate of 10.3% declined to 7.4% and remained stable during a 4-month post-intervention observation period. Among 1,394 families screened for adverse SDH, 48% reported and received assistance with ≥ 1 concern. The length of stay increased from 4.10 days in 2013 to 4.30 days in 2017. CONCLUSIONS: An intervention bundle, including SDH, was associated with a sustained reduction in readmission rates to 2 general pediatric services. Transitional care that addresses multiple domains of family need during a child’s health crisis can help reduce pediatric readmissions.


title: Survey-based Work System Assessment to Facilitate Large-scale Dissemination of Healthcare Quality Improvement Programs

text: INTRODUCTION: The dissemination of quality improvement (QI) interventions to a broader range of healthcare settings requires a proactive assessment of local work systems and processes. The objective of this study was to examine the feasibility of using a survey-based work system assessment (WSA) tool to facilitate the dissemination of a program for optimizing blood culture (BC) use. METHODS: Informed by findings from an onsite, interview-based WSA at 2 hospitals, a 50-item WSA survey was devised and administrated to 15 hospitals participating in a QI collaborative. WSA survey data were summarized, shared, and discussed with individual hospitals to inform the adaptation and implementation of the BC program. Physician champions leading the local QI team assessed the use of the WSA survey by completing an 8-item survey. RESULTS: A total of 347 clinicians completed the WSA survey, and physician champions at 12 hospitals evaluated the use of the WSA survey. Both the WSA survey data and the evaluation of the WSA survey showed that the survey-based WSA tool could help participating hospitals understand their current BC ordering practices and identify potential barriers to implementing the program from the perspectives of different clinicians. CONCLUSIONS: We demonstrated how a survey-based tool could be used to facilitate WSA in the dissemination of a program for improving BC use to a multisite collaborative. A survey-based WSA tool can be used to facilitate future large-scale intervention dissemination efforts.


title: Qualitative Study to Understand Pediatric Hospitalists and Emergency Medicine Physicians’ Perspectives of Clinical Pathways

text: INTRODUCTION: Healthcare costs are rising, and clinical pathways (CPW) are one means to promote high-value care by standardizing care and improving outcomes without compromising cost or quality. However, providers do not always follow CPW, and our understanding of their perceptions is limited. Our objective was to examine pediatric hospital medicine (PHM) and pediatric emergency medicine (PEM) physician perspectives of CPW. METHODS: We conducted semistructured, in-depth, one-on-one qualitative interviews with PHM and PEM physicians between February 2017 and August 2017. Interviews were audio-recorded, professionally transcribed, and accuracy verified. Using an inductive analytic strategy, we systematically coded the data to identify themes. RESULTS: We interviewed 15 PHM and 15 PEM physicians. These providers identified many benefits and limitations of CPW, which positively or negatively impact resource utilization, communication, education of personnel, patients, and families, as well as practice behaviors and attitudes. Perceived benefits included (1) reduction of unnecessary utilization, (2) standardization of care, (3) improved communication, (4) education of oneself and others, and (5) confidence and validation when actions align with CPW. Limitations of CPW were (1) resource utilization for revisions, updates, and dissemination; (2) “tunnel vision” and cognitive biases; (3) loss of autonomy; (4) prescriptive medicine; (5) information overload; (6) pressure to adhere; and (7) guilt if actions do not align with CPW. CONCLUSIONS: CPW are tools with advantages and disadvantages that are used and viewed differently by providers. Such insight into how physicians perceive CPW may help to optimize hospital improvement work and enhance high-value care.


title: Handoff Communication between Remote Healthcare Facilities

text: INTRODUCTION: Handoffs and transitions of care are common weak points in healthcare provider communication as patients move between sites. With no consistent pattern of communication between St. Jude Children’s Research Hospital (St. Jude) and its affiliated clinics, the Affiliate Program Office at St. Jude developed and implemented a standardized communication tool to facilitate patient transitions between different healthcare sites. METHODS: Each team of providers created flow diagrams to define the current state of communication when patients were transitioning between remote sites. Fishbone diagrams identified the common barriers to effective communication as a lack of consistent communication and ownership. We developed a communication tool to address these barriers, which was disseminated by secure email. We measured the percent usage of the completed hand-off tool before a patient transitioned, staff experience, and the number of errors. RESULTS: The time to send or receive the communication bundle was <10 minutes. Within 3 months of implementing the SMART bundle at 3 pilot sites, the bundle was used completely in 6 of 8 patient transitions and was associated with somewhat improved staff satisfaction. We identified no adverse events related to the communication bundle. CONCLUSIONS: In this small pilot study, we accomplished closed-loop communication between geographically remote healthcare sites by using an electronically transmitted standardized communication bundle.


title: The Vitals Risk Index—Retrospective Performance Analysis of an Automated and Objective Pediatric Early Warning System

text: INTRODUCTION: Pediatric in-hospital cardiac arrests and emergent transfers to the pediatric intensive care unit (ICU) represent a serious patient safety concern with associated increased morbidity and mortality. Some institutions have turned to the electronic health record and predictive analytics in search of earlier and more accurate detection of patients at risk for decompensation. METHODS: Objective electronic health record data from 2011 to 2017 was utilized to develop an automated early warning system score aimed at identifying hospitalized children at risk of clinical deterioration. Five vital sign measurements and supplemental oxygen requirement data were used to build the Vitals Risk Index (VRI) model, using multivariate logistic regression. We compared the VRI to the hospital’s existing early warning system, an adaptation of Monaghan’s Pediatric Early Warning Score system (PEWS). The patient population included hospitalized children 18 years of age and younger while being cared for outside of the ICU. This dataset included 158 case hospitalizations (102 emergent transfers to the ICU and 56 “code blue” events) and 135,597 control hospitalizations. RESULTS: When identifying deteriorating patients 2 hours before an event, there was no significant difference between Pediatric Early Warning Score and VRI’s areas under the receiver operating characteristic curve at false-positive rates ≤ 10% (pAUC(10) of 0.065 and 0.064, respectively; P = 0.74), a threshold chosen to compare the 2 approaches under clinically tolerable false-positive rates. CONCLUSIONS: The VRI represents an objective, simple, and automated predictive analytics tool for identifying hospitalized pediatric patients at risk of deteriorating outside of the ICU setting.


title: Improving Accuracy and Timeliness of Nursing Documentation of Pediatric Early Warning Scores

text: INTRODUCTION: Accurate and timely documentation of pediatric early warning scores (PEWS) by the bedside nurse into the electronic health record (EHR) is important to promote early identification of patients in stages of deterioration. Through the implementation of a PEWS calculator embedded in the EHR, we hope to improve the accuracy of the recorded score and reduce the time between vital sign collection and final documentation in the EHR. METHODS: Identification of the highest PEWS value in the 24 hours before all unplanned transfers or rapid response activations without a transfer occurred between the period November 1, 2013, through December 31, 2016. The accuracy of the calculated cardiac or respiratory subscore based on heart rate or the respiratory rate at the time of PEWS calculation was determined. We tracked the calculation of the time to chart via the difference between nursing documentation of PEWS compared to vital sign collection. Before September 3, 2015, PEWS was calculated mentally by the bedside nurse; afterward, the nurse entered the unique PEWS features into the EHR, and the EHR automatically calculated PEWS. RESULTS: This study evaluated 2,409 PEWS scores, 1,411 before and 998 after initiation of the PEWS calculator. Accuracy before the EHR calculator was 71%, and the median time to document was 55 minutes. Following the implementation of the calculator, no scores were incorrectly calculated too low, and the median time to document was 20 minutes. CONCLUSIONS: Transition to an EHR-based PEWS calculator eliminated inaccurately low PEWS values and reduced time to document.


title: Improving Disposition Decision-Making for Pediatric Diabetic Ketoacidosis: A Quality Improvement Study

text: INTRODUCTION: In many centers, children with diabetic ketoacidosis (DKA) receive care either in an endocrinology ward or a pediatric intensive care unit (PICU). We conducted a quality improvement (QI) initiative to reduce potentially avoidable PICU admissions of children with DKA without increasing endocrinology ward-to-PICU transfers. METHODS: A survey of providers demonstrated opportunities to increase awareness of institutional criteria for PICU admissions of children with DKA. We created an electronic health record (EHR) dot-phrase, prepopulated with these criteria, and placed a note in the EHR for all patients with DKA as a reference for all providers. An EHR-based data report was created to monitor the disposition of DKA patients and the use of the dot-phrase (process measure). The primary outcome measure was the potentially avoidable PICU admissions for patients with DKA. Endocrinology ward-to-PICU transfers were tracked as a balancing measure to ensure safe disposition. RESULTS: After the implementation of the dot-phrase, use was variable, but averaged 33.4% over 1 year. The percentage of DKA admissions classified as potentially avoidable PICU stays decreased from 4.1% to 0.5%, with a concurrent decrease in the total percentage of PICU admissions for DKA from 19.1% to 8.4%. The percentage of endocrinology ward-to-PICU transfers also declined from 0.8% to 0%. CONCLUSIONS: A novel EHR-based intervention increasing awareness and documentation of established pediatric DKA management guidelines can be used to safely reduce PICU admissions for DKA without increasing the rate of endocrinology ward-to-intensive care unit transfers.


title: Optimizing Analgesic Use During Infant Lumbar Puncture in the Emergency Department

text: INTRODUCTION: Lumbar puncture (LP) for the collection of cerebrospinal fluid is an important diagnostic tool for the evaluation of febrile or ill-appearing infants. This invasive procedure is painful for patients; inadequate analgesia may have lasting effects. The American Academy of Pediatrics recommends analgesia during all LP procedures, and oral sucrose alone does not offer sufficient analgesia. Our objective was to identify analgesic use trends during infant LP in our emergency department and create a system of analgesic administration. We aimed for complete compliance with one method of analgesia and an increase in our use of 2 or more methods to 85% over 12 months. METHODS: We utilized Plan-Do-Study-Act cycle methodology and retrospective chart review. Five interventions focused on staff communication, collaboration, and education. Inclusion criteria: infants <60 days who underwent LP procedure due to fever >38°C, hypothermia <36.5°C of unknown origin, or ill-appearance. RESULTS: One hundred infant LPs analyzed: 52 preintervention and 48 intervention. The use of one analgesic increased from 98% preintervention to 100%. The use of 2 or more analgesics increased from 58% preintervention to 87%. Topical lidocaine use increased from 56% preintervention to 73%. LP success rates were high in both groups, with no statistically significant change in the success rate. CONCLUSION: We created a streamlined process to ensure all infants undergoing lumbar puncture received at least 1 analgesic and increased the proportion of infants treated with 2 or more analgesics. This work could be expanded to improve analgesia during other invasive procedures in the emergency department.