Publications by authors named "Elizabeth Mitchell"

112 Publications

Longitudinal analysis of cardiac abnormalities in pediatric patients with sickle cell anemia and effect of hydroxyurea therapy.

Blood Adv 2021 Sep 16. Epub 2021 Sep 16.

Cohen Children's Medical Center, New Hyde Park, New York, United States.

Cardiac abnormalities such as left ventricular hypertrophy, dilation and pulmonary hypertension in sickle cell anemia, have been previously described. Hydroxyurea, a disease modifying therapy for sickle cell anemia, has been used for several decades. Longitudinal assessment of echocardiographic abnormalities in children and young adults with sickle cell anemia on hydroxyurea therapy is lacking. In this retrospective study, we aim to determine the prevalence of echocardiographic abnormalities in children and young adults with sickle cell anemia and to examine the effects of hydroxyurea on reverse cardiac remodeling. We reviewed the records of patients with sickle cell anemia who underwent routine cardiac screening at Cohen Children's Medical Center between 2010 and 2017, followed by retrospective longitudinal analysis of echocardiograms performed on patients receiving treatment with hydroxyurea. Data on a total of 100 patients with sickle cell anemia were analyzed; 60 (60%) were on hydroxyurea. Twenty-five (41.6%) of the patients on hydroxyurea had been treated for less than 1 year; these patients had a significantly greater prevalence of left ventricular dilation compared to those who had been on treatment for more than 1 year. Serial echocardiograms were then analyzed on patients receiving hydroxyurea. Left ventricular dilation and hypertrophy improved significantly with hydroxyurea treatment. Additionally, the left ventricular volume and mass correlated negatively with duration of treatment with hydroxyurea. Our study provides evidence that prolonged hydroxyurea therapy may lead to reverse cardiac remodeling. Future studies should attempt to follow this patient cohort for a longer duration.
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http://dx.doi.org/10.1182/bloodadvances.2021005076DOI Listing
September 2021

Exploiting Scanning Surveillance Data to Inform Future Strategies for the Control of Endemic Diseases: The Example of Sheep Scab.

Front Vet Sci 2021 16;8:647711. Epub 2021 Jul 16.

School of Veterinary Medicine, University of Glasgow, Glasgow, United Kingdom.

Scanning surveillance facilitates the monitoring of many endemic diseases of livestock in Great Britain, including sheep scab, an ectoparasitic disease of major welfare and economic burden. There is, however, a drive to improve the cost-effectiveness of animal health surveillance, for example by thoroughly exploiting existing data sources. By analysing the Veterinary Investigation Diagnosis Analysis (VIDA) database, this study aimed to enhance the use of existing scanning surveillance data for sheep scab to identify current trends, highlighting geographical "hotspots" for targeted disease control measures, and identifying a denominator to aid the interpretation of the diagnostic count data. Furthermore, this study collated and assessed the impact of past targeted disease control initiatives using a temporal aberration detection algorithm, the Farrington algorithm, to provide an evidence base towards developing cost-effective disease control strategies. A total of 2,401 positive skin scrapes were recorded from 2003 to 2018. A statistically significant decline in the number of positive skin scrapes diagnosed ( < 0.001) occurred across the study period, and significant clustering was observed in Wales, with a maximum of 47 positive scrapes in Ceredigion in 2007. Scheduled ectoparasite tests was also identified as a potential denominator for the interpretation of positive scrapes by stakeholders. Across the study period, 11 national disease control initiatives occurred: four in Wales, three in England, and four in Scotland. The majority ( = 8) offered free diagnostic testing while the remainder involved knowledge transfer either combined with free testing or skills training and the introduction of the Sheep Scab (Scotland) Order 2010. The Farrington algorithm raised 20 alarms of which 11 occurred within a period of free testing in Wales and one following the introduction of the Sheep Scab (Scotland) Order 2010. In summary, our analysis of the VIDA database has greatly enhanced our knowledge of sheep scab in Great Britain, firstly by identifying areas for targeted action and secondly by offering a framework to measure the impact of future disease control initiatives. Importantly this framework could be applied to inform future strategies for the control of other endemic diseases.
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http://dx.doi.org/10.3389/fvets.2021.647711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322841PMC
July 2021

Six Month Follow-up of Patients With Multi-System Inflammatory Syndrome in Children.

Pediatrics 2021 Oct 29;148(4). Epub 2021 Jul 29.

Divisions of Pediatric Cardiology.

Background And Objectives: Myocardial dysfunction and coronary abnormalities are prominent features of multisystem inflammatory syndrome in children (MIS-C). In this study we aim to evaluate the early and midterm outcomes of MIS-C.

Methods: This is a longitudinal 6-month cohort study of all children admitted and treated for MIS-C from April 17 to June 20, 2020. Patients were followed ∼2 weeks, 8 weeks, and 6 months postadmission, with those with coronary aneurysms evaluated more frequently.

Results: Acutely, 31 (62%) patients required intensive care with vasoactive support, 26 (52%) had left ventricular (LV) systolic dysfunction, 16 (32%) had LV diastolic dysfunction, 8 (16%) had coronary aneurysms score ≥2.5), and 4 (8%) had coronary dilation score <2.5). A total of 48 patients (96%) received immunomodulatory treatment. At 2 weeks, there was persistent mild LV systolic dysfunction in 1 patient, coronary aneurysms in 2, and dilated coronary artery in 1. By 8 weeks through 6 months, all patients returned to functional baseline with normal LV systolic function and resolution of coronary abnormalities. Cardiac MRI performed during recovery in select patients revealed no myocardial edema or fibrosis. Some patients demonstrated persistent diastolic dysfunction at 2 weeks (5, 11%), 8 weeks (4, 9%), and 6 months (1, 4%).

Conclusions: Children with MIS-C treated with immunomodulators have favorable early outcomes with no mortality, normalization of LV systolic function, recovery of coronary abnormalities, and no inflammation or scarring on cardiac MRI. Persistence of diastolic dysfunction is of uncertain significance and indicates need for larger studies to improve understanding of MIS-C. These findings may help guide clinical management, outpatient monitoring, and considerations for sports clearance.
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http://dx.doi.org/10.1542/peds.2021-050973DOI Listing
October 2021

Multisystem inflammatory syndrome in children (MIS-C) and the prothrombotic state: Coagulation profiles and rotational thromboelastometry in a MIS-C cohort.

J Thromb Haemost 2021 07 4;19(7):1764-1770. Epub 2021 Jun 4.

Division of Pediatric Hematology/Oncology and Cellular Therapy, Cohen Children's Medical Center, New Hyde Park, NY, USA.

Background: Adults infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have had high rates of thrombosis. A novel condition in children infected with SARS-CoV-2, multisystem inflammatory syndrome in children (MIS-C), has limited data on their prothrombotic state or need for thromboprophylaxis.

Objectives: We aimed to analyze the prothrombotic state using coagulation profiles, rotational thromboelastometry (ROTEM) parameters and clinical outcomes, to determine if this could aid in risk stratification for thromboprophylaxis.

Methods: This analysis included patients (<21 years of age) with a diagnosis of MIS-C (n = 40) and controls (presenting with suspicion of MIS-C but later ruled out; n = 26).

Results: MIS-C patients had higher levels of inflammatory markers including D-dimer (p < .0001), compared with controls, along with evidence of hypercoagulability on ROTEM with elevated evaluation of fibrinogen activity (FIBTEM) maximum clot firmness (MCF) (p < .05). For MIS-C patients with D-dimers >1000 ng/ml, there was a significant correlation of FIBTEM MCF (p < .0001) with a mean value of 37.4 (standard deviation 5.1). D-dimer >2144 ng/ml was predictive of intensive care unit admission (area under the curve [AUC] 0.80; 95% confidence interval, 0.60-0.99; p < .01; sensitivity: 82%, specificity: 75%), and elevated FIBTEM MCF (AUC 1 for >2500 ng/ml). MIS-C patients (50%) received enoxaparin thromboprophylaxis (in addition to aspirin) with significant improvement in their inflammatory and ROTEM parameters upon outpatient follow-up; none developed symptomatic thrombosis.

Conclusions: Despite an observed prothrombotic state, none of the MIS-C patients (on aspirin alone or in combination with enoxaparin) developed symptomatic thrombosis. ROTEM, in addition to coagulation profiles, may be helpful to tailor thromboprophylaxis in critically ill MIS-C patients.
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http://dx.doi.org/10.1111/jth.15340DOI Listing
July 2021

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel for the prevention of heartworm disease in cats.

Parasite 2021 2;28:30. Epub 2021 Apr 2.

College of Veterinary Medicine, Cornell University, Ithaca, 14850 NY, USA.

NexGard Combo is a novel topical endectoparasiticide formulation for cats combining the insecticide/acaricide esafoxolaner, the nematodicide eprinomectin and the cestodicide praziquantel. The efficacy of this novel formulation for the prevention of heartworm disease in cats was tested in two experimental studies using an induced infection model and a randomized, blinded, placebo-controlled study design, and two USA isolates of Dirofilaria immitis. In each study, 20 naïve cats were each inoculated sub-cutaneously with 100 third-stage larvae of D. immitis 30 days before treatment. Following randomization to two treatment groups of ten cats, each cat was treated topically once, either with the minimum recommended dose of the novel formulation, or with an identical volume of placebo. Five months after treatment (6 months after infections), the cats were humanely euthanized for parasite recovery and count. Efficacy was calculated by comparison of the numbers of adult D. immitis recovered in the control and in the novel formulation groups. In the control groups of each study, D. immitis were recovered in seven and nine cats (respective worm counts ranges 1-7 and 1-16, respective geometric means 1.6 and 5.1). In both studies, none of the treated cats harbored any D. immitis at necropsy and the calculated efficacy of the novel formulation was 100%. There were no adverse reactions related to treatment with the novel formulation. The results of these two studies demonstrate that a topical NexGard Combo application at the minimum label dose is well-tolerated and efficacious in preventing heartworm disease in cats.
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http://dx.doi.org/10.1051/parasite/2021026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019556PMC
April 2021

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel in cats against Toxocara cati and Dipylidium caninum.

Parasite 2021 2;28:28. Epub 2021 Apr 2.

Boehringer-Ingelheim Animal Health, 3239 Satellite Blvd, Duluth, GA 30096, USA.

NexGard Combo, a novel topical antiparasitic product for cats, combines the insecticide/acaricide esafoxolaner with the nematocide eprinomectin and cestodicide praziquantel. The efficacy of this combination product was evaluated against two common endoparasites of global occurrence in cats, the nematode Toxocara cati and the cestode Dipylidium caninum, in five controlled studies using naturally or experimentally infected cats with parasites of North American, South African or European origin. Cats evaluated in these studies harbored patent infection of the target parasite confirmed through a pre-treatment fecal examination. In each study, cats were allocated randomly to two groups of equal size (8 or 10 cats per group per study), one group treated with a placebo (mineral oil) and the other with NexGard Combo. Both treatments were administered once as a spot-on at 0.12 mL per kg body weight to deliver the minimum label dosage (1.44 mg/kg esafoxolaner, 0.48 mg/kg eprinomectin, and 10.0 mg/kg praziquantel) to the NexGard Combo-treated cats. To determine efficacy, geometric mean parasite counts seven to 12 days after treatment of placebo-treated (control) cats and NexGard Combo-treated cats were compared. The efficacy of NexGard Combo was 98.8% and 100% against adult T. cati in two studies; and 98.0%, 98.3% and 93.2% against D. caninum in three studies. No adverse events related to treatment were observed throughout the studies. These studies demonstrate high efficacy against these major feline endoparasites and excellent acceptability of the novel topical antiparasitic combination of esafoxolaner, eprinomectin and praziquantel.
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http://dx.doi.org/10.1051/parasite/2021024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019557PMC
April 2021

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against Ixodes ricinus and Ixodes scapularis in cats.

Parasite 2021 2;28:23. Epub 2021 Apr 2.

Boehringer-Ingelheim Animal Health, 29 Avenue Tony Garnier, 69007 Lyon, France.

Esafoxolaner is a purified enantiomer of afoxolaner with insecticidal and acaricidal properties. It is combined with eprinomectin and praziquantel in a novel topical endectoparasiticide formulation for cats. The efficacy of this novel formulation was evaluated in three Ixodes ricinus and two Ixodes scapularis experimental studies, with comparable designs. In each study, cats were randomly allocated, based on a pre-treatment tick infestation and count, to a placebo control group or a group treated with the minimum recommended dose of the novel formulation. Cats were infested two days before treatment and weekly thereafter. Immediate efficacy was evaluated 48 h after treatment; persistent efficacy was evaluated 48 h after new weekly infestations for at least one month after the treatment (in one of the studies, the first two weeks of persistent efficacy against I. ricinus were not tested). Efficacy was calculated at each timepoint by comparison of arithmetic means of live ticks found in the control and the treated groups. In the three studies targeting I. ricinus, immediate and persistent efficacies ranged between 91% and 100% for five weeks. In the two studies targeting I. scapularis, immediate and persistent efficacies ranged between 95% and 100%, and 98% and 100% for one month, respectively. These studies provide robust evidence of efficacy of the novel topical formulation of esafoxolaner, eprinomectin and praziquantel against experimental I. ricinus and I. scapularis infestations for at least one month in cats.
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http://dx.doi.org/10.1051/parasite/2021019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019549PMC
April 2021

Acute kidney injury in pediatric patients hospitalized with acute COVID-19 and multisystem inflammatory syndrome in children associated with COVID-19.

Kidney Int 2021 07 3;100(1):138-145. Epub 2021 Mar 3.

Division of Pediatric Nephrology, Department of Pediatrics, Cohen Children's Medical Center, New Hyde Park, New York, USA.

This study describes the incidence, associated clinical characteristics and outcomes of acute kidney injury in a pediatric cohort with COVID-19 and Multisystem Inflammatory Syndrome in Children (MIS-C). We performed a retrospective study of patients 18 years of age and under admitted to four New York hospitals in the Northwell Health System interned during the height of the COVID-19 pandemic, between March 9 and August 13, 2020. Acute kidney injury was defined and staged according to Kidney Disease: Improving Global Outcomes criteria. The cohort included 152 patients; 97 acute-COVID-19 and 55 with MIS-C associated with COVID-19. Acute kidney injury occurred in 8 with acute-COVID-19 and in 10 with MIS-C. Acute kidney injury, in unadjusted models, was associated with a lower serum albumin level (odds ratio 0.17; 95% confidence interval 0.07, 0.39) and higher white blood cell counts (odds ratio 1.11; 95% confidence interval 1.04, 1.2). Patients with MIS-C and acute kidney injury had significantly greater rates of systolic dysfunction, compared to those without (80% vs 49%). In unadjusted models, patients with acute kidney injury had 8.4 days longer hospitalizations compared to patients without acute kidney injury (95% confidence interval, 4.4-6.7). Acute kidney injury in acute-COVID-19 and MIS-C may be related to inflammation and/or dehydration. Further research in larger pediatric cohorts is needed to better characterize risk factors for acute kidney injury in acute-COVID-19 and with MIS-C consequent to COVID-19.
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http://dx.doi.org/10.1016/j.kint.2021.02.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927648PMC
July 2021

Racial and Ethnic Disparities in the Prevalence of Stress and Worry, Mental Health Conditions, and Increased Substance Use Among Adults During the COVID-19 Pandemic - United States, April and May 2020.

MMWR Morb Mortal Wkly Rep 2021 Feb 5;70(5):162-166. Epub 2021 Feb 5.

In 2019, approximately 51 million U.S. adults aged ≥18 years reported any mental illness,* and 7.7% reported a past-year substance use disorder (1). Although reported prevalence estimates of certain mental disorders, substance use, or substance use disorders are not generally higher among racial and ethnic minority groups, persons in these groups are often less likely to receive treatment services (1). Persistent systemic social inequities and discrimination related to living conditions and work environments, which contribute to disparities in underlying medical conditions, can further compound health problems faced by members of racial and ethnic minority groups during the coronavirus disease 2019 (COVID-19) pandemic and worsen stress and associated mental health concerns (2,3). In April and May 2020, opt-in Internet panel surveys of English-speaking U.S. adults aged ≥18 years were conducted to assess the prevalence of self-reported mental health conditions and initiation of or increases in substance use to cope with stress, psychosocial stressors, and social determinants of health. Combined prevalence estimates of current depression, initiating or increasing substance use, and suicidal thoughts/ideation were 28.6%, 18.2%, and 8.4%, respectively. Hispanic/Latino (Hispanic) adults reported a higher prevalence of psychosocial stress related to not having enough food or stable housing than did adults in other racial and ethnic groups. These estimates highlight the importance of population-level and tailored interventions for mental health promotion and mental illness prevention, substance use prevention, screening and treatment services, and increased provision of resources to address social determinants of health. How Right Now (Qué Hacer Ahora) is an evidence-based and culturally appropriate communications campaign designed to promote and strengthen the emotional well-being and resiliency of populations adversely affected by COVID-19-related stress, grief, and loss (4).
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http://dx.doi.org/10.15585/mmwr.mm7005a3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861483PMC
February 2021

A Systematic Review of Surface Contamination, Stability, and Disinfection Data on SARS-CoV-2 (Through July 10, 2020).

Environ Sci Technol 2021 04 23;55(7):4162-4173. Epub 2020 Nov 23.

Tufts University School of Engineering, Medford, Massachusetts, 02155, United States.

We conducted a systematic review of hygiene intervention effectiveness against SARS-CoV-2, including developing inclusion criteria, conducting the search, selecting articles for inclusion, and summarizing included articles. Overall, 96 268 articles were screened and 78 articles met inclusion criteria with outcomes in surface contamination, stability, and disinfection. Surface contamination was assessed on 3343 surfaces using presence/absence methods. Laboratories had the highest percent positive surfaces (21%, = 83), followed by patient-room healthcare facility surfaces (17%, = 1170), non-COVID-patient-room healthcare facility surfaces (12%, = 1429), and household surfaces (3%, = 161). Surface stability was assessed using infectivity, SARS-CoV-2 survived on stainless steel, plastic, and nitrile for half-life 2.3-17.9 h. Half-life decreased with temperature and humidity increases, and was unvaried by surface type. Ten surface disinfection tests with SARS-CoV-2, and 15 tests with surrogates, indicated sunlight, ultraviolet light, ethanol, hydrogen peroxide, and hypochlorite attain 99.9% reduction. Overall there was (1) an inability to align SARS-CoV-2 contaminated surfaces with survivability data and effective surface disinfection methods for these surfaces; (2) a knowledge gap on fomite contribution to SARS-COV-2 transmission; (3) a need for testing method standardization to ensure data comparability; and (4) a need for research on hygiene interventions besides surfaces, particularly handwashing, to continue developing recommendations for interrupting SARS-CoV-2 transmission.
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http://dx.doi.org/10.1021/acs.est.0c05651DOI Listing
April 2021

NT-proBNP levels and cardiopulmonary function in children with sickle cell disease.

Pediatr Pulmonol 2021 02 3;56(2):495-501. Epub 2020 Dec 3.

Department of Pediatric Pulmonary Medicine and Cystic Fibrosis, Department of Pediatrics, Cohen Children's Medical Center, New Hyde Park, New York, USA.

Patients with sickle cell disease (SCD) are living longer and subsequently more apt to develop cardiopulmonary dysfunction. N-terminal pro-brain natriuretic peptide (NT-proBNP) levels have been used in adults with SCD to assess for pulmonary hypertension and mortality. While the incidence of PH is low in pediatrics, it is reasonable to presume that NT-proBNP levels can be used to assess risk for the development of cardiopulmonary morbidity. We hypothesized that NT-proBNP levels would be increased in patients with SCD compared to age-adjusted healthy children; additionally, these levels would be associated with labs indicative of hemolysis and would demonstrate evidence of obstructive lung disease and cardiac dysfunction. We retrospectively evaluated patients with SCD, 8-18 years old, at a large, tertiary care children's hospital. NT-proBNP levels were assessed in correlation with hemolytic lab work, spirometry, and echocardiographic data. The age group 8-14 years old, 75% of our cohort's population, had a median NT-proBNP of 70 pg/ml, greater than their age-adjusted counterparts (52 pg/ml). NT-proBNP levels were associated with an increased degree of hemolysis when compared with hemoglobin (Hb) (r = -0.43, p < .0001), reticulocyte count (r = .25, p = .01) and lactate dehydrogenase levels (r = .47, p < .0001). An inverse trend was found between NT-proBNP and spirometric data. Finally, a positive correlation was found between NT-proBNP and diastolic left ventricular size (r = .28, p = .047]. The correlations found suggest that NT-proBNP may be used prospectively to identify patients with SCD at increased risk for the development of cardiopulmonary dysfunction.
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http://dx.doi.org/10.1002/ppul.25155DOI Listing
February 2021

Toxoplasma gondii seropositivity and serointensity and cognitive function in adults.

PLoS Negl Trop Dis 2020 10 15;14(10):e0008733. Epub 2020 Oct 15.

Department of Psychology, Brigham Young University, Provo, Utah.

Infecting approximately one-third of the world's human population, Toxoplasma gondii has been associated with cognitive function. Here, we sought to further characterize the association between Toxoplasma gondii and cognitive function in a community sample of adults aged approximately 40 to70 years. Using adjusted linear regression models, we found associations of Toxoplasma gondii seropositivity with worse reasoning (b = -.192, p < .05) and matrix pattern completion (b = -.681, p < .01), of higher anti-Toxoplasma gondii p22 antibody levels with worse reasoning (b = -.078, p < .01) and slower Trails (numeric) performance (b = 5.962, p < .05), of higher anti-Toxoplasma gondii sag1 levels with worse reasoning (b = -.081, p < .05) and worse matrix pattern completion (b = -.217, p < .05), and of higher mean of the anti-Toxoplasma gondii p22 and sag1 levels with worse reasoning (b = -.112, p < .05), slower Trails (numeric) performance (b = 9.195, p < .05), and worse matrix pattern completion (b = -.245, p < .05). Neither age nor educational attainment moderated associations between the measures of Toxoplasma gondii seropositivity or serointensity. Sex, however, moderated the association between the sag1 titer and digit-symbol substitution and the association between the mean of the p22 and sag1 levels and digit-symbol substitution, and income moderated the association between Toxoplasma gondii seropositivity and numeric memory and the association between the p22 level and symbol-digit substitution. Based on the available neuropsychological tasks in this study, Toxoplasma gondii seropositivity and serointensity were associated with some aspects of poorer executive function in adults.
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http://dx.doi.org/10.1371/journal.pntd.0008733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561134PMC
October 2020

Cardiac Dysfunction and Shock in Pediatric Patients With COVID-19.

JACC Case Rep 2020 Jul 18;2(9):1267-1270. Epub 2020 Jun 18.

Department of Pediatric Critical Care Medicine, Cohen Children's Medical Center, Zucker School of Medicine, Hofstra University, New Hyde Park, New York.

Coronavirus disease-2019 (COVID-19) has been reported to cause significant morbidity in adults, with reportedly a lesser impact on children. Cardiac dysfunction has only been described in adults thus far. We describe 3 cases of previously healthy children presenting with shock and COVID-19-related cardiac inflammation. ().
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http://dx.doi.org/10.1016/j.jaccas.2020.05.082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301074PMC
July 2020

Hemispheric asymmetry of the dayside aurora due to imbalanced solar insolation.

Sci Rep 2020 Aug 10;10(1):13451. Epub 2020 Aug 10.

The Johns Hopkins University Applied Physics Laboratory, Space Exploration Sector, 11100 Johns Hopkins Road, Laurel, MD, 20723, USA.

Unlike the nightside aurora, which is controlled mainly by magnetic field reconnection in the magnetotail, the dayside aurora is closely associated with magnetic field merging at the dayside magnetopause. About two decades ago, it was discovered that the aurora is also controlled by solar insolation. Because the finding was based on data acquired mainly in the Northern Hemisphere, an outstanding question is if the auroral solar insolation effect also exists in the Southern Hemisphere. The present study addresses this question by studying dayside auroras from both hemispheres. We analyze 6 years' worth of Earth disk emissions at far ultraviolet wavelengths acquired by the Global UltraViolet Imager on-board the Thermosphere Ionosphere Mesosphere Energetics and Dynamics satellite from 2002 to 2007. It is found that the solar insolation effect also exists in the Southern Hemisphere. In essence, the energy flux deposited as electron precipitation, is larger when the polar hemisphere is sunlit and is smaller when the polar hemisphere is dark. Because auroras are produced mainly by electron precipitation and because electrons are the main current carrier, this north-south asymmetry is consistent with the previous finding that larger (smaller) field-aligned currents are flowing out of the sunlit (dark) hemisphere. This trend is independent of the solar wind driving, suggesting that it is an effect associated with solar insolation. A small north-south asymmetry in the dayside auroral energy flux was identified. We discuss the asymmetry in the context of magnetospheric current and voltage generators.
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http://dx.doi.org/10.1038/s41598-020-70018-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418003PMC
August 2020

Incidence of arrhythmias and electrocardiographic abnormalities in symptomatic pediatric patients with PCR-positive SARS-CoV-2 infection, including drug-induced changes in the corrected QT interval.

Heart Rhythm 2020 11 1;17(11):1960-1966. Epub 2020 Jul 1.

Section of Pediatric Cardiology and; Department of Pediatrics, Cohen Children's Medical Center, Northwell Health System, Donald and Barbara Zucker School of Medicine at Hofstra University, New Hyde Park, New York.

Background: There is limited data regarding the electrophysiological abnormalities and arrhythmias in children with COVID-19, including those associated with treatment using potentially proarrhythmic hydroxychloroquine (HCQ) and azithromycin (AZN).

Objectives: To describe the electrophysiologic findings and arrhythmias associated with pediatric COVID-19 and its treatment.

Methods: A single-center retrospective chart review was undertaken and included all patients with (1) symptoms of COVID-19 and (2) PCR-positive nasopharyngeal swabs for SARS-CoV-2 who were placed on continuous telemetry for the duration of their hospitalization during March through May, 2020.

Results: Thirty-six patients were included in the study. Significant arrhythmias were found in 6 (nonsustained ventricular tachycardia in 5 and sustained atrial tachycardia in 1). All were self-resolving and half prompted prophylactic antiarrhythmic therapy. Patients with significant arrhythmias were likely to have noncardiac comorbidities (4/6), but these were not more common than in patients without arrhythmias (20/30, P = 1). The use of HCQ was associated with statistically significant QTc prolongation (413 ± 19 ms vs 425 ± 16 ms, P =.005). QTc was not statistically different in patients with and without arrhythmias (425 ± 15 ms vs 425 ± 15 ms, P = 1).

Conclusions: In pediatric patients with PCR-positive active COVID-19 infection, significant arrhythmias are infrequent, but are more common than expected in a general pediatric population. Comorbidities are not more common in patients with arrhythmias than in patients without arrhythmias. COVID-19 treatment using HCQ is associated with QTc prolongation but was not associated with arrhythmias in pediatric patients.
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http://dx.doi.org/10.1016/j.hrthm.2020.06.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328618PMC
November 2020

Characteristics, Cardiac Involvement, and Outcomes of Multisystem Inflammatory Syndrome of Childhood Associated with severe acute respiratory syndrome coronavirus 2 Infection.

J Pediatr 2020 09 14;224:141-145. Epub 2020 Jun 14.

Department of Pediatrics, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Hempstead, NY; Institute of Health Innovations and Outcomes Research, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY.

We report on the presentation and course of 33 children with multisystem inflammatory syndrome in children and confirmed severe acute respiratory syndrome coronavirus 2 infection. Hemodynamic instability and cardiac dysfunction were prominent findings, with most patients exhibiting rapid resolution following anti-inflammatory therapy.
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http://dx.doi.org/10.1016/j.jpeds.2020.06.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293762PMC
September 2020

Comparison of the Bacterial Gut Microbiome of North American spp. With and Without .

Front Microbiol 2020 13;11:364. Epub 2020 Mar 13.

Tick-Borne Disease Research Laboratory, Department of Microbiology, Immunology, and Genetics, University of North Texas Health Science Center, Fort Worth, TX, United States.

Chagas disease, caused by the hemoflagellate protist , affects nearly 6 million people worldwide, mainly in Latin America. Hematophagous triatomine insects ("kissing bugs") are the primary vectors of throughout the Americas and feed on a variety of animals, including humans. Control of triatomines is central to the control of infection. Recent advances in mitigation of other insect-borne diseases via the manipulation of insect-associated bacteria as a way to halt or slow disease transmission has opened questions to the applicability of these methods to Chagas disease vectors. Few studies have examined the hindgut microbiome of triatomines found in North America. In the current study, two species of triatomines were collected across Texas, United States, screened for the presence of , and analyzed for the bacterial composition of their hindguts using a 16S rRNA gene-fragment metabarcoding approach. We compared diversity of microbial community profiles across 74 triatomine insects to address the hypothesis that the richness and abundance of bacterial groups differ by infection and strain type, blood meal engorgement status, insect species, sex, and collection location. The gut microbial community of individual triatomines was characterized by low intraindividual taxonomic diversity and high interindividual variation that was weakly predicted by triatomine species, and was not predicted by triatomine sex, collection location, infection status, or blood meal score. However, we did find bacterial groups enriched in -positive individuals, including Enterobacterales, and . Additionally, we detected subspecies in three triatomine individuals; this species is commonly associated with reptiles and domesticated animals and is a pathogen of humans. These data suggest that spp. in Texas have variable patterns of colonized and transient bacteria, and may aid in development of novel means to interfere with transmission of the Chagas disease parasite . Deeper understanding of the effects of parasite infection on diverse insect vector microbiomes may highlight disease transmission risk and facilitate discovery of possible intervention strategies for biological control of this emerging vector-borne disease of global health significance.
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http://dx.doi.org/10.3389/fmicb.2020.00364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082358PMC
March 2020

Facilitating Growth through Frustration: Using Genomics Research in a Course-Based Undergraduate Research Experience.

J Microbiol Biol Educ 2020 28;21(1). Epub 2020 Feb 28.

Biology, University of San Diego, San Diego, CA 92110, USA.

A hallmark of the research experience is encountering difficulty and working through those challenges to achieve success. This ability is essential to being a successful scientist, but replicating such challenges in a teaching setting can be difficult. The Genomics Education Partnership (GEP) is a consortium of faculty who engage their students in a genomics Course-Based Undergraduate Research Experience (CURE). Students participate in genome annotation, generating gene models using multiple lines of experimental evidence. Our observations suggested that the students' learning experience is continuous and recursive, frequently beginning with frustration but eventually leading to success as they come up with defendable gene models. In order to explore our "formative frustration" hypothesis, we gathered data from faculty via a survey, and from students via both a general survey and a set of student focus groups. Upon analyzing these data, we found that all three datasets mentioned frustration and struggle, as well as learning and better understanding of the scientific process. Bioinformatics projects are particularly well suited to the process of iteration and refinement because iterations can be performed quickly and are inexpensive in both time and money. Based on these findings, we suggest that a dynamic of "formative frustration" is an important aspect for a successful CURE.
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http://dx.doi.org/10.1128/jmbe.v21i1.2005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048401PMC
February 2020

Loss of myoepithelial calponin-1 characterizes high-risk ductal carcinoma in situ cases, which are further stratified by T cell composition.

Mol Carcinog 2020 07 5;59(7):701-712. Epub 2020 Mar 5.

Department of Cell, Developmental, and Cancer Biology, Oregon Health and Science University, Portland, Oregon.

A hallmark of ductal carcinoma in situ (DCIS) progression is a loss of the surrounding ductal myoepithelium. However, whether compromise in myoepithelial differentiation, rather than overt cellular loss, can be used to predict the risk of DCIS progression is unknown. Here we address this question utilizing pure and mixed DCIS cases (N = 30) as surrogates for DCIS at low and high risk for progression, respectively. We used multiplex immunohistochemical staining to evaluate the relationship between myoepithelial cell differentiation and lymphoid immune cell types associated with poor prognostic DCIS. Our results show that myoepithelial calponin-1 discriminates between pure and mixed DCIS lesions better than histological subtype, presence of necrosis, or nuclear grade. Additionally, focal loss of myoepithelial cells associated with increased PD-1+CD8+ T cells, which suggests a link between the myoepithelium and immune surveillance. To identify associations between calponin-1 expression and immune response, we performed unsupervised hierarchical clustering of myoepithelial and immune cell biomarkers on 219 DCIS lesions from 30 cases. Notably, the majority of pure (low-risk) DCIS lesions clustered in a high calponin-1, T cell low group, whereas the majority of mixed (high-risk) DCIS lesions clustered in a low calponin-1, T cell high group, specifically with CD8+ and PD-1+CD8+ T cells. However, a subset of pure DCIS lesions had a similar calponin-1 and immune signature as the majority of mixed DCIS lesions, which have low calponin-1 and T cell enrichment-raising the possibility that these pure DCIS lesions might be at a high risk for progression.
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http://dx.doi.org/10.1002/mc.23171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317523PMC
July 2020

Exposure Risk Events in 10 Clinical Laboratories, New York City, USA, 2015 to 2017.

J Clin Microbiol 2020 01 28;58(2). Epub 2020 Jan 28.

Occupational Health Services, Montefiore Medical Center, Bronx, New York, USA.

From 2015 to 2017, 11 confirmed brucellosis cases were reported in New York City, leading to 10 exposure risk events ( events) in 7 clinical laboratories (CLs). Most patients had traveled to countries where brucellosis is endemic and presented with histories and findings consistent with brucellosis. CLs were not notified that specimens might yield a hazardous organism, as the clinicians did not consider brucellosis until they were notified that bacteremia with was suspected. In 3 events, the CLs did not suspect that slow-growing, small Gram-negative bacteria might be harmful. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), which has a limited capacity to identify biological threat agents (BTAs), was used during 4 events, which accounted for 84% of exposures. In 3 of these incidents, initial staining of liquid media showed Gram-positive rods or cocci, including some cocci in chains, suggesting streptococci. Over 200 occupational exposures occurred when the unknown isolates were manipulated and/or tested on open benches, including by procedures that could generate infectious aerosols. During 3 events, the CLs examined and/or manipulated isolates in a biological safety cabinet (BSC); in each CL, the CL had previously isolated Centers for Disease Control and Prevention recommendations to prevent laboratory-acquired brucellosis (LAB) were followed; no seroconversions or LAB cases occurred. Laboratory assessments were conducted after the events to identify facility-specific risks and mitigations. With increasing MALDI-TOF MS use, CLs are well-advised to adhere strictly to safe work practices, such as handling and manipulating all slow-growing organisms in BSCs and not using MALDI-TOF MS for identification until BTAs have been ruled out.
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http://dx.doi.org/10.1128/JCM.01096-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989065PMC
January 2020

Developing and Testing the Detén El Zika Campaign in Puerto Rico.

J Health Commun 2019 31;24(12):900-911. Epub 2019 Oct 31.

Center for Communication Science, RTI International, Rockville, MD, USA.

Responding to an emerging health threat often requires rapid deployment of behavior change communication. Health communication best practices include developing and testing draft messages and materials to ensure that they resonate with and inspire priority groups to act. However, when faced with an emergency health threat, the timeline for these activities can be compressed from months to weeks. This article discusses the rapid development and implementation of a Zika virus prevention campaign for pregnant women in Puerto Rico. The goal of the campaign was to increase knowledge among and motivate pregnant women, their partners and family members, and the community to follow Zika virus prevention recommendations. The steps in campaign development include environmental scanning, concept development and testing, and message testing to ensure development of campaign materials that resonated with and were well-received by key audience groups. The materials adhere to principles of behavior change communication, and offer our insights for development of future campaigns when under time constraints.
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http://dx.doi.org/10.1080/10810730.2019.1683655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747955PMC
September 2020

High risk (B3) breast lesions: What is the incidence of malignancy for individual lesion subtypes? A systematic review and meta-analysis.

Eur J Surg Oncol 2019 04 11;45(4):519-527. Epub 2018 Dec 11.

Hull York Medical School, Institute of Clinical and Applied Health Research, The Allam Medical Building, University of Hull, Hull, HU6 7RX, UK.

Introduction: Provide evidence to support evolving management strategies for high-risk (B3) breast lesions by assessing risk of carcinoma in subgroups of B3 lesions using systematic review and meta-analysis.

Methods: Databases identified observational studies between 1980 and 2015 that reported on underestimation of malignancy following B3 lesion diagnosis at core needle biopsy. Critical appraisal, quality assessment, data extraction and meta-analysis was undertaken to calculate rate of malignancy of the whole B3 group and individual lesions. Study heterogeneity and association between variables and underestimation rate was investigated using random effects logistic modelling.

Results: Meta-analysis, using data from 129 studies, assessed 11 423 lesions of which 2160 were upgraded to malignancy after surgical excision biopsy (17% malignancy rate, 95% CI 15-19%). Malignancy rates varied from 6% in radial scars with no atypia (95% CI 2-13%, I2 72.8%), to 32% in papillomas with atypia (95% CI 23-41%, I2 57.4%). Differences in upgrade rates between atypical and non-atypical lesions were statistically significant (p < 0.05). Study heterogeneity could not be explained by differences in core biopsy size or year of publication.

Conclusions: This comprehensive, inclusive assessment of all published literature, provides an accurate estimate of malignancy risk in subgroups of B3 lesions, to guide tailored management strategies. Some lesions have a high risk of malignancy, while others have a much lower risk, and could be safely managed with surveillance strategies rather than surgery.
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http://dx.doi.org/10.1016/j.ejso.2018.12.008DOI Listing
April 2019

North-South Asymmetry in the Geographic Location of Auroral Substorms correlated with Ionospheric Effects.

Sci Rep 2018 Nov 22;8(1):17230. Epub 2018 Nov 22.

The Johns Hopkins University Applied Physics Laboratory, Laurel, Maryland, 20723, USA.

Energetic particles of magnetospheric origin constantly strike the Earth's upper atmosphere in the polar regions, producing optical emissions known as the aurora. The most spectacular auroral displays are associated with recurrent events called magnetospheric substorms (aka auroral substorms). Substorms are initiated in the nightside magnetosphere on closed magnetic field lines. As a consequence, it is generally thought that auroral substorms should occur in both hemispheres on the same field line (i.e., magnetically conjugated). However, such a hypothesis has not been verified statistically. Here, by analyzing 2659 auroral substorms acquired by the Ultraviolet Imager on board the NASA satellite "Polar", we have discovered surprising evidence that the averaged location for substorm onsets is not conjugate but shows a geographic preference that cannot be easily explained by current substorm theories. In the Northern Hemisphere (NH) the auroral substorms occur most frequently in Churchill, Canada (~90°W) and Khatanga, Siberia (~100°E), up to three times as often as in Iceland (~22°W). In the Southern Hemisphere (SH), substorms occur more frequently over a location in the Antarctic ocean (~120°E), up to ~4 times more than over the Antarctic Continent. Such a large difference in the longitudinal distribution of north and south onset defies the common belief that substorms in the NH and SH should be magnetically conjugated. A further analysis indicates that these substorm events occurred more frequently when more of the ionosphere was dark. These geographic areas also coincide with regions where the Earth's magnetic field is largest. These facts suggest that auroral substorms occur more frequently, and perhaps more intensely, when the ionospheric conductivity is lower. With much of the magnetotail energy coming from the solar wind through merging of the interplanetary and Earth's magnetic field, it is generally thought that the occurrence of substorms is externally controlled by the solar wind and plasma instability in the magnetotail. The present study results provide a strong argument that the ionosphere plays a more active role in the occurrence of substorms.
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http://dx.doi.org/10.1038/s41598-018-35091-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6250675PMC
November 2018

A METHOD FOR QUANTIFICATION OF CALPONIN EXPRESSION IN MYOEPITHELIAL CELLS IN IMMUNOHISTOCHEMICAL IMAGES OF DUCTAL CARCINOMA IN SITU.

Proc IEEE Int Symp Biomed Imaging 2018 Apr 24;2018:796-799. Epub 2018 May 24.

Department of Biomedical Engineering and Computational Biology Program.

Ductal carcinoma in situ (DCIS) is breast cancer confined within mammary ducts, surrounded by an intact myoepithelial cell layer that prevents local invasion. A DCIS diagnosis confers increased lifetime risk of developing invasive breast cancer (IBC) and results in surgical excision with radiation, and possibly endocrine- or chemo-therapy. DCIS is known to be over treated, with associated co-morbidities. Biomarkers are needed that delineate patients at low risk of DCIS progression from patients requiring more aggressive treatment. Investigating the role of myoepithelial cell differentiation in barrier function is anticipated to provide insight into DCIS progression and delineate between low and high risk lesions. Here, we develop a high throughput technique to assess loss of myoepithelial differentiation markers. This method facilitates automated analysis of a clinically relevant histopathologic feature, as demonstrated by a high correlation with pathologist annotation (r = 0.959), and further, contributes analytical foundations to a multiplexed immunohistochemistry (IHC) approach.
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http://dx.doi.org/10.1109/ISBI.2018.8363692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196724PMC
April 2018

Examining the Utility of Coronary Artery Lack of Tapering and Perivascular Brightness in Incomplete Kawasaki Disease.

Pediatr Cardiol 2019 Jan 8;40(1):147-153. Epub 2018 Sep 8.

Division of Pediatric Cardiology, Cohen Children's Medical Center of New York - Hofstra Northwell School of Medicine, 269-01 76th Ave, New Hyde Park, NY, 11040, USA.

Background: In 2017, the AHA published revised guidelines for the diagnosis of Kawasaki disease (KD). In the absence of compelling data supporting or refuting the utility of lack of tapering (LT) and perivascular brightness (PB), expert panel consensus removed LT and PB from consideration. We hypothesize that LT and PB are unreliable, subjective findings, non-specific to KD, which can be seen in systemic febrile illnesses without KD and in normal controls.

Methods: We performed a single-center retrospective study from 1/2008 to 12/2016. De-identified coronary artery (CA) echocardiographic clips from patients 0-10 years old were interpreted blindly by six pediatric cardiologists. Subjects were grouped as follows: (1) healthy: afebrile with benign murmur, (2) KD: IVIG treatment, 4-5 clinical criteria at presentation, (3) incomplete KD (iKD): IVIG, 1-3 clinical criteria, (4) Febrile: ≥3 days of fever, no IVIG, KD not suspected. The presence or absence of LT and PB was recorded. Inter-rater and intra-rater reliabilities were analyzed using intra-class correlation coefficient, Fleiss' Kappa and Cohen's Kappa coefficients.

Results: We interpreted 117 echocardiograms from healthy (27), KD (30), iKD (32), and febrile (28) subjects. Analysis showed moderate agreement in CA z score measurements. LT and PB were observed by most readers in control groups. LT exhibited fair inter-reader agreement (reliability coefficient 0.36) and PB slight inter-reader agreement (reliability coefficient 0.13). Intra-rater reliability was inconsistent for both parameters.

Conclusions: LT and PB are subjective, poorly reproducible features that can be seen in febrile patients without KD and in healthy children.
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http://dx.doi.org/10.1007/s00246-018-1971-zDOI Listing
January 2019

The future for diagnostic tests of acute kidney injury in critical care: evidence synthesis, care pathway analysis and research prioritisation.

Health Technol Assess 2018 05;22(32):1-274

Leeds Teaching Hospitals NHS Trust, Leeds, UK.

Background: Acute kidney injury (AKI) is highly prevalent in hospital inpatient populations, leading to significant mortality and morbidity, reduced quality of life and high short- and long-term health-care costs for the NHS. New diagnostic tests may offer an earlier diagnosis or improved care, but evidence of benefit to patients and of value to the NHS is required before national adoption.

Objectives: To evaluate the potential for AKI in vitro diagnostic tests to enhance the NHS care of patients admitted to the intensive care unit (ICU) and identify an efficient supporting research strategy.

Data Sources: We searched ClinicalTrials.gov, The Cochrane Library databases, Embase, Health Management Information Consortium, International Clinical Trials Registry Platform, MEDLINE, Register of Current Controlled Trials, PubMed and Web of Science databases from their inception dates until September 2014 (review 1), November 2015 (review 2) and July 2015 (economic model). Details of databases used for each review and coverage dates are listed in the main report.

Review Methods: The AKI-Diagnostics project included horizon scanning, systematic reviewing, meta-analysis of sensitivity and specificity, appraisal of analytical validity, care pathway analysis, model-based lifetime economic evaluation from a UK NHS perspective and value of information (VOI) analysis.

Results: The horizon-scanning search identified 152 potential tests and biomarkers. Three tests, Nephrocheck (Astute Medical, Inc., San Diego, CA, USA), NGAL and cystatin C, were subjected to detailed review. The meta-analysis was limited by variable reporting standards, study quality and heterogeneity, but sensitivity was between 0.54 and 0.92 and specificity was between 0.49 and 0.95 depending on the test. A bespoke critical appraisal framework demonstrated that analytical validity was also poorly reported in many instances. In the economic model the incremental cost-effectiveness ratios ranged from £11,476 to £19,324 per quality-adjusted life-year (QALY), with a probability of cost-effectiveness between 48% and 54% when tests were compared with current standard care.

Limitations: The major limitation in the evidence on tests was the heterogeneity between studies in the definitions of AKI and the timing of testing.

Conclusions: Diagnostic tests for AKI in the ICU offer the potential to improve patient care and add value to the NHS, but cost-effectiveness remains highly uncertain. Further research should focus on the mechanisms by which a new test might change current care processes in the ICU and the subsequent cost and QALY implications. The VOI analysis suggested that further observational research to better define the prevalence of AKI developing in the ICU would be worthwhile. A formal randomised controlled trial of biomarker use linked to a standardised AKI care pathway is necessary to provide definitive evidence on whether or not adoption of tests by the NHS would be of value.

Study Registration: The systematic review within this study is registered as PROSPERO CRD42014013919.

Funding: The National Institute for Health Research Health Technology Assessment programme.
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http://dx.doi.org/10.3310/hta22320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004543PMC
May 2018

Strategies to improve recruitment to randomised trials.

Cochrane Database Syst Rev 2018 02 22;2:MR000013. Epub 2018 Feb 22.

Health Services Research Unit, University of Aberdeen, Foresterhill, Aberdeen, UK, AB25 2ZD.

Background: Recruiting participants to trials can be extremely difficult. Identifying strategies that improve trial recruitment would benefit both trialists and health research.

Objectives: To quantify the effects of strategies for improving recruitment of participants to randomised trials. A secondary objective is to assess the evidence for the effect of the research setting (e.g. primary care versus secondary care) on recruitment.

Search Methods: We searched the Cochrane Methodology Review Group Specialised Register (CMR) in the Cochrane Library (July 2012, searched 11 February 2015); MEDLINE and MEDLINE In Process (OVID) (1946 to 10 February 2015); Embase (OVID) (1996 to 2015 Week 06); Science Citation Index & Social Science Citation Index (ISI) (2009 to 11 February 2015) and ERIC (EBSCO) (2009 to 11 February 2015).

Selection Criteria: Randomised and quasi-randomised trials of methods to increase recruitment to randomised trials. This includes non-healthcare studies and studies recruiting to hypothetical trials. We excluded studies aiming to increase response rates to questionnaires or trial retention and those evaluating incentives and disincentives for clinicians to recruit participants.

Data Collection And Analysis: We extracted data on: the method evaluated; country in which the study was carried out; nature of the population; nature of the study setting; nature of the study to be recruited into; randomisation or quasi-randomisation method; and numbers and proportions in each intervention group. We used a risk difference to estimate the absolute improvement and the 95% confidence interval (CI) to describe the effect in individual trials. We assessed heterogeneity between trial results. We used GRADE to judge the certainty we had in the evidence coming from each comparison.

Main Results: We identified 68 eligible trials (24 new to this update) with more than 74,000 participants. There were 63 studies involving interventions aimed directly at trial participants, while five evaluated interventions aimed at people recruiting participants. All studies were in health care.We found 72 comparisons, but just three are supported by high-certainty evidence according to GRADE.1. Open trials rather than blinded, placebo trials. The absolute improvement was 10% (95% CI 7% to 13%).2. Telephone reminders to people who do not respond to a postal invitation. The absolute improvement was 6% (95% CI 3% to 9%). This result applies to trials that have low underlying recruitment. We are less certain for trials that start out with moderately good recruitment (i.e. over 10%).3. Using a particular, bespoke, user-testing approach to develop participant information leaflets. This method involved spending a lot of time working with the target population for recruitment to decide on the content, format and appearance of the participant information leaflet. This made little or no difference to recruitment: absolute improvement was 1% (95% CI -1% to 3%).We had moderate-certainty evidence for eight other comparisons; our confidence was reduced for most of these because the results came from a single study. Three of the methods were changes to trial management, three were changes to how potential participants received information, one was aimed at recruiters, and the last was a test of financial incentives. All of these comparisons would benefit from other researchers replicating the evaluation. There were no evaluations in paediatric trials.We had much less confidence in the other 61 comparisons because the studies had design flaws, were single studies, had very uncertain results or were hypothetical (mock) trials rather than real ones.

Authors' Conclusions: The literature on interventions to improve recruitment to trials has plenty of variety but little depth. Only 3 of 72 comparisons are supported by high-certainty evidence according to GRADE: having an open trial and using telephone reminders to non-responders to postal interventions both increase recruitment; a specialised way of developing participant information leaflets had little or no effect. The methodology research community should improve the evidence base by replicating evaluations of existing strategies, rather than developing and testing new ones.
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http://dx.doi.org/10.1002/14651858.MR000013.pub6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078793PMC
February 2018

A qualitative study of patients' feedback about Outpatient Parenteral Antimicrobial Therapy (OPAT) services in Northern England: implications for service improvement.

BMJ Open 2018 01 10;8(1):e019099. Epub 2018 Jan 10.

Leeds Teaching Hospitals NHS Trust, Leeds, UK.

Objective: Outpatient parenteral antimicrobial therapy (OPAT) provides opportunities for improved cost savings, but in the UK, implementation is patchy and a variety of service models are in use. The slow uptake in the UK and Europe is due to a number of clinical, financial and logistical issues, including concern about patient safety. The measurement of patient experience data is commonly used to inform commissioning decisions, but these focus on functional aspects of services and fail to examine the relational aspects of care. This qualitative study examines patients' experiences of OPAT.

Design: In-depth, semistructured interviews.

Setting: Purposive sample of OPAT patients recruited from four acute National Health Service (NHS) Trusts in Northern England. These NHS Trusts between them represented both well-established and recently set-up services running nurse at home, hospital outpatient and/or self-administration models.

Participants: We undertook 28 semistructured interviews and one focus group (n=4).

Results: Despite good patient outcomes, experiences were coloured by patients' personal situation and material circumstances. Many found looking after themselves at home more difficult than they expected, while others continued to work despite their infection. Expensive car parking, late running services and the inconvenience of waiting in for the nurse to arrive frustrated patients, while efficient services, staffed by nurses with the specialist skills needed to manage intravenous treatment had the opposite effect. Many patients felt a local, general practitioner or community health centre based service would resolve many of the practical difficulties that made OPAT inconvenient. Patients could find OPAT anxiety provoking but this could be ameliorated by staff taking the time to reassure patients and provide tailored information.

Conclusion: Services configurations must accommodate the diversity of the local population. Poor communication can leave patients lacking the confidence needed to be a competent collaborator in their own care and affect their perceptions of the service.
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http://dx.doi.org/10.1136/bmjopen-2017-019099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5781150PMC
January 2018

Mechanical loading regulates organization of the actin cytoskeleton and column formation in postnatal growth plate.

Mol Biol Cell 2017 Jul 24;28(14):1862-1870. Epub 2017 May 24.

Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294

Longitudinal growth of bones occurs at the growth plates where chondrocytes align into columns that allow directional growth. Little is known about the mechanisms controlling the ability of chondrocytes to form columns. We hypothesize that mechanical load and the resulting force on chondrocytes are necessary during active growth for proper growth plate development and limb length. To test this hypothesis, we created a mouse model in which a portion of the sciatic nerve from one hind limb was transected at postnatal day 8 to cause paralysis to that limb. At 6 and 12 wk postsurgery, the hind limb had significantly less bone mineral density than contralateral controls, confirming reduced load. At 8 and 14 wk postsurgery, tibiae were significantly shorter than controls. The paralyzed growth plate showed disruptions to column organization, with fewer and shorter columns. Polarized light microscopy indicated alterations in collagen fiber organization in the growth plate. Furthermore, organization of the actin cytoskeleton in growth plate chondrocytes was disrupted. We conclude that mechanical load and force on chondrocytes within the growth plate regulate postnatal development of the long bones.
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http://dx.doi.org/10.1091/mbc.E17-02-0084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541837PMC
July 2017
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