Publications by authors named "John Rose"

458 Publications

The Experiences of Carers of Adults With Intellectual Disabilities During the First COVID-19 Lockdown Period.

J Policy Pract Intellect Disabil 2021 May 15. Epub 2021 May 15.

Swansea Trials Unit, Clinical Research Facility, Institute of Life Science, Swansea University Swansea SA2 8PP UK.

Background: The recent COVID-19 pandemic led to widespread international restrictions, severely impacting on health and social care services. For many individuals with an intellectual disability (ID) this meant reduced access to services and support for them and their carers.

Aim: The aim of this study was to gain insight into the ways parents of adults with ID coped during the first 2020 lockdown period.

Methods: Eight parents of adults with ID were interviewed. The recordings of these interviews were subjected to a thematic analysis.

Results: Four main themes were identified: powerless and unappreciated; coping under lockdown; support; and the impact of lockdown on well-being.

Conclusions: The parents of adults with ID who made up our sample reported that they received little support from services and experienced a sense of powerlessness. Nevertheless, they were open to accepting support from family and friends and showed remarkable resilience. These findings are discussed in the light of the Willner et al. (2020) survey results on parental mental health and coping, and suggestions for future service provision during pandemic conditions are proposed.
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http://dx.doi.org/10.1111/jppi.12382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242525PMC
May 2021

Evaluation of High Altitude Interstitial Pulmonary Edema in Healthy Participants Using Rapid 4-View Lung Ultrasound Protocol During Staged Ascent to Everest Base Camp.

Wilderness Environ Med 2021 Jun 23. Epub 2021 Jun 23.

Department of Emergency Medicine, University of California at Davis, Sacramento, California.

Introduction: Prior research identified possible interstitial pulmonary fluid, concerning for early high altitude pulmonary edema (HAPE), in a large percentage of trekkers above 3000 m using a comprehensive 28-view pulmonary ultrasound protocol. These trekkers had no clinical symptoms of HAPE despite these ultrasound findings. The more common 4-view lung ultrasound protocol (LUP) is accurate in rapidly detecting interstitial edema during resource-rich care. The objective of this study was to evaluate whether the 4-view LUP detects interstitial fluid in trekkers ascending to Everest Base Camp.

Methods: Serial 4-view LUP was performed on 15 healthy trekkers during a 9-d ascent from Kathmandu to Everest Base Camp. Ascent protocols complied with Wilderness Medical Society guidelines for staged ascent. A 4-view LUP was performed in accordance with the published 2012 international consensus protocols on lung ultrasound. Symptom assessment and 4-view LUP were obtained at 6 waypoints along the staged ascent. A 4-view LUP was positive for interstitial edema if ≥3 B-lines were detected in 2 ultrasound windows.

Results: A single participant had evidence of interstitial lung fluid at 5380 m as defined by the 4-view LUP. There was no evidence of interstitial fluid in any participant below 5380 m. One participant was evacuated for acute altitude sickness at 4000 m but showed no preceding sonographic evidence of interstitial fluid.

Conclusions: In this small study, sonographic detection of interstitial fluid, suggestive of early HAPE, was not identified by the 4-view LUP protocol.
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http://dx.doi.org/10.1016/j.wem.2021.03.004DOI Listing
June 2021

Experiences of mental health professionals providing services to adults with intellectual disabilities and mental health problems: A systematic review and meta-synthesis of qualitative research studies.

J Intellect Disabil 2021 Jun 24:17446295211016182. Epub 2021 Jun 24.

1724University of Birmingham, UK.

Background: Mental health professionals play an important role in providing care and treatment for adults with intellectual disabilities. A number of studies use qualitative methods to explore the experiences of these professionals and their perspectives regarding the mental health services for this population. A systematic review using meta-ethnographic approach was undertaken to summarise this research.

Method: A systematic search found 14 relevant studies which were critically appraised. Key themes from these studies were extracted and synthesised.

Results: Three main themes were identified: 1) Understanding the person, 2) Relational interaction and 3) Organisational factors.

Conclusions: The findings of this review identified the issues mental health professionals raised in relation to their work. They described the complex presenting problems as intense yet fulfilling therapeutic relationships with their clients and their wish to improve their knowledge and skills. They identified organisational issues that need to be addressed to improve staff morale and efficiency.
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http://dx.doi.org/10.1177/17446295211016182DOI Listing
June 2021

Synthesis of the bis(cyclohexenone) core of (-)-lomaiviticin A.

Chem Sci 2020 Jul 9;11(28):7462-7467. Epub 2020 Jul 9.

Department of Chemistry, Yale University New Haven Connecticut 06520 USA

(-)-Lomaiviticin A is a complex -symmetric bacterial metabolite comprising two diazotetrahydrobenzo[]fluorene (diazofluorene) residues and four 2,6-dideoxy glycosides, α-l-oleandrose and ,-dimethyl-β-l-pyrrolosamine. The two halves of lomaiviticin A are linked by a single carbon-carbon bond oriented with respect to the oleandrose residues. While many advances toward the synthesis of lomaiviticin A have been reported, including synthesis of the aglycon, a route to the bis(cyclohexenone) core bearing any of the carbohydrate residues has not been disclosed. Here we describe a short route to a core structure of lomaiviticin A bearing two α-l-oleandrose residues. The synthetic route features a Stille coupling to form the conjoining carbon-carbon bond of the target and a double reductive transposition to establish the correct stereochemistry at this bond. Two synthetic routes were developed to elaborate the reductive transposition product to the bis(cyclohexenone) target. The more efficient pathway features an interrupted Barton vinyl iodide synthesis followed by oxidative elimination of iodide to efficiently establish the enone functionalities in the target. The bis(cyclohexenone) product may find use in a synthesis of lomaiviticin A itself.
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http://dx.doi.org/10.1039/d0sc02770gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159427PMC
July 2020

Lose Weight to Donate: Development of a Program to Optimize Potential Donors With Hepatic Steatosis or Obesity for Living Liver Donation.

Transplant Direct 2021 Jun 25;7(6):e702. Epub 2021 May 25.

Division of Transplant Surgery, University of Virginia Health System, Charlottesville, VA.

Background: Living donor liver transplantation offers an attractive option to reduce the waitlist mortality. However, in recent years, the rising prevalence of obesity and nonalcoholic fatty liver disease has posed a serious threat to the donor pool while simultaneously increasing demand for liver transplant. To our knowledge, there have been no major published studies in the United States documenting a diet and exercise intervention to expand the living donor pool. Hereby, we established a pilot program called "Lose Weight to Donate" and present our initial experience.

Methods: Our center instituted a remotely monitored diet and exercise pilot program to increase eligibility for living liver donation. Potential donors with any of the following were included: body mass index >30 kg/m, hepatic steatosis >5% on screening MRI, or isolated hypertension.

Results: Over 19 mo, 7 individuals enrolled in the program of remote monitoring for at least 6-8 wk. Initial and follow-up abdominal MRI was performed in 5 of these individuals to assess steatosis, anatomy, and volume. Initial steatosis was highly variable (fat signal fraction range, 8%-26%). Follow-up MRI fat signal fraction values and hepatic volume all decreased to varying degrees. Ultimately, 2 of 7 individuals donated, whereas a third was approved, but the intended recipient was transplanted in the interim.

Conclusions: These results indicate the feasibility of a remotely monitored program to expand donation in light of the rising incidence of hepatic steatosis and obesity.
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http://dx.doi.org/10.1097/TXD.0000000000001161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154492PMC
June 2021

Prognostic Impact of Tumor Size on Pancreatic Neuroendocrine Tumor Recurrence May Have Racial Variance.

Pancreas 2021 03;50(3):347-352

From the Department of Surgery, University of Alabama at Birmingham, Birmingham, AL.

Objective: The incidence of pancreatic neuroendocrine tumors (PNETs) has increased over the last decade. Black patients have worse survival outcomes. This study investigates whether oncologic outcomes are racially disparate at a single institution.

Methods: Retrospective analysis was performed on 151 patients with resected PNETs between 2010 and 2019.

Results: More White males and Black females presented with PNETs (P = 0.02). White patients were older (65 years vs 60 years; P = 0.03), more likely to be married (P < 0.01), and had higher median estimated yearly incomes ($28,973 vs $17,767; P < 0.01) than Black patients. Overall and disease-free survival were not different. Black patients had larger median tumor sizes (30 mm vs 23 mm; P = 0.02). Tumor size was predictive of recurrence only for White patients (hazard ratio, 1.02; P = 0.01). Collectively, tumors greater than 20 mm in size were more likely to have recurrence (P = 0.048), but this cutoff was not predictive in either racial cohort independently.

Conclusions: Black patients undergoing curative resection of PNETs at our institution presented with larger tumors, but that increased size is not predictive of disease-free survival in this population.
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http://dx.doi.org/10.1097/MPA.0000000000001776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041062PMC
March 2021

The experiences of mothers of children and young people with intellectual disabilities during the first COVID-19 lockdown period.

J Appl Res Intellect Disabil 2021 Mar 23. Epub 2021 Mar 23.

Swansea Trials Unit, Clinical Research Facility, Institute of Life Science, Swansea University, Swansea, UK.

Background: Recent COVID-19 lockdown restrictions resulted in reduced access to educational, professional and social support systems for children with intellectual disabilities and their carers.

Aim: The aim of this study was to gain insight into the ways mothers of children with intellectual disabilities coped during the first 2020 lockdown period.

Methods: Eight mothers of children with intellectual disabilities were interviewed. The recordings of these interviews were subjected to a thematic analysis.

Results: Three main themes were identified: carrying the burden; a time of stress; and embracing change and looking to the future.

Conclusions: All mothers experienced increased burden and stress. However, some also described some positive impact of lockdown conditions on them as well as on their child's well-being and behaviour. These findings are discussed in the light of the (Journal of Applied Research in Intellectual Disabilities, 33, 2020, 1523) survey results on parental coping and suggestions for future service provision during pandemic conditions are proposed.
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http://dx.doi.org/10.1111/jar.12884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250127PMC
March 2021

High-b diffusivity of MS lesions in cervical spinal cord using ultrahigh-b DWI (UHb-DWI).

Neuroimage Clin 2021 8;30:102610. Epub 2021 Mar 8.

Neuroimmunology and Neurovirology Division, Department of Neurology, University of Utah, Utah, USA; Neurology Service, VA Salt Lake City Health Care System, Utah, USA. Electronic address:

Purpose: The purpose of this study was to investigate UHb-rDWI signal in white matter tracts of the cervical spinal cord (CSC) and compare quantitative values between healthy control WM with both MS NAWM and MS WM lesions.

Methods: UHb-rDWI experiments were performed on (a) 7 MS patients with recently active or chronic lesions in CSC and on (b) 7 healthy control of similar age range and gender distribution to MS subjects. All MRI data were acquired using clinical 3T MRI system. Axial high-b diffusion images were acquired using 2D single-shot DW stimulated EPI with reduced FOV and a CSC-dedicated 8 channel array coil. High-b diffusion coefficient D was estimated by fitting the signal-b curve to a double or single-exponential function.

Results: The high-b diffusivity D values were measured as (0.767 ± 0.297) × 10 mm/s in the posterior column lesions, averaged over 6 MS patients, and 0.587 × 10 mm/s in the corticospinal tract for another patient. The averaged D values of the 7 healthy volunteers from the posterior and lateral column were (0.0312 ± 0.0306) × 10 and (0.0505 ± 0.0205) × 10 mm/s, respectively. UHb-rDWI signal-b curves of the MS patients revealed to noticeably behave differently to that of the healthy controls. The patient signal-b curves decayed with greater high-b decay constants to reach lower signal intensities relative to signal-b curves of the healthy controls.

Conclusion: UHb-DWI of the CSC reveals a marked difference in signal-b-curves and D values in MS lesions compared to NAWM and healthy control WM. Based on physical principles, we interpret these altered observations of quantitative diffusion values to be indicative of demyelination. Further studies in animal models will be required to fully interpret UHb-DWI quantitative diffusion values during demyelination and remyelination.
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http://dx.doi.org/10.1016/j.nicl.2021.102610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985401PMC
March 2021

Implementation of a visual feedback system for motion management during radiation therapy.

J Cancer Res Ther 2021 Jan-Mar;17(1):148-151

Department of Radiation Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India.

Purpose: To describe the details of an in-house video goggles feedback system assembled from several commercially available components. The objective of this paper is to share our experience with this system, provide details on the equipment needed, system assembly, patient set up and user settings on some components.

Materials And Methods: The system consisted of goggles (FPView3DHD, ITV, USA), RJ45(Registered Jack) to Digital Visual Interface (DVI) converter (Tripplite), DVI to HDMI converters, Local Area Network(LAN) cable, HDMI and power extender cables. The video coaching system was implemented both in CT simulator (GE Discovery)) and in treatment delivery machine True Beam v2.1 Varian Medical Systems (VMS, Palo Alto), which was integrated with respiratory motion management (RPM V 1.7.5) system.

Results: The video feedback system is in clinical use since Aug 2017, so far, we have treated 13 patients, with approximately 150 fractions. The performance of the device was found to be satisfactory. All the patients were coached for DIBH and the usage of the goggles, which includes wearing the goggles, display details of the monitor, and the threshold levels of the breathing wave cycle. The patients understand the instructions very well and hence regulate the breathing cycle, which improves the treatment accuracy and efficiency.

Conclusion: Video feedback system for motion management, for patients undergoing radiotherapy was implemented successfully both in CT simulator and in linear accelerator.
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http://dx.doi.org/10.4103/jcrt.JCRT_95_18DOI Listing
March 2021

Assessment of Surgical Care Provided in National Health Services Hospitals in Mozambique: The Importance of Subnational Metrics in Global Surgery.

World J Surg 2021 05 31;45(5):1306-1315. Epub 2021 Jan 31.

Division of Pediatric Surgery, Rady Children's Hospital, University of California, San Diego, CA, USA.

Introduction: Surgery plays a critical role in sustainable healthcare systems. Validated metrics exist to guide implementation of surgical services, but low-income countries (LIC) struggle to report recommended metrics and this poses a critical barrier to addressing unmet need. We present a comprehensive national sample of surgical encounters from a LIC by assessing the National Health Services of Mozambique.

Material And Methods: A prospective cohort of all surgical encounters from Mozambique's National Health Service was gathered for all provinces between July and December 2015. Primary outcomes were timely access, provider densities for surgery, anesthesiology, and obstetrics (SAO) per 100,000 population, annualized surgical procedure volume per 100,000, and postoperative mortality (POMR). Secondary outcomes include operating room density and efficiency.

Results: Fifty-four hospitals had surgical capacity in 11 provinces with 47,189 surgeries. 44.9% of Mozambique's population lives in Districts without access to surgical services. National SAO density was 1.2/100,000, ranging from 0.4/100,000 in Manica Province to 9.8/100,000 in Maputo City. Annualized national surgical case volume was 367 procedures/100,000 population, ranging from 180/100,000 in Zambezia Province to 1,897/100,000 in Maputo City. National POMR was 0.74% and ranged from 0.23% in Maputo Province to 1.78% in Niassa Province.

Discussion: Surgical delivery in Mozambique falls short of international targets. Subnational deficiencies and variations between provinces pose targets for quality improvement in advancing national surgical plans. This serves as a template for LICs to follow in gathering surgical metrics for the WHO and the World Bank and offers short- and long-term targets for surgery as a component of health systems strengthening.
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http://dx.doi.org/10.1007/s00268-020-05925-0DOI Listing
May 2021

Postoperative Hyperthermia and Hemodynamic Instability in a Suspected Malignant Hyperthermia-Susceptible Patient: A Case Report.

A A Pract 2021 Jan 19;15(1):e01314. Epub 2021 Jan 19.

From the Department of Anesthesiology, Perioperative and Pain Medicine, Mount Sinai Morningside and West Hospitals, New York, New York.

Malignant hyperthermia (MH) is a rare but potentially fatal complication of exposure to certain anesthetic drugs. However, stress-induced MH, initially observed in pigs undergoing intense physical or emotional strain, has been reported in the absence of anesthetic exposure. In this case report, we describe a case of postoperative hyperthermia and cardiac dysfunction suspicious for stress-induced MH occurring after an endobronchial biopsy in a patient with recurrent undiagnosed fevers. We also examine our diagnosis of stress-induced MH and possible preventive measures to avoid this complication.
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http://dx.doi.org/10.1213/XAA.0000000000001314DOI Listing
January 2021

Lymphocyte reconstitution after DMF discontinuation in clinical trial and real-world patients with MS.

Neurol Clin Pract 2020 Dec;10(6):510-519

Department of Neurology (AC), Inselspital, Bern University Hospital, University of Bern, Switzerland; Division of Neuroimmunology and Neurovirology (JR), University of Utah, Salt Lake City, UT; Brain Institute (JR), University of Utah, Salt Lake City, UT; Department of Neurology (JR), University of Utah, Salt Lake City, UT; Rocky Mountain Multiple Sclerosis Center at the University of Colorado (EA), Aurora, CO; Department of Neurology and Center for Neuroinflammation and Experimental Therapeutics (AB-O), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Children's Hospital of Philadelphia (AB-O), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Central Clinical School (HB), Monash University, VIC, Australia; Mellen Center for Multiple Sclerosis Treatment and Research (RJF), Cleveland Clinic, OH; Department of Neurology (RG), St. Josef-Hospital, Ruhr University Bochum, Germany; South Shore Neurologic Association PC (MG), Patchogue, NY; Eastern Health MS Service (JH), Box Hill, VIC, Australia; Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital (TS), University of Melbourne, Parkville, VIC, Australia; Department of Neurology and Neurotherapeutics (KW), University of Texas Southwestern Medical Center, Multiple Sclerosis and Neuroimmunology Imaging Program, Clinical Center for Multiple Sclerosis, Dallas, TX; Department of Neuroscience (DF, PS), Neurology Unit, Azienda Ospedaliera Universitaria, Modena, Italy; Liverpool Hospital (SH), NSW, Australia; Department of Medicine (TK), CORe Unit, University of Melbourne, VIC, Australia; Department of Neurology (TK), Royal Melbourne Hospital, VIC, Australia; School of Medicine and Public Health (JL-S), University Newcastle, NSW, Australia; Department of Neurology (JL-S), John Hunter Hospital, Hunter New England Health, Newcastle, NSW, Australia; Department of Neurology (C. McGuigan), St. Vincent's University Hospital and University College, Dublin, Ireland; Envision Pharma Group (KS), Fairfield, CT; and Biogen (CC, SF, FW, C. Miller), Cambridge, MA.

Background: Delayed-release dimethyl fumarate (DMF) has demonstrated robust efficacy in treating patients with relapsing-remitting multiple sclerosis. Decreases in absolute lymphocyte count (ALC) are a well-known pharmacodynamic effect of DMF treatment, but lymphocyte recovery dynamics are not well characterized after discontinuation of DMF.

Methods: Data sources included the Biogen DMF integrated clinical trial data set, a retrospective US chart abstraction study, and data from MSBase. We assessed rate and time course of lymphocyte reconstitution after DMF discontinuation.

Results: The majority of patients who developed lymphopenia while treated with DMF and subsequently discontinued treatment experienced ALC reconstitution. The median time to reach ALC ≥0.8 × 10/L was 2-4 months after discontinuation for patients treated in real-world data sets; the median time to reach ALC ≥0.91 × 10/L was 2 months after discontinuation in DMF clinical trials. Severity of lymphopenia on treatment and decline in ALC within the first 6 months did not affect the ALC reconstitution rate after DMF discontinuation; rather, on-treatment lymphopenia duration influenced the reconstitution rate. In patients with severe, prolonged lymphopenia for ≥3 years, lymphocyte reconstitution to ≥0.91 × 10/L was 12-18 months vs 2-3 months in patients with lymphopenia persisting <6 months.

Conclusions: The majority of patients who discontinued DMF due to lymphopenia experienced ALC reconstitution within 2-4 months following DMF discontinuation. This may help guide clinicians in managing patients who develop lymphopenia during DMF treatment. Prolonged lymphopenia on DMF treatment is associated with slow lymphocyte recovery after DMF discontinuation.
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http://dx.doi.org/10.1212/CPJ.0000000000000800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837440PMC
December 2020

Preferences for a COVID-19 vaccine in Australia.

Vaccine 2021 01 16;39(3):473-479. Epub 2020 Dec 16.

Centre for Business Intelligence and Data Analytics, Business School, University of Technology Sydney, 14/28 Ultimo Rd, Ultimo, NSW 2007, Australia.

In absence of a COVID-19 vaccine, testing, contact tracing and social restrictions are among the most powerful strategies adopted around the world to slow down the spread of the pandemic. Citizens of most countries are suffering major physical, psychological and economic distress. At this stage, a safe and effective COVID-19 vaccine is the most sustainable option to manage the current pandemic. However, vaccine hesitancy by even a small subset of the population can undermine the success of this strategy. The objective of this research is to investigate the vaccine characteristics that matter the most to Australian citizens and to explore the potential uptake of a COVID-19 vaccine in Australia. Through a stated preference experiment, preferences towards a COVID-19 vaccine of 2136 residents of the Australian states and territories were collected and analysed via a latent class model. Results show that preferences for mild adverse cases, mode of administration, location of administration, price and effectiveness are heterogeneous. Conversely, preferences for immediacy and severe reactions are homogeneous, with respondents preferring a shorter period until vaccine is available and lower instances of severe side effects. The expected uptake of the vaccine is estimated under three different scenarios, with the value of 86% obtained for an average scenario. By calculating individual preferences, the willingness to pay is estimated for immediacy, effectiveness, mild and severe side effects.
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http://dx.doi.org/10.1016/j.vaccine.2020.12.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832016PMC
January 2021

Autologous Hematopoietic Stem Cell Transplantation for Stiff-Person Spectrum Disorder: A Clinical Trial.

Neurology 2021 02 14;96(6):e817-e830. Epub 2020 Dec 14.

From the Division of Immunotherapy (R.K.B., X.H., K.Q., I.A.), Department of Medicine, Department of Neurology (R.B., T.S.), Department of Preventive Medicine (I.H.), and Department of Pathology and Cell and Developmental Biology (T.S.), Northwestern University, Chicago, IL; and Department of Neurology (J.R.), University of Utah, Salt Lake City.

Objective: To test the hypothesis that autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) is safe and shows efficacy in the treatment of stiff-person spectrum disorder (SPSD).

Methods: Twenty-three participants were treated in a prospective open-label cohort study of safety and efficacy. After stem cell mobilization with cyclophosphamide (2 g/m) and filgrastim (5-10 µg/kg/d), participants were treated with cyclophosphamide (200 mg/kg) divided as 50 mg/kg IV on day -5 to day -2; rabbit anti-thymocyte globulin (thymoglobulin) given intravenously at 0.5 mg/kg on day -5, 1 mg/kg on days -4 and -3, and 1.5 mg/kg on days -2, and -1 (total dose 5.5 mg/kg); and rituximab 500 mg IV on days -6 and +1. Unselected peripheral blood stem cells were infused on day 0. Safety was assessed by survival and National Cancer Institute common toxicity criteria for adverse events during HSCT. Outcome was assessed by ≥50% decrease or discontinuation of antispasmodic drugs and by quality of life instruments.

Results: There was no treatment-related mortality. One participant died 1 year after transplantation of disease progression. Of the 74% of participants who responded, 47% have stayed in remission for a mean of 3.5 years; 26% did not respond. Compared to nonresponders, responders were more likely to have pretransplantation intermittent muscle spasms (16 of 17 vs 0 of 6), normal reflexes (12 of 17 vs 0 of 6), and positive CSF anti-glutamic acid decarboxylase serology (12 of 14 vs 2 of 6). Compared to responders, nonresponders were more likely to have lead pipe rigidity (4 of 6 vs 0 of 17) and EMG-documented simultaneous contraction of agonist/antagonist limb muscles (4 of 6 vs 1 of 17). Pre-HSCT use of prescription serotonin selective receptor inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI) was more common in those who relapsed or never responded (9 of 12) compared to those responders who never relapsed (0 of 11).

Conclusion: In this cohort, HSCT was safe, but the beneficial effect of HSCT was variable and confined predominately to participants with episodic spasms and normal tendon reflexes without simultaneous cocontraction of limb agonist/antagonist muscles who were not taking SSRI or SNRI antidepressants.

Classification Of Evidence: This study provides Class IV evidence that, for a subset of people with SPSD, autologous nonmyeloablative HSCT improves outcomes.

Clinicaltrialsgov Identifier: NCT02282514.
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http://dx.doi.org/10.1212/WNL.0000000000011338DOI Listing
February 2021

Choice of speed under compromised Dynamic Message Signs.

PLoS One 2020 11;15(12):e0243567. Epub 2020 Dec 11.

Business School, University of Technology Sydney, Sydney, Australia.

This study explores speed choice behavior of travelers under realistic and fabricated Dynamic Message Signs (DMS) content. Using web-based survey information of 4,302 participants collected by Amazon Mechanical Turk in the United States, we develop a set of multivariate latent-based ordered probit models participants. Results show female, African-Americans, drivers with a disability, elderly, and drivers who trust DMS are likely to comply with the fabricated messages. Drivers who comply with traffic regulations, have a good driving record, and live in rural areas, as well as female drivers are likely to slow down under fabricated messages. We highlight that calling or texting, taking picture, and tuning the radio are distracting activities leading drivers to slow down or stop under fictitious scenarios.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243567PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732086PMC
February 2021

Evaluation of Serial Chest Radiographs of High-Altitude Pulmonary Edema Requiring Medical Evacuation from South Pole Station, Antarctica: From Diagnosis to Recovery.

Mil Med 2020 Dec 3. Epub 2020 Dec 3.

Department of Emergency Medicine, University of California at Davis, Sacramento, CA 95817, USA.

Introduction: Chest radiography is a diagnostic tool commonly used by medical providers to assess high-altitude pulmonary edema (HAPE). Although HAPE often causes a pattern of pulmonary edema with right lower lung predominance, previous research has shown that there is no single radiographic finding associated with the condition. The majority of research involves a retrospective analysis of chest radiographs taken at the time of HAPE diagnosis. Little is known about the radiographic progression of HAPE during treatment or medical evacuation.

Materials And Methods: Three sequential chest radiographs were obtained from two patients diagnosed with HAPE at the Amundsen-Scott South Pole Station, Antarctica, who required treatment and medical evacuation. Deidentified and temporally randomized images were reviewed in a blinded fashion by two radiologists. A score of 0 (normal lung) to 4 (alveolar disease) was assigned for each of the four lung quadrants for an aggregate possible score ranging from 0 to 16 for each radiograph.

Results: Patient 1's initial radiograph showed severe HAPE with an initial score of 13. Despite a rapid clinical improvement after medical evacuation, he continued to show multifocal radiographic evidence of disease in all the lung quadrants on day 1 (score of 11) and day 2 (score of 5). Patient 2's radiographs showed less severe disease at presentation (score of 6). Despite the need for continued treatment, his radiographs showed a rapid improvement, with radiographic score decreasing to 3 on day 1 and 1 on day 3.

Conclusion: The chest radiographs showed serial improvement after medical evacuation in both patients. There was not a strong correlation between clinical symptoms and radiographic severity in subsequent images.
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http://dx.doi.org/10.1093/milmed/usaa490DOI Listing
December 2020

Global Burn Registry Perspective on Head and Neck Burns.

Ann Plast Surg 2021 07;87(1):33-38

From the Division of Plastic Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.

Introduction: As exposed regions of the body, the head and neck are at increased risk of burn injury. The cosmetic and functional importance of these anatomical regions means that burns can result in substantial morbidity and mortality. Our objective was to characterize predictive factors for surgery and discharge condition in patients with head and neck burns internationally.

Methods: We conducted an epidemiological study of all head and neck burns in 14 countries reported in the World Health Organization Global Burn Registry. Multivariate regression was used to identify variables predictive of surgical treatment and discharge condition.

Results: We identified 1014 patients who sustained head and neck burns; the majority were adults (60%). Both adults and children admitted to hospital with head and neck burn injuries were less likely to be treated surgically in lower-middle-income countries (LMIC) than in higher-income countries (P < 0.001). Increasing age and greater total surface body area (TBSA) were significant predictors of surgical intervention in children with head and neck burn injuries (P < 0.001). Total surface body area, associated injuries, ocular burns, female sex, and LMIC residency were all significant predictors of mortality in adult patients with head and neck burns (P < 0.050). Conversely, TBSA was the only variable that independently increased the risk of death in children with head and neck burns (P < 0.001).

Conclusions: Certain groups are at increased risk of an adverse outcome after admission with a head and neck burn injury. Given the reduced incidence of surgical intervention and the elevated mortality risk in LMICs, global health initiatives should be targeted to these countries.
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http://dx.doi.org/10.1097/SAP.0000000000002585DOI Listing
July 2021

Effects of Continuous Albuterol Inhalation on Serum Metabolome in Healthy Subjects: More Than Just Lactic Acid.

J Clin Pharmacol 2021 May 28;61(5):649-655. Epub 2020 Nov 28.

Department of Emergency Medicine, University of California at Davis, Sacramento, California, USA.

Treatment with β2-agonists may cause elevated lactic acid, the end product of anaerobic metabolism of glucose. It has been proposed that lactic acidosis associated with β2-agonists is caused by changes to direct biochemical impacts on glycolysis, gluconeogenesis, pyruvate metabolism, and free fatty acid production. However, much remains unknown, and there is a paucity of evidence regarding the underlying chemical changes associated with this lactic acidosis. The goal of our study was to investigate the impact of 1 hour of continuous albuterol on the untargeted serum metabolome of healthy subjects. Twenty-four healthy participants received 7.5 mg of continuous albuterol for 1 hour. Baseline, 1-hour, and 2-hour lactic acid levels were drawn. Samples obtained at baseline and 1 hour were sent for untargeted metabolomic profiling. Participants had a baseline lactic acid of 1.45 ± 0.46 mmol/L. On average, lactate levels increased 0.33 ± 0.67 mmol/L after 1 hour (P = .02) and remained elevated at 2 hours (0.32 ± 0.72 mmol/L, P = .02), although there was overlap in lactate levels across times. For metabolomic analysis, fatty acids, organic acids, and sugars were elevated, and amino acids were reduced. Lactic acid and pyruvic acid metabolites, however, did not significantly change (after false discovery rate adjustment). In healthy participants, continuous albuterol alters the serum metabolome, but this change may not be clinically significant. The data support recent hypotheses that β2-receptor activation stimulates lactic acid production, altering aerobic glycolysis, gluconeogenesis, and free fatty acid production.
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http://dx.doi.org/10.1002/jcph.1781DOI Listing
May 2021

Vicarious trauma in therapists: a meta-ethnographic review.

Behav Cogn Psychother 2020 Oct 30:1-15. Epub 2020 Oct 30.

Centre for Applied Psychology, School of Psychology, University of Birmingham, Edgbaston, BirminghamB15 2TT, UK.

Background: Hearing about trauma can leave a mark on an individual, leading to a significant change in worldview that shatters their existing beliefs and is pervasive across view of self, other and the world. Individuals present with a range of symptoms that mimic post-traumatic stress disorder although the symptoms are less severe. Despite this, some individuals can experience growth through an enriched understanding of self and other. This altered perspective enables individuals to respond in ways that promote growth and positivity in their own lives.

Aims: The aim of this review was to synthesise existing qualitative literature exploring how therapists experience working with trauma survivors.

Method: A systematic literature search found 16 studies which were selected for review following the application of inclusion/exclusion criteria and quality appraisal. Noblit and Hare's (1988) approach to meta-ethnography was followed.

Results: The themes identified outline a cognitive model of vicarious trauma whereby therapists presented with cognitive, emotional, physiological and behavioural 'symptoms' due to marked changes in schemata following repeated exposure to trauma. The literature suggests that therapists experience growth and development alongside vicarious trauma through witnessing clients' resilience and growth.

Conclusion: This meta-ethnographic review suggests that the impact of working with trauma is profound and complex for therapists bearing witness to their client's pain and concurrently, their growth.
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http://dx.doi.org/10.1017/S1352465820000776DOI Listing
October 2020

Effect of the COVID-19 pandemic on the mental health of carers of people with intellectual disabilities.

J Appl Res Intellect Disabil 2020 Nov 21;33(6):1523-1533. Epub 2020 Sep 21.

The Challenging Behaviour Foundation, Chatham, UK.

Introduction: The measures implemented to manage the COVID-19 pandemic have been shown to impair mental health. This problem is likely to be exacerbated for carers.

Method: Informal carers (mainly parents) of children and adults with intellectual disabilities, and a comparison group of parents of children without disabilities, completed an online questionnaire. Almost all the data were collected while strict lockdown conditions were in place.

Results: Relative to carers of children without intellectual disability, carers of both children and adults with intellectual disability had significantly greater levels of a wish fulfilment coping style, defeat/entrapment, anxiety, and depression. Differences were 2-3 times greater than reported in earlier pre-pandemic studies. Positive correlations were found between objective stress scores and all mental health outcomes. Despite their greater mental health needs, carers of those with intellectual disability received less social support from a variety of sources.

Conclusions: The greater mental health needs of carers in the context of lesser social support raises serious concerns. We consider the policy implications of these findings.
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http://dx.doi.org/10.1111/jar.12811DOI Listing
November 2020

The Ideal Microsurgery Fellowship: A Survey of Fellows and Fellowship Directors.

J Reconstr Microsurg 2021 Feb 1;37(2):167-173. Epub 2020 Sep 1.

Department of Surgery, Division of Plastic and Reconstructive Surgery, University of California San Diego, San Diego, California.

Background:  Although microsurgery fellowships have existed since the 1980s, there is no established curriculum. Microsurgery fellowships vary greatly in clinical caseload, case diversity, and training resources, and there is no consensus on the appropriate composition of a microsurgery fellowship. This study surveys fellowship directors (FD) and recent microsurgery fellows (MFs), graduates, to describe the ideal microsurgery fellowship program.

Methods:  A 15-item questionnaire was sent to 38 FDs and 90 recent microsurgery fellowship graduates. This questionnaire addressed program attributes, case volumes and compositions, ideal experiences, and time allocation to different fellowship experiences. Data were analyzed using descriptive statistics, -tests, and Chi-squared tests.

Results:  The FD and MF surveys had a response rate of 47 and 49%, respectively. Both MF and FD agreed that exposure to microsurgical breast reconstruction is the most important characteristic of a microsurgery fellowship ( = 0.94). MF ranked replantation and supermicro/lymphatic surgery as the next most important microsurgical cases, while FD ranked the anterolateral thigh (ALT) flap and free fibula flap ( < 0.001). Both agreed that revisional surgery after microsurgical reconstruction is a very valuable fellowship experience ( = 0.679). Both agreed that 1 day of clinic a week is sufficient.

Conclusion:  Microsurgical training programs vary in quality and resources. The ideal microsurgery fellowship prioritized breast reconstruction, head and neck reconstruction, and lower extremity reconstruction. Although microsurgical technical expertise is important, a fellowship should also train in revisional surgeries and clinical decision making.
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http://dx.doi.org/10.1055/s-0040-1715879DOI Listing
February 2021

Improved relapse recovery in paediatric compared to adult multiple sclerosis.

Brain 2020 09;143(9):2733-2741

Mayo Clinic Paediatric Multiple Sclerosis Center, Mayo Clinic, Rochester, MN, USA.

Incomplete relapse recovery contributes to disability accrual and earlier onset of secondary progressive multiple sclerosis. We sought to investigate the effect of age on relapse recovery. We identified patients with multiple sclerosis from two longitudinal prospective studies, with an Expanded Disability Status Scale (EDSS) score within 30 days after onset of an attack, and follow-up EDSS 6 months after attack. Adult patients with multiple sclerosis (n = 632) were identified from the Comprehensive Longitudinal Investigations in Multiple Sclerosis at Brigham study (CLIMB), and paediatric patients (n = 132) from the US Network of Paediatric Multiple Sclerosis Centers (NPMSC) registry. Change in EDSS was defined as the difference in EDSS between attack and follow-up. Change in EDSS at follow-up compared to baseline was significantly lower in children compared to adults (P = 0.001), as were several functional system scores. Stratification by decade at onset for change in EDSS versus age found for every 10 years of age, EDSS recovery is reduced by 0.15 points (P < 0.0001). A larger proportion of children versus adults demonstrated improvement in EDSS following an attack (P = 0.006). For every 10 years of age, odds of EDSS not improving increase by 1.33 times (P < 0.0001). Younger age is associated with improved recovery from relapses. Age-related mechanisms may provide novel therapeutic targets for disability accrual in multiple sclerosis.
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http://dx.doi.org/10.1093/brain/awaa199DOI Listing
September 2020

Pediatric Multiple Sclerosis Severity Score in a large US cohort.

Neurology 2020 09 20;95(13):e1844-e1853. Epub 2020 Jul 20.

From Partners Pediatric Multiple Sclerosis Center (J.D.S., T.C.), Massachusetts General Hospital; Harvard Medical School (J.D.S.), Boston, MA; Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital (J.D.S., L.B., M.G.), MA; Children's Hospital Los Angeles (J.D.S.); Keck School of Medicine at the University of Southern California (J.D.S.), Los Angeles; Data Coordinating and Analysis Center (M.W., S.R., J.R., T.C.C.), University of Utah, Salt Lake City; Pediatric Multiple Sclerosis Center (G.A.), Loma Linda University Children's Hospital, CA; Pediatric MS Center at NYU Langone Health (A.B., L.K.), New York, NY; Washington University (M.S.G., S.M.), St. Louis, MO; Pediatric Multiple Sclerosis Center (J.S.G.), University of California San Diego; UAB Center for Pediatric-Onset Demyelinating Disease (Y.H., J.N.), University of Alabama at Birmingham; The Blue Bird Circle Clinic for Multiple Sclerosis (T.L.), Texas Children's Hospital, Baylor College of Medicine, Houston; Mellen Center for Multiple Sclerosis (M.M., M. Rensel), Cleveland Clinic, OH; Mayo Clinic Pediatric Multiple Sclerosis Center (M. Rodriguez, J.-M.T.), Mayo Clinic, Rochester, MN; Rocky Mountain Multiple Sclerosis Center (T.S.), Children's Hospital Colorado, University of Colorado at Denver, Aurora; Pediatric Multiple Sclerosis Center (E.W.), University of California San Francisco; Jacobs Pediatric Multiple Sclerosis Center (B.W.-G.), State University of New York at Buffalo; and Department of Neurology (B.F.H.), Stanford University School of Medicine, Palo Alto, CA.

Objective: To characterize disease severity and distribution of disability in pediatric-onset multiple sclerosis (POMS) and to develop an optimized modeling scale for measuring disability, we performed a multicenter retrospective analysis of disability scores in 873 persons with POMS over time and compared this to previously published data in adults with multiple sclerosis (MS).

Methods: This was a retrospective analysis of prospectively collected data collected from 12 centers of the US Network of Pediatric MS Centers. Patients were stratified by the number of years from first symptoms of MS to Expanded Disability Status Scale (EDSS) assessment and an MS severity score (Pediatric Multiple Sclerosis Severity Score [Ped-MSSS]) was calculated per criteria developed by Roxburgh et al. in 2005.

Results: In total, 873 patients were evaluated. In our cohort, 52%, 19.4%, and 1.5% of all patients at any time point reached an EDSS of 2.0, 3.0, and 6.0. Comparison of our Ped-MSSS scores and previously published adult Multiple Sclerosis Severity Scores (MSSS) showed slower progression of Ped-MSSS with increasing gaps between higher EDSS score and years after diagnosis. Decile scores in our POMS cohort for EDSS of 2.0, 3.0, and 6.0 were 8.00/9.46/9.94, 7.86/9.39/9.91, and 7.32/9.01/9.86 at 2, 5, and 10 years, respectively. Notable predictors of disease progression in both EDSS and Ped-MSSS models were ever having a motor relapse and EDSS at year 1. Symbol Digit Modalities Test (SDMT) scores were inversely correlated with duration of disease activity and cerebral functional score.

Conclusions: Persons with POMS exhibit lower EDSS scores compared to persons with adult-onset MS. Use of a Ped-MSSS model may provide an alternative to EDSS scoring in clinical assessment of disease severity and disability accrual.
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http://dx.doi.org/10.1212/WNL.0000000000010414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682820PMC
September 2020

Modified Alphavirus-Vesiculovirus Hybrid Vaccine Vectors for Homologous Prime-Boost Immunotherapy of Chronic Hepatitis B.

Vaccines (Basel) 2020 Jun 5;8(2). Epub 2020 Jun 5.

CaroGen Corporation, Farmington, CT 06032, USA.

Virus-like vesicles (VLV) are hybrid vectors based on an evolved Semliki Forest virus (SFV) RNA replicon and the envelope glycoprotein (G) from vesicular stomatitis virus (VSV) [...].
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http://dx.doi.org/10.3390/vaccines8020279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349932PMC
June 2020

Suppression of unwanted CRISPR-Cas9 editing by co-administration of catalytically inactivating truncated guide RNAs.

Nat Commun 2020 06 1;11(1):2697. Epub 2020 Jun 1.

Department of Genome Sciences, University of Washington, Seattle, WA, 98195, USA.

CRISPR-Cas9 nucleases are powerful genome engineering tools, but unwanted cleavage at off-target and previously edited sites remains a major concern. Numerous strategies to reduce unwanted cleavage have been devised, but all are imperfect. Here, we report that off-target sites can be shielded from the active Cas9•single guide RNA (sgRNA) complex through the co-administration of dead-RNAs (dRNAs), truncated guide RNAs that direct Cas9 binding but not cleavage. dRNAs can effectively suppress a wide-range of off-targets with minimal optimization while preserving on-target editing, and they can be multiplexed to suppress several off-targets simultaneously. dRNAs can be combined with high-specificity Cas9 variants, which often do not eliminate all unwanted editing. Moreover, dRNAs can prevent cleavage of homology-directed repair (HDR)-corrected sites, facilitating scarless editing by eliminating the need for blocking mutations. Thus, we enable precise genome editing by establishing a flexible approach for suppressing unwanted editing of both off-targets and HDR-corrected sites.
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http://dx.doi.org/10.1038/s41467-020-16542-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264211PMC
June 2020

Comment on "Managing COVID-19 in Surgical Systems": An Opportunity for Global Surgery to Advance Global Health.

Ann Surg 2020 May 1. Epub 2020 May 1.

Department of Plastic and Reconstructive Surgery, Johns Hopkins School of Medicine, Baltimore, MD Program in Global Surgery and Social Change, Harvard Medical School, Boston, MA Department of Plastic and Oral Surgery, Boston Children's Hospital, Boston, MA.

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http://dx.doi.org/10.1097/SLA.0000000000003966DOI Listing
May 2020

Neurosarcoidosis: Longitudinal experience in a single-center, academic healthcare system.

Neurol Neuroimmunol Neuroinflamm 2020 07 13;7(4). Epub 2020 May 13.

From the Department of Neurology (J.L., M.M.P.S., J. Galli, R.B., L.D.D., J. Klein, J.R., J. Greenlee, S.L.C.), University of Utah; George E. Wahlen Veterans Affairs Medical Center (J.L., M.M.P.S., J. Galli, S.L.C.); Department of Radiology and Imaging Sciences (K.L.S.), and Departments of Internal Medicine and Bioinformatics (J. Kresser), University of Utah, Salt Lake City.

Objective: To characterize patients with neurosarcoidosis within the University of Utah healthcare system, including demographics, clinical characteristics, treatment, and long-term outcomes.

Methods: We describe the clinical features and outcomes of patients with neurosarcoidosis within the University of Utah healthcare system (a large referral center for 10% of the continental United States by land mass). Patients were selected who met the following criteria: (1) at least one , 9th revision code 135 or , 10th revision code D86* (sarcoidosis) and (2) at least one outpatient visit with a University of Utah clinician in the Neurology Department within the University of Utah electronic health record.

Results: We identified 56 patients meeting the study criteria. Thirty-five patients (63%) were women, and most patients (84%) were white. Twelve patients (22%) met the criteria for definite neurosarcoidosis, 36 patients (64%) were diagnosed with probable neurosarcoidosis, and 8 patients (14%) were diagnosed with possible neurosarcoidosis. A total of 8 medications were used for the treatment of neurosarcoidosis. Prednisone was the first-line treatment in 51 patients (91%). Infliximab was the most effective therapy, with 87% of patients remaining stable or improving on infliximab. Treatment response for methotrexate and azathioprine was mixed, and mycophenolate mofetil and rituximab were the least effective treatments in this cohort.

Conclusions: This is a comprehensive characterization of neurosarcoidosis within a single healthcare system at the University of Utah that reports long-term response to treatment and outcomes of patients with neurosarcoidosis. Our results suggest the use of infliximab as a first-line therapy for neurosarcoidosis.
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http://dx.doi.org/10.1212/NXI.0000000000000743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238893PMC
July 2020

Real-World Effectiveness of Initial Disease-Modifying Therapies in Pediatric Multiple Sclerosis.

Ann Neurol 2020 07 14;88(1):42-55. Epub 2020 May 14.

UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.

Objective: To assess real-world effectiveness of initial treatment with newer compared to injectable disease-modifying therapies (DMTs) on disease activity in pediatric multiple sclerosis (MS) and clinically isolated syndrome (CIS).

Methods: This is a cohort study of children with MS/CIS followed at 12 clinics in the US Network of Pediatric MS Centers, who received initial therapy with newer (fingolimod, dimethyl fumarate, teriflunomide, natalizumab, rituximab, ocrelizumab) or injectable (interferon-β, glatiramer acetate) DMTs. Propensity scores (PSs) were computed, including preidentified confounders. Relapse rate while on initial DMT was modeled with negative binomial regression, adjusted for PS-quintile. Time to new/enlarging T2-hyperintense and gadolinium-enhancing lesions on brain magnetic resonance imaging were modeled with midpoint survival analyses, adjusted for PS-quintile.

Results: A total of 741 children began therapy before 18 years, 197 with newer and 544 with injectable DMTs. Those started on newer DMTs were older (15.2 vs injectable 14.4 years, p = 0.001) and less likely to have a monofocal presentation. In PS-quintile-adjusted analysis, those on newer DMTs had a lower relapse rate than those on injectables (rate ratio = 0.45, 95% confidence interval (CI) = 0.29-0.70, p < 0.001; rate difference = 0.27, 95% CI = 0.14-0.40, p = 0.004). One would need to treat with newer rather than injectable DMTs for 3.7 person-years to prevent 1 relapse. Those started on newer DMTs had a lower rate of new/enlarging T2 (hazard ratio [HR] = 0.51, 95% CI = 0.36-0.72, p < 0.001) and gadolinium-enhancing lesions (HR = 0.38, 95% CI = 0.23-0.63, p < 0.001) than those on injectables.

Interpretation: Initial treatment of pediatric MS/CIS with newer DMTs led to better disease activity control compared to injectables, supporting greater effectiveness of newer therapies. Long-term safety data for newer DMTs are required. ANN NEUROL 2020 ANN NEUROL 2020;88:42-55.
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http://dx.doi.org/10.1002/ana.25737DOI Listing
July 2020

Transactions from the 69th Annual Meeting of the American Crystallographic Association: Data best practices-current state and future needs.

Struct Dyn 2020 Mar 24;7(2):021301. Epub 2020 Mar 24.

Cell Systems Science Group, National Institute of Standards and Technology, Gaithersburg, Maryland 20899, USA.

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http://dx.doi.org/10.1063/4.0000011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093206PMC
March 2020

Griffithsin Inhibits Nipah Virus Entry and Fusion and Can Protect Syrian Golden Hamsters From Lethal Nipah Virus Challenge.

J Infect Dis 2020 May;221(Supplement_4):S480-S492

Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus that causes fatal encephalitis and respiratory disease in humans. There is currently no approved therapeutic for human use against NiV infection. Griffithsin (GRFT) is high-mannose oligosaccharide binding lectin that has shown in vivo broad-spectrum activity against viruses, including severe acute respiratory syndrome coronavirus, human immunodeficiency virus 1, hepatitis C virus, and Japanese encephalitis virus. In this study, we evaluated the in vitro antiviral activities of GRFT and its synthetic trimeric tandemer (3mG) against NiV and other viruses from 4 virus families. The 3mG had comparatively greater potency than GRFT against NiV due to its enhanced ability to block NiV glycoprotein-induced syncytia formation. Our initial in vivo prophylactic evaluation of an oxidation-resistant GRFT (Q-GRFT) showed significant protection against lethal NiV challenge in Syrian golden hamsters. Our results warrant further development of Q-GRFT and 3mG as potential NiV therapeutics.
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http://dx.doi.org/10.1093/infdis/jiz630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199786PMC
May 2020