scholarly journals Inflammatory, but not respiratory symptoms, associated with ongoing upper airway viral replication in outpatients with uncomplicated COVID-19

2021 ◽  
Author(s):  
Karen B. Jacobson ◽  
Natasha Purington ◽  
Julie Parsonnet ◽  
Jason Andrews ◽  
Vidhya Balasubramanian ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Median Time ◽  
Symptom Onset ◽  
Respiratory Symptoms ◽  
Linear Models ◽  
Clinical Trial Design ◽  
Upper Airway ◽  
Symptom Resolution ◽  
Viral Shedding ◽  
History Of

AbstractBackgroundThe vast majority of SARS-CoV-2 infections are uncomplicated and do not require hospitalization, but contribute to ongoing transmission. Our understanding of the clinical course of uncomplicated COVID-19 remains limited.MethodsWe detailed the natural history of uncomplicated COVID-19 among 120 outpatients enrolled in a randomized clinical trial of Peginterferon Lambda. We characterized symptom trajectory and clusters using exploratory factor analysis, assessed predictors of symptom resolution and cessation of oropharyngeal viral shedding using Cox proportional hazard models, and evaluated associations between symptoms and viral shedding using mixed effects linear models.ResultsHeadache, myalgias and chills peaked at day 4 after symptom onset; cough peaked on day 9. Two distinct symptom cluster trajectories were identified; one with mild, upper respiratory symptoms, and the other with more severe and prolonged inflammatory symptoms. The median time to symptom resolution from earliest symptom onset was 17 days (95% CI 14-18). Neither enrollment SARS-CoV-2 IgG levels (Hazard ratio [HR] 1.88, 95% CI 0.84-4.20) nor oropharyngeal viral load at enrollment (HR 1.01, 95% CI 0.98-1.05) were significantly associated with the time to symptom resolution. The median time to cessation of viral shedding was 10 days (95% CI 8-12), with higher SARS-CoV-2 IgG levels at enrollment associated with hastened resolution of viral shedding (HR 3.12, 95% CI 1.4-6.9, p=0.005). Myalgia, joint pains, and chills were associated with a significantly greater odds of oropharyngeal SARS-CoV-2 RNA detection.ConclusionsIn this outpatient cohort, inflammatory symptoms peaked early and were associated with ongoing SARS-CoV-2 replication. SARS-CoV-2 antibody levels were associated with more rapid viral shedding cessation, but not with time to symptom resolution. These findings have important implications for COVID-19 screening approaches and clinical trial design.

scholarly journals Adenotonsillar Hypertrophy as a Cause of Failure to Thrive

1990 ◽  
Vol 4 (8) ◽  
pp. 485-488
Author(s):  
Ann G Sheehan ◽  
R Brent Scott ◽  
Helen M Machida
Keyword(s):  
Respiratory Symptoms ◽  
Upper Airway ◽  
Failure To Thrive ◽  
Adenotonsillar Hypertrophy ◽  
Cause Of Failure ◽  
History Of ◽  
Laboratory Investigations ◽  
Upper Respiratory ◽  
Partial Upper Airway Obstruction ◽  
Upper Respiratory Symptoms

Two infant aged 11 and 15 months presented to the Gastroenterology Clinic at Alberta Children's Hospital because of failure to thrive. Clinical and laboratory investigations excluded any underlying abnormality of 1he gastrointestinal tract. Because of a history of obstructive upper respiratory symptoms, both were referred for ear, nose and throat evaluation, and both were found to have partial upper airway obstruction secondary to adenotonsillar hypertrophy. Subsequent adenotonsillectomy led to resolution of obstructive upper respiratory symptoms and dramatic increases in weight gain and growth. Adenotonsillar hypertrophy should be included among the potential causes of failure to thrive in infancy, especially if the child has a history of obstructive upper respiratory symptoms.

scholarly journals Genotype-Specific Lesion Growth Rates in Stargardt Disease

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1981
Author(s):  
Rachael C. Heath Jeffery ◽  
Jennifer A. Thompson ◽  
Johnny Lo ◽  
Tina M. Lamey ◽  
Terri L. McLaren ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Growth Rates ◽  
Trial Design ◽  
Primary Outcome ◽  
Fundus Autofluorescence ◽  
Clinical Trial Design ◽  
Effective Radius ◽  
Stargardt Disease ◽  
History Of ◽  
Lesion Growth

Reported growth rates (GR) of atrophic lesions in Stargardt disease (STGD1) vary widely. In the present study, we report the longitudinal natural history of patients with confirmed biallelic ABCA4 mutations from five genotype groups: c.6079C>T, c.[2588G>C;5603A>T], c.3113C>T, c.5882G>A and c.5603A>T. Fundus autofluorescence (AF) 30° × 30° images were manually segmented for boundaries of definitely decreased autofluorescence (DDAF). The primary outcome was the effective radius GR across five genotype groups. The age of DDAF formation in each eye was calculated using the x-intercept of the DDAF effective radius against age. Discordance between age at DDAF formation and symptom onset was compared. A total of 75 eyes from 39 STGD1 patients (17 male [44%]; mean ± SD age 45 ± 19 years; range 21–86) were recruited. Patients with c.3113C>T or c.6079C>T had a significantly faster effective radius GR at 0.17 mm/year (95% CI 0.12 to 0.22; p < 0.001 and 0.14 to 0.21; p < 0.001) respectively, as compared to those patients harbouring c.5882G>A at 0.06 mm/year (95% CI 0.03–0.09), respectively. Future clinical trial design should consider the effect of genotype on the effective radius GR and the timing of DDAF formation relative to symptom onset.

scholarly journals Inflammatory but not respiratory symptoms are associated with ongoing upper airway viral shedding in outpatients with uncomplicated COVID-19

2021 ◽  
pp. 115612
Author(s):  
Karen B. Jacobson ◽  
Natasha Purington ◽  
Julie Parsonnet ◽  
Jason Andrews ◽  
Vidhya Balasubramanian ◽  
...  
Keyword(s):  
Respiratory Symptoms ◽  
Upper Airway ◽  
Viral Shedding

scholarly journals 278. Immunocompromised Patients with Prolonged Viral Shedding of SARS-COV-2

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S244-S245
Author(s):  
Jessica Tarabay ◽  
Ahmed Babiker ◽  
Max W Adelman ◽  
Victoria D Stittleburg ◽  
Jay Varkey ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Symptom Onset ◽  
B Cell Lymphoma ◽  
N Gene ◽  
Prior History ◽  
Cell Transplant ◽  
Immunocompromised Patients ◽  
Subgenomic Rna ◽  
Viral Shedding ◽  
History Of

Abstract Background Most individuals diagnosed with mild to moderate COVID-19 are no longer infectious after day 10 of symptom onset and those with severe or critical illness from COVID are typically not infection after day 20 day of symptom onset. Recovered persons can continue to test positive for SARS-CoV-2 by PCR via detection of non-viable RNA in nasopharyngeal specimens for up to three months (or longer) after illness onset. It is also know known that severely immunocompromised patients may produce replication-competent virus greater than 20 days from symptom onset and may require, per CDC recommendations, “additional testing and consultation with infectious diseases specialists and infection control experts”. We aim to discuss four case studies of severely immunocompromised patients who exhibited signs of persistent COVID-19 infection of COVID and how we managed transmission-based precautions in our hospital through sequencing and evaluation of cycle thresholds (CT) values and subgenomic RNA detection. Methods Residual nasopharyngeal (NP) samples were collected on patients exhibiting persistent COVID like symptoms. These samples underwent N gene and N gene subgenomic RNA (sgRNA) real-time reverse transcription polymerase chain reaction (rRT-PCR) testing. Results Analysis of longitudinal SARS-CoV-2 sequence data demonstrated within-patient virus evolution, including mutations in the receptor binding domain and deletions in the N-terminal domain of the spike protein, which have been implicated in antibody escape. See Figures 1 and 2. Figure 1. Timelines of Identified Patients 1 and 2 Patient 1: 46-year-old woman with recently diagnosed stage IV diffuse large B-cell lymphoma for which she was treated with 2 cycles of R-CHOP. Patient 2: 38-year-old woman with history of myelodysplastic syndrome, peripheral blood stem cell transplant with chronic graft versus host disease of the GI tract, skin, and eyes as well as CMV enteritis, and she was maintained on rituximab, mycophenolate mofetil, prednisone, and monthly IVIG without recent changes to her immunosuppression. Figure 2. Timeline of Identified Patients 3 and 4 Patient 3: 44 year-old man with prior history of thymoma s/p thymectomy Patient 4: 46 year-old man who was initially diagnosed with marginal zone lymphoma approximately 2.5 years ago. He was initially treated with bendamustine and rituximab and achieved remission. He was then continued on maintenance rituximab without significant complications for a planned two years. Conclusion Differentiating between prolonged viral shedding of non-infectious RNA and persistent replicating viable virus can be difficult to determine without full evaluation of a patient’s clinical picture and timeline. Consultation between laboratory, infectious diseases, and infection prevention experts to provide appropriate level of guidance for precautions and treatment may be warranted. Testing by PCR and analysis of CT values may provide key findings of viral replication in immunocompromised hosts, indicating the need for evaluation of additional treatment and maintaining isolation status in healthcare settings. Disclosures All Authors: No reported disclosures

scholarly journals Corticosteroid Treatment Impact on Spinal Deformity in Duchenne Muscular Dystrophy

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Ilaria Sanzarello ◽  
Luciano Merlini ◽  
Francesco Traina ◽  
Michele Attilio Rosa ◽  
Cesare Faldini
Keyword(s):  
Clinical Trial ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Spinal Deformity ◽  
Trial Design ◽  
Progressive Disease ◽  
Clinical Trial Design ◽  
Corticosteroid Treatment ◽  
Surgical Interventions ◽  
History Of

Duchenne muscular dystrophy is a progressive disease with loss of ambulation at around 9-10 years of age, followed, if untreated, by development of scoliosis, respiratory insufficiency, and death in the second decade of life. This review highlights the natural history of the disease, in particular, with regard to the development of the spinal deformity and how this complication has been modified by surgical interventions and overall by corticosteroid treatment. The beneficial effect of corticosteroids may have also an impact on the clinical trial design of the new emerging causative therapies.

Integrating radiomics into clinical trial design

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Jessica J. Waninger ◽  
Michael D. Green ◽  
Catherine Cheze Le Rest ◽  
Benjamin Rosen ◽  
Issam El Naqa
Keyword(s):  
Clinical Trial ◽  
Trial Design ◽  
Clinical Trial Design

Gestational diabetes mellitus: are mothers being followed-up? A retrospective study

2018 ◽  
Vol 68 (suppl 1) ◽  
pp. bjgp18X697469
Author(s):  
Rebecca Ward ◽  
Fahmy W Hanna ◽  
Ann Shelley-Hitchen ◽  
Ellen Hodgson ◽  
Adrian Heald ◽  
...  
Keyword(s):  
Gestational Diabetes ◽  
Median Time ◽  
Post Partum ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Tertiary Referral Centre ◽  
Alternative Approach ◽  
Nice Guidance ◽  
History Of

BackgroundWomen with gestational diabetes (GDM) have an elevated risk of developing type 2 diabetes (T2DM). NICE Guidance recommends women who develop GDM are screened 6 weeks post-partum and annually thereafter.AimTo evaluate conformity to guidance of screening in women with GDM by 6-week post-partum fasting plasma glucose (FPG) and annual FPG and determine time between delivery and development of T2DM.MethodRecords at a tertiary referral centre were used to identify women (n = 54) diagnosed with GDM by antenatal oral glucose tolerance test between July 1999 and January 2007. Data from laboratory records were used to collect investigations of glycaemic status during the follow-up period (median follow-up 12.4 years, range 9.5–17.1 years).ResultsOf 252 women, 102 (40.2%) did not have a FPG at 6 weeks (+/−2 weeks). Of these, median time to first test was 1.2 years (range 0.04–10.8 years), with only 43.1% followed-up within 1 year. In those who had a 6-week FPG, 17 (11.3%) women had no further tests. A total of 84 (33% of those with gestational diabetes in the index pregnancy) women were diagnosed with T2DM; median time from delivery to diagnosis was 5.2 years (range 0.35–15.95). We found the only significant factor for a follow-up test at 1-year post-partum was the use of insulin.ConclusionOur data suggest an alternative approach is needed for monitoring women with a history of GDM. This needs to be appropriate for a generally healthy group in which traditional screening mechanisms may not be adequate or sufficient.

Digital Technology in Clinical Trials for Multiple Sclerosis: a systematic review. (Preprint)

2020 ◽  
Author(s):  
Marcello De Angelis ◽  
Luigi Lavorgna ◽  
Antonio Carotenuto ◽  
Martina Petruzzo ◽  
Roberta Lanzillo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Outcome Measures ◽  
Digital Technology ◽  
Clinical Trial Design ◽  
Motor Rehabilitation ◽  
Robot Assisted ◽  
Future Directions ◽  
Treatment Side Effects

BACKGROUND Clinical trials in multiple sclerosis (MS) have leveraged the use of digital technology to overcome limitations in treatment and disease monitoring. OBJECTIVE To review the use of digital technology in concluded and ongoing MS clinical trials. METHODS In March 2020, we searched for “multiple sclerosis” and “trial” on pubmed.gov and clinicaltrials.gov using “app”, “digital”, “electronic”, “internet” and “mobile” as additional search words, separately. Overall, we included thirty-five studies. RESULTS Digital technology is part of clinical trial interventions to deliver psychotherapy and motor rehabilitation, with exergames, e-training, and robot-assisted exercises. Also, digital technology has become increasingly used to standardise previously existing outcome measures, with automatic acquisitions, reduced inconsistencies, and improved detection of symptoms. Some trials have been developing new patient-centred outcome measures for the detection of symptoms and of treatment side effects and adherence. CONCLUSIONS We will discuss how digital technology has been changing MS clinical trial design, and possible future directions for MS and neurology research.

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