A neuropathic etiology has been suggested for patients with chronic laryngopharyngitis symptoms without visible structural pathology. Prior studies have shown that treatment with neuro-modulating ...medications is beneficial, but it is unknown if this was due to placebo effect. Our objective was to compare the efficacy of amitriptyline versus placebo in treating chronic laryngopharyngeal neuropathy.
Prospective, randomized placebo-controlled trial.
Patients were randomized to receive placebo or amitriptyline for 8weeks. Primary outcome was change in modified Reflux Symptom Index (mRSI) score. Secondary outcomes were change in Voice Handicap Index-10 (VHI) scores, rates of adverse effects, and overall symptom severity.
Eighteen patients completed the study. The average difference in mRSI and VHI-10 scores after treatment were not significantly different between study arms. However, more subjects taking amitriptyline felt their symptoms had subjectively improved (6 out of 9, 67%), while the remainder noted no change. In the placebo group, only 4 out of 9 subjects (44%) felt their symptoms were better and 2 felt worse. Subjects took an average of 25mg of amitriptyline or placebo daily by the end of the 8-week treatment period. No serious adverse effects were noted.
Although there was a trend toward greater subjective improvement in overall symptoms with amitriptyline, interpretation is limited due to the small sample size. Larger randomized controlled trials to determine the efficacy of neuro-modulating agents in the treatment of chronic laryngopharyngeal neuropathy, as well as better metrics to characterize this disorder, are warranted.
•25% of participants had never received AED treatment.•72% of participants met our criteria for poorly controlled epilepsy.•Traditional medicine use was more frequent among children.•A history of ...>100 lifetime seizures was a predictor of unintentional injury.•Burn injuries were statistically significantly associated with being female.
To characterize people with epilepsy (PWE) presenting to a free neurology consultation and antiepileptic drug (AED) service in the Republic of Guinea.
Guinea is a low-income country in West Africa that recently experienced an Ebola Virus Disease epidemic. Community-dwelling PWE were seen at a public referral hospital in Conakry, the capital city. During two visits in 2017, an African-U.S. team performed structured interviews and electroencephalograms and provided AEDs.
Of 257 participants (143 children, 122 female), 25% had untreated epilepsy and 72% met our criteria for poorly controlled epilepsy. 59% had >100 lifetime seizures, and 58% reported a history consistent with status epilepticus. 38 school-aged children were not in school and 26 adults were unemployed. 115 were not currently taking an AED, including 50 participants who had previously taken an AED and stopped. Commonly cited reasons for AED discontinuation were perceived side effects, unaffordability, and unavailability of AEDs. Traditional medicine use was more frequent among children versus adults (92/143 vs. 60/114, p = 0.048). 57 participants had head injuries, 29 had burns, and 18 had fractures. In a multivariable regression analysis, >100 lifetime seizure count was strongly associated with seizure-related injury (p < 0.001). Burns were more likely to occur among females (p = 0.02).
There is an urgent need to improve the standard of care for PWE in Guinea. Several missed opportunities were identified, including low use of AEDs and high use of traditional medicines, particularly in children. Targeted programs should be developed to prevent unintentional injury and improve seizure control.
As Ambulatory Surgical Centers (ASCs) become more common in academic medical centers, large hospital systems must determine how to shift resident education from inpatient to outpatient surgical ...centers. This study aims to define stakeholders’ views regarding the integration of surgical residents into ASCs.
Long-form interviews lasting 30 to 60 minutes were conducted. Interviews were hand-transcribed and analyzed by qualitative analysis to determine benefits of learning in ASCs for residents, challenges that arise from integrating residents, and recommendations to improve resident incorporation.
Interviews were conducted using a video conferencing platform.
Residency program directors, attending surgeons, graduate medical learners, and a nursing manager were interviewed. Twenty-one total interviews were conducted, representing ten different departments.
Stakeholders agreed that residents benefit from being placed in ASCs because the fast, surgical pace allows the residents to engage in more cases. However, different stakeholders highlighted different challenges, all centered around the notion of inter-stakeholder conflict due to conflicting priorities among residents, attending physicians, and administration. Likewise, recommendations differed by stakeholder group–faculty members sought more defined learning objectives and enhanced communication, whereas residents desired that ambulatory surgical time be more structured.
Despite the pressures of rapid case turnover, stakeholders agreed that there are many benefits to resident education in ASCs. Findings related to challenges and recommendations support the need to strengthen communication between stakeholder groups and better plan for resident integration into ASCs.
Abstract
Background
Outpatient coronavirus disease 2019 (COVID-19) has been insufficiently characterized. To determine the progression of disease and determinants of hospitalization, we conducted a ...prospective cohort study.
Methods
Outpatient adults with positive reverse transcription polymerase chain reaction results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recruited by phone between April 21 and July 23, 2020, after receiving outpatient or emergency department testing within a large health network in Maryland, United States. Symptoms were collected by participants on days 0, 3, 7, 14, 21, and 28, and portable pulse oximeter oxygen saturation (SaO2), heart rate, and temperature were collected for 15 consecutive days. Baseline demographics, comorbid conditions, and vital signs were evaluated for risk of subsequent hospitalization using negative binomial and logistic regression.
Results
Among 118 SARS-CoV-2-infected outpatients, the median age (interquartile range IQR) was 56.0 (50.0–63.0) years, and 50 (42.4%) were male. Among individuals in the first week of illness (n = 61), the most common symptoms included weakness/fatigue (65.7%), cough (58.8%), headache (45.6%), chills (38.2%), and anosmia (27.9%). Participants returned to their usual health a median (IQR) of 20 (13–38) days from symptom onset, and 66.0% of respondents were at their usual health during the fourth week of illness. Over 28 days, 10.9% presented to the emergency department and 7.6% required hospitalization. The area under the receiver operating characteristics curve for the initial home SaO2 for predicting subsequent hospitalization was 0.86 (95% CI, 0.73–0.99).
Conclusions
Symptoms often persisted but uncommonly progressed to hospitalization among outpatients with COVID-19. Home SaO2 may be a helpful tool to stratify risk of hospitalization.
Background
Constitutive activation of nuclear factor κB (NF‐κB) is associated with poor prognosis. Irinotecan demonstrates single‐agent activity in head and neck cancer but activates NF‐κB, promoting ...cell survival and resistance. Bortezomib is a proteasome inhibitor that inactivates NF‐κB.
Patients and Methods
We performed a randomized phase II trial of bortezomib on days 1, 4, 8, and 11 and irinotecan on days 1 and 8 of each 21‐day cycle or single‐agent bortezomib on days 1, 4, 8, and 11 on a 21‐day cycle. The addition of irinotecan to bortezomib was allowed in patients who progressed on bortezomib alone.
Results
The response rate of bortezomib and irinotecan was 13%. One patient had a partial response to bortezomib alone (response rate 3%). No responses were seen in patients with addition of irinotecan at time of progression on bortezomib.
Conclusions
The bortezomib‐based regimens evaluated in this study have minimal activity in recurrent or metastatic head and neck cancer. Head Neck, 2013
Abstract
Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic control will require widespread access to accurate diagnostics. Salivary sampling circumvents swab supply ...chain bottlenecks, is amenable to self-collection, and is less likely to create an aerosol during collection compared with the nasopharyngeal swab.
Methods
We compared real-time reverse-transcription polymerase chain reaction Abbott m2000 results from matched salivary oral fluid (gingival crevicular fluid collected in an Oracol device) and nasal-oropharyngeal (OP) self-collected specimens in viral transport media from a nonhospitalized, ambulatory cohort of coronavirus disease 2019 (COVID-19) patients at multiple time points. These 2 sentences should be at the beginning of the results.
Results
There were 171 matched specimen pairs. Compared with nasal-OP swabs, 41.6% of the oral fluid samples were positive. Adding spit to the oral fluid percent collection device increased the percent positive agreement from 37.2% (16 of 43) to 44.6% (29 of 65). The positive percent agreement was highest in the first 5 days after symptoms and decreased thereafter. All of the infectious nasal-OP samples (culture positive on VeroE6 TMPRSS2 cells) had a matched SARS-CoV-2 positive oral fluid sample.
Conclusions
In this study of nonhospitalized SARS-CoV-2-infected persons, we demonstrate lower diagnostic sensitivity of self-collected oral fluid compared with nasal-OP specimens, a difference that was especially prominent more than 5 days from symptom onset. These data do not justify the routine use of oral fluid collection for diagnosis of SARS-CoV-2 despite the greater ease of collection. It also underscores the importance of considering the method of saliva specimen collection and the time from symptom onset especially in outpatient populations.
In a study of nonhospitalized COVID-19 patients, the oral fluid salivary sample type was insensitive compared to nasal-OP specimen types overall, but was improved with the addition of spit and most sensitive in the first 5 days after symptom onset.
The Cancer Genome Atlas (TCGA) network study of 12 cancer types
(PanCancer 12) revealed frequent mutation of TP53, and amplification and
expression of related TP63 isoform ΔNp63 in squamous cancers. ...Further,
aberrant expression of inflammatory genes and TP53/p63/p73 targets were detected
in the PanCancer 12 project, reminiscent of gene programs co-modulated by
cREL/ΔNp63/TAp73 transcription factors we uncovered in head and neck
squamous cell carcinomas (HNSCC). However, how inflammatory gene signatures and
cREL/p63/p73 targets are co-modulated genome-wide is unclear. Here, we examined
how inflammatory factor TNF-α broadly modulates redistribution of cREL
with ΔNp63α/TAp73 complexes and signatures genome-wide in the
HNSCC model UM-SCC46 using chromatin immunoprecipitation sequencing (ChIP-seq).
TNF-α enhanced genome-wide co-occupancy of cREL with ΔNp63α
on TP53/p63 sites, while unexpectedly promoting redistribution of TAp73 from
TP53 to Activator Protein-1 (AP-1) sites. cREL, ΔNp63α, and TAp73
binding and oligomerization on NF-κB, TP53 or AP-1 specific sequences
were independently validated by ChIP-qPCR, oligonucleotide-binding assays, and
analytical ultracentrifugation. Function of the binding activity was confirmed
using TP53, AP-1, and NF-κB specific response elements, or
p21,
SERPINE1
, and
IL-6
promoter luciferase reporter
activities. Concurrently, TNF-α regulated a broad gene network with
co-binding activities for cREL, ΔNp63α, and TAp73 observed upon
array profiling and RT-PCR. Overlapping target gene signatures were observed in
squamous cancer subsets and in inflamed skin of transgenic mice overexpressing
ΔNp63α. Furthermore, multiple target genes identified in this
study were linked to TP63 and TP73 activity and increased gene expression in
large squamous cancer samples from PanCancer 12 TCGA by CircleMap. PARADIGM
inferred pathway analysis revealed the network connection of TP63 and
NF-κB complexes through an AP-1 hub, further supporting our findings.
Thus, inflammatory cytokine TNF-α mediates genome-wide redistribution of
the cREL/p63/p73, and AP-1 interactome, to diminish TAp73 tumor suppressor
function and reciprocally activate NF-κB and AP-1 gene programs
implicated in malignancy.
Abstract
In an outpatient cohort in Maryland, clustering of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity within households was high, with 76% of 74 households reporting at ...least 1 other symptomatic person and 66% reporting another person who tested SARS-CoV-2 positive. SARS-CoV-2 positivity among household members was associated with larger household size and bedroom sharing.
Objective:
This study aimed to analyze differences in the evaluation of laryngopharyngeal neuropathy by laryngologists in the United States and Europe.
Methods:
Members of the American Laryngological ...Association (ALA) and the European Laryngological Society (ELS) were surveyed. Questionnaires were emailed to all 179 members of the ALA and all 324 members of the ELS.
Results:
Of the ALA members surveyed, 40 (23.3%) responded, compared to 72 members (22.2%) of the ELS group. Of the ALA respondents, 79.5% identified laryngology as their primary area of practice, whereas 56.9% of ELS respondents identified devoting more than 50% of their practice to laryngology. Of ELS laryngologists, 81.1% received training in laryngology or associated subspecialties. For diagnosing laryngopharyngeal neuropathy, the average comfort level on the Likert scale was significantly greater for ALA members than ELS members (P < .01). Furthermore, ALA laryngologists were less likely to consider laryngopharyngeal reflux as an overdiagnosed condition compared to ELS laryngologists (P < .05).
Conclusion:
Laryngologists in the United States and Europe vary significantly in their familiarity with laryngopharyngeal neuropathy. This could reflect either differences in awareness concerning this condition or a more critical perspective of European providers regarding the chronic laryngopharyngeal neuropathy (CLPN) diagnosis. As CLPN is still lacking definitive proof, the addition of European researchers could aid in validating CLPN and determining its overall effect on the chronic cough population.
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