...if the patient is admitted, a rapid diagnosis ofinfluenza can help inform early appropriate infection prevention measures to prevent nosocomial influenza virus transmission to vulnerable ...inpatients. Depending upon the epidemiology of a given flu season, many respiratory tract infections denoted as influenza-like illness are due to other circulating respiratory viruses that cannot be reliably distinguished from influenza on clinical symptoms alone. ...rapid influenza tests can assist with clinical care and treatment decisions for patients in a variety of settings, including outpatient clinics, chronic care facilities, EDs, and hospitals. ...rapid identification of an outbreak in a community or chronic care facility allows for appropriate public health measures. ...significant costs savings have been demonstrated with appropriate discontinuation of infection control measures when a respiratory pathogen aside from influenza was identified that did not require isolation.
Allosteric potentiators amplify the sensitivity of physiologic control circuits, a mode of action that could provide therapeutic advantages. This hypothesis was tested with the dopamine D1 receptor ...potentiator DETQ 2-(2,6-dichlorophenyl)-1-((1S,3R)-3-(hydroxymethyl)-5-(2-hydroxypropan-2-yl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one. In human embryonic kidney 293 (HEK293) cells expressing the human D1 receptor, DETQ induced a 21-fold leftward shift in the cAMP response to dopamine, with a K
of 26 nM. The maximum response to DETQ alone was ∼12% of the maximum response to dopamine, suggesting weak allosteric agonist activity. DETQ was ∼30-fold less potent at rat and mouse D1 receptors and was inactive at the human D5 receptor. To enable studies in rodents, an hD1 knock-in mouse was generated. DETQ (3-20 mg/kg orally) caused a robust (∼10-fold) increase in locomotor activity (LMA) in habituated hD1 mice but was inactive in wild-type mice. The LMA response to DETQ was blocked by the D1 antagonist SCH39166 and was dependent on endogenous dopamine. LMA reached a plateau at higher doses (30-240 mg/kg) even though free brain levels of DETQ continued to increase over the entire dose range. In contrast, the D1 agonists SKF 82958, A-77636, and dihydrexidine showed bell-shaped dose-response curves with a profound reduction in LMA at higher doses; video-tracking confirmed that the reduction in LMA caused by SKF 82958 was due to competing stereotyped behaviors. When dosed daily for 4 days, DETQ continued to elicit an increase in LMA, whereas the D1 agonist A-77636 showed complete tachyphylaxis by day 2. These results confirm that allosteric potentiators may have advantages compared with direct-acting agonists.
We investigated how aging affects the integration of temporal rate for auditory flutter (amplitude modulation) presented with visual flicker. Since older adults were poorer at detecting auditory ...amplitude modulation, modulation depth was individually adjusted so that temporal rate was equally discriminable for 10 Hz flutter and flicker, thereby balancing the reliability of rate information available to each sensory modality. With age-related sensory differences normalized in this way, rate asynchrony skewed both auditory and visual rate judgments to the same extent in younger and older adults. Therefore, reliability-based weighting of temporal rate is preserved in older adults. Concurrent presentation of synchronous 10 Hz flicker and flutter improved temporal rate discrimination consistent with statistically optimal integration in younger but not older adults. In a control experiment, younger adults were presented with the same physical auditory stimulus as older adults. This time, rate asynchrony skewed perceived rate with greater auditory weighting rather than balanced integration. Taken together, our results indicate that integration of discrepant auditory and visual rates is not altered due to the healthy aging process once sensory deficits are accounted for, but that aging does abolish the minor improvement in discrimination performance seen in younger observers when concordant rates are integrated.
Pathology Consultation on Influenza Diagnostics McMullen, Allison R; Anderson, Neil W; Burnham, Carey-Ann D
American journal of clinical pathology,
04/2016, Letnik:
145, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Objectives: To describe the strengths and limitations of the available influenza diagnostics, with a focus on rapid antigen detection assays and nucleic acid detection assays.
Methods: A case-based ...presentation is used to illustrate the potential limitations of rapid antigen detection assays for influenza.
Results: Influenza is a seasonal illness; estimates attribute influenza to approximately 200,000 hospitalizations and 41,000 deaths in the United States annually. Antigen detection assays for influenza are rapid and convenient, and thus are widely used in a variety of health care settings, even though the sensitivity of these assays may be suboptimal. The United States Food and Drug Administration has recently created new guidelines intended to improve the oversight and performance characteristics of influenza antigen detection assays. Molecular assays, although more costly and complex, are more sensitive and may be designed to simultaneously detect multiple respiratory pathogens within a single assay.
Conclusions: Diagnostic assays for influenza can vary greatly with regards to analytical performance characteristics, complexity, turnaround time and cost. This can have important patient care and infection prevention implications.
The emergence of illicit fentanyl use has resulted in considerable morbidity and mortality. Although illicit use of other opioids has been associated with transmission of viral and bacterial ...infections, limited data exist for the prevalence of infectious diseases among illicit fentanyl users. The purpose of this study was to assess the likelihood of infectious disease testing and infection prevalence among illicit fentanyl users.
Results from urine drug screens (UDSs) performed from August 13, 2019, to October 16, 2019, were obtained from the laboratory information system with concurrent microbial testing. Patients were categorized based on UDS results, and illicit drug use was inferred from physician encounter notes in the electronic medical record.
Suspected illicit drugs users with fentanyl detected by UDS were more likely to be screened odds ratio (OR): 1.7; 95% CI, 1.26-2.4 and test positive for hepatitis C virus (HCV) by immunoassay (OR: 5.89; 95% CI, 2.93-11.31) than patients without drugs detected. Patients with suspected illicit fentanyl use who were discharged from the emergency department (ED) were less likely to be tested for HCV than patients in outpatient settings (OR: 3.47; 95% CI, 1.05-10.4) and inpatient settings (OR: 17.43; 95% CI, 6.53-45.88). Patients with suspected illicit fentanyl use were more likely to have infected abscesses or wounds (OR: 5.12; 95% CI, 2.07-13.7) and Staphylococcus aureus infections (OR: 4.5; 95% CI, 1.59-12.28) than patients without drugs detected.
Patients with a positive UDS for fentanyl and suspected illicit use were more likely to test positive for HCV, were rarely screened for HCV in the ED, and had an increased risk of invasive S. aureus wound or abscess infection. These findings may represent considerable barriers to care for patients who use fentanyl illicitly.
With more than 900 000 confirmed cases worldwide and nearly 50 000 deaths during the first 3 months of 2020, the coronavirus disease 2019 (COVID-19) pandemic has emerged as an unprecedented health ...care crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe cases. For these regions, health care delivery has been disrupted and compromised by critical resource constraints in diagnostic testing, hospital beds, ventilators, and health care workers who have fallen ill to the virus exacerbated by shortages of personal protective equipment. Although mild cases mimic common upper respiratory viral infections, respiratory dysfunction becomes the principal source of morbidity and mortality as the disease advances. Thoracic imaging with chest radiography and CT are key tools for pulmonary disease diagnosis and management, but their role in the management of COVID-19 has not been considered within the multivariable context of the severity of respiratory disease, pretest probability, risk factors for disease progression, and critical resource constraints. To address this deficit, a multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing patients with COVID-19 across a spectrum of health care environments evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions, and resource constraints. Fourteen key questions, corresponding to 11 decision points within the three scenarios and three additional clinical situations, were rated by the panel based on the anticipated value of the information that thoracic imaging would be expected to provide. The results were aggregated, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of chest radiography and CT in the management of COVID-19.
Widespread testing of SARS-CoV-2 has resulted in shortages of collection devices and transport media. We evaluated the stability of flocked swabs inoculated with SARS-CoV-2-containing specimen ...incubated dry (i.e. without transport medium) at room temperature.
A pool of SARS-CoV-2 positive specimen was used to inoculate flocked swabs. Five swabs were placed immediately into UTM following inoculation, and tested immediately (day 0). Fifteen of the swabs were placed into sterile 15 mL conical tubes and incubated at room temperature for one, two, or seven days. Following incubation, swabs were hydrated in separate vials of UTM and tested. This protocol was repeated for viral transport media (VTM) and saline. As a comparison, a series of swabs was prepared and tested in parallel, but stored in the corresponding liquid transport media (UTM, VTM, or saline) and incubated at room temperature. Testing was performed at 1, 2, and 7 days post inoculation in duplicate. All molecular testing was performed using the Roche cobas SARS-CoV-2 assay.
All dry swabs tested at days 1, 2, and 7 provided results that were within two cycle thresholds (Cts) of the average Ct values for swabs hydrated in the same media and tested on day 0. There was no statistical difference in Ct values between swabs incubated in liquid media versus dry swabs incubated at room temperature prior to hydration in liquid media.
The utilization of "dry swabs" may simplify specimen collection, negate the need for liquid transport media, and mitigate safety risks while preserving the accuracy of testing.
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