Respiratory virus detection among healthcare professionals in Brazil: work-related contact and episode recurrence during the COVID-19 pandemic.

OBJECTIVES: Since the beginning of the COVID-19 pandemic, changes in the circulation of respiratory viruses have been observed after measures to control the spread of SARS-CoV-2 were implemented. In this sense, we aimed to understand the circulation of the respiratory virus and its impact in a controlled healthy population of healthcare professional (HCP) volunteers in phase III of the clinical trial of the ChadOx nCoV1 conducted in São Paulo, Brazil. STUDY DESIGN: This was a nested observational cohort study within a clinical trial. METHODS: We performed RT-qPCR to detect SARS-CoV-2, influenza virus A and B (IVA and IVB), respiratory syncytial virus (RSV), human rhinovirus (HRV), human metapneumovirus (hMPV), human coronaviruses (hCoVs: HKU-1, NL63, OC43, and 229-E), parainfluenza virus (PiV) I-IV, and q-PCR for adenovirus in nasopharyngeal and oropharyngeal samples obtained from HCP enrolled in the clinical trial to assess respiratory viruses infection among vaccinated and non-vaccinated. RESULTS: From July 2020 to January 2022, 876 samples were included from 737 volunteers (median age: 33 years, 62.9% female). New episodes were registered for 119 individuals. We observed an overall positivity of 37.7% for SARS-CoV-2 and 16.4% for other respiratory viruses; HRV was the second most detected virus (8%), followed by RSV (2.4%). Fully vaccinated individuals accounted for 53.3% of collected samples, and 52.9% presented at least one respiratory virus infection, with SARS-CoV-2 being the most predominant etiologic agent (62.3%). Influenza and hMPV were not detected among the tested samples. Among the subjects that presented more than one episode, SARS-CoV-2 and HRV infections were related to direct contact with patients (P < 0.002). CONCLUSIONS: Data show high infection rates among HCPs even under mask policies and contact precautions, highlighting the need for improvement in infection control measures in this population regardless of the vaccination program.

Rhinovirus detection using different PCR-based strategies.

Human rhinoviruses (HRVs) are the major cause of the common cold. HRVs were recently reclassified into the Enterovirus genus (HEV) in the Picornaviridae family. HRVs and other members of the HEV genus share many common features, including sense RNA genomes and partial nucleotide sequence identity. The aim of this study was to evaluate different HRV detection strategies. Samples from adults with acute respiratory infection (n = 291) who were treated in Sao Paulo Hospital (2001-2003) were tested using three assays. The first assay detected picornaviruses by RT-PCR and hybridization, the second detected rhinoviruses using RT-PCR/sequencing, and the third differentiated HRV from HEV using duplex semi-nested-RT-PCR. Analysis of the results obtained from the first two strategies revealed 83% concordance. Discordant samples were then evaluated by the third protocol, and 82% were negative. The picornavirus detection protocol was more sensitive but less specific than the rhinovirus detection protocols. The semi-nested protocol utilized in the present study was less sensitive and was not useful in differentiating HRV from HEV. Sequencing assays examining different genes would address the best strategy of confirming rhinovirus and enterovirus infections.

Evaluation of a rapid test (QuickVue) compared with the shell vial assay for detection of influenza virus clearance after antiviral treatment.

QuickVue influenza rapid diagnostic test (Quidel Corp., San Diego, CA, USA) was compared with the classical shell vial assay for evaluation of influenza virus clearance in patients treated with antiviral drugs. The shell vial assay was carried out on nasopharyngeal samples obtained from volunteers for a neuraminidase-inhibitor clinical trial protocol with 24 h or less from the onset of symptoms of influenza before the use of antiviral (day 1). Follow-up included samples collected after 24 and 72 h of therapy (day 2 and 4). The rapid test was retrospectively carried out in frozen samples. Test results on 99 samples from 33 adults were compared and the shell vial assay was considered the gold standard. The overall rate of detection for the shell vial assay was 39.4% and for QuickVue was 35.5%, with a concordance of 79.8%. The sensitivity obtained for QuickVue was 74.4% and the specificity was 82.7%. Comparison of test results day by day in the follow-up resulted: day 1, higher sensitivity of QuickVue test (85.5%, 24/29); day 2, agreement on positive and negative results between QuickVue and shell vial was 60.6% (20/33); day 4, all test results in samples collected after 72 h of therapy were negative. The QuickVue test showed good sensitivity for the diagnosis of influenza-like illnesses. This rapid test kit can be an alternative tool for interventions in disease management.

Tolerability and serum levels of benoxaprofen in healthy volunteers.

Tolerability, serum levels and urinary excretion of benoxaprofen (B) in therapeutic doses of 400 or 600 mg as a capsule were studied in 22 healthy volunteers after single or multiple doses. B was determined by a HPLC procedure. Apart from a skin reaction in one patient, no major problems were encountered by patients. Mean serum peak values after 400 and 600 mg were 49.84 and 94.54 micrograms/ml respectively. Mean time to peak was 5.6 hours and mean half-life ranged between 45.38 (400 mg regimen) and 63.48 hours (600 mg regimen). Urinary excretion was only a fraction of the doses ingested: 14.39% after a single dose; 35.5% after multiple doses. This may depend on other pathways of elimination of the drug because steady state is reached according to half-life.

Pharmacokinetics of benperidol in volunteers after oral administration.

Benperidol in a 4 mg single dose was administered orally to five healthy male volunteers. The drug was rapidly absorbed (tmax = 2.27 +/- 0.57 h) and largely distributed, the volume of distribution being 5.19 +/- 1.99 l.kg-1. Elimination half-life was 7.65 +/- 2.14 h. Urinary excretion represented only a minimal fraction of ingested dose (0.1 +/- 0.007%). Variability of the area under the curve makes a first-pass metabolism a reasonable possibility. Acute dystonias appeared in two subjects.

Stereospecific disposition of flunoxaprofen enantiomers in human beings.

The absorption and disposition kinetics of the enantiomers of the nonsteroidal antiinflammatory drug flunoxaprofen were studied in six healthy volunteers after oral administration of either R,S(+/-)-flunoxaprofen or R(-)-flunoxaprofen. The apparent values of the volume of distribution and systemic clearance of the S(+)-enantiomer were significantly lower than those of the R(-)-enantiomer. There was no significant difference in the absorption and elimination half-lives between the two isomers. The S(+)- to R(-)-isomer plasma concentration ratio increased with time with an apparent inversion half-time of about 50 h. This observation suggests metabolic inversion of R(-)- to S(+)-enantiomer, although the possibilities of stereoselective bioavailability or interaction between the two isomers can not be excluded.

Absorption and disposition kinetics of flunoxaprofen and benoxaprofen in healthy volunteers.

Flunoxaprofen is a new nonsteroidal antiinflammatory agent that, like benoxaprofen, inhibits leukotriene rather than prostaglandin synthesis. The absorption and disposition kinetics of flunoxaprofen and benoxaprofen have been compared in six healthy volunteers after oral administration of 100 mg of each drug. The two drugs showed similar absorption characteristics, whereas the distribution and elimination processes were much faster for flunoxaprofen. The renal route of elimination appeared to contribute significantly less to the disposition of flunoxaprofen. These kinetic characteristics render less likely the risk of excessive drug accumulation with flunoxaprofen, especially in the presence of reduced renal function.

[Diagnostic value of 5'nucleotidase in primary and secondary neoplasms of the liver]. / Valore diagnostico della 5'nucleotidasi nelle neoplasie primitive e secondarie del fegato.

64 patients with various malignant neoplasms (6 primary and 18 secondary liver cancers, 40 tumors without evidence of hepatic involvement) entered a comparative study measuring serum levels of 5'nucleotidase, AFP, TPA, CEA, CA 19-9. In primary liver cancer, 5'nucleotidase true positive rate was 100% (vs 67% of AFP, TPA, CA 19-9 and 33% of CEA); in secondary liver tumors it was 67% (vs 11% of AFP, 44% of CEA, 55% of CA 19-9 100% of TPA). Diagnostic sensitivity was 75% and specificity 90.5%.

Rhinovirus detection using different PCR-based strategies

Human rhinoviruses (HRVs) are the major cause of the common cold. HRVs were recently reclassified into the Enterovirus genus (HEV) in the Picornaviridae family. HRVs and other members of the HEV genus share many common features, including sense RNA genomes and partial nucleotide sequence identity. The aim of this study was to evaluate different HRV detection strategies. Samples from adults with acute respiratory infection (n = 291) who were treated in Sao Paulo Hospital (2001-2003) were tested using three assays. The first assay detected picornaviruses by RT-PCR and hybridization, the second detected rhinoviruses using RT-PCR/sequencing, and the third differentiated HRV from HEV using duplex semi-nested-RT-PCR. Analysis of the results obtained from the first two strategies revealed 83% concordance. Discordant samples were then evaluated by the third protocol, and 82% were negative. The picornavirus detection protocol was more sensitive but less specific than the rhinovirus detection protocols. The semi-nested protocol utilized in the present study was less sensitive and was not useful in differentiating HRV from HEV. Sequencing assays examining different genes would address the best strategy of confirming rhinovirus and enterovirus infections.

Reaction of primary aromatic amines with alkyl carbonates over NaY faujasite: a convenient and selective access to mono-N-alkyl anilines.

At atmospheric pressure and at 130-160 degrees C, primary aromatic amines (p-XC6H4NH2, X = H, Cl, NO2) are mono-N-alkylated in a single step, with symmetrical and asymmetrical dialkyl carbonates [ROCOOR', R = Me, R' = MeO(CH2)2O(CH2)2; R = R' = Et; R = R' = benzyl; R = R' = allyl; R = Et, R' = MeO(CH2)2O(CH2)2], in the presence of a commercially available NaY faujasite. No solvents are required. Mono-N-alkyl anilines are obtained with a very high selectivity (90-97%), in good to excellent yields (68-94%), on a preparative scale. In the presence of triglyme as a solvent, the mono-N-alkyl selectivity is independent of concentration and polarity factors. The reaction probably takes place within the polar zeolite cavities, and through the combined effect of the dual acid-base properties of the catalyst.

Electrochemical detection of benperidol in serum for drug monitoring in humans.

A high-pressure liquid chromatographic (HPLC) method for the serum assay of benperidol is described. One ml of serum is required for a single estimation. The method involves a simple and rapid extraction step (BondElut columns), HPLC separation (C8 10-mu column), and electrochemical detection (+0.65 V). Haloperidol is used as internal standard. On the basis of this procedure, recovery (93-97%) and reproducibility (intra-assay and inter-assay coefficients of variation less than 9%) are satisfactory. The detection limit is 0.2 ng/ml of serum. After therapeutic doses, trough serum levels ranged from 3.8 to 12 ng/ml in five patients.