Analytical and clinical evaluation of four commercial SARS-CoV-2 serological immunoassays in hospitalized patients and ambulatory individuals.

BACKGROUND: This study aimed to compare four anti-SARS-CoV-2 immunoassays in populations presenting different clinical severity levels. METHODS: Three populations were included: "severe-to-critical" ICU-hospitalized patients (n = 18), "mild-to-moderate" hospitalized patients (n = 16) and non-hospitalized symptomatic patients (n = 24). Four commercial immunoassays were analyzed and validated: anti-IgG ARCHITECT® (Abbott), anti-Total antibodies (Ab) VITROS® (Ortho Clinical Diagnostics), anti-IgG NovaLisa® (NovaTec Immundiagnostica) and Healgen® IgM and IgG (Zhejiang Orient Gene Biotech). Sensitivities were evaluated according to days post-symptoms onset (pso). Specificities were evaluated on SARS-CoV-2-negative control sera collected before January 2020. RESULTS: A majority of severe-to-critically ill patients showed detectable Ab already at day 14 and sensitivities reached 100 % after 22 days pso. For patients with "mild-to-moderate" illness, sensitivities increased by at least 5-fold from day 0 to day 14 pso. Non-hospitalized symptomatic individuals already seroconverted at day 14 days pso with 100 % sensitivities for Total Ab VITROS®. Specificities were evaluated at 97 % for ARCHITECT® and NovaLisa®, 98 % for VITROS® and at 94 % for Healgen® combined IgM and IgG. Five "severe-to-critically" ill patients presented high positive Ab levels for at least 16 weeks pso. CONCLUSION: The Ab levels and the evaluated sensitivities, representing the true positive rate, increased overtime and were related to the COVID-19 severity. Automated Total Ab immunoassay showed better sensitivities and specificity for immunological surveillance and vaccine evaluation.

Physical stability of highly concentrated injectable drugs solutions used in intensive care units.

BACKGROUND: The intensive care department of the institution use drug solutions within higher concentration to avoid fluid overload. The purpose of the study is to prove the physical stability of different injectable drugs within high concentration (amiodarone 25mg/mL, isosorbide 0.60mg/mL, lorazepam 0.16mg/mL, noradrenalin 0.120 and 0.240mg/mL, salbutamol 0.06mg/mL and sodium valproate 12mg/mL) to ensure the patients safety. METHODS: Five of 30 or 50mL polypropylene syringes were prepared for each solution under aseptic conditions and stored at room temperature. Immediately after the preparation (hour 0) and after 1, 4, 8, 24 and 48hours, 2mL of each solution were withdrawn from each syringe and placed in glass tubes to proceed to the stability test. All specimens were visually inspected in front of a black and of a white background and aliquots of each solution were centrifuged to proceed to microscopic inspection with a ten-fold magnification. The pH of each solution was measured with glass electrode pH-meter (Inolab level 1, WTW Weilhem, Germany with biotrode electrode, Hamilton, Bonaduz, Switzerland) and spectrophotometric measurements (Genesys 10 series, New-York, USA) were performed at three wavelengths (350, 410 and 550nm) to avoid the apparition of turbidity. RESULTS: For all the drugs included in the study, there was no significant change in pH, no color change, no turbidity or opacity and no precipitation observed in the solutions during the storage at room temperature for 48hours. No microaggregates were detected by microscope neither revealed by a change of absorbance. CONCLUSION: Within these limits, the preparations of amiodarone in 5% glucose polypropylene syringes and isosorbide, lorazepam, noradrenalin, salbutamol, valproate in 0.9% sodium chloride polypropylene syringes are physically stable at room temperature for 48hours. These results allow us to consider a study of chemical stability by high-performance liquid chromatography (HPLC).

Does an interaction exist between ketamine hydrochloride and Becton Dickinson syringes?

INTRODUCTION: An international alert from Becton Dickinson (BD) has noted the possibility of interaction between several molecules and some syringes. The Centralized IntraVenous Additives Service of the institution was using 3 mL BD syringes to store ketamine HCl. This study evaluated the interaction between ketamine and these syringes. METHOD: A batch of BD syringes produced in Europe and left in quarantine from the day of the international alert has been tested at 22, 29, 36, 43 and 50 days of storage at room temperature. At each time, the pH of the solutions was measured. The solutions were inspected visually and by microscope, and spectrophotometric measurements were performed. The concentrations were measured by a validated ultra-high-performance liquid chromatography-diode array detector. RESULTS: Neither physical change nor pH modification was observed during the study. According to a lower limit of the 95% unilateral CI on the mean >90% of the theoretical concentration, the solutions remain stable for at least 50 days. CONCLUSION: In our study conditions, ketamine can be stored for at least 50 days without risk of sorption with syringes.

Long-term stability of dexamethasone and alizapride or ondansetron in sodium chloride 0.9% polyolefin bag at 5±3°C.

INTRODUCTION: The aim of the study was to investigate the long-term stability of dexamethasone 10mg associated with alizapride 100mg or ondansetron 8mg in 100mL of 0.9% sodium chloride solution stored at 5±3°C. METHOD: Solutions of 0.9% sodium chloride 100mL in polyolefin bags (n=5) containing approximately dexamethasone (DEX) 10mg associated with alizapride (ALI) 100mg or ondansetron (OND) 8mg were prepared under aseptic conditions and stored about 30 days at 5±3°C. ALI, DEX and OND concentrations were measured by high-performance liquid chromatography (HPLC). Optic density measurement at different wavelengths, pH measurement and optic microscope observations were performed periodically during the storage. A forced degradation test with HCL 5M and NaOH 5M before and after heating at 100°C was also performed. Solutions were considered stable if the 95% one-sided lower confidence limit of the concentration remains superior to 90% of the initial concentration or 95% of the initial concentration when any signs of physical instability exist as recently recommend. RESULTS: The calibration was linear over the following range from 20 to 1.25mg/100mL for DEX, from 200 to 12.5mg/100mL for ALI and from 20 to 1.25mg/100mL for OND with a calculated correlation coefficient (r2) of 0.998, 0.999 and 0.999, respectively. The inter- and intra-assay precision was below 10% for both mixtures. All formulations were physically stable during the storage. The lower confidence limit of the concentration for these solutions remains superior to 90% of the initial concentration at this date as recommended by the Food and Drug Administration (FDA) until 30 days. CONCLUSION: The HPLC method is specific and reproducible and can easily be adopted for monitoring the quality control in the production of DEX-ALI and DEX-OND bags. Solutions of DEX-ALI and DEX-OND were physically and chemically stable for 30 days in polyolefin bags stored at 5±3°C and could therefore be prepared in advance.

Secondary neutron doses in a compact proton therapy system.

Proton therapy offers several advantages compared with classical radiotherapy owing to a better dose conformity to the tumour volume. However, proton interactions with beam transport elements and the human tissues lead to the production of secondary neutrons, resulting in an extra whole-body dose with some carcinogenic potential. In this study, the secondary neutron doses generated with an active beam scanning system and with two compact proton therapy systems recently appeared on the market are compared.

SU-E-T-299: Proton Pencil Beam Spot Scanning Phase Space in the IBA System and the Clinical Implications for Superficial Targets.

PURPOSE: In the treatment of superficial lesions with proton Pencil Beam Scanning (PBS), spot size is dominated by the nozzle contribution. Accuracy of phase-space modeling is therefore paramount. IBA's Dedicated (DN) and Universal Nozzles (UN) have different designs and, consequently, characteristics. Here we report the phase spaces of these two nozzles, without and with a range shifter (RS). METHODS: In-air spot fluence measurements were made for five proton energies: 225, 210, 180, 150 and 115 MeV and at five distances from isocenter pertinent to SAD-type treatments: +33, +20, +10, 0 and -10 cm ('+' implies upstream), without and with a 7.5 cm water-equivalently-thick RS (sufficient to pull back the lowest energy Bragg peak to patient surface), fixed with its upstream side 41 cm from isocenter. Data collected on a fixed horizontal beam-line with a DN and a gantry-mounted UN were compared. The full-width-at-half-maximum (FWHM) of a Gaussian fit to each spot fluence profile was extracted along the two principal axes. RESULTS: With no RS, the proton spots are ∼20-70% larger at isocenter in the UN than in the DN. Spots are less asymmetric, and eccentricity increases more slowly with energy, in the UN than in the DN. Over the 33 cm in-air travel upstream of isocenter, the spot FWHM varies by less than ∼2 mm. However, spot asymmetry becomes more severe upstream (for 115 MeV spots, 30-40% compared to <20% at isocenter for DN, but similar and <10% for UN). With an RS, spot FWHM at isocenter increases by 12.7 mm from 8.3 mm (DN) and 10.7 mm from 13 mm (UN) for 150 MeV protons (typical for brain treatments). With no RS, relatively distance-independent spot size facilitates SAD-type treatments. For patients with superficial lesions, where an RS is required and the phase space varies rapidly with distance, the RS should be permitted at two additional locations. US Army Medical Research and Materiel Command under Contact Agreement No. DAMD17-W81XWH-04-2-0022.

Indications for flexible versus rigid bronchoscopy in children with suspected foreign-body aspiration.

Diagnostic indications for flexible bronchoscopy in the initial investigation of children with suspected foreign-body (FB) aspiration have not been evaluated prospectively. We prospectively collected history, clinical, and radiologic findings at prebronchoscopic examination of all children referred for suspected FB aspiration between February 1993 and September 1995. Children with asphyxiating FB aspiration, requiring immediate rigid bronchoscopy, were excluded. If there was clear evidence of FB aspiration from the physical and radiographic findings, rigid bronchoscopy was directly performed. If the evidence was not convincing, children underwent diagnostic flexible bronchoscopy under local anesthesia. If an FB was found, rigid bronchoscopy was always performed for extraction. Eighty-three consecutive children (median age: 24 mo) were included. Among 28 who underwent rigid bronchoscopy first, 23 had an FB. Among the 55 children who underwent flexible bronchoscopy first, 17 had an FB. Predictive signs of a bronchial FB were a radiopaque FB, and associated unilaterally decreased breath sounds and obstructive emphysema (positive predictive value = 0.94). We propose the following management algorithm: Rigid bronchoscopy is performed first in case of asphyxia, a radiopaque FB, or association of unilaterally decreased breath sounds and obstructive emphysema. In any other case, flexible bronchoscopy is performed first for diagnostic purposes. If applied retrospectively to the 83 children in our study, this algorithm would have decreased the negative first rigid bronchoscopy rate to 4%. Flexible bronchoscopy is a safe and cost-saving diagnostic procedure in children with suspected FB aspiration.

Sudden death revealing Chiari type 1 malformation in two children.

We report the first two fatal cases of sudden unprovoked cardiorespiratory arrest in children with previously undiagnosed Arnold-Chiari type 1 malformation. This diagnosis should be considered in children with unexplained cardiorespiratory arrest. The risk of sudden death in Arnold-Chiari type 1 malformation reinforces the indication for early neurosurgical procedure.

[Is pericerebral hemorrhage a cause of severe malaise in infants?]. / L'hémorragie péricérébrale est-elle une cause de malaise grave du nourrisson?

The authors report 7 cases of infants presenting with an apparent life-threatening event associated with acute pericerebral haemorrhage (subarachnoid haemorrhage and/or subdural hematoma) without evidence of traumatism, abuse, or shaking. Clinical characteristics were the same in all cases, including limpness, severe dysautonomic disorders, and pallor; all infants had retinal and pre-retinal haemorrhages. Two infants died; the five survivors have severe neurologic sequelae. The symptoms revealing an infant's pericerebral haemorrhage are usually axial hypotonia and pallor. Traumatism remains the most common aetiology and must be searched for. Non-traumatic aetiologies are unusual and were excluded in these reported cases. The 'shaken baby' syndrome is not the sole aetiology of an apparent spontaneous pericerebral haemorrhage: a slight bump associated with predisposing vascular factors particular to infancy could be involved. When confronted with an apparent life-threatening event associating limpness and pallor, one must consider the diagnosis of pericerebral haemorrhage.