Durability of humoral and cellular immunity six months after the BNT162b2 bivalent booster.

Studies about the duration of the humoral and cellular response following the bivalent booster administration are still scarce. We aimed at assessing the humoral and cellular response in a cohort of healthcare workers that received this booster. Blood samples were collected before the administration of the bivalent booster from Pfizer-BioNTech and after 14, 28, 90, and 180 days. Neutralizing antibodies against either the D614G strain, the delta variant, the BA.5 variant, or the XBB.1.5 subvariant were measured. The cellular response was assessed by measurement of the release of interferon gamma from T cells in response to an in vitro SARS-CoV-2 stimulation. A substantial waning of neutralizing antibodies was observed after 6 months (23.1-fold decrease), especially considering the XBB.1.5 subvariant. The estimated T1/2 of neutralizing antibodies was 16.1 days (95% CI = 10.2-38.4 days). Although most participants still present a robust cellular response after 6 months (i.e., 95%), a significant decrease was also observed compared to the peak response (0.95 vs. 0.41 UI/L, p = 0.0083). A significant waning of the humoral and cellular response was observed after 6 months. These data can also help competent national authorities in their recommendation regarding the administration of an additional booster.

Interventions to improve appropriateness of laboratory testing in the intensive care unit: a narrative review.

Healthcare expenses are increasing, as is the utilization of laboratory resources. Despite this, between 20% and 40% of requested tests are deemed inappropriate. Improper use of laboratory resources leads to unwanted consequences such as hospital-acquired anemia, infections, increased costs, staff workload and patient stress and discomfort. The most unfavorable consequences result from unnecessary follow-up tests and treatments (overuse) and missed or delayed diagnoses (underuse). In this context, several interventions have been carried out to improve the appropriateness of laboratory testing. To date, there have been few published assessments of interventions specific to the intensive care unit. We reviewed the literature for interventions implemented in the ICU to improve the appropriateness of laboratory testing. We searched literature from 2008 to 2023 in PubMed, Embase, Scopus, and Google Scholar databases between April and June 2023. Five intervention categories were identified: education and guidance (E&G), audit and feedback, gatekeeping, computerized physician order entry (including reshaping of ordering panels), and multifaceted interventions (MFI). We included a sixth category exploring the potential role of artificial intelligence and machine learning (AI/ML)-based assisting tools in such interventions. E&G-based interventions and MFI are the most frequently used approaches. MFI is the most effective type of intervention, and shows the strongest persistence of effect over time. AI/ML-based tools may offer valuable assistance to the improvement of appropriate laboratory testing in the near future. Patient safety outcomes are not impaired by interventions to reduce inappropriate testing. The literature focuses mainly on reducing overuse of laboratory tests, with only one intervention mentioning underuse. We highlight an overall poor quality of methodological design and reporting and argue for standardization of intervention methods. Collaboration between clinicians and laboratory staff is key to improve appropriate laboratory utilization. This article offers practical guidance for optimizing the effectiveness of an intervention protocol designed to limit inappropriate use of laboratory resources.

Beneficial Effects of Tacrolimus on Brain-Death-Associated Right Ventricular Dysfunction in Pigs.

BACKGROUND: Right ventricular (RV) dysfunction remains a major problem after heart transplantation and may be associated with brain death (BD) in a donor. A calcineurin inhibitor tacrolimus was recently found to have beneficial effects on heart function. Here, we examined whether tacrolimus might prevent BD-induced RV dysfunction and the associated pathobiological changes. METHODS: After randomized tacrolimus (n = 8; 0.05 mg·kg-1·day-1) or placebo (n = 9) pretreatment, pigs were assigned to a BD procedure and hemodynamically investigated 1, 3, 5, and 7 h after the Cushing reflex. After euthanasia, myocardial tissue was sampled for pathobiological evaluation. Seven pigs were used as controls. RESULTS: Calcineurin inhibition prevented increases in pulmonary vascular resistance and RV-arterial decoupling induced by BD. BD was associated with an increased RV pro-apoptotic Bax-to-Bcl2 ratio and RV and LV apoptotic rates, which were prevented by tacrolimus. BD induced increased expression of the pro-inflammatory IL-6-to-IL-10 ratio, their related receptors, and vascular cell adhesion molecule-1 in both the RV and LV. These changes were prevented by tacrolimus. RV and LV neutrophil infiltration induced by BD was partly prevented by tacrolimus. BD was associated with decreased RV expression of the ß-1 adrenergic receptor and sarcomere (myosin heavy chain [MYH]7-to-MYH6 ratio) components, while ß-3 adrenergic receptor, nitric oxide-synthase 3, and glucose transporter 1 expression increased. These changes were prevented by tacrolimus. CONCLUSIONS: Brain death was associated with isolated RV dysfunction. Tacrolimus prevented RV dysfunction induced by BD through the inhibition of apoptosis and inflammation activation.

Kinetics and ability of binding antibody and surrogate virus neutralization tests to predict neutralizing antibodies against the SARS-CoV-2 Omicron variant following BNT162b2 booster administration.

OBJECTIVES: To assess the long-term humoral immunity induced by booster administration, as well as the ability of binding antibody and surrogate virus neutralization tests (sVNT) to predict neutralizing antibodies (NAbs) against the SARS-CoV-2 Omicron variant. METHODS: A total of 269 sera samples were analyzed from 64 healthcare workers who had received a homologous booster dose of BNT162b2. Neutralizing antibodies assessed by sVNT and anti-RBD IgG measured with the sCOVG assay (Siemens Healthineers®) were analyzed at five timepoints; before and up to 6 months following the booster. Antibody titers were correlated with neutralizing antibodies against the Omicron BA.1 variant obtained by pseudovirus neutralization test (pVNT) as a reference method. RESULTS: While Wild-type sVNT percentage of inhibition (POI) remained above 98.6% throughout the follow-up period after booster administration, anti-RBD IgG and NAbs assessed by Omicron BA.1 pVNT showed respectively a 3.4-fold and 13.3-fold decrease after 6 months compared to the peak reached at day 14. NAbs assessed by Omicron sVNT followed a steady decline until reaching a POI of 53.4%. Anti-RBD IgG and Omicron sVNT assays were strongly correlated (r=0.90) and performed similarly to predict the presence of neutralizing antibodies with Omicron pVNT (area under the ROC: 0.82 for both assays). In addition, new adapted cut-off values of anti-RBD IgG (>1,276 BAU/mL) and Omicron sVNT (POI>46.6%) were found to be better predictors of neutralizing activity. CONCLUSIONS: This study showed a significant drop in humoral immunity 6 months after booster administration. Anti-RBD IgG and Omicron sVNT assays were highly correlated and could predict neutralizing activity with moderate performance.

Peri-infection titers of neutralizing and binding antibodies as a predictor of COVID-19 breakthrough infections in vaccinated healthcare professionals: importance of the timing.

OBJECTIVES: The BNT162b2 messenger RNA vaccine is highly effective in reducing COVID-19 infection, hospitalization and death. However, many subjects developed a breakthrough infection despite a full vaccination scheme. Since the waned efficacy of mRNA vaccines is correlated with the decrease of antibodies occurring over time, we aimed at evaluating whether lower levels of antibodies were associated with an increased risk of breakthrough infection in a cohort of breakthrough subjects that received three vaccine doses. METHODS: Total binding antibodies against the RBD of the S1 subunit (Roche Diagnostics, Machelen, Belgium) and neutralizing antibodies using the Omicron B.1.1.529 variant pseudovirus were measured. Based on individual kinetic curves, the antibody titer of each subject was interpolated just before the breakthrough infection and compared to a matched-control group that did not develop a breakthrough infection. RESULTS: Lower levels of total binding and neutralizing antibodies were observed compared to the control group (6.900 [95% CI; 5.101-9.470] vs. 11.395 BAU/mL [8.627-15.050] [p=0.0301] and 26.6 [18.0-39.3] vs. 59.5 dilution titer-1 [32.3-110] [p=0.0042], respectively). The difference between breakthrough and control subjects was mostly observed for neutralizing antibodies before three months after the homologous booster administration (46.5 [18.2-119] vs. 381 [285-509] [p=0.0156]). Considering the measurement of total binding antibodies before 3 months, there was no significant difference (p=0.4375). CONCLUSIONS: In conclusion, our results showed that subjects that developed a breakthrough infection had lower levels of neutralizing and total binding antibodies compared to controls. The difference was mostly noticeable considering neutralizing antibodies, especially for infections occurring before 3 months after the booster administration.

An ultra-high-performance chromatography method to study the long term stability of gemcitabine in dose banding conditions.

Gemcitabine is an analogue of cytidine arabinoside, used alone or in combination chemotherapy to treat various type of cancer. The dose-banding of gemcitabine provides the opportunity to anticipate the preparation of this anticancer drug on condition of carrying out stability studies. The aim of this study is to develop and validate a stability-indicating ultra-high-performance Liquid Chromatography (UHPLC) method for measuring the concentration of gemcitabine and to evaluate its stability at standardised rounded doses in polyolefin bags. The UHPLC with photodiode array (PDA) detector method was developed and validated (linearity, precision, accuracy, limits of detection and quantification, robustness and degradation test). Thirty polyolefin bags of gemcitabine (1600 mg/292 ml (n = 10), 1800 mg/297 ml (n = 10) and 2000 mg/303 ml (n = 10)) were prepared under aseptic conditions and stored at 5 ± 3 °C and 23 ± 2 °C for 49 days. Physical stability tests were periodically performed: visual and microscopic inspection and optical densities. The chemical stability was evaluated through pH monitoring and chromatographic assays. The results confirm the stability of Gemcitabine at selected standardised rounded doses of 1600 mg, 1800 mg and 2000 mg in NaCl 0.9% polyolefin bags for at least 49 days at 5 ± 3 °C and 23 ± 2 °C, allowing in-advance preparation.

Long-term physicochemical stability of 5-fluorouracil at selected standardised rounded doses in polyolefin bags.

BACKGROUND: Chemotherapy doses are usually prescribed on the basis of body surface area but dose banding is emerging as an efficient alternative. Dose banding presents the possibility of in-advance preparation in a Centralized Intravenous Admixture Service. AIM OF THE STUDY: To evaluate the long-term stability of 5-fluorouracil at banded doses (700 mg and 800 mg) in polyolefin bags. MATERIALS AND METHODS: Ten polyolefin bags were prepared under aseptic conditions and stored at 23 ± 2°C for 24 days. Five of them were composed of 14 mL 5-fluorocuracil (700 g) in 100 mL 0.9% sodium chloride solution and the five other of 16 mL 5-fluorouracil (800 mg) in 100 mL 0.9% sodium chloride solution. At defined times, physical stability parameters were assessed: optical densities, pH measurements, visual and microscopical inspections. Solutions concentrations were measured using high-performance liquid chromatography coupled with a photodiode array detector. RESULTS: No change was observed on pH and optical density measurements during the study period. Visual and microscopical inspections remained free of colour change, precipitate, microagregate or crystal. The concentrations of 5-Fluorouracil in 800 mg bags remained stable for 24 days while the concentration in 700 mg bags showed a stability of at least 17 days. CONCLUSION: Five-fluorouracil at banded doses of 700 and 800 mg in polyolefin bags is physicochemically stable for at least 17 days at 23 ± 2°C. These results support the possibility of in advance centralised preparation.

Evaluation of 30-days stability of morphine hydrochloride and clonidine at high and low concentrations in polypropylene syringes.

OBJECTIVES: Clonidine is an alpha-2 adrenoreceptor agonist and is frequently combined with opioids (ie, morphine hydrochloride (HCl)) for the management of chronic pain. In palliative care, the administration of clonidine and morphine HCl is recommended in case of tolerance effect. This study aimed to evaluate the physical and chemical stability of this admixture at high and low concentrations in 14 and 48 mL polypropylene syringes. METHODS: The stability of a low concentration admixture of clonidine (Catapressan 0.15 mg/mL, Boehringer Ingelheim, Germany) and morphine (morphine HCl 40 mg/mL, Sterop, Belgium) at 0.003 and 0.417 mg/mL, respectively, was evaluated by using five polypropylene syringes of 48 mL. The high concentration admixture consisted of 0.032 mg/mL clonidine and 4.286 mg/mL morphine HCl and was evaluated by using five polypropylene syringes of 14 mL. All syringes were stored for 30 days at 5°C±3°C. Periodic samples were visually and microscopically examined to observe any particle appearance or colour change. pH and absorbance at three wavelengths (350, 410 and 550 nm) were monitored. The concentrations were measured by ultra-high performance liquid chromatography-photodiode array detection. RESULTS: During the 30 days, there was no change in colour or appearance of opacity, turbidity or precipitation, and pH remained stable. The low and high concentration admixtures were considered chemically stable since the lower limit of the 90% CI remained superior to 90% of the initial concentration. Concentration measurements showed that the degradation rate was less than 1% over 10 days for each component in both admixtures. CONCLUSIONS: The admixture of clonidine and morphine HCl at low and high concentrations in polypropylene syringes appeared to be physically and chemically stable throughout the study period of 30 days at 5°C±3°C. In conclusion, the admixture can be prepared in advance under aseptic conditions by a centralised intravenous additive service in the pharmacy department.

Vaccine-induced binding and neutralizing antibodies against Omicron 6 months after a homologous BNT162b2 booster.

Evidence about the long-term persistence of the booster-mediated immunity against Omicron is mandatory for pandemic management and deployment of vaccination strategies. A total of 155 healthcare professionals (104 COVID-19 naive and 51 with a history of SARS-CoV-2 infection) received a homologous BNT162b2 booster. Binding antibodies against the spike protein and neutralizing antibodies against Omicron were measured at several time points before and up to 6 months after the booster. Geometric mean titers of measured antibodies were correlated to vaccine efficacy (VE) against symptomatic disease. Compared to the highest response, a significant 10.2- and 11.5-fold decrease in neutralizing titers was observed after 6 months in participants with and without history of SARS-CoV-2 infection. A corresponding 2.5- and 2.9-fold decrease in binding antibodies was observed. The estimated T1/2 of neutralizing antibodies in participants with and without history of SARS-CoV-2 infection was 42 (95% confidence interval [CI]: 25-137) and 36 days (95% CI: 25-65). Estimated T1/2 were longer for binding antibodies: 168 (95% CI: 116-303) and 139 days (95% CI: 113-180), respectively. Both binding and neutralizing antibodies were strongly correlated to VE (r = 0.83 and 0.89). However, binding and neutralizing antibodies were modestly correlated, and a high proportion of subjects (36.7%) with high binding antibody titers (i.e., >8434 BAU/ml) did not have neutralizing activity. A considerable decay of the humoral response was observed 6 months after the booster, and was strongly correlated with VE. Our study also shows that commercial assays available in clinical laboratories might require adaptation to better predict neutralization in the Omicron era.

Lung Transplant Recipients Immunogenicity after Heterologous ChAdOx1 nCoV-19-BNT162b2 mRNA Vaccination.

(1) Background: High immunosuppressive regimen in lung transplant recipients (LTRs) hampers the immune response to vaccination. We prospectively investigated the immunogenicity of heterologous ChAdOx1 nCoV-19-BNT162b2 mRNA vaccination in an LTR cohort. (2) Methods: Forty-nine COVID-19 naïve LTRs received a two-dose regimen ChAdOx1 nCoV-19 vaccine. A subset of 32 patients received a booster dose of BNT162b2 mRNA vaccine 18 weeks after the second dose. (3) Results: Two-doses of ChAdOx1 nCoV-19 induced poor immunogenicity with 7.2% seropositivity at day 180 and low neutralizing capacities. The BNT162b2 mRNA vaccine induced significant increases in IgG titers with means of 197.8 binding antibody units per milliliter (BAU/mL) (95% CI 0-491.4) and neutralizing antibodies, with means of 76.6 AU/mL (95% CI 0-159.6). At day 238, 32.2% of LTRs seroconverted after the booster dose. Seroneutralization capacities against Delta and Omicron variants were found in only 13 and 9 LTRs, respectively. Mycophenolate mofetil and high-dose corticosteroids were associated with a weak serological response. (4) Conclusions: The immunogenicity of a two-dose ChAdOx1 nCoV-19 vaccine regimen was very poor in LTRs, but was significantly enhanced after the booster dose in one-third of LTRs. In immunocompromised individuals, the administration of a fourth dose may be considered to increase the immune response against SARS-CoV-2.

Physical and Chemical Stability of Pharmaceutical Preparation of Bumetanide and Scopolamine.

Death rattle, which could often be associated with a pulmonary fluid overload, occurs in 25% to 90% of dying patients. The co-administration of scopolamine (anticholinergic drug) and bumetanide (loop diuretic) could be considered in order to avoid unnecessary fluid overload at end-stage of life. The objective of this study was to investigate the physical and chemical stabilities of the admixture bumetanide and scopolamine in order to prepare them in advance by a centralized intravenous additive service in-hospital pharmacy. The stability of the lowest (LOW) concentration was evaluated on five polypropylene syringes containing the admixture bumetanide (Burinex, 2 mg/4 mL) and scopolamine (0.25 mg/mL) at 41.67 µg/mL and 5.21 µg/mL. The highest (HIGH) concentration with 125 µg/mL of bumetanide and 31.25 µg/mL of scopolamine was evaluated on five polypropylene syringes. All syringes were stored for 18 days at 5°C ± 3°C. Periodic samples were visually and microscopically examined to observe any particle appearance or color change. The pH and absorbance at 3 wavelengths (350 nm, 410 nm, and 550 nm) were monitored. The concentrations were measured by ultra-high performance liquid chromatography-photodiode array detection, using a newly developed method. During the 18 days of test, there was no change in color or appearance of opacity, turbidity, or precipitation, and the pH remained stable. Mean concentrations of bumetanide and scopolamine at LOW and HIGH concentrations after 18 days remained statistically unchanged. The lower limits of the 95% confidence intervals of both molecules at LOW and HIGH concentrations remained higher than a 90% threshold of concentration, indicating the mixture was chemically stable. Degradation rates of bumetanide and scopolamine content at LOW and HIGH concentrations should not exceed a maximum of 0.70% every 10 days. This study was the first to show that the admixture of bumetanide and scopolamine is physically and chemically stable at two concentrations used in a palliative-care unit. This combination available in ready-to-use polypropylene syringes presents numerous advantages for patient's comfort and safety.

Microwave Freeze-thaw Technique for Injectable Drugs: A Review Updated from 1980 to 2021.

The objective of this review was to collect information and results about the method of the microwave freeze-thaw treatment of injectable drugs and whether the method can support the development of Centralized Intravenous Admixtures Services. A systematic review of the scientific literature about injectable drug stability studies was performed. The data are presented in a table, which describes the name of the drug, producer, final concentration, temperature and time of freezing storage, type of microwave oven, thawing power, method of dosage, and the results after treatment or final long-term storage at 5°C ± 3°C. From 1980 to 2021, 60 drugs were studied by the microwave freeze-thaw treatment, and the results were presented in 49 publications. Forty papers were presented by 8 teams (2 to 18 by team). The temperatures of freezing storage varied from -70°C to -10°C, the time storage from 4 hours to 12 months, and the thaw from low to full power. Drug concentrations were mainly determined by high-performance liquid chromatography. Most of the 59 drugs were stable during and after treatment. Only three teams tested the long-term stability after the microwave freeze-thaw treatment, the first for ganciclovir after 7 days, the second for ceftizoxime after 30 days, and the third for 20 drugs after 11 to 70 days. This review can help Centralized Intravenous Additive Services take charge of the productions of ready-to-use injectable drugs.

Waning of IgG, Total and Neutralizing Antibodies 6 Months Post-Vaccination with BNT162b2 in Healthcare Workers.

Data about the long-term duration of antibodies after SARS-CoV-2 vaccination are still scarce and are important to design vaccination strategies. In this study, 231 healthcare professionals received the two-dose regimen of BNT162b2. Of these, 158 were seronegative and 73 were seropositive at baseline. Samples were collected at several time points. The neutralizing antibodies (NAbs) and antibodies against the nucleocapsid and the spike protein of SARS-CoV-2 were measured. At day 180, a significant antibody decline was observed in seronegative (-55.4% with total antibody assay; -89.6% with IgG assay) and seropositive individuals (-74.8% with total antibody assay; -79.4% with IgG assay). The estimated half-life of IgG from the peak humoral response was 21 days (95% CI: 13-65) in seronegative and 53 days (95% CI: 40-79) in seropositive individuals. The estimated half-life of total antibodies was longer and ranged from 68 days (95% CI: 54-90) to 114 days (95% CI: 87-167) in seropositive and seronegative individuals, respectively. The decline of NAbs was more pronounced (-98.6%) and around 45% of the subjects tested were negative at day 180. Whether this decrease correlates with an equivalent drop in the clinical effectiveness against the virus would require appropriate clinical studies.

Antibody titres decline 3-month post-vaccination with BNT162b2.

Several studies reported on the humoral response in subjects having received the BNT162b2 mRNA COVID-19 vaccine. However, data on the kinetics of antibodies 3 months post-vaccination are currently lacking and are important to drive the future vaccination strategy. The CRO-VAX HCP study is an ongoing multicentre, prospective and interventional study designed to assess the antibody response in a population of healthcare professionals who had received two doses of the BNT162b2 mRNA COVID-19 vaccine. Two hundred individuals underwent a blood drawn within 2 days before the first vaccine dose. One-hundred and forty-two persons (71%) were categorized as seronegative at baseline while 58 (29%) were seropositive. Samples were then collected after 14, 28, 42, 56, and 90 days. Antibodies against the SARS-CoV-2 nucleocapsid and the receptor binding domain of the S1 subunit of the spike protein were measured in all individuals at different time points. Using a one-compartment kinetics model, the time to maximum concentration was estimated at 36 ± 3 days after the first dose and the estimated half-life of antibodies was 55 days (95% CI: 37-107 days) in seronegative participants. In seropositive participants, the time to maximum concentration was estimated at 24 ± 4 days and the estimated half-life was 80 days (95% CI: 46-303 days). The antibody response was higher in seropositive compared to seronegative participants. In both seropositive and seronegative subjects, a significant antibody decline was observed at 3 months compared to the peak response. Nevertheless, the humoral response remained robust in all participants.

Confounding Factors Influencing the Kinetics and Magnitude of Serological Response Following Administration of BNT162b2.

BACKGROUND: Little is known about potential confounding factors influencing the humoral response in individuals having received the BNT162b2 vaccine. METHODS: Blood samples from 231 subjects were collected before and 14, 28, and 42 days following coronavirus disease 2019 (COVID-19) vaccination with BNT162b2. Anti-spike receptor-binding-domain protein (anti-Spike/RBD) immunoglobulin G (IgG) antibodies were measured at each time-point. Impact of age, sex, childbearing age status, hormonal therapy, blood group, body mass index and past-history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were assessed by multivariable analyses. RESULTS AND CONCLUSIONS: In naïve subjects, the level of anti-Spike/RBD antibodies gradually increased following administration of the first dose to reach the maximal response at day 28 and then plateauing at day 42. In vaccinated subjects with previous SARS-CoV-2 infection, the plateau was reached sooner (i.e., at day 14). In the naïve population, age had a significant negative impact on anti-Spike/RBD titers at days 14 and 28 while lower levels were observed for males at day 42, when corrected for other confounding factors. Body mass index (BMI) as well as B and AB blood groups had a significant impact in various subgroups on the early response at day 14 but no longer after. No significant confounding factors were highlighted in the previously infected group.

Early antibody response in health-care professionals after two doses of SARS-CoV-2 mRNA vaccine (BNT162b2).

OBJECTIVES: Data on the immune response after two doses of BNT162b2 are so far limited. Previously infected individuals were excluded from pivotal clinical trials and the optimum dose regimen in this population has not been clearly studied. The CRO-VAX HCP study aims to investigate the early antibody response in a population of health-care professionals having received two doses of the BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine. METHODS: The CRO-VAX HCP study is a multicentre, prospective, interventional study conducted in several sites in Belgium. The study included 231 health-care professional volunteers who received the two-dose regimen of the BNT162b2 mRNA COVID-19 vaccine. Of these, 73 were previously infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 158 were uninfected and seronegative. In the first group, blood samples were collected at baseline and after 2, 4, 7, 10, 14, 21 and 28 days. In the second group, samples were obtained at baseline and after 14 and 28 days. Antibodies against the SARS-CoV-2 nucleocapsid and the receptor binding domain of the S1 subunit of the spike protein were measured in all individuals at different time-points. RESULTS: In uninfected individuals, 95.5% (95% CI 91.0%-98.2%) developed anti-spike antibodies after 14 days and a 24.9-fold rise (95% CI 21.4%-28.9%) in antibody titre was observed after the second dose. In previously infected individuals, peak antibody response was reached after 7 days (i.e. 6347 U/mL) and the second dose did not lead to significantly higher antibody titres (i.e. 8856-11 911 U/mL). Antibody titres were higher in previously infected individuals. CONCLUSIONS: This study supports the concept that a single dose of BNT162b2 would be sufficient in previously infected individuals.

Long-term physico-chemical stability of 5-fluorouracile at standardised rounded doses (SRD) in MyFuser® portable infusion pump.

Management of chemotherapies is a strategic issue for european healthcare. Dose-banding enables to reduce waiting time of patients in day care units and drug wastage. The aim of this study was to assess the stability of 5-Fluorouracile (5-FU) at standardised rounded doses of 4 and 5 g in MyFuser® portable infusion pump for in-advance preparation. Ten MyFuser® (4 and 5 gr 5-FU added to NaCl 0.9%) were prepared under aseptic conditions and stored at room temperature (23 ± 2 °C) for 28 days then at 30 °C for three days. Physical stability tests were periodically performed: visual and microscopic inspection, pH measurements and optical densities. The concentration of solutions was measured by High Performance Liquid Chromatography/UV detector. Results confirm the stability of 5-FU at selected SRD of 4 g and 5 g with NaCl 0.9% in MyFuser® for at least 28 days at room temperature and three days at 30 °C, allowing in-advance preparation.

Long term stability of an admixture of alizapride and ondansetron in 0.9% sodium chloride solution polyolefin bags stored at 5±3°C.

BACKGROUND: Patients undergoing chemotherapeutic treatment are currently treated by a concomittent infusion of alizapride and ondansetron. To optimise the procedure and to ensure patients' safety, the admixture could be prepared in advance by the Centralized Intravenous Additive Service (CIVAS) provided that the stability of the mixture has been proven beforhand to reduce nausea and vomiting.Aim of the study: to evaluate the long-term stability of an admixture of alizapride 0.926 mg/l and ondansetron 0.074 mg/ml in 0.9% sodium chloride polyolefin bags stored at 5 ± 3°C. MATERIAL AND METHODS: Five polyolefin bags containing 100 ml sodium chloride 0.9% added with 4 ml alizapride (100 mg) and 4 ml ondansetron (8 mg) were prepared in aseptic conditions and stored at 5 ± 3°C for 56 days. Periodically, physical stability tests were performed including: pH measurements, optical density measurements at 350, 410 and 550 nm to track turbidity appearance, visual and microscopical inspections to detect colour changes, precipitation, microaggregates or crystals. The concentrations of the solutions were measured by High Performance Liquid Chromatography coupled with an UV detector. RESULTS: There was no change in pH and optical densities during the study period. Visual and microscopical inspections didn't show any change of colour neither precipitation, microaggregate or crystal. The alizapride and ondansetron concentrations remained stable over the study. CONCLUSION: The admixture of alizapride and ondansetron in 0.9% sodium chloride solution polyolefin bags is physicochemically stable up to 56 days at 5 ± 3°C. These results support the possibility of preparing the solutions in advance by a CIVAS.

Biotin interferences: Have we neglected the impact on serological markers?

BACKGROUND: Biotin has been reported to be a leading cause of interference on several immunoassay platforms using the streptavidin-biotin immobilization system. While biotin interferences have now been well characterized for several assays, only few data are available on their impact on serological markers of infectious viral diseases. METHODS: Overall, 10 healthy volunteers (HVs) received a single 100 mg dose of biotin to evaluate its effect on hepatitis B serological markers. Blood samples were taken several times before and after biotin intake. In addition, spiking experiments were applied to investigate biotin's impact on anti-HIV/p24 Ag and anti-HCV antibody levels. Several procedures designed to overcome this interference were evaluated. RESULTS: Biotin intake resulted in a false-negative anti-HBs immunological status (<10 mIU/mL) in 40.0% of cases. According to our anti-HBc and anti-HBe results, biotin intake was associated with 90.0% and 80.0% of false positive results, respectively. At the theoretical biotin peak concentration following a 100 mg intake, 50.0% and 66.6% of anti-HIV and anti-HCV results were false negatives, respectively. All the procedures evaluated to overcome the interference were proven effective. CONCLUSION: HBV, HCV, and HIV serological markers are likely to be highly sensitive to biotin. Our data confirm that the scope of biotin interference is broader than commonly described.