Pharmacokinetics and safety of bromotetrandrine (BrTet, W198) after single-dose intravenous administration in healthy Chinese volunteers

Objective: To investigate the safety and pharmacokinetics of bromotetrandrine (BrTet, W198), a novel inhibitor of P‐glycoprotein (P‐gp), after single‐dose i.v. infusion in healthy Chinese volunteers. Methods: We conducted a randomized, dose‐escalating, phase I clinical study for that purpose. Thirty healthy subjects received BrTet at the doses of 10, 20 or 30 mg/m² by i.v. infusion. Plasma and urine concentrations of bromotetrandrine were determined by using a liquid chromatography–tandem mass spectrometric (LC/MS/MS) method. AUC was calculated by the trapezoidal rule extrapolation method. C_max, T_max, t_1/2α, t_1/2β, Cl and V_d were compiled from the plasma concentration–time data. Results: Bromotetrandrine was generally well tolerated at all doses. No serious or severe adverse events were found in the study. The pharmacokinetic parameters of BrTet after single i.v. infusion doses of BrTet 10, 20 and 30 mg/m² were as follows: T_max were 1·5 h in three groups, C_max were 24·79, 39·59 and 64·31 μg/L, t_1/2α were 0·37, 0·29 and 0·30 h, t_1/2β were 62·88, 56·45 and 52·20 h. AUC_0–194h were 345·83, 688·15 and 1096·28 μg h/L, Cl were 23·68, 25·69 and 25·66 L h/m², V_d were 157·73,156·96 and 140·73 L/m². In urine, the total eliminate rate of originate compound was 0·61 ± 0·19%. Conclusions: This study suggested that bromotetrandrine was well tolerated in healthy volunteers within the dose range evaluated. The pharmacokinetics parameters of bromotetrandrine indicated that the compound was rapidly distributed and accumulated in the tissues, and slowly cleared from plasma, which supported the use of BrTet for a once or twice dosing per chemotherapy cycle.     

Exploring Australian emergency department clinicians' knowledge,attitudes and adherence to the national peripheral intravenous catheter clinical care standard: A cross-sectional national survey

Objective

This study aimed to (i) capture clinicians' knowledge, attitude and adherence to the first Australian national peripheral intravenous catheter (PIVC) Clinical Care Standard, (ii) examine the instrument performance of the knowledge related questions and (iii) explore the educational needs for, and barriers to, Standard adherence among Australian ED clinicians.

Methods

A cross-sectional national online survey was conducted from March to June 2022, using a snowball sampling method. The survey used 5-point Likert scales and multiple-choice questions to capture respondents' knowledge, attitude and adherence to the Standard as well as the educational needs for, and barriers to, Standard adherence.

Results

In total, 433 ED nurses and doctors responded. Although nearly half (n = 206, 47.6%; 95% confidence interval [CI] 55.5–65.8) of respondents claimed that they were unfamiliar with the Standard, questions on PIVC knowledge yielded that most respondents had adequate knowledge of most of the key standards. Respondents' attitudes towards multiple intravenous insertion attempts and ongoing PIVC competency monitoring are not in agreement with the Standard. Self-reported practices regarding routine insertion of idle catheters (55%; 95% CI 49.9–59.9), using antecubital fossa as the first insertion site (84%; 95% CI 80–87), insertion without confidence (46%; 95% CI 41.2–51.1) and lack of routine reviewing the ongoing needs of PIVC (40%; 95% CI 35.3–45.1) were not aligned with the Standard. Unawareness of the Standard and non-practical recommendations were rated as the top barriers to Standard adherence.

Conclusion

The findings of the survey suggest that the Standard may need modification to align with the needs of ED clinicians. Future studies need to explore the applicability and relevancy of some recommendations in the ED settings as they may cause low adherence to the Standard.     

Post-rhinoplasty complications with previous hyaluronic acid injection history: Cerebral infarction and vision loss

Background

Rhinoplasty is becoming increasingly frequent as the pursuit of aesthetics by people accelerates. In recent years, the proportion of people opting for rhinoplasty injections has gradually increased. This has led to numerous reports citing catastrophic postoperative complications such as skin necrosis, cerebral infarction, and visual impairment.

Aim

The aim of our report is to discuss the possible etiological factors for this post-rhinoplasty complication and provides a rationale for HA injection history as a risk factor in rhinoplasty.

Methods

We report a rare case that received nasal HA injections in the past without any untoward incident. She opted for a second rhinoplasty 2 years after her initial nasal HA injections. This second intervention led to post-injection loss of vision in one eye and cerebral infarction. Following clinical and radiological examination, digital subtraction angiography (DSA) and superselective intra-arterial thrombolysis were performed.

Results

The patient did not develop disuse exotropia or ocular atrophy, but the left eye remained without light perception, which implies that intra-arterial thrombolytic therapy may be a positive and effective method to maintain the normal appearance of the eye.

Conclusion

It is advisable for patient safety to maintain a long interval of time between hyaluronidase injection and repeat rhinoplasty. Clinicians should become familiar with the anatomical peculiarities of the patient and be gentle during the rhinoplasty procedure.     

Stimulation of human cytotoxic T cells with HIV-1-derived peptides presented by recombinant HLA-A2 peptide complexes

HLA-A2 heavy chain and beta 2-microglobulin were expressed in Escherichia coli, and refolded in the presence of peptides derived from HIV-1 RT and gag proteins. When recombinant HLA-A2 molecules were attached to cells lacking HLA-A2, the cells became susceptible to lysis by HLA-A2-restricted cytotoxic T lymphocyte (CTL) clones specific for peptides derived from RT and gag proteins. Limiting dilution analyses of peripheral blood mononuclear cells from HIV-1-infected individuals showed that the recombinant HLA-A2 peptide complexes covalently immobilized on microspheres stimulated the development of HLA-A2 peptide-specific CTL. Preformed HLA-peptide complexes may provide an alternative to immunization procedures that depend upon intracellular processing of antigen to elicit T cell responses.      

Evidence from proton magnetic resonance spectroscopy for a metabolic cascade of neuronal damage in shaken baby syndrome

OBJECTIVE: The purpose of this study was to use proton magnetic resonance spectroscopy (MRS) as a metabolic assay to describe biochemical changes during the evolution of neuronal injury in infants after shaken baby syndrome (SBS), that explain the disparity between apparent physical injury and the neurological deficit after SBS. METHODOLOGY: Three infants [6 months (A), 5 weeks (B), 7 months (C)] with SBS were examined repeatedly using localized quantitative proton MRS. Examinations were performed on days 7 and 13 (A), on days 1, 3, 5, and 12 (B), and on days 7 and 19 (C) posttrauma. Long-term follow-up examinations were performed 5 months posttrauma (A) and 4.6 months posttrauma (B). Data were compared to control data from 52 neurologically normal infants presented in a previous study. RESULTS: Spectra from parietal white matter obtained at approximately the same time after injury (5 to 7 days) showed markedly different patterns of abnormality. Infant A shows near normal levels of the neuronal marker N-acetyl aspartate, creatine, and phosphocreatine, although infant C shows absent N-acetyl aspartate, almost absent creatine and phosphocreatine, and a great excess of lactate/lipid and lipid. Analysis of the time course in infant B appears to connect these variations as markers of the severity of head injury suffered in the abuse, indicating a progression of biochemical abnormality. The principal cerebral metabolites detected by MRS that remain normal up to 24 hours fall precipitately to approximately 40% of normal within 5 to 12 days, with lactate/lipid and lipid levels more than doubling concentration between days 5 and 12. CONCLUSIONS: A strong impression is gained of MRS as a prognostic marker because infant A recovered although infants B and C remained in a state consistent with compromised neurological capacity. Loss of integrity of the proton MR spectrum appears to signal irreversible neurological damage and occurs at a time when clinical and neurological status gives no indication of long-term outcome. These results suggest the value of sequential MRS in the management of SBS.