The immunogenicity and safety of a reduced PRP-content DTPw-HBV/Hib vaccine when administered according to the accelerated EPI schedule

Background  

Combination vaccines improve coverage, compliance and effectively introduce new antigens to mass vaccination programmes. This was a phase III, observer-blind, randomized study of GSK Biologicals diphtheria-tetanus-whole cell pertussis vaccine combined with hepatitis B and Haemophilus influenzae type b vaccines, containing a reduced amount of polyribosyl-ribitol-phosphate (PRP) and a DTPw component manufactured at a different site (DTPw-HBV/Hib_2.5 [Kft]). The primary aim of this study was to demonstrate that DTPw-HBV/Hib_2.5 [Kft] was not inferior to the licensed DTPw-HBV/Hib (Tritanrix(tm)-HepB/Hiberix(tm)) vaccine or the DTPw-HBV/Hib_2.5 vaccine, also containing a reduced amount of PRP, with respect to the immune response to the PRP antigen, when administered to healthy infants, according to the Expanded Programme for Immunization (EPI) schedule at 6, 10 and 14 weeks of age.     

Soluble Epoxide Hydrolase in Atherosclerosis

Like many eicosanoids, epoxyeicosatrienoic acids (EETs) have multiple biological functions, including reduction of blood pressure, inflammation, and atherosclerosis in multiple species. Hydration of EETs by the soluble epoxide hydrolase (sEH) is the major route of their degradation to the less bioactive diols. Inhibition of the sEH stabilizes EETs, thus, enhancing the beneficial effects of EETs. Human data show an association of sEH (Ephx2) gene polymorphisms with increased risk of atherosclerosis and cardiovascular diseases. These data suggest a potential therapeutic effect of sEH inhibitors (sEHI) in the treatment of atherosclerosis. Indeed, two laboratories reported independently that using different sEHIs in apolipoprotein E–deficient mice significantly attenuated atherosclerosis development and aneurysm formation. The antiatherosclerotic effects of sEHI are correlated with elevation in EET levels and associated with reduction of low-density lipoprotein and elevation of high-density lipoprotein cholesterols, as well as attenuation of expression of proinflammatory genes and proteins. In addition, the antihypertensive effects and improvement of endothelial function also contribute to the mechanism of the antiatherosclerotic effects of sEHI. The broad spectrum of biological action of EETs and sEHIs with multiple biological beneficial actions provides a promising new class of therapeutics for atherosclerosis and other cardiovascular diseases.     

A modified lightwand-guided nasotracheal intubation technique for oromaxillofacial surgical patients

Study ObjectiveTo investigate the efficiency of a double curve nasotracheal tube on lightwand-guided nasotracheal intubation.DesignProspective, randomized, controlled trial.SettingUniversity medical center hospital.Patients60 ASA physical status I and II patients undergoing oromaxillofacial surgery.Interventions and MeasurementsPatients undergoing surgery with nasotracheal intubation and general anesthesia were randomly enrolled in the laryngoscopy group or the lightwand group. The same type of double curve nasotracheal tube was used in both groups. In the laryngoscopy group, intubation was assisted with a Macintosh No. 3 standard curved blade and Magill forceps. In the lightwand group, intubation was aided with a flexible lightwand device (without the inner stiff stylet). Intubation time was divided into two parts: Part one, from selected naris to oropharynx; Part two, from oropharynx into trachea. Part one, Part two, and total intubation time, hemodynamic responses to nasotracheal intubation, and adverse events or complications were recorded.Main ResultsTotal intubation times in the lightwand group and the laryngoscopy group were 22.8 ± 8.0 sec vs 30.3 ± 8.2 sec (P < 0.001), respectively. The lightwand group had comparable hemodynamic responses to those of the laryngoscopy group. Adverse events and complications were all self-limited, with similar occurrence in both groups.ConclusionFor patients undergoing oromaxillofacial surgery, modified lightwand-guided nasotracheal intubation is feasible with a double curve nasotracheal tube and is an efficient alternative technique.     

Pharmacokinetic optimization of four soluble epoxide hydrolase inhibitors for use in a murine model of inflammation

Background and purpose:

Early soluble epoxide hydrolase inhibitors (sEHIs) such as 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) are effective anti-hypertensive and anti-inflammatory agents in various animal models. However, their poor metabolic stability and limited water solubility make them difficult to use pharmacologically. Here we present the evaluation of four sEHIs for improved pharmacokinetic properties and the anti-inflammatory effects of one sEHI.

Experimental approach:

The pharmacokinetic profiles of inhibitors were determined following p.o. (oral) administration and serial bleeding in mice. Subsequently the pharmacokinetics of trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), the most promising inhibitor, was further studied following s.c. (subcutaneous), i.v. (intravenous) injections and administration in drinking water. Finally, the anti-inflammatory effect of t-AUCB was evaluated by using a lipopolysaccharide (LPS)-treated murine model.

Key“ results:

Better pharmacokinetic parameters (higher C_max, longer t_1/2 and greater AUC) were obtained from the tested inhibitors, compared with AUDA. Oral bioavailability of t-AUCB (0.1 mg·kg⁻¹) was 68 ± 22% (n = 4), and giving t-AUCB in drinking water is recommended as a feasible, effective and easy route of administration for chronic studies. Finally, t-AUCB (p.o.) reversed the decrease in plasma ratio of lipid epoxides to corresponding diols (a biomarker of soluble epoxide hydrolase inhibition) in lipopolysaccharide-treated mice. The in vivo potency of 1 mg·kg⁻¹ of t-AUCB (p.o.) was better in this inflammatory model than that of 10 mg·kg⁻¹ of AUDA-butyl ester (p.o) at 6 h after treatment.

Conclusions and implications:

t-AUCB is a potent sEHI with improved pharmacokinetic properties. This compound will be a useful tool for pharmacological research and a promising starting point for drug development.     

A rare case of cardiogenic shock caused by takotsubo syndrome associated with SARS-CoV-2 infection: The value of echocardiography in the diagnosis and monitoring of the efficacy of extracorporeal membrane oxygenation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mainly invades the respiratory system, but may also cause various cardiovascular complications. We report a rare case of myocarditis associated with SARS-CoV-2 infection. A 61-year-old man was admitted to the hospital with a positive nucleic acid test for SARS-CoV-2. A sudden increase in troponin level (up to .144 ng/mL) was observed on the 8th day after admission. He developed symptoms of heart failure and progressed rapidly to cardiogenic shock. Echocardiography on the same day showed reduced left ventricular ejection fraction, reduced cardiac output, and segmental ventricular wall motion abnormalities. Takotsubo cardiomyopathy associated with SARS-CoV-2 infection was considered based on the typical echocardiography findings. We immediately started veno-arterial extracorporeal membrane oxygenation (VA-ECMO) treatment. The patient was successfully withdrawn from VA-ECMO after 8 days following recovery of ejection fraction to 65% and all indicators qualifying the withdrawal criteria. Echocardiography plays an important role in dynamic monitoring of cardiac changes in such cases and can help determine the timing of extracorporeal membrane oxygenation treatment and withdrawal.     

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.     

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.     

Who can give ‘spiritual care’? The management of spiritually sensitive interactions between nurses and patients

kevern p. (2012) Journal of Nursing Management  20, 981–989
Who can give ‘spiritual care’? The management of spiritually sensitive interactions between nurses and patients Aims This article considers the purpose of contemporary ‘spiritual care’ in order to help managers make informed decisions about its appropriate delivery in a clinical context. Background Although there are national policies in place concerning spiritual care, surveys indicate that nurses are reluctant to engage with the spiritual needs of patients. Evaluation A consideration of the character of spiritual care indicates the need to take account of the context of contemporary Western society. A model drawn from the social psychology of religion is used to analyse the different types of nurse–patient interaction available in the provision of spiritual care. Key Issues Although religious and spiritual commitments can vary widely, they are subject to the same pressures in a secular and pluralist social context. This enables some general guidelines to be developed. Conclusions Effective spiritual care requires a consideration of both the patient’s and the nurse’s implicit and explicit religious commitments. Implications for nursing management Nurse managers need to take account of the personal commitments of nurses when directing them to offer spiritual care. This article offers a diagnostic tool for deploying nurses in an appropriate way.