Communication skills and raising awareness in clinical practice: an Italian experience

Following reflection by a member of the healthcare team relating to a particularly difficult situation where communication between the healthcare professional, patient and family was felt to be challenging, there was a general consensus of interest in how we communicate, best practice methods and training opportunities. In order to look at the communication practice, skills and training within the department, it was felt best to identify how the team felt about their own communications skills as a baseline for development of this area of practice

Is there a role for ‘modified VAD’ in the treatment of multiple myeloma?

VAD, (Vincristine, Doxorubicin and Dexamethasone) was initially proposed as a salvage therapy for myeloma patients in whom prior alkylating agent therapy failed, although in recent years VAD has been surpassed by novel combination therapies with new biological agents such as thalidomide (and its derivative, lenalidomide) and bortezomib. After the excellent results obtained by the novel agents, VAD can no longer be proposed in preparation to autologous transplantation, although there are still indications that VAD remains useful and clinically relevant in the initial treatment of symptomatic multiple myeloma

In vitro characterisation of solid drug nanoparticle compositions of efavirenz in a brain endothelium cell line

The antiretroviral drug efavirenz displays many desirable pharmacokinetic properties such as a long half‐life enabling once daily dosing but suffers from central nervous system safety issues. Various nanotechnologies have been explored to mitigate some of the limitations with efavirenz. While there has been progress in increasing the bioavailability, there has been no attempt to assess the impact of increased exposure to efavirenz on central nervous system safety. The uptake of aqueous and solid drug nanoparticle (SDN) formulations of efavirenz was assessed in the human cerebral microvessel endothelial cells/D3 brain endothelial cell line. The mechanisms of uptake were probed using a panel of transport and endocytosis inhibitors. The cellular accumulation of an efavirenz aqueous solution was significantly reduced by amantadine, but this was not observed with SDNs. The uptake of efavirenz SDNs was reduced by dynasore, but concentrations of the efavirenz aqueous solution were not affected. These data indicate that efavirenz is a substrate for transporters in brain endothelial cells (amantadine is an inhibitor of organic cation transporters 1 and 2), and formation of SDNs may bypass this interaction in favour of a mechanism involving dynamin‐mediated endocytosis

Methodological needs in the quality and safety characterisation of nanotechnology-based health products: Priorities for method development and standardisation

Nanotechnology-based health products are providing innovative solutions in health technologies and the pharmaceutical field, responding to unmet clinical needs. However, suitable standardised methods need to be available for quality and safety assessments of these innovative products prior to their translation into the clinic and for monitoring their performance when manufacturing processes are changed. The question arises which technological solutions are currently available within the scientific community to support the requested characterisation of nanotechnology-based products, and which methodological developments should be prioritized to support product developers in their regulatory assessment. To this end, the work presented here explored the state-of-the-art methods to identify methodological gaps associated with the preclinical characterisation of nanotechnology-based medicinal products and medical devices. The regulatory information needs, as expressed by regulatory authorities, were extracted from the guidance documents released so far for nanotechnology-based health products and mapped against available methods, thus allowing an analysis of methodological gaps and needs. In the first step, only standardised methods were considered, leading to the identification of methodological needs in five areas of characterisation, including: (i) surface properties, (ii) drug loading and release, (iii) kinetic properties in complex biological media, (iv) ADME (absorption, distribution, metabolism and excretion) parameters and (v) interaction with blood and the immune system. In the second step, a detailed gap analysis included analytical approaches in earlier stages of development, and standardised test methods from outside of the nanotechnology field that could address the identified areas of gaps. Based on this analysis, three categories of methodological needs were identified, including (i) method optimisation/adaptation to nanotechnological platforms, (ii) method validation/standardisation and (iii) method development for those areas where no technological solutions currently exist. The results of the analysis presented in this work should raise awareness within the scientific community on existing and emerging methodological needs, setting priorities for the development and standardisation of relevant analytical and toxicological methods allowing the development of a robust testing strategy for nanotechnology-based health products

Delivery of antimicrobial stewardship competencies in UK pre-registration nurse education programmes: a national cross-sectional survey

Background: Registered nurses perform numerous functions critical to the success of antimicrobial stewardship but only 63% of pre-registration nursing programmes include any teaching about stewardship. Updated nursing standards highlight nurses require antimicrobial stewardship knowledge and skills. Aim: To explore the delivery of key antimicrobial stewardship competencies within updated pre-registration nursing programmes. Method: A cross-sectional survey design. Data was collected between March and June 2021. Findings: Lecturers from 35 universities responsible for teaching antimicrobial stewardship participated. The provision of antimicrobial stewardship teaching and learning was inconsistent across programmes with competencies in infection prevention and control, patient centred care, and interprofessional collaborative practice taking precedent over those pertaining to the use, management, and monitoring of antimicrobials. On-line learning and teaching surrounding hand hygiene, personal protective equipment, and immunisation theory was reported to have increased during the pandemic. Only a small number of respondents reported that students shared taught learning with other healthcare professional groups. Conclusion: There is a need to ensure consistency in antimicrobial stewardship across programmes, and greater knowledge pertaining to the use, management and monitoring of antimicrobials should be included. Programmes need to adopt teaching strategies and methods that allow nurses to develop interprofessional skill in order to practice collaboratively

Population Pharmacokinetic and Pharmacogenetic Analysis of Nevirapine in Hypersensitive and Tolerant HIV-Infected Patients from Malawi

We modeled nevirapine (NVP) pharmacokinetics in HIV-infected Malawian patients to assess the relationship between drug exposure and patient characteristics, genetic polymorphisms, and development of hypersensitivity reaction (HSR). One thousand one hundred seventeen patients were prospectively recruited and followed for 26 weeks with multiple or single serum samples obtained in a subset of patients for NVP quantification. Single nucleotide polymorphisms (SNPs) within CYP2B6 and CYP3A4 genes were typed. Nonlinear mixed effects modeling was utilized to assess the influence of patient characteristics and host genetics on NVP apparent oral clearance (CL/F) and to explore the relationship between NVP CL/F and HSR. Published haplotype distributions were used to simulate NVP concentrations in Caucasians versus Africans. One hundred eighty patients (101 female) were included in the model; 25 experienced HSR. No associations between patient demographics or HSR and NVP CL/F were evident. A significant relationship between CYP2B6 c.983T>C and CYP2B6 c.516G>T and NVP CL/F was observed (P < 0.01). NVP CL/F was reduced by 23% and 36% in patients with CYP2B6 983TT/516TT and 983TC/516GG or GT, respectively, compared to the reference genotype. Simulated exposures suggested similar proportions (13 to 17%) of patients with subtherapeutic NVP among Caucasians and an African population. Influence of CYP2B6 polymorphisms on NVP CL/F in this population is in agreement with other reports. Our data indicate a lack of association between NVP exposure and HSR. Based on these data, dose optimization based solely on ethnicity (without individual gene testing) is unlikely to impact on risk of treatment failure or toxicity even in an African population with high carriage of poor metabolizer mutations