Dutch Healthcare Professionals’ Opinion on the Allocation of Responsibilities concerning Prescribing and Administering Medically Indicated Vaccines to Immunocompromised Patients

Background: Specific vaccines are indicated for immunocompromised patients (ICPs) due to their vulnerability to infections. Recommendation of these vaccines by healthcare professionals (HCPs) is a crucial facilitator for vaccine uptake. Unfortunately, the responsibilities to recommend and administer these vaccines are not clearly allocated among HCPs involved in the care of adult ICPs. We aimed to evaluate HCPs’ opinions on directorship and their role in facilitating the uptake of medically indicated vaccines as a basis to improve vaccination practices. Methods: A cross-sectional survey was performed among in-hospital medical specialists (MSs), general practitioners (GPs), and public health specialists (PHSs) in the Netherlands to assess their opinion on directorship and the implementation of vaccination care. Additionally, perceived barriers, facilitators, and possible solutions to improve vaccine uptake were investigated. Results: In total, 306 HCPs completed the survey. HCPs almost unanimously (98%) reported that according to them, the primary treating physician is responsible for recommending medically indicated vaccines. Administering these vaccines was seen as a more shared responsibility. The most important barriers experienced by HCPs in recommending and administering were reimbursement problems, a lack of a national vaccination registration system, insufficient collaboration among HCPs, and logistical problems. MSs, GPs and PHSs all mentioned the same three solutions as important strategies to improve vaccination practices, i.e., reimbursement of vaccines, reliable and easily accessible registration of received vaccines, and arrangements for collaboration among the different HCPs that are involved in care. Conclusion: The improvement in vaccination practices in ICPs should focus on better collaboration among MSs, GPs, and PHSs, who should know each other’s expertise; clear agreement on responsibility; reimbursement for vaccines; and the availability of clear registration of vaccination history.</p

Dutch Healthcare Professionals' Opinion on the Allocation of Responsibilities concerning Prescribing and Administering Medically Indicated Vaccines to Immunocompromised Patients

Background: Specific vaccines are indicated for immunocompromised patients (ICPs) due to their vulnerability to infections. Recommendation of these vaccines by healthcare professionals (HCPs) is a crucial facilitator for vaccine uptake. Unfortunately, the responsibilities to recommend and administer these vaccines are not clearly allocated among HCPs involved in the care of adult ICPs. We aimed to evaluate HCPs’ opinions on directorship and their role in facilitating the uptake of medically indicated vaccines as a basis to improve vaccination practices. Methods: A cross-sectional survey was performed among in-hospital medical specialists (MSs), general practitioners (GPs), and public health specialists (PHSs) in the Netherlands to assess their opinion on directorship and the implementation of vaccination care. Additionally, perceived barriers, facilitators, and possible solutions to improve vaccine uptake were investigated. Results: In total, 306 HCPs completed the survey. HCPs almost unanimously (98%) reported that according to them, the primary treating physician is responsible for recommending medically indicated vaccines. Administering these vaccines was seen as a more shared responsibility. The most important barriers experienced by HCPs in recommending and administering were reimbursement problems, a lack of a national vaccination registration system, insufficient collaboration among HCPs, and logistical problems. MSs, GPs and PHSs all mentioned the same three solutions as important strategies to improve vaccination practices, i.e., reimbursement of vaccines, reliable and easily accessible registration of received vaccines, and arrangements for collaboration among the different HCPs that are involved in care. Conclusion: The improvement in vaccination practices in ICPs should focus on better collaboration among MSs, GPs, and PHSs, who should know each other’s expertise; clear agreement on responsibility; reimbursement for vaccines; and the availability of clear registration of vaccination history

Efficacy and Safety of Tepotinib in Asian Patients With Advanced NSCLC With MET Exon 14 Skipping Enrolled in VISION

BACKGROUND: Tepotinib, a MET inhibitor approved for the treatment of MET exon 14 (METex14) skipping NSCLC, demonstrated durable clinical activity in VISION (Cohort A + C; N = 313): objective response rate (ORR) 51.4% (95% CI: 45.8, 57.1); median duration of response (mDOR) 18.0 months (95% CI: 12.4, 46.4). We report outcomes in Asian patients from VISION (Cohort A + C) (cut-off: November 20, 2022). METHODS: Patients with advanced METex14 skipping NSCLC, detected by liquid or tissue biopsy, received tepotinib 500 mg (450 mg active moiety) once daily. PRIMARY ENDPOINT: objective response (RECIST 1.1) by independent review. Secondary endpoints included: DOR, progression-free survival (PFS), overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: Across treatment lines in 106 Asian patients (39.6% female, 43.4% smoking history, 79.2% adenocarcinoma, 47.2% treatment-naive), ORR was 56.6% (95% CI: 46.6, 66.2), mDOR 18.5 months (10.4, ne), mPFS 13.8 months (10.8, 22.0), and mOS 25.5 months (19.3, 36.4). Consistent efficacy observed, regardless of baseline characteristics. HRQoL remained stable during treatment. Treatment-related adverse events (TRAEs) occurred in 95.3% of patients (39.6% Grade ≥3). Most common TRAEs: peripheral edema (62.3%), creatinine increase (38.7%). CONCLUSIONS: Tepotinib demonstrated robust and durable efficacy, with a manageable safety profile, in Asian patients with METex14 skipping NSCLC. CLINICAL TRIAL REGISTRATION: NCT02864992

The changing landscape of disaster volunteering: opportunities, responses and gaps in Australia

There is a growing expectation that volunteers will have a greater role in disaster management in the future compared to the past. This is driven largely by a growing focus on building resilience to disasters. At the same time, the wider landscape of volunteering is fundamentally changing in the twenty-first century. This paper considers implications of this changing landscape for the resilience agenda in disaster management, with a focus on Australia. It first reviews major forces and trends impacting on disaster volunteering, highlighting four key developments: the growth of more diverse and episodic volunteering styles, the impact of new communications technology, greater private sector involvement and growing government expectations of and intervention in the voluntary sector. It then examines opportunities in this changing landscape for the Australian emergency management sector across five key strategic areas and provides examples of Australian responses to these opportunities to date. The five areas of focus are: developing more flexible volunteering strategies, harnessing spontaneous volunteering, building capacity to engage digital (and digitally enabled) volunteers, tapping into the growth of employee and skills-based volunteering and co-producing community-based disaster risk reduction. Although there have been considerable steps taken in Australia in some of these areas, overall there is still a long way to go before the sector can take full advantage of emerging opportunities. The paper thus concludes by identifying important research and practice gaps in this area

Molecular analysis of enrichment cultures of ammonia oxidizers from the Salar de Huasco, a high altitude saline wetland in northern Chile

We analyzed enrichment cultures of ammonia-oxidizing bacteria (AOB) collected from different areas of Salar de Huasco, a high altitude, saline, pH-neutral water body in the Chilean Altiplano. Samples were inoculated into mineral media with 10 mM NH4+ at five different salt concentrations (10, 200, 400, 800 and 1,400 mM NaCl). Low diversity (up to three phylotypes per enrichment) of beta-AOB was detected using 16S rDNA and amoA clone libraries. Growth of beta-AOB was only recorded in a few enrichment cultures and varied according to site or media salinity. In total, five 16S rDNA and amoA phylotypes were found which were related to Nitrosomonas europaea/Nitrosococcus mobilis, N. marina and N. communis clusters. Phylotype 1-16S was 97% similar with N. halophila, previously isolated from Mongolian soda lakes, and phylotypes from amoA sequences were similar with yet uncultured beta-AOB from different biofilms. Sequences related to N. halophila were frequently found at all salinities. Neither gamma-AOB nor ammonia-oxidizing Archaea were recorded in these enrichment cultures

Piezo1 integration of vascular architecture with physiological force

The mechanisms by which physical forces regulate endothelial cells to determine the complexities of vascular structure and function are enigmatic¹⁻⁵. Studies of sensory neurons have suggested Piezo proteins as subunits of Ca²⁺-permeable non-selective cationic channels for detection of noxious mechanical impact⁶⁻⁸. Here we show Piezo1 (Fam38a) channels as sensors of frictional force (shear stress) and determinants of vascular structure in both development and adult physiology. Global or endothelial-specific disruption of mouse Piezo1 profoundly disturbed the developing vasculature and was embryonic lethal within days of the heart beating. Haploinsufficiency was not lethal but endothelial abnormality was detected in mature vessels. The importance of Piezo1 channels as sensors of blood flow was shown by Piezo1 dependence of shear-stress-evoked ionic current and calcium influx in endothelial cells and the ability of exogenous Piezo1 to confer sensitivity to shear stress on otherwise resistant cells. Downstream of this calcium influx there was protease activation and spatial reorganization of endothelial cells to the polarity of the applied force. The data suggest that Piezo1 channels function as pivotal integrators in vascular biology

Perturbation-Response Scanning Reveals Ligand Entry-Exit Mechanisms of Ferric Binding Protein

We study apo and holo forms of the bacterial ferric binding protein (FBP) which exhibits the so-called ferric transport dilemma: it uptakes iron from the host with remarkable affinity, yet releases it with ease in the cytoplasm for subsequent use. The observations fit the “conformational selection” model whereby the existence of a weakly populated, higher energy conformation that is stabilized in the presence of the ligand is proposed. We introduce a new tool that we term perturbation-response scanning (PRS) for the analysis of remote control strategies utilized. The approach relies on the systematic use of computational perturbation/response techniques based on linear response theory, by sequentially applying directed forces on single-residues along the chain and recording the resulting relative changes in the residue coordinates. We further obtain closed-form expressions for the magnitude and the directionality of the response. Using PRS, we study the ligand release mechanisms of FBP and support the findings by molecular dynamics simulations. We find that the residue-by-residue displacements between the apo and the holo forms, as determined from the X-ray structures, are faithfully reproduced by perturbations applied on the majority of the residues of the apo form. However, once the stabilizing ligand (Fe) is integrated to the system in holo FBP, perturbing only a few select residues successfully reproduces the experimental displacements. Thus, iron uptake by FBP is a favored process in the fluctuating environment of the protein, whereas iron release is controlled by mechanisms including chelation and allostery. The directional analysis that we implement in the PRS methodology implicates the latter mechanism by leading to a few distant, charged, and exposed loop residues. Upon perturbing these, irrespective of the direction of the operating forces, we find that the cap residues involved in iron release are made to operate coherently, facilitating release of the ion