Human resource management at the intensive care unit:A pragmatic review and future research agenda for building a learning health system

Recently, the importance of efficient and effective health care has been recognized, especially during the acute phase of the Coronavirus Disease-2019 (COVID-19) pandemic. Intensive care units (ICUs) have faced an immense workload, with massive numbers of patients being treated in a very short period of time. In general, ICUs are required to deliver high-quality care at all times during the year. At the same time, high-quality organizational goals may not be aligned with the interests, motivation, and development of individual staff members (eg, nurses, and doctors). For management of the ICU, it is important to balance the organizational goals and development of the staff members (“their human capital”), usually referred to as human resource management. Although many studies have considered this area, no holistic view of the topic has been presented. Such a holistic view may help leadership and/or other stakeholders at the ICU to design a better learning health system. This pragmatic review aims to provide a conceptual model for the management of ICUs. Future research may also use this conceptual model for studying important factors for designing and understanding human resources in an ICU.</p

Barriers to patient enrolment in phase III cancer clinical trials:interviews with clinicians and pharmaceutical industry representatives

OBJECTIVES: Phase III cancer clinical trials are expensive and time-consuming phases in drug development. Effective patient enrolment can reduce delays and save costs, offering patients an opportunity to benefit from innovative treatments. However, the current evidence base does not fully explain the persistence of barriers to patient enrolment in phase III cancer clinical trials. The aim was to explore clinicians' and pharmaceutical representatives' views on these barriers. DESIGN: A qualitative study was performed. In-depth information was collected from 15 experts in the field of oncology clinical trials, in particular clinical oncologists acting as principal investigators (PIs) and clinical research associates. By means of semistructured interviews, based on a questionnaire derived from our newly developed conceptual framework, they were asked to identify barriers to patient enrolment they had experienced and comment on barriers identified in literature. FINDINGS: Existing knowledge on barriers to patient enrolment was confirmed by all interviewees. Two new key barriers to patient enrolment were identified, that is, insufficient attention to the importance of clinical trial-based research in medical training and a trust gap between PIs and pharmaceutical representatives. A third important barrier was increasingly narrow patient inclusion criteria. CONCLUSIONS: The success rate of patient enrolment in phase III cancer clinical trials highly depends on the clinicians' willingness to take part in clinical trials. Raising awareness of the importance of clinical trials in medical training and among practising oncologists is recommended. Furthermore, to reduce barriers to patient enrolment, it is essential that both clinicians and pharmaceutical representatives acknowledge each other's expertise, become acquainted with each other's procedures and regulations, and work on building trust relationships. Finally, in accordance with our key findings, we propose to add two new barriers to our newly developed conceptual framework; insufficient attention to clinical trial research in medical training and trust gap.</p

Prices of Orphan Drugs in Four Western European Countries Before and After Market Exclusivity Expiry:A Cross-Country Comparison of List Prices and Purchase Prices

Background: Increasing pharmaceutical expenditure challenges the sustainability and accessibility of healthcare systems across Europe. Confidentiality restraints hinder assessment of actual prices of Orphan Medicinal Products (OMPs). Hence, we assessed the real prices of brand-name OMPs around market exclusivity expiry (MEE). Objective: We aimed to explore developments in published list prices (LPs) and confidential hospital purchase prices (PPs) of brand-name OMPs relative to their market exclusivity status in Western European countries with similar GDPs. Methods: We analyzed LPs and PPs of 13 selected OMPs purchased by university hospitals in Western European countries between 2000 and 2020. For confidentially reasons, proportions were used, with the Dutch LPs of the selected OMPs at the year of MEE serving as reference values. PPs included pre-purchase discounts. Rebates were not considered. Results: Data were analyzed from hospitals in Denmark (DK) (n = 1), France (FR) (n = 1), Germany (DE) (n = 2), and the Netherlands (NL) (n = 1). Average LPs and PPs of included OMPs dropped gradually but limited over time, with no explicit price drop after MEE. LP levels differed more per country than PP levels: LP range before MEE was 164% (DE)–101% (FR) and after MEE was 135% (DE)–82% (FR); PP range before MEE was 150% (DE)–102% (FR) and after MEE was 107% (DE)–80% (FR). Overall differences between LPs and PPs were &lt; 3% in all countries, except for Denmark. Conclusion: No evident price drops of included brand-name OMPs were observed around MEE and differences in purchase prices are modest in the selected Western European countries. Results were not subject to significance testing. More robust data are needed to strengthen negotiations with suppliers.</p

No association between use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers prior to hospital admission and clinical course of COVID-19 in the COvid MEdicaTion (COMET) study

Since the outbreak of SARS-CoV-2, also known as COVID-19, conflicting theories have circulated on the influence of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) on incidence and clinical course of COVID-19, but data are scarce. The COvid MEdicaTion (COMET) study is an observational, multinational study that focused on the clinical course of COVID-19 (i.e. hospital mortality and intensive care unit [ICU] admission), and included COVID-19 patients who were registered at the emergency department or admitted to clinical wards of 63 participating hospitals. Pharmacists, clinical pharmacologists or treating physicians collected data on medication prescribed prior to admission. The association between the medication and composite clinical endpoint, including mortality and ICU admission, was analysed by multivariable logistic regression models to adjust for potential confounders. A total of 4870 patients were enrolled. ACEi were used by 847 (17.4%) patients and ARB by 761 (15.6%) patients. No significant association was seen with ACEi and the composite endpoint (adjusted odds ratio [OR] 0.94; 95% confidence interval [CI] 0.79 to 1.12), mortality (OR 1.03; 95%CI 0.84 to 1.27) or ICU admission (OR 0.96; 95%CI 0.78 to 1.19) after adjustment for covariates. Similarly, no association was observed between ARB and the composite endpoint (OR 1.09; 95%CI 0.90 to 1.30), mortality (OR 1.12; OR 0.90 to 1.39) or ICU admission (OR 1.21; 95%CI 0.98 to 1.49). In conclusion, we found no evidence of a harmful or beneficial effect of ACEi or ARB use prior to hospital admission on ICU admission or hospital mortality

Original COVID-19 priming regimen impacts the immunogenicity of bivalent BA.1 and BA.5 boosters

Waning antibody responses after COVID-19 vaccination combined with the emergence of the SARS-CoV-2 Omicron lineage led to reduced vaccine effectiveness. As a countermeasure, bivalent mRNA-based booster vaccines encoding the ancestral spike protein in combination with that of Omicron BA.1 or BA.5 were introduced. Since then, different BA.2-descendent lineages have become dominant, such as XBB.1.5, JN.1, or EG.5.1. Here, we report post-hoc analyses of data from the SWITCH-ON study, assessing how different COVID-19 priming regimens affect the immunogenicity of bivalent booster vaccinations and breakthrough infections (NCT05471440). BA.1 and BA.5 bivalent vaccines boosted neutralizing antibodies and T-cells up to 3 months after boost; however, cross-neutralization of XBB.1.5 was poor. Interestingly, different combinations of prime-boost regimens induced divergent responses: participants primed with Ad26.COV2.S developed lower binding antibody levels after bivalent boost while neutralization and T-cell responses were similar to mRNA-based primed participants. In contrast, the breadth of neutralization was higher in mRNA-primed and bivalent BA.5 boosted participants. Combined, our data further support the current use of monovalent vaccines based on circulating strains when vaccinating risk groups, as recently recommended by the WHO. We emphasize the importance of the continuous assessment of immune responses targeting circulating variants to guide future COVID-19 vaccination policies.</p

Original COVID-19 priming regimen impacts the immunogenicity of bivalent BA.1 and BA.5 boosters

Waning antibody responses after COVID-19 vaccination combined with the emergence of the SARS-CoV-2 Omicron lineage led to reduced vaccine effectiveness. As a countermeasure, bivalent mRNA-based booster vaccines encoding the ancestral spike protein in combination with that of Omicron BA.1 or BA.5 were introduced. Since then, different BA.2-descendent lineages have become dominant, such as XBB.1.5, JN.1, or EG.5.1. Here, we report post-hoc analyses of data from the SWITCH-ON study, assessing how different COVID-19 priming regimens affect the immunogenicity of bivalent booster vaccinations and breakthrough infections (NCT05471440). BA.1 and BA.5 bivalent vaccines boosted neutralizing antibodies and T-cells up to 3 months after boost; however, cross-neutralization of XBB.1.5 was poor. Interestingly, different combinations of prime-boost regimens induced divergent responses: participants primed with Ad26.COV2.S developed lower binding antibody levels after bivalent boost while neutralization and T-cell responses were similar to mRNA-based primed participants. In contrast, the breadth of neutralization was higher in mRNA-primed and bivalent BA.5 boosted participants. Combined, our data further support the current use of monovalent vaccines based on circulating strains when vaccinating risk groups, as recently recommended by the WHO. We emphasize the importance of the continuous assessment of immune responses targeting circulating variants to guide future COVID-19 vaccination policies.</p

Immunogenicity of a bivalent BA.1 COVID-19 booster vaccine in people with HIV in the Netherlands

OBJECTIVE: We evaluated the immunogenicity of a bivalent BA.1 COVID-19 booster vaccine in people with HIV (PWH).DESIGN: Prospective observational cohort study.METHODS: PWH aged ≥45 years received Wuhan-BA.1 mRNA-1273.214 and those &lt; 45 years Wuhan-BA.1 BNT162b2. Participants were propensity score-matched 1:2 to people without HIV (non-PWH) by age, primary vaccine platform (mRNA-based or vector-based), number of prior COVID-19 boosters and SARS-CoV-2 infections, and spike (S1)-specific antibodies on the day of booster administration. The primary endpoint was the geometric mean ratio (GMR) of ancestral S1-specific antibodies from day 0 to 28 in PWH compared to non-PWH. Secondary endpoints included humoral responses, T-cell responses, and cytokine responses up to 180 days post-vaccination.RESULTS:Forty PWH received mRNA-1273.214 (N = 35) or BNT162b2 (N = 5) following mRNA-based (N = 29) or vector-based (N = 11) primary vaccination. PWH were predominantly male (87% vs 26% of non-PWH) and median 57 years (interquartile range [IQR] 53-59). Their median CD4+ T-cell count was 775 (IQR 511-965) and the plasma HIV-RNA load was &lt; 50 copies/mL in 39/40. The GMR of S1-specific antibodies by 28 days post-vaccination was comparable between PWH (4.48, 95% confidence interval [CI] 3.24-6.19) and non-PWH (4.07, 95% CI 3.42-4.83). S1-specific antibody responses were comparable between PWH and non-PWH up to 180 days, and T-cell responses up to 90 days post-vaccination. IFN-γ, IL-2, and IL-4 cytokine concentrations increased 28 days post-vaccination in PWH.CONCLUSION: A bivalent BA.1 booster vaccine was immunogenic in well-treated PWH, eliciting comparable humoral responses to non-PWH. However, T-cell responses waned faster after 90 days in PWH compared to non-PWH.</p

Immunogenicity of a bivalent BA.1 COVID-19 booster vaccine in people with HIV in the Netherlands

OBJECTIVE: We evaluated the immunogenicity of a bivalent BA.1 COVID-19 booster vaccine in people with HIV (PWH).DESIGN: Prospective observational cohort study.METHODS: PWH aged ≥45 years received Wuhan-BA.1 mRNA-1273.214 and those &lt; 45 years Wuhan-BA.1 BNT162b2. Participants were propensity score-matched 1:2 to people without HIV (non-PWH) by age, primary vaccine platform (mRNA-based or vector-based), number of prior COVID-19 boosters and SARS-CoV-2 infections, and spike (S1)-specific antibodies on the day of booster administration. The primary endpoint was the geometric mean ratio (GMR) of ancestral S1-specific antibodies from day 0 to 28 in PWH compared to non-PWH. Secondary endpoints included humoral responses, T-cell responses, and cytokine responses up to 180 days post-vaccination.RESULTS:Forty PWH received mRNA-1273.214 (N = 35) or BNT162b2 (N = 5) following mRNA-based (N = 29) or vector-based (N = 11) primary vaccination. PWH were predominantly male (87% vs 26% of non-PWH) and median 57 years (interquartile range [IQR] 53-59). Their median CD4+ T-cell count was 775 (IQR 511-965) and the plasma HIV-RNA load was &lt; 50 copies/mL in 39/40. The GMR of S1-specific antibodies by 28 days post-vaccination was comparable between PWH (4.48, 95% confidence interval [CI] 3.24-6.19) and non-PWH (4.07, 95% CI 3.42-4.83). S1-specific antibody responses were comparable between PWH and non-PWH up to 180 days, and T-cell responses up to 90 days post-vaccination. IFN-γ, IL-2, and IL-4 cytokine concentrations increased 28 days post-vaccination in PWH.CONCLUSION: A bivalent BA.1 booster vaccine was immunogenic in well-treated PWH, eliciting comparable humoral responses to non-PWH. However, T-cell responses waned faster after 90 days in PWH compared to non-PWH.</p

Barriers to patient enrolment in phase III cancer clinical trials: interviews with clinicians and pharmaceutical industry representatives

OBJECTIVES: Phase III cancer clinical trials are expensive and time-consuming phases in drug development. Effective patient enrolment can reduce delays and save costs, offering patients an opportunity to benefit from innovative treatments. However, the current evidence base does not fully explain the persistence of barriers to patient enrolment in phase III cancer clinical trials. The aim was to explore clinicians' and pharmaceutical representatives' views on these barriers. DESIGN: A qualitative study was performed. In-depth information was collected from 15 experts in the field of oncology clinical trials, in particular clinical oncologists acting as principal investigators (PIs) and clinical research associates. By means of semistructured interviews, based on a questionnaire derived from our newly developed conceptual framework, they were asked to identify barriers to patient enrolment they had experienced and comment on barriers identified in literature. FINDINGS: Existing knowledge on barriers to patient enrolment was confirmed by all interviewees. Two new key barriers to patient enrolment were identified, that is, insufficient attention to the importance of clinical trial-based research in medical training and a trust gap between PIs and pharmaceutical representatives. A third important barrier was increasingly narrow patient inclusion criteria. CONCLUSIONS: The success rate of patient enrolment in phase III cancer clinical trials highly depends on the clinicians' willingness to take part in clinical trials. Raising awareness of the importance of clinical trials in medical training and among practising oncologists is recommended. Furthermore, to reduce barriers to patient enrolment, it is essential that both clinicians and pharmaceutical representatives acknowledge each other's expertise, become acquainted with each other's procedures and regulations, and work on building trust relationships. Finally, in accordance with our key findings, we propose to add two new barriers to our newly developed conceptual framework; insufficient attention to clinical trial research in medical training and trust gap