Controlled Mechanical Ventilation in Critically Ill Patients and the Potential Role of Venous Bagging in Acute Kidney Injury.

A very low incidence of acute kidney injury (AKI) has been observed in COVID-19 patients purposefully treated with early pressure support ventilation (PSV) compared to those receiving mainly controlled ventilation. The prevention of subdiaphragmatic venous congestion through limited fluid intake and the lowering of intrathoracic pressure is a possible and attractive explanation for this observed phenomenon. Both venous congestion, or "venous bagging", and a positive fluid balance correlate with the occurrence of AKI. The impact of PSV on venous return, in addition to the effects of limiting intravenous fluids, may, at least in part, explain this even more clearly when there is no primary kidney disease or the presence of nephrotoxins. Optimizing the patient-ventilator interaction in PSV is challenging, in part because of the need for the ongoing titration of sedatives and opioids. The known benefits include improved ventilation/perfusion matching and reduced ventilator time. Furthermore, conservative fluid management positively influences cognitive and psychiatric morbidities in ICU patients and survivors. Here, it is hypothesized that cranial lymphatic congestion in relation to a more positive intrathoracic pressure, i.e., in patients predominantly treated with controlled mechanical ventilation (CMV), is a contributing risk factor for ICU delirium. No studies have addressed the question of how PSV can limit AKI, nor are there studies providing high-level evidence relating controlled mechanical ventilation to AKI. For this perspective article, we discuss studies in the literature demonstrating the effects of venous congestion leading to AKI. We aim to shed light on early PSV as a preventive measure, especially for the development of AKI and ICU delirium and emphasize the need for further research in this domain.

Role of knowledge and reasoning processes as predictors of resident physicians' susceptibility to anchoring bias in diagnostic reasoning: a randomised controlled experiment.

BACKGROUND: Diagnostic errors have been attributed to reasoning flaws caused by cognitive biases. While experiments have shown bias to cause errors, physicians of similar expertise differed in susceptibility to bias. Resisting bias is often said to depend on engaging analytical reasoning, disregarding the influence of knowledge. We examined the role of knowledge and reasoning mode, indicated by diagnosis time and confidence, as predictors of susceptibility to anchoring bias. Anchoring bias occurs when physicians stick to an incorrect diagnosis triggered by early salient distracting features (SDF) despite subsequent conflicting information. METHODS: Sixty-eight internal medicine residents from two Dutch university hospitals participated in a two-phase experiment. Phase 1: assessment of knowledge of discriminating features (ie, clinical findings that discriminate between lookalike diseases) for six diseases. Phase 2 (1 week later): diagnosis of six cases of these diseases. Each case had two versions differing exclusively in the presence/absence of SDF. Each participant diagnosed three cases with SDF (SDF+) and three without (SDF-). Participants were randomly allocated to case versions. Based on phase 1 assessment, participants were split into higher knowledge or lower knowledge groups. MAIN OUTCOME MEASUREMENTS: frequency of diagnoses associated with SDF; time to diagnose; and confidence in diagnosis. RESULTS: While both knowledge groups performed similarly on SDF- cases, higher knowledge physicians succumbed to anchoring bias less frequently than their lower knowledge counterparts on SDF+ cases (p=0.02). Overall, physicians spent more time (p<0.001) and had lower confidence (p=0.02) on SDF+ than SDF- cases (p<0.001). However, when diagnosing SDF+ cases, the groups did not differ in time (p=0.88) nor in confidence (p=0.96). CONCLUSIONS: Physicians apparently adopted a more analytical reasoning approach when presented with distracting features, indicated by increased time and lower confidence, trying to combat bias. Yet, extended deliberation alone did not explain the observed performance differences between knowledge groups. Success in mitigating anchoring bias was primarily predicted by knowledge of discriminating features of diagnoses.

A Systematic Review of the Pulmonary Microbiome in Patients with Acute Exacerbation COPD Requiring ICU Admission.

Background: Chronic obstructive pulmonary disease (COPD) is a major health concern. Acute exacerbations (AECOPD) may require intensive care unit (ICU) admission and mechanical ventilation. Acute infections and chronic colonization of the respiratory system are known to precipitate AECOPD. Detailed knowledge of the respiratory microbiome could lead to effective treatment and prevention of exacerbations. Objective: The aim of this review is to summarize the available evidence on the respiratory microbiome of patients with a severe AECOPD requiring mechanical ventilation and intensive care admission. Methods: A systematic literature search was conducted to identify the published papers until January 2023. The collected data were then subjected to qualitative analysis. After the first analysis, a secondary focused review of the most recent publications studying the relationship between microbiome and mortality in AECOPD was performed. Results: Out of 120 screened articles six articles were included in this review. Potentially pathogenic microorganisms (PPMs) were identified in 30% to 72% of the patients with community-acquired bacteria, gram-negative enteric bacilli, Stenotrophomonas and Pseudomonas being the most frequently isolated. During hospitalization, 21% of patients experienced colonization by PPMs. Adequate antimicrobial therapy resulted in the eradication of 77% of the identified PPMs. However, 24% of the bacteria displayed multi-drug resistance leading to prolonged or failure of eradication. Conclusion: PPMs are prevalent in a significant proportion of patients experiencing an AECOPD. The most identified PPMs include community-acquired pathogens and gram-negative enteric bacilli. Notably, no differences in mortality or duration of ventilation were observed between patients with and without isolated PPMs. However, the included studies did not investigate the virome of the patients, which may influence the microbiome and the outcome of infection. Therefore, further research is essential to comprehensively investigate the complete microbial and viral composition of the lower respiratory system in COPD patients admitted to the ICU.

Increased incidence of Mycoplasma pneumoniae infections and hospital admissions in the Netherlands, November to December 2023.

Mycoplasma pneumoniae is an important cause of pneumonia and extra-pulmonary manifestations. We observed a rise in admissions due to M. pneumoniae infections starting October 2023 in a regional hospital in the Netherlands and an increased incidence in national surveillance data. The incidence in the Netherlands has not been that high since 2011. The patients had a lower median age compared with 2019 and 2020 (28 vs 40 years). M. pneumoniae should be considered in patients with respiratory symptoms, especially children.

Influenza: seasonality and travel-related considerations.

RATIONALE FOR REVIEW: This review aims to summarize the transmission patterns of influenza, its seasonality in different parts of the globe, air travel- and cruise ship-related influenza infections and interventions to reduce transmission. KEY FINDINGS: The seasonality of influenza varies globally, with peak periods occurring mainly between October and April in the northern hemisphere (NH) and between April and October in the southern hemisphere (SH) in temperate climate zones. However, influenza seasonality is significantly more variable in the tropics. Influenza is one of the most common travel-related, vaccine-preventable diseases and can be contracted during travel, such as during a cruise or through air travel. Additionally, travellers can come into contact with people from regions with ongoing influenza transmission. Current influenza immunization schedules in the NH and SH leave individuals susceptible during their respective spring and summer months if they travel to the other hemisphere during that time. CONCLUSIONS/RECOMMENDATIONS: The differences in influenza seasonality between hemispheres have substantial implications for the effectiveness of influenza vaccination of travellers. Health care providers should be aware of influenza activity when patients report travel plans, and they should provide alerts and advise on prevention, diagnostic and treatment options. To mitigate the risk of travel-related influenza, interventions include antivirals for self-treatment (in combination with the use of rapid self-tests), extending the shelf life of influenza vaccines to enable immunization during the summer months for international travellers and allowing access to the influenza vaccine used in the opposite hemisphere as a travel-related vaccine. With the currently available vaccines, the most important preventive measure involves optimizing the seasonal influenza vaccination. It is also imperative that influenza is recognized as a travel-related illness among both travellers and health care professionals.

Levels of Fibrinogen Variants Are Altered in Severe COVID-19.

Background Fibrinogen variants as a result of alternative messenger RNA splicing or protein degradation can affect fibrin(ogen) functions. The levels of these variants might be altered during coronavirus disease 2019 (COVID-19), potentially affecting disease severity or the thrombosis risk. Aim To investigate the levels of fibrinogen variants in plasma of patients with COVID-19. Methods In this case-control study, we measured levels of functional fibrinogen using the Clauss assay. Enzyme-linked immunosorbent assays were used to measure antigen levels of total, intact (nondegraded Aα chain), extended Aα chain (α E ), and γ' fibrinogen in healthy controls, patients with pneumococcal infection in the intensive care unit (ICU), ward patients with COVID-19, and ICU patients with COVID-19 (with and without thrombosis, two time points). Results Healthy controls and ward patients with COVID-19 ( n = 10) showed similar fibrinogen (variant) levels. ICU patients with COVID-19 who later did ( n = 19) or did not develop thrombosis ( n = 18) and ICU patients with pneumococcal infection ( n = 6) had higher absolute levels of functional, total, intact, and α E fibrinogen than healthy controls ( n = 7). The relative α E fibrinogen levels were higher in ICU patients with COVID-19 than in healthy controls, while relative γ' fibrinogen levels were lower. After diagnosis of thrombosis, only the functional fibrinogen levels were higher in ICU patients with COVID-19 and thrombosis than in those without, while no differences were observed in the other fibrinogen variants. Conclusion Our results show that severe COVID-19 is associated with increased levels of α E fibrinogen and decreased relative levels of γ' fibrinogen, which may be a cause or consequence of severe disease, but this is not associated with the development of thrombosis.

Early Patient-Triggered Pressure Support Breathing in Mechanically Ventilated Patients with COVID-19 May Be Associated with Lower Rates of Acute Kidney Injury.

BACKGROUND: Acute respiratory distress syndrome (ARDS) in COVID-19 patients often necessitates mechanical ventilation. Although much has been written regarding intensive care admission and treatment for COVID-19, evidence on specific ventilation strategies for ARDS is limited. Support mode during invasive mechanical ventilation offers potential benefits such as conserving diaphragmatic motility, sidestepping the negative consequences of the longer usage of neuromuscular blockers, and limiting the occurrence of ventilator-induced lung injury (VILI). METHODS: In this retrospective cohort study of mechanically ventilated and confirmed non-hyperdynamic SARS-CoV-2 patients, we studied the relation between the occurrence of kidney injury and the decreased ratio of support to controlled ventilation. RESULTS: Total AKI incidence in this cohort was low (5/41). In total, 16 of 41 patients underwent patient-triggered pressure support breathing at least 80% of the time. In this group we observed a lower percentage of AKI (0/16 vs. 5/25), determined as a creatinine level above 177 µmol/L in the first 200 h. There was a negative correlation between time spent on support ventilation and peak creatinine levels (r = -0.35 (-0.6-0.1)). The group predominantly on control ventilation showed significantly higher disease severity scores. CONCLUSIONS: Early patient-triggered ventilation in patients with COVID-19 may be associated with lower rates of acute kidney injury.

Exotic viral hepatitis: A review on epidemiology, pathogenesis, and treatment.

Certain "exotic" viruses are known to cause clinical diseases with potential liver involvement. These include viruses, beyond regular hepatotropic viruses (hepatitis A, -B(D), -C, -E, cytomegalovirus, Epstein-Barr virus), that can be found in (sub)tropical areas and can cause "exotic viral hepatitis". Transmission routes typically involve arthropods (Crimean Congo haemorrhagic fever, dengue, Rift Valley fever, yellow fever). However, some of these viruses are transmitted by the aerosolised excreta of rodents (Hantavirus, Lassa fever), or via direct contact or contact with bodily fluids (Ebola). Although some exotic viruses are associated with high fatality rates, such as Ebola for example, the clinical presentation of most exotic viruses can range from mild flu-like symptoms, in most cases, right through to being potentially fatal. A smaller percentage of people develop severe disease with haemorrhagic fever, possibly with (fulminant) hepatitis. Liver involvement is often caused by direct tropism for hepatocytes and Kupffer cells, resulting in virus-mediated and/or immune-mediated necrosis. In all exotic hepatitis viruses, PCR is the most sensitive diagnostic method. The determination of IgM/IgG antibodies is a reasonable alternative, but cross-reactivity can be a problem in the case of flaviviruses. Licenced vaccines are available for yellow fever and Ebola, and they are currently under development for dengue. Therapy for exotic viral hepatitis is predominantly supportive. To ensure that preventive measures can be introduced to control possible outbreaks, the timely detection of these viruses is very important.

Serum Markers Associated with Disease Severity in a Bosnian Hemorrhagic Fever with Renal Syndrome Cohort.

Puumala orthohantavirus (PUUV) is endemic in Europe and can cause hemorrhagic fever with renal syndrome (nephropathia epidemica). Disease features include fever, thrombocytopenia, and acute kidney injury (AKI). This retrospective cohort study of forty PUUV patients aims to characterize associations of serum immunological, hemostatic or kidney injury markers to disease severity. While interleukin-18 (IL-18) was significantly increased in severely thrombocytopenic patients (<100 × 109 platelets/L) compared to patients with higher platelet counts, RANTES was significantly decreased in these patients. These data suggest that patients with significant thrombocytopenia might have experienced pronounced Th1 immune responses. When kidney dysfunction was used as the primary disease outcome, recently identified AKI biomarkers (Cystatin C, insulin-like growth factor-binding protein 7, Nephrin, and trefoil factor 3) were significantly upregulated in patients with severe PUUV infection, defined as the estimated glomerular filtration rate (eGFR) below 30 m/min/1.73 m2. The increased expression of these markers specifically indicates pathology in glomeruli and proximal tubuli. Furthermore, E-selectin was significantly higher while interferon gamma-induced protein 10 (IP-10) was significantly lower in PUUV patients with more severe kidney dysfunction compared to patients with higher eGFR-values. Increased E-selectin illustrates the central role of endothelial cell activation, whereas decreased IP-10 could indicate a less important role of this cytokine in the pathogenesis of kidney dysfunction.

Altered fibrin network structure and fibrinolysis in intensive care unit patients with COVID-19, not entirely explaining the increased risk of thrombosis.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 infection is associated with an increased incidence of thrombosis. OBJECTIVES: By studying the fibrin network structure of coronavirus disease 2019 (COVID-19) patients, we aimed to unravel pathophysiological mechanisms that contribute to this increased risk of thrombosis. This may contribute to optimal prevention and treatment of COVID-19 related thrombosis. PATIENTS/METHODS: In this case-control study, we collected plasma samples from intensive care unit (ICU) patients with COVID-19, with and without confirmed thrombosis, between April and December 2020. Additionally, we collected plasma from COVID-19 patients admitted to general wards without thrombosis, from ICU patients with pneumococcal infection, and from healthy controls. Fibrin fiber diameters and fibrin network density were quantified in plasma clots imaged with stimulated emission depletion microscopy and confocal microscopy. Finally, we determined the sensitivity to fibrinolysis. RESULTS: COVID-19 ICU patients (n = 37) and ICU patients with pneumococcal disease (n = 7) showed significantly higher fibrin densities and longer plasma clot lysis times than healthy controls (n = 7). No differences were observed between COVID-19 ICU patients with and without thrombosis, or ICU patients with pneumococcal infection. At a second time point, after diagnosis of thrombosis or at a similar time point in patients without thrombosis, we observed thicker fibers and longer lysis times in COVID-19 ICU patients with thrombosis (n = 19) than in COVID-19 ICU patients without thrombosis (n = 18). CONCLUSIONS: Our results suggest that severe COVID-19 is associated with a changed fibrin network structure and decreased susceptibility to fibrinolysis. Because these changes were not exclusive to COVID-19 patients, they may not explain the increased thrombosis risk.

Predictors of poor haematopoietic stem cell mobilisation in patients with haematological malignancies at a South African centre.

BACKGROUND: Autologous stem cell transplant (ASCT) is an established consolidation strategy in the treatment of haematological malignancies, however poor mobilisation (PM) can contribute to patient morbidity and high resource utilisation. Identifying the incidence, risk factors for PM and engraftment outcomes are important goals in our resource limited setting. METHODS: We retrospectively analyzed patients with haematological malignancies that consecutively underwent ASCT at Groote Schuur hospital, Cape Town, South Africa from January 2013 to January 2019. RESULTS: 146 patients - majority with multiple myeloma (MM)(41,8%), F:M= 1:2, underwent leukapheresis with median age of 32 years (range, 9 - 66 years). PM occurred in 25/146 (17%), mobilisation failure (MF) in 3/146 (2%) and super mobilisation (SMs) in 99/146 (68%), respectively. Risk factors for PM were: diagnosis of acute leukaemia (RR = 25, 95% CI 3.4 - 183, p = 0.002) and Hodgkin lymphoma (RR = 19, 95% CI 2.6 - 142, p = 0.004); low white cell count (WCC) at harvest (WCC < 9 × 109/L (RR=4.3, 95% CI 2.3 - 8.3, p < 0.0001) and two vs one line of prior therapy (RR = 3.1, 95% CI 1.45 - 6.7, p = 0.0037). Median days to neutrophil and platelet engraftment were 14 days (95% CI 14-15 days) and 16 days (95% CI 15-16 days) respectively. CONCLUSION: PM occurred in 17% of a contemporary South African ASCT cohort, albeit with a low MF rate (2%). There was surprisingly high rate (68%) of SMs, possibly reflective of superfluous mobilisation strategy in MM patients. We identified predictive factors for PM that will lead to enhanced cost-effective use of plerixafor.

Interferon-α2 Auto-antibodies in Convalescent Plasma Therapy for COVID-19.

PURPOSE: To study the effect of interferon-α2 auto-antibodies (IFN-α2 Abs) on clinical and virological outcomes in critically ill COVID-19 patients and the risk of IFN-α2 Abs transfer during convalescent plasma treatment. METHODS: Sera from healthy controls, cases of COVID-19, and other respiratory illness were tested for IFN-α2 Abs by ELISA and a pseudo virus-based neutralization assay. The effects of disease severity, sex, and age on the risk of having neutralizing IFN-α2 Abs were determined. Longitudinal analyses were performed to determine association between IFN-α2 Abs and survival and viral load and whether serum IFN-α2 Abs appeared after convalescent plasma transfusion. RESULTS: IFN-α2 neutralizing sera were found only in COVID-19 patients, with proportions increasing with disease severity and age. In the acute stage of COVID-19, all sera from patients with ELISA-detected IFN-α2 Abs (13/164, 7.9%) neutralized levels of IFN-α2 exceeding physiological concentrations found in human plasma and this was associated with delayed viral clearance. Convalescent plasma donors that were anti-IFN-α2 ELISA positive (3/118, 2.5%) did not neutralize the same levels of IFN-α2. Neutralizing serum IFN-α2 Abs were associated with delayed viral clearance from the respiratory tract. CONCLUSIONS: IFN-α2 Abs were detected by ELISA and neutralization assay in COVID-19 patients, but not in ICU patients with other respiratory illnesses. The presence of neutralizing IFN-α2 Abs in critically ill COVID-19 is associated with delayed viral clearance. IFN-α2 Abs in COVID-19 convalescent plasma donors were not neutralizing in the conditions tested.

Measles seroprevalence among Dutch travelling families.

BACKGROUND: While measles vaccination is widely implemented in national immunisation programmes, measles incidence rates are increasing worldwide. Dutch inhabitants who were born between 1965-1975 may have fallen between two stools, lacking protection from a natural infection, and having missed the introduction of the measles vaccination schedule. With this study we aim to find the measles seroprevalence in travellers born between 1965 and 1975, compared to those born before 1965 and after 1975. METHODS: Families travelling to Eastern Europe or outside Europe during the preceding year were recruited via Dutch secondary schools between 2016 and 2018. Their vaccination status was assessed using questionnaires, vaccination records and measles serology in dried blood spot (DBS) eluates. Measles virus antibody concentrations were determined with an ELISA (EUROIMMUNE®) and a subset was retested with a focus reduction neutralization assay (FRNT). RESULTS: In 188 (79%) of the 239 available DBS eluates, the ELISA could detect sufficient measles virus-specific IgG antibodies. Of the negative samples that were retested with FRNT, 85% remained negative, resulting in an overall seroprevalence of 82% [95% CI 76-86]. Children had a lower seroprevalence (72%) than adults (87%). Travellers born between 1965 and 1975 were protected in 89%. CONCLUSIONS: In this study, we report a measles seroprevalence of 82% among Dutch travelling families. Remarkably, seroprevalence rates were lowest in children (12-18 years) instead of travellers born between 1965 and 1975. Although a fraction of people without detectable antibodies may be protected by other immune mechanisms, these data suggest that measles (re)vaccination should be considered for travellers to endemic regions.

Thrombocytopenia in Virus Infections.

Thrombocytopenia, which signifies a low platelet count usually below 150 × 109/L, is a common finding following or during many viral infections. In clinical medicine, mild thrombocytopenia, combined with lymphopenia in a patient with signs and symptoms of an infectious disease, raises the suspicion of a viral infection. This phenomenon is classically attributed to platelet consumption due to inflammation-induced coagulation, sequestration from the circulation by phagocytosis and hypersplenism, and impaired platelet production due to defective megakaryopoiesis or cytokine-induced myelosuppression. All these mechanisms, while plausible and supported by substantial evidence, regard platelets as passive bystanders during viral infection. However, platelets are increasingly recognized as active players in the (antiviral) immune response and have been shown to interact with cells of the innate and adaptive immune system as well as directly with viruses. These findings can be of interest both for understanding the pathogenesis of viral infectious diseases and predicting outcome. In this review, we will summarize and discuss the literature currently available on various mechanisms within the relationship between thrombocytopenia and virus infections.

Empowering Dutch and Surinamese children to prevent viral infections: implications from an international education module.

Viral infections have a large share in human morbidity and mortality. Next to vaccinations and hygiene measures, health education plays a role in preventing infections. Social scientists argue that empowerment should be included in health education, as increasing knowledge is insufficient to achieve sustainable behaviour change. Within the international education module 'Viruskenner', primary school students learn how to prevent virus infections by identifying health risks and developing interventions. This qualitative formative study explored to what extent Viruskenner creates conditions in which empowerment processes can arise and take place in the Netherlands and Suriname. Indicators of empowerment, as defined in the literature and placed in the attitude, social influence, and self-efficacy model, were assessed during semi-structured interviews (n = 24) with students, parents, teachers and facilitators. We conclude that Viruskenner is successful in creating conditions for empowerment processes to arise and take place, specifically in attitude and self-efficacy. According to interviewees, the module raised students' motivation, skills and confidence to take action to improve health behaviour. Educators played a stimulating role in the participatory setting in both countries, while content relevance and community involvement differed between the Netherlands and Suriname. These outcomes could improve this module and possibly other health education programmes.

Evaluation of the Hepatitis B Vaccination Programme in Medical Students in a Dutch University Hospital.

Healthcare workers (HCW) are at increased risk of contracting hepatitis B virus (HBV) and are, therefore, vaccinated pre-exposure. In this study, the HBV vaccination programme for medical students in a university hospital in the Netherlands was evaluated. In the first part, the effectiveness of the programme, which consisted of a vaccination with Engerix-B® at 0, 1, and 6 months, was retrospectively evaluated over 7 years (2012-2019). In the second part of this study, we followed students (the 2019 cohort) who had previously been vaccinated against HBV vaccination (4-262 months prior to primary presentation) in order to investigate the most efficient strategy to obtain an adequate anti hepatitis B surface antigen titre. In the latter, titre determination was performed directly during primary presentation instead of giving previously vaccinated students a booster vaccination first. The vaccination programme, as evaluated in the retrospective first part of the study, was effective (surpassed the protection limit of 10 IU/L) in 98.8 percent of the students (95% CI (98.4-99.2)). In the second part of our study, we found that 80 percent (95% CI (70-87)) of the students who had previously been vaccinated against HBV were still sufficiently protected and did not require a booster vaccination. With this strategy, the previously vaccinated students needed an average of 1.4 appointments instead of the 2 appointments needed with the former strategy. This knowledge is important and can save time and resources in the process of occupational HBV vaccination of HCW.

Specific Disease Knowledge as Predictor of Susceptibility to Availability Bias in Diagnostic Reasoning: a Randomized Controlled Experiment.

BACKGROUND: Bias in reasoning rather than knowledge gaps has been identified as the origin of most diagnostic errors. However, the role of knowledge in counteracting bias is unclear. OBJECTIVE: To examine whether knowledge of discriminating features (findings that discriminate between look-alike diseases) predicts susceptibility to bias. DESIGN: Three-phase randomized experiment. Phase 1 (bias-inducing): Participants were exposed to a set of clinical cases (either hepatitis-IBD or AMI-encephalopathy). Phase 2 (diagnosis): All participants diagnosed the same cases; 4 resembled hepatitis-IBD, 4 AMI-encephalopathy (but all with different diagnoses). Availability bias was expected in the 4 cases similar to those encountered in phase 1. Phase 3 (knowledge evaluation): For each disease, participants decided (max. 2 s) which of 24 findings was associated with the disease. Accuracy of decisions on discriminating features, taken as a measure of knowledge, was expected to predict susceptibility to bias. PARTICIPANTS: Internal medicine residents at Erasmus MC, Netherlands. MAIN MEASURES: The frequency with which higher-knowledge and lower-knowledge physicians gave biased diagnoses based on phase 1 exposure (range 0-4). Time to diagnose was also measured. KEY RESULTS: Sixty-two physicians participated. Higher-knowledge physicians yielded to availability bias less often than lower-knowledge physicians (0.35 vs 0.97; p = 0.001; difference, 0.62 [95% CI, 0.28-0.95]). Whereas lower-knowledge physicians tended to make more of these errors on subjected-to-bias than on not-subjected-to-bias cases (p = 0.06; difference, 0.35 [CI, - 0.02-0.73]), higher-knowledge physicians resisted the bias (p = 0.28). Both groups spent more time to diagnose subjected-to-bias than not-subjected-to-bias cases (p = 0.04), without differences between groups. CONCLUSIONS: Knowledge of features that discriminate between look-alike diseases reduced susceptibility to bias in a simulated setting. Reflecting further may be required to overcome bias, but succeeding depends on having the appropriate knowledge. Future research should examine whether the findings apply to real practice and to more experienced physicians.

Determinants of Vaccination Uptake in Risk Populations: A Comprehensive Literature Review.

Vaccination uptake has decreased globally in recent years, with a subsequent rise of vaccine-preventable diseases. Travellers, immunocompromised patients (ICP), and healthcare workers (HCW) are groups at increased risk for (severe) infectious diseases due to their behaviour, health, or occupation, respectively. While targeted vaccination guidelines are available, vaccination uptake seems low. In this review, we give a comprehensive overview of determinants-based on the integrated change model-predicting vaccination uptake in these groups. In travellers, low perceived risk of infection and low awareness of vaccination recommendations contributed to low uptake. Additionally, ICP were often unaware of the recommended vaccinations. A physician's recommendation is strongly correlated with higher uptake. Furthermore, ICP appeared to be mainly concerned about the risks of vaccination and fear of deterioration of their underlying disease. For HCW, perceived risk of (the severity of) infection for themselves and for their patients together with perceived benefits of vaccination contribute most to their vaccination behaviour. As the determinants that affect uptake are numerous and diverse, we argue that future studies and interventions should be based on multifactorial health behaviour models, especially for travellers and ICP as only a limited number of such studies is available yet.

Orthohantavirus Pathogenesis and Cell Tropism.

Orthohantaviruses are zoonotic viruses that are naturally maintained by persistent infection in specific reservoir species. Although these viruses mainly circulate among rodents worldwide, spill-over infection to humans occurs. Orthohantavirus infection in humans can result in two distinct clinical outcomes: hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). While both syndromes develop following respiratory transmission and are associated with multi-organ failure and high mortality rates, little is known about the mechanisms that result in these distinct clinical outcomes. Therefore, it is important to identify which cell types and tissues play a role in the differential development of pathogenesis in humans. Here, we review current knowledge on cell tropism and its role in pathogenesis during orthohantavirus infection in humans and reservoir rodents. Orthohantaviruses predominantly infect microvascular endothelial cells (ECs) of a variety of organs (lungs, heart, kidney, liver, and spleen) in humans. However, in this review we demonstrate that other cell types (e.g., macrophages, dendritic cells, and tubular epithelium) are infected as well and may play a role in the early steps in pathogenesis. A key driver for pathogenesis is increased vascular permeability, which can be direct effect of viral infection in ECs or result of an imbalanced immune response in an attempt to clear the virus. Future studies should focus on the role of identifying how infection of organ-specific endothelial cells as well as other cell types contribute to pathogenesis.