For decades, public health experts and journalists worldwide warned about a viral pandemic capable of causing illness and loss of life. Previous outbreaks of SARS, Ebola, and MERS highlighted this... Show moreFor decades, public health experts and journalists worldwide warned about a viral pandemic capable of causing illness and loss of life. Previous outbreaks of SARS, Ebola, and MERS highlighted this threat, which occupied top positions in risk assessments globally. Yet even with knowledge and precedent, the COVID-19 pandemic caught the world off guard. It revealed a world inadequately prepared and plunged societies into a state of disruption, with over 7 million deaths reported to the World Health Organization by April 2024. How did this tragedy foretold take the world by such surprise? In The COVID-19 Intelligence Failure: Why Warning Was Not Enough, Erik J. Dahl explores this question from the vantage point of the United States.In his book, Dahl, who is highly regarded for his expertise on intelligence failures, analyzes past and present intelligence efforts to underline the shortcomings and successes of the U.S. intelligence community's anticipation of the pandemic, comparing the anticipation and response to COVID-19 with historical failed warnings, such as those preceding 9/11 and Pearl Harbor. Show less
Thromboembolic complications remain a major public health burden, making antithrombotic agents one of the most widely prescribed groups of medication, but the treatment is often challenging as it... Show moreThromboembolic complications remain a major public health burden, making antithrombotic agents one of the most widely prescribed groups of medication, but the treatment is often challenging as it at the same time increases risk of bleeding. With nationwide data from Statistics Netherlands, antithrombotic therapy and relevant clinical outcomes were comprehensively examined in the patient population of atrial fibrillation, overall or among those with comorbid cancer. The results suggest the patient population was increasingly receiving anticoagulants, driven by the newly introduced medication- direct oral anticoagulant and guided by the CHA2DS2-VASc score, and meanwhile the patient population experienced fewer ischemic stroke and major bleeding. In spite of these promising changes, suboptimal medication adherence and potential underuse of anticoagulants remain directions for further improvement. Antithrombotic agent use during pregnancy was also examined in the general Dutch pregnant population, which featured a surge in antiplatelet prescriptions, and risk of preeclampsia/eclampsia decreased and several newborn outcomes improved simultaneously. Together, the studies presented in this thesis provide an overview of antithrombotic therapy in the Netherlands in recent years, providing insights for further improving this treatment and relevant patient outcomes. Show less
The outbreaks of AIDS and COVID-19 showed clearly how infectious viruses can influence people’s lives. Investigating the changes in the host metabolism may provide a paradigm shift to consider... Show moreThe outbreaks of AIDS and COVID-19 showed clearly how infectious viruses can influence people’s lives. Investigating the changes in the host metabolism may provide a paradigm shift to consider immune-metabolic interactions as therapeutic targets. The aim of this thesis is to examine the interplay between the immune system and metabolism during viral infections, such as HIV and coronavirus. These investigations will utilize metabolomic and lipidomic mass spectrometry techniques to gain a comprehensive understanding of the metabolic changes that occur during viral infections. To enhance the coverage of the lipidome, a new method will be developed. Show less
The emergence of complex diseases resulting from abnormal cell-cell signaling and the spread of infectious diseases caused by pathogens are significant threats to humanity. Unraveling the dynamic... Show moreThe emergence of complex diseases resulting from abnormal cell-cell signaling and the spread of infectious diseases caused by pathogens are significant threats to humanity. Unraveling the dynamic mechanisms underlying cell-cell signaling and infectious disease spreading is crucial for effective disease prevention and treatment. As science and technology advance, the availability and diversity of observational and experimental data related to these biological processes continue to grow. In this thesis, we integrate multisource data with dynamic modeling to investigate the biological mechanisms of Notch signaling in biological development and to develop prevention and control strategies for infectious diseases. Show less
Immunoglobulin G (IgG) antibodies play an important role in the immune response against viruses such as SARS-CoV-2. As the effector functions of IgG are modulated by N-glycosylation of the Fc... Show moreImmunoglobulin G (IgG) antibodies play an important role in the immune response against viruses such as SARS-CoV-2. As the effector functions of IgG are modulated by N-glycosylation of the Fc region, the structure and possible function of the IgG N-glycome has been under investigation in relation to divergent COVID-19 disease courses. Through LC-MS analysis we studied both total IgG1 and spike protein-specific IgG1 Fc glycosylation of 129 German and 163 Brazilian COVID-19 patients representing diverse patient populations. We found that hospitalized COVID-19 patients displayed decreased levels of total IgG1 bisection and galactosylation and lowered anti-S IgG1 fucosylation and bisection as compared to mild outpatients. Anti-S IgG1 glycosylation was dynamic over the disease course and both anti-S and total IgG1 glycosylation were correlated to inflammatory markers. Further research is needed to dissect the possible role of altered IgG glycosylation profiles in (dys)regulating the immune response in COVID-19. Show less
To ensure the continuity of care during the COVID-19 pandemic, clinicians in Child and Adolescent Psychiatry (CAP) were forced to immediately adapt in-person treatment into remote treatment. This... Show moreTo ensure the continuity of care during the COVID-19 pandemic, clinicians in Child and Adolescent Psychiatry (CAP) were forced to immediately adapt in-person treatment into remote treatment. This study aimed to examine the effects of pre-COVID-19 training in- and use of telepsychiatry on CAP clinicians' impressions of telepsychiatry during the first two weeks of the Dutch COVID-19 related lockdown, providing a first insight into the preparations necessary for the implementation and provision of telepsychiatry during emergency situations. All clinicians employed by five specialized CAP centres across the Netherlands were invited to fill in a questionnaire that was specifically developed to study CAP clinicians' impressions of telepsychiatry during the COVID-19 pandemic. A total of 1065 clinicians gave informed consent and participated in the study. A significant association was found between pre-COVID-19 training and/or use of telepsychiatry and CAP clinicians' impressions of telepsychiatry. By far, the most favourable impressions were reported by participants that were both trained and made use of telepsychiatry before the pandemic. Participants with either training or use separately reported only slightly more favourable impressions than participants without any previous training or use. The expertise required to provide telepsychiatry is not one-and-the-same as the expertise that is honed through face-to-face consultation. The findings of this study strongly suggest that, separately, both training and (clinical) practice fail to sufficiently support CAP clinicians in the implementation and provision of telepsychiatry. It is therefore recommended that training and (clinical) practice are provided in conjunction. Show less
The impact of COVID-19 on population health is recognised as being substantial, yet few studies have attempted to quantify to what extent infection causes mild or moderate symptoms only, requires... Show moreThe impact of COVID-19 on population health is recognised as being substantial, yet few studies have attempted to quantify to what extent infection causes mild or moderate symptoms only, requires hospital and/or ICU admission, results in prolonged and chronic illness, or leads to premature death. We aimed to quantify the total disease burden of acute COVID-19 in the Netherlands in 2020 using the disability-adjusted life-years (DALY) measure, and to investigate how burden varies between age-groups and occupations. Using standard methods and diverse data sources (mandatory notifications, population-level seroprevalence, hospital and ICU admissions, registered COVID-19 deaths, and the literature), we estimated years of life lost (YLL), years lived with disability, DALY and DALY per 100,000 population due to COVID-19, excluding post-acute sequelae, stratified by 5-year age-group and occupation category. The total disease burden due to acute COVID-19 was 286,100 (95% CI: 281,700-290,500) DALY, and the per-capita burden was 1640 (95% CI: 1620-1670) DALY/100,000, of which 99.4% consisted of YLL. The per-capita burden increased steeply with age, starting from 60 to 64 years, with relatively little burden estimated for persons under 50 years old. SARS-CoV-2 infection and associated premature mortality was responsible for a considerable direct health burden in the Netherlands, despite extensive public health measures. DALY were much higher than for other high-burden infectious diseases, but lower than estimated for coronary heart disease. These findings are valuable for informing public health decision-makers regarding the expected COVID-19 health burden among population subgroups, and the possible gains from targeted preventative interventions. Show less
Background Thrombosis is reported to occur more often among patients with COVID-19 than otherwise expected in the setting of viral pneumonia and sepsis. Systemic inflammatory biomarkers may be... Show moreBackground Thrombosis is reported to occur more often among patients with COVID-19 than otherwise expected in the setting of viral pneumonia and sepsis. Systemic inflammatory biomarkers may be associated with venous thromboembolism (VTE) risk. The ISTH subcommittee on Predictive and Diagnostic Variables in Thrombotic Disease aimed to report the evidence on prognostic biomarkers for VTE in hospitalized patients with COVID-19. Methods Using a standardized Preferred Reporting Items for Systematic Reviews and Meta-analysis methodology, we conducted a systematic literature review to identify studies reporting prognostic biomarkers for VTE among hospitalized patients with COVID-19. Eligible studies included adults hospitalized with COVID-19 and reported the prognostic associations between any biomarker measured on admission, and the subsequent diagnosis of deep vein thrombosis or pulmonary embolism. Two authors reviewed titles and abstracts, and three authors extracted study data and performed review of bias. Results were displayed descriptively. Meta-analysis was not possible. Results From the initial 196 identified studies, full-text review was performed for 72 studies. Admission D-dimer levels were associated with VTE during hospitalization in five studies, and elevated platelet count was associated with VTE during hospitalization in one study. The risk of bias ranged from low to high for included studies. Overall, there was a paucity of high-quality prognostic studies. Studies on other biomarkers did not meet the systematic review inclusion criteria. Conclusions Admission D-dimer was associated with VTE diagnosis during hospitalization for COVID-19; however, prospective validation of this finding is needed to identify optimal D-dimer thresholds to guide VTE prophylaxis measures. Show less
Venous thromboembolism (VTE), in particular acute pulmonary embolism (PE), has been shown to be a frequent and potentially fatal complication of coronavirus disease 2019 (COVID-19). In response to... Show moreVenous thromboembolism (VTE), in particular acute pulmonary embolism (PE), has been shown to be a frequent and potentially fatal complication of coronavirus disease 2019 (COVID-19). In response to the observed thrombotic complications, a large number of studies has been devoted to the understanding and management of COVID-19-associated coagulopathy. Notably, only a limited number of mostly retrospective studies has focused on the optimal diagnostic strategy for suspected PE in COVID-19 patients. As in other special populations, the accuracy of diagnostic algorithms for PE-exclusion has been debated in this specific patient subgroup as the specificity of D-dimer assays and clinical decision rules (CDRs) may be lower than normal. From this viewpoint, we discuss the current state-of-the-art diagnostic algorithms for acute PE with a focus on patients with COVID-19 in the perspective of other special patient populations. Furthermore, we summarize current knowledge regarding the natural history of PE resolution with anticoagulant treatment in patients with COVID-19. Show less
Rooijakkers, M.J.P.; Li, W.W.L.; Stens, N.A.; Vis, M.M.; Tonino, P.A.L.; Timmers, L.; ... ; Royen, N. van 2022
Introduction The coronavirus disease 2019 (COVID-19) pandemic has put tremendous pressure on healthcare systems. Most transcatheter aortic valve implantation (TAVI) centres have adopted different... Show moreIntroduction The coronavirus disease 2019 (COVID-19) pandemic has put tremendous pressure on healthcare systems. Most transcatheter aortic valve implantation (TAVI) centres have adopted different triage systems and procedural strategies to serve highest-risk patients first and to minimise the burden on hospital logistics and personnel. We therefore assessed the impact of the COVID-19 pandemic on patient selection, type of anaesthesia and outcomes after TAVI. Methods We used data from the Netherlands Heart Registration to examine all patients who underwent TAVI between March 2020 and July 2020 (COVID cohort), and between March 2019 and July 2019 (pre-COVID cohort). We compared patient characteristics, procedural characteristics and clinical outcomes. Results We examined 2131 patients who underwent TAVI (1020 patients in COVID cohort, 1111 patients in pre-COVID cohort). EuroSCORE II was comparable between cohorts (COVID 4.5 +/- 4.0 vs pre-COVID 4.6 +/- 4.2, p = 0.356). The number of TAVI procedures under general anaesthesia was lower in the COVID cohort (35.2% vs 46.5%, p < 0.001). Incidences of stroke (COVID 2.7% vs pre-COVID 1.7%, p = 0.134), major vascular complications (2.3% vs 3.4%, p = 0.170) and permanent pacemaker implantation (10.0% vs 9.4%, p = 0.634) did not differ between cohorts. Thirty-day and 150-day mortality were comparable (2.8% vs 2.2%, p = 0.359 and 5.2% vs 5.2%, p = 0.993, respectively). Conclusions During the COVID-19 pandemic, patient characteristics and outcomes after TAVI were not different than before the pandemic. This highlights the fact that TAVI procedures can be safely performed during the COVID-19 pandemic, without an increased risk of complications or mortality. Show less
Adamina, M.; Ademuyiwa, A.; Adisa, A.; Bhangu, A.A.; Bravo, A.M.; Cunha, M.F.; ... ; Gill, R. 2022
Aim The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer... Show moreAim The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. Methods This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. Results Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. Conclusion One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease. Show less
The COVID-19 pandemic has a major impact on society, particularly affecting its vulnerable members, including pregnant women and their unborn children. Pregnant mothers reported fear of infection,... Show moreThe COVID-19 pandemic has a major impact on society, particularly affecting its vulnerable members, including pregnant women and their unborn children. Pregnant mothers reported fear of infection, fear of vertical transmission, fear of poor birth and child outcomes, social isolation, uncertainty about their partner's presence during medical appointments and delivery, increased domestic abuse, and other collateral damage, including vaccine hesitancy. Accordingly, pregnant women's known vulnerability for mental health problems has become a concern during the COVID-19 pandemic, also because of the known effects of prenatal stress for the unborn child. The current narrative review provides a historical overview of transgenerational effects of exposure to disasters during pregnancy, and the role of maternal prenatal stress. We place these effects into the perspective of the COVID-19 pandemic. Hereby, we aim to draw attention to the psychological impact of the COVID-19 pandemic on women of reproductive age (15-49 year) and its potential associated short-term and long-term consequences for the health of children who are conceived, carried, and born during this pandemic. Timely detection and intervention during the first 1000 days is essential to reduce the burden of transgenerational effects of the COVID-19 pandemic. Show less
Gordon, A.L.; Achterberg, W.P.; Delden, J.J.M. van 2022
The COVID-19 pandemic has particularly adversely affected older people with frailty and functional dependency. Essential regular contact with care staff has been evidenced as an important source of... Show moreThe COVID-19 pandemic has particularly adversely affected older people with frailty and functional dependency. Essential regular contact with care staff has been evidenced as an important source of infection for this group. Vaccinating care staff can reduce the incidence, duration and severity of infection, preventing onward transmission to older people and minimising the harm associated with discontinuity caused by staff absence. Voluntary vaccination programmes for staff are more likely to be effective when associated with information and education, community engagement and financial incentives, but programmes using all of these approaches have failed to establish consistently high vaccination rates among care staff during the pandemic. Mandatory vaccination, proposed as a solution in some countries, can increase vaccination rates. It is only ethical if a vaccine is effective and cost-effective, the risk associated with vaccinating care workers is proportionate to the risk reduction achieved through vaccination, and where all efforts to encourage voluntary vaccination have been exhausted. Even when these conditions have been met, careful attention is required to ensure that the penalties associated with conscientious objection are proportionate and to ensure that implementation is equitable in a way that does not disadvantage particular groups of staff. Show less
Background The current global pandemic of Coronavirus Disease 2019 (COVID-19) has profoundly impacted medical practitioners worldwide. This survey was formed by the Radiology Section of the... Show moreBackground The current global pandemic of Coronavirus Disease 2019 (COVID-19) has profoundly impacted medical practitioners worldwide. This survey was formed by the Radiology Section of the European Union of Medical Specialists (UEMS) to establish the use of personal protective equipment (PPE) by European radiologists committed to providing face-to-face ultrasound services after the first few months of the COVID-19 global pandemic. Results The results showed a heterogeneous picture within Europe regarding PPE used by European radiologists providing face-to-face ultrasound services. Ranging from full protection including full limb protection and double gloves to no PPE at all. In general, European radiologists were using more PPE when providing face-to-face ultrasound services in COVID-19 positive patients than in COVID-19 asymptomatic patients. In many member countries of the Radiology Section of the UEMS (19/30), there were no national guidelines with regard to the use of PPE by healthcare professionals committed to providing face-to-face ultrasound services. Conclusions Our results showed that harmonization on a European level regarding the recommended use of PPE for European radiologists providing face-to-face ultrasound services is lacking. When the position statements and best practice recommendations on standards in ultrasound are revised, we recommend adding a paragraph on PPE. Show less
Background We investigated whether we could use influenza data to develop prediction models for COVID-19 to increase the speed at which prediction models can reliably be developed and validated... Show moreBackground We investigated whether we could use influenza data to develop prediction models for COVID-19 to increase the speed at which prediction models can reliably be developed and validated early in a pandemic. We developed COVID-19 Estimated Risk (COVER) scores that quantify a patient's risk of hospital admission with pneumonia (COVER-H), hospitalization with pneumonia requiring intensive services or death (COVER-I), or fatality (COVER-F) in the 30-days following COVID-19 diagnosis using historical data from patients with influenza or flu-like symptoms and tested this in COVID-19 patients. Methods We analyzed a federated network of electronic medical records and administrative claims data from 14 data sources and 6 countries containing data collected on or before 4/27/2020. We used a 2-step process to develop 3 scores using historical data from patients with influenza or flu-like symptoms any time prior to 2020. The first step was to create a data-driven model using LASSO regularized logistic regression, the covariates of which were used to develop aggregate covariates for the second step where the COVER scores were developed using a smaller set of features. These 3 COVER scores were then externally validated on patients with 1) influenza or flu-like symptoms and 2) confirmed or suspected COVID-19 diagnosis across 5 databases from South Korea, Spain, and the United States. Outcomes included i) hospitalization with pneumonia, ii) hospitalization with pneumonia requiring intensive services or death, and iii) death in the 30 days after index date. Results Overall, 44,507 COVID-19 patients were included for model validation. We identified 7 predictors (history of cancer, chronic obstructive pulmonary disease, diabetes, heart disease, hypertension, hyperlipidemia, kidney disease) which combined with age and sex discriminated which patients would experience any of our three outcomes. The models achieved good performance in influenza and COVID-19 cohorts. For COVID-19 the AUC ranges were, COVER-H: 0.69-0.81, COVER-I: 0.73-0.91, and COVER-F: 0.72-0.90. Calibration varied across the validations with some of the COVID-19 validations being less well calibrated than the influenza validations. Conclusions This research demonstrated the utility of using a proxy disease to develop a prediction model. The 3 COVER models with 9-predictors that were developed using influenza data perform well for COVID-19 patients for predicting hospitalization, intensive services, and fatality. The scores showed good discriminatory performance which transferred well to the COVID-19 population. There was some miscalibration in the COVID-19 validations, which is potentially due to the difference in symptom severity between the two diseases. A possible solution for this is to recalibrate the models in each location before use. Show less
Schmidt, E.; Schalk, J.; Ridder, M.; Pas, S. van der; Groeneveld, S.; Bussemaker, J. 2022
Purpose This illustrative case study describes and evaluates drivers of effective inter-organizational collaboration to mitigate the impact and spread of COVID-19 among homeless people in two... Show morePurpose This illustrative case study describes and evaluates drivers of effective inter-organizational collaboration to mitigate the impact and spread of COVID-19 among homeless people in two cities in the Netherlands. The aims of this study are: (1) to explore the strategic and operational policy responses in two local integrated care settings at the start of the crisis, (2) to identify best policy practices and lessons learned. The authors interpret and evaluate the findings by combining insights from the population health management (PHM) and collaborative governance literature. Design/methodology/approach The authors describe and illustrate the experiences of two Dutch municipalities, Rotterdam and The Hague, in the early policy responses to sudden operational challenges around the impact of COVID-19 on homeless people as experienced by local decision-makers, medical doctors and clients. Findings The authors show that best policy practices revolve around (1) using data and risk stratification methods for identifying and targeting populations at-risk in local policy making, and (2) having an inter-organizational data sharing architecture in place ex ante. These two factors were clear prerequisites for tailor-made policy responses for newly-defined groups at risk with the existing and well-documented vulnerable population, and executing crisis-induced tasks efficiently. Originality/value This paper is among the first to illustrate the potential of combining collaborative governance and PHM perspectives to identify key drivers of effective local governance responses to a healthcare crisis in an integrated care setting. Show less
Sikharulidze, G.; Ratiani, L.; Sordia, M.; Sikharulidze, E.; Khutsishvili, T.; Lejava, K.; Vermetten, E. 2022
Background: The global pandemic which the world has been facing for the past two years has demonstrated the need to study the effects of this virus on mental health. Various studies showed that... Show moreBackground: The global pandemic which the world has been facing for the past two years has demonstrated the need to study the effects of this virus on mental health. Various studies showed that COVID-19 could be a threat to people's mental health and physical health, yet the findings are still very limited. The purpose of the study was to fill an existing gap in the corresponding literature by analyzing Post Traumatic Stress Disorder (PTSD) symptoms, somatic complaints, depression, and anxiety in COVID-19 patients and studying their comorbidity to determine the impact of the virus on the patients' mental well- being.Methods: Patients diagnosed with COVID-19 took part in the study one month after their discharge from the hospital, accounting for 10% of all COVID-19 patients across Georgia during the research. PTSD Checklist (PCL-5) was used. Depression, somatic symptoms, and anxiety were assessed using the Patient Health Questionnaire (PHQ).Results: The results have shown that COVID-19, as a traumatic event, presents an association with PTSD, depression, anxiety, and somatic complaints. A high prevalence of depression (38,6%), anxiety (34,9%), and somatic symptoms (47%) was displayed. The overall indirect effect of PTSD on somatic symptoms was significant through depression and anxiety: 0.16, 95% CI [0.08, 0.26]. According to the report, the indirect effect of PTSD on somatic symptoms of depression was 0.12, 95% CI [0.05, 0.20].Conclusion: The study presents important findings on the relations between COVID-19 and patients mental health. Somatic complaints, depression, anxiety, and PTSD symptoms were prevalent in participants even after a month since they had COVID-19. Correlations between somatic complaints, anxiety, depression, and PTSD were also demonstrated. Even though there are various limitations to this study, how COVID-19 could affect mental health warrants further, more detailed research, which is necessary. Show less
