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Plasma markers in pulmonary hypertension subgroups correlate with patient survival
No full textBackground: Recent studies have provided evidence for an important contribution of the immune system in the pathophysiology of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). In this report, we investigated whether the inflammatory profile of pulmonary hypertension patients changes over time and correlates with patient WHO subgroups or survival. Methods: 50 PAH patients (16 idiopathic (I)PAH, 24 Connective Tissue Disease (CTD)-PAH and 10 Congenital Heart Disease (CHD)-PAH), 37 CTEPH patients and 18 healthy controls (HCs) were included in the study. Plasma inflammatory markers at baseline and after 1-year follow-up were measured using ELISAs. Subsequently, correlations with hemodynamic parameters and survival were explored and data sets were subjected to unbiased multivariate analyses. Results: At diagnosis, we found that plasma levels of interleukin-6 (IL-6) and the chemokines (C-X3-C) motif legend CXCL9 and CXCL13 in CTD-PAH patients were significantly increased, compared with HCs. In idiopathic PAH patients the levels of tumor growth factor-β (TGFβ), IL-10 and CXCL9 were elevated, compared with HCs. The increased CXCL9 and IL-8 concentrations in CETPH patients correlated significantly with decreased survival, suggesting that CXCL9 and IL-8 may be prognostic markers. After one year of treatment, IL-10, CXCL13 and TGFβ levels changed significantly in the PAH subgroups and CTEPH patients. Unbiased multivariate analysis revealed clustering of PH patients based on inflammatory mediators and clinical parameters, but did not separate the WHO subgroups. Importantly, these multivariate analyses separated patients with < 3 years and > 3 years survival, in particular when inflammatory mediators were combined with clinical parameters. Discussion: Our study revealed elevated plasma levels of inflammatory mediators in different PAH subgroups and CTEPH at baseline and at 1-year follow-up, whereby CXCL9 and IL-8 may prove to be prognostic markers for CTEPH patients. While this study is exploratory and hypothesis generating, our data indicate an important role for IL-8 and CXCL9 in CHD and CTEPH patients considering the increased plasma levels and the observed correlation with survival. Conclusion: In conclusion, our studies identified an inflammatory signature that clustered PH patients into WHO classification-independent subgroups that correlated with patient survival.</p
The Dutch Data Warehouse, a multicenter and full-admission electronic health records database for critically ill COVID-19 patients
No full textBackground: The Coronavirus disease 2019 (COVID-19) pandemic has underlined the urgent need for reliable, multicenter, and full-admission intensive care data to advance our understanding of the course of the disease and investigate potential treatment strategies. In this study, we present the Dutch Data Warehouse (DDW), the first multicenter electronic health record (EHR) database with full-admission data from critically ill COVID-19 patients. Methods: A nation-wide data sharing collaboration was launched at the beginning of the pandemic in March 2020. All hospitals in the Netherlands were asked to participate and share pseudonymized EHR data from adult critically ill COVID-19 patients. Data included patient demographics, clinical observations, administered medication, laboratory determinations, and data from vital sign monitors and life support devices. Data sharing agreements were signed with participating hospitals before any data transfers took place. Data were extracted from the local EHRs with prespecified queries and combined into a staging dataset through an extract–transform–load (ETL) pipeline. In the consecutive processing pipeline, data were mapped to a common concept vocabulary and enriched with derived concepts. Data validation was a continuous process throughout the project. All participating hospitals have access to the DDW. Within legal and ethical boundaries, data are available to clinicians and researchers. Results: Out of the 81 intensive care units in the Netherlands, 66 participated in the collaboration, 47 have signed the data sharing agreement, and 35 have shared their data. Data from 25 hospitals have passed through the ETL and processing pipeline. Currently, 3464 patients are included in the DDW, both from wave 1 and wave 2 in the Netherlands. More than 200 million clinical data points are available. Overall ICU mortality was 24.4%. Respiratory and hemodynamic parameters were most frequently measured throughout a patient's stay. For each patient, all administered medication and their daily fluid balance were available. Missing data are reported for each descriptive. Conclusions: In this study, we show that EHR data from critically ill COVID-19 patients may be lawfully collected and can be combined into a data warehouse. These initiatives are indispensable to advance medical data science in the field of intensive care medicine.</p
Life satisfaction:
No full textIn the evaluation of well-being, it is not only important what people have in absolute terms, but also how this compares to reference points in relative terms. We explore the relevance of relative comparisons by testing the effect of people's self-rated position on potential reference points for income and health on their subjective well-being. We used Multiple Discrepancies Theory as a framework to identify seven potentially relevant reference points for income and health. A representative sample (N = 550) of the Netherlands assessed their income and health relative to these reference points. In addition, we elicited monthly household income, health status (EQ-5D-5L), and subjective well-being (SWLS). In line with the literature, we found a negative convex relationship between subjective well-being and age and a positive relationship with being employed, income, and health. For income, subjective well-being was also associated with how current income compared to respondents' needs and progression over time, and for health especially with how current health compared to what they felt they deserved. Our findings suggest that income and health are important for subjective well-being both in absolute and relative terms. We found negative effects on life satisfaction if some of the domain specific reference points were not met
Talking the same language on patient empowerment
No full textContext: The literature on self-management interventions (SMIs) is growing exponentially, but it is characterized by heterogeneous reporting that limits comparability across studies and interventions. Building an SMI taxonomy is the first step towards creating a common language for stakeholders to drive research in this area and promote patient self-management and empowerment. Objective: To develop and validate the content of a comprehensive taxonomy of SMIs for long-term conditions that will help identify key characteristics and facilitate design, reporting and comparisons of SMIs. Methods: We employed a mixed-methods approach incorporating a literature review, an iterative consultation process and mapping of key domains, concepts and elements to develop an initial SMI taxonomy that was subsequently reviewed in a two-round online Delphi survey with a purposive sample of international experts. Results: The final SMI taxonomy has 132 components classified into four domains: intervention characteristics, expected patient/caregiver self-management behaviours, outcomes for measuring SMIs and target population characteristics. The two-round Delphi exercise involving 27 international experts demonstrated overall high agreement with the proposed items, with a mean score (on a scale of 1-9) per component of 8.0 (range 6.1-8.8) in round 1 and 8.1 (range 7.0-8.9) in round 2. Conclusions: The SMI taxonomy contributes to building a common framework for the patient self-management field and can help implement and improve patient empowerment and facilitate comparative effectiveness research of SMIs. Patient or public contribution. Patients’ representatives contributed as experts in the Delphi process and as partners of the consortium.</p
Impact of assumptions on future costs, disutility and mortality in cost-effectiveness analysis; a model exploration
No full textIntroduction In cost-effectiveness analyses, the future costs, disutility and mortality from alternative causes of morbidity are often not completely taken into account. We explored the impact of different assumed values for each of these factors on the cost-effectiveness of screening for colorectal cancer (CRC) and esophageal adenocarcinoma (EAC). Methods Twenty different CRC screening strategies and two EAC screening strategies were evaluated using microsimulation. Average health-related expenses, disutility and mortality by age for the U.S. general population were estimated using surveys and lifetables. First, we evaluated strategies under default assumptions, with average mortality, and no accounting for health-related costs and disutility. Then, we varied costs, disutility and mortality between 100% and 150% of the estimated population averages, with 125% as the best estimate. Primary outcome was the incremental cost per quality-adjusted life-year (QALY) gained among efficient strategies. Results The set of efficient strategies was robust to assumptions on future costs, disutility and mortality from other causes of morbidity. However, the incremental cost per QALY gained increased with higher assumed values. For example, for CRC, the ratio for the recommended strategy increased from 32,600 with average assumption levels, 111,100 with 50% increased levels. Similarly, for EAC, the incremental costs per QALY gained for the recommended EAC screening strategy increased from 198,300 with 50% increased assumptions. In sensitivity analyses without discounting or including only above-average expenses, the impact of assumptions was relatively smaller, but best estimates of the cost per QALY gained remained substantially higher than default estimates. Conclusions Assumptions on future costs, utility and mortality from other causes of morbidity substantially impact cost-effectiveness outcomes of cancer screening. More empiric evidence and consensus are needed to guide assumptions in future analyses.</p
Did the COVID-19 pandemic change the willingness to pay for an early warning system for infectious diseases in Europe?
No full textThe COVID-19 pandemic highlights the need for effective infectious disease outbreak prevention. This could entail installing an integrated, international early warning system, aiming to contain and mitigate infectious diseases outbreaks. The amount of resources governments should spend on such preventive measures can be informed by the value citizens attach to such a system. This was already recognized in 2018, when a contingent valuation willingness to pay (WTP) experiment was fielded, eliciting the WTP for such a system in six European countries. We replicated that experiment in the spring of 2020 to test whether and how WTP had changed during an actual pandemic (COVID-19), taking into account differences in infection rates and stringency of measures by government between countries. Overall, we found significant increases in WTP between the two time points, with mean WTP for an early warning system increasing by about 50% (median 30%), from around €20 to €30 per month. However, there were marked differences between countries and subpopulations, and changes were only partially explained by COVID-19 burden. We discuss possible explanations for and implication of our findings.</p
Paving the way for immunotherapy in pediatric acute myeloid leukemia
No full textImmunotherapeutic agents may be an attractive option to further improve outcomes and to reduce treatment-related toxicity for pediatric AML. While improvements in outcome have been observed with immunotherapy in many cancer types, immunotherapy development and implementation into patient care for both adult and pediatric AML has been hampered by an incomplete understanding of the bone marrow environment and a paucity of tumor-specific antigens. Since only a minority of patients respond in most immunotherapy trials across different cancer types, it will be crucial to understand which children with AML are likely to respond to or may benefit from immunotherapies. Immune cell profiling efforts hold promise to answer this question, as illustrated by the development of predictive scores in solid cancers. Such information on the number and phenotype of immune cells during current treatment regimens will be pivotal to generate hypotheses on how and when to intervene with immunotherapy in pediatric AML. In this review, we discuss the current understanding of the number and phenotype of immune cells in the bone marrow in pediatric AML, ongoing immunotherapy trials and how comprehensive immune profiling efforts may pave the way for successful clinical trials (and, ultimately, implementation into patient care).</p
Development of an ICF Core Set for adults with cerebral palsy
No full textAIM: To examine the most relevant aspects of functioning of adults with cerebral palsy (CP) from their perspective, in order to develop an International Classification of Functioning, Disability and Health (ICF) Core Set for adults with CP. METHOD: We conducted six focus group discussions with adults with CP without intellectual disability and seven interviews with adults with CP with intellectual disability and caregivers, addressing all ICF components. Meaningful concepts were identified from verbatim transcripts and linked to ICF categories by two independent researchers. RESULTS: In total, 31 adults with CP without intellectual disability (mean [SD] age 46y 1mo [14y 1mo]; 20 females, 11 males; Gross Motor Function Classification System [GMFCS] levels I-IV) and seven adults with CP and intellectual disability (mean [SD] age 25y 8mo [6y 8mo]; four females, three males; GMFCS levels III-V) participated. We identified 132 unique second-level categories: 47 body functions, seven body structures, 43 activities and participation, and 35 environmental factors. The most frequently mentioned categories were emotional function, pain, muscle tone function, support of family, products and technology, and health services. INTERPRETATION: Adults with CP experienced problems in a broad range of body functions and activities and indicated the importance of environmental factors for functioning. The identified categories will be added to the list of candidate items to reach consensus on an ICF Core Set for adults with CP. What this paper adds Including the lived experience is crucial for fully understanding functioning of adults with cerebral palsy (CP). Adults with CP perceive environmental factors as essential elements for everyday functioning. Adults with intellectual disability should be considered as a group with specific problems.</p
Niclosamide is active in vitro against mycetoma pathogens
No full textRedox-active drugs are the mainstay of parasite chemotherapy. To assess their repurposing potential for eumycetoma, we have tested a set of nitroheterocycles and peroxides in vitro against two isolates of Madurella mycetomatis, the main causative agent of eumycetoma in Sudan. All the tested compounds were inactive except for niclosamide, which had minimal inhibitory concentrations of around 1 µg/mL. Further tests with niclosamide and niclosamide ethanolamine demonstrated in vitro activity not only against M. mycetomatis but also against Actinomadura spp., causative agents of actinomycetoma, with minimal inhibitory concentrations below 1 µg/mL. The experimental compound MMV665807, a related salicylanilide without a nitro group, was as active as niclosamide, indicating that the antimycetomal action of niclosamide is independent of its redox chemistry (which is in agreement with the complete lack of activity in all other nitroheterocyclic drugs tested). Based on these results, we propose to further evaluate the salicylanilides, niclosamidein particular, as drug repurposing candidates for mycetoma.</p