Evaluation of Disease Burden by (Separate) Patient-reported, Clinical, and Laboratory Factor Scores in Patients With Established Rheumatoid Arthritis: A Factor Analysis Replication

Rheumatoid arthritis (RA) can cause significant burden to patients. Some of these aspects are directly related to disease activity and are manageable with antirheumatic drugs, whereas others require nonpharmacological interventions.

Reducing bias in risk indices for COVID-19

Spatiotemporal modelling of infectious diseases such as coronavirus disease 2019 (COVID-19) involves using a variety of epidemiological metrics such as regional proportion of cases and/or regional positivity rates. Although observing changes of these indices over time is critical to estimate the regional disease burden, the dynamical properties of these measures, as well as crossrelationships, are usually not systematically given or explained. Here we provide a spatiotemporal framework composed of six commonly used and newly constructed epidemiological metrics and conduct a case study evaluation. We introduce a refined risk estimate that is biased neither by variation in population size nor by the spatial heterogeneity of testing. In particular, the proposed methodology would be useful for unbiased identification of time periods with elevated COVID-19 risk without sensitivity to spatial heterogeneity of neither population nor testing coverage.We offer a case study in Poland that shows improvement over the bias of currently used methods. Our results also provide insights regarding regional prioritisation of testing and the consequences of potential synchronisation of epidemics between regions. The approach should apply to other infectious diseases and other geographical areas.

Targeted vaccination and the speed of SARS-CoV-2 adaptation

The limited supply of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) raises the question of targeted vaccination. Many countries have opted to vaccinate older and more sensitive hosts first to minimize the disease burden. However, what are the evolutionary consequences of targeted vaccination? We clarify the consequences of different vaccination strategies through the analysis of the speed of viral adaptation measured as the rate of change of the frequency of a vaccine-adapted variant. We show that such a variant is expected to spread faster if vaccination targets individuals who are likely to be involved in a higher number of contacts. We also discuss the pros and cons of dose-sparing strategies. Because delaying the second dose increases the proportion of the population vaccinated with a single dose, this strategy can both speed up the spread of the vaccine-adapted variant and reduce the cumulative number of deaths. Hence, strategies that are most effective at slowing viral adaptation may not always be epidemiologically optimal. A careful assessment of both the epidemiological and evolutionary consequences of alternative vaccination strategies is required to determine which individuals should be vaccinated first.

The global burden and attributable risk factors of chronic lymphocytic leukemia in 204 countries and territories from 1990 to 2019: analysis based on the global burden of disease study 2019

Background Chronic lymphocytic leukemia (CLL) is the most prevalent subtype of leukemia in Western countries, causing a substantial health burden on patients and society. Comprehensive evaluation of the epidemiological characteristics of CLL is warranted, especially in the current context of global population aging. The main objective of this study is evaluating the disease burden of CLL at global, regional, and national levels from 1990 to 2019. As secondary objectives, we studied the influence of demographic factors and performed risk factor analysis. We hope this study could provide evidence for the evaluation of the effectiveness of previous prevention strategies and the formulation of future global health policies. Results Based on data of CLL between 1990 to 2019 from the Global Burden of Disease (GBD) study 2019, we depicted the age, gender, and regional structure of the CLL burden population and described the impact of social development on the disease burden of CLL. The distribution and changing trends of attributable risk factors were also investigated. The global burden of CLL has increased dramatically. A high incidence has been achieved in males and elder people. Countries and territories with high social-demographic index (SDI) tended to have higher global burden than low-SDI region. Of risk factors, high body mass index and smoking were the major contributors for CLL-related mortality and disability adjusted life-years (DALYs). Conclusion In summary, the global CLL burden continues to rise over the past 30 years. The relocation of medical resource should be considered on a global scale. Graphical Abstract

Epidemiology of West Nile virus in Africa: An underestimated threat

Background West Nile virus is a mosquito-borne flavivirus which has been posing continuous challenges to public health worldwide due to the identification of new lineages and clades and its ability to invade and establish in an increasing number of countries. Its current distribution, genetic variability, ecology, and epidemiological pattern in the African continent are only partially known despite the general consensus on the urgency to obtain such information for quantifying the actual disease burden in Africa other than to predict future threats at global scale. Methodology and principal findings References were searched in PubMed and Google Scholar electronic databases on January 21, 2020, using selected keywords, without language and date restriction. Additional manual searches of reference list were carried out. Further references have been later added accordingly to experts’ opinion. We included 153 scientific papers published between 1940 and 2021. This review highlights: (i) the co-circulation of WNV-lineages 1, 2, and 8 in the African continent; (ii) the presence of diverse WNV competent vectors in Africa, mainly belonging to the Culex genus; (iii) the lack of vector competence studies for several other mosquito species found naturally infected with WNV in Africa; (iv) the need of more competence studies to be addressed on ticks; (iv) evidence of circulation of WNV among humans, animals and vectors in at least 28 Countries; (v) the lack of knowledge on the epidemiological situation of WNV for 19 Countries and (vii) the importance of carrying out specific serological surveys in order to avoid possible bias on WNV circulation in Africa. Conclusions This study provides the state of art on WNV investigation carried out in Africa, highlighting several knowledge gaps regarding i) the current WNV distribution and genetic diversity, ii) its ecology and transmission chains including the role of different arthropods and vertebrate species as competent reservoirs, and iii) the real disease burden for humans and animals. This review highlights the needs for further research and coordinated surveillance efforts on WNV in Africa.

Associations between sociodemographic factors, health spending, disease burden, and life expectancy of older adults (70 + years old) in 22 countries in the Western Pacific Region, 1995–2019: estimates from the Global Burden of Disease (GBD) Study 2019

The needs of the aging populations are putting increasing burden on healthcare particularly in the Western Pacific Region (WPR), which is the home of aging economies such as Hong Kong and Japan alongside rapid increases in older people in low- and middle-income countries (LMICs). However, little is known about the associations between sociodemographic factors, disease burden, and life expectancy in WPR. The current study conducted secondary analysis on the Global Burden of Disease (GBD) estimates of populations aged 70 years and older in WPR countries between 1995 and 2019. Correlation tests, linear mixed regressions and generalized additive mixture models were run to examine the associations of interest. Unsupervised machine learning was conducted to segment the data automatically, at cluster analysis. The sociodemographic development index was found an important factor to the disease burden in terms of Years Lived with Disability (YLD) rate and mortality rate among older adults. YLD rate and mortality rate of non-communicable diseases (NCDs) attributable to different risk groups were significant contributors to higher expectation of Lost Healthy Years (LHE) and shorter life expectancy respectively in the context of rising YLD rate, particularly in LMICs. Three clusters of countries with similar characteristics were identified. NCDs were the most significant contributors to shorter life expectancy within which the time living in poor health did not improve. Better management of NCDs in aging populations should be emphasized in all countries. The country clusters may help in a more regional strategic planning.

Ablation of VLA4 in multiple myeloma cells redirects tumor spread and prolongs survival

Multiple myeloma (MM) is a cancer of bone marrow (BM) plasma cells, which is increasingly treatable but still incurable. In 90% of MM patients, severe osteolysis results from pathological interactions between MM cells and the bone microenvironment. Delineating specific molecules and pathways for their role in cancer supportive interactions in the BM is vital for developing new therapies. Very Late Antigen 4 (VLA4, integrin α4β1) is a key player in cell–cell adhesion and signaling between MM and BM cells. We evaluated a VLA4 selective near infrared fluorescent probe, LLP2A-Cy5, for in vitro and in vivo optical imaging of VLA4. Furthermore, two VLA4-null murine 5TGM1 MM cell (KO) clones were generated by CRISPR/Cas9 knockout of the Itga4 (α4) subunit, which induced significant alterations in the transcriptome. In contrast to the VLA4+ 5TGM1 parental cells, C57Bl/KaLwRij immunocompetent syngeneic mice inoculated with the VLA4-null clones showed prolonged survival, reduced medullary disease, and increased extramedullary disease burden. The KO tumor foci showed significantly reduced uptake of LLP2A-Cy5, confirming in vivo specificity of this imaging agent. This work provides new insights into the pathogenic role of VLA4 in MM, and evaluates an optical tool to measure its expression in preclinical models.