Exploring Definitions and Predictors of Severe Asthma Clinical Remission Post-Biologic in Adults.

RATIONALE: There is no consensus on criteria to include in an asthma remission definition in real-life. Factors associated with achieving remission post-biologic-initiation remain poorly understood. OBJECTIVES: To quantify the proportion of adults with severe asthma achieving multi-domain-defined remission post-biologic-initiation and identify pre-biologic characteristics associated with achieving remission which may be used to predict it. METHODS: This was a longitudinal cohort study using data from 23 countries from the International Severe Asthma Registry. Four asthma outcome domains were assessed in the 1-year pre- and post-biologic-initiation. A priori-defined remission cut-offs were: 0 exacerbations/year, no long-term oral corticosteroid (LTOCS), partly/well-controlled asthma, and percent predicted forced expiratory volume in one second ≥80%. Remission was defined using 2 (exacerbations + LTOCS), 3 (+control or +lung function) and 4 of these domains. The association between pre-biologic characteristics and post-biologic remission was assessed by multivariable analysis. MEASUREMENTS AND MAIN RESULTS: 50.2%, 33.5%, 25.8% and 20.3% of patients met criteria for 2, 3 (+control), 3 (+lung function) and 4-domain-remission, respectively. The odds of achieving 4-domain remission decreased by 15% for every additional 10-years asthma duration (odds ratio: 0.85; 95% CI: 0.73, 1.00). The odds of remission increased in those with fewer exacerbations/year, lower LTOCS daily dose, better control and better lung function pre-biologic-initiation. CONCLUSIONS: One in 5 patients achieved 4-domain remission within 1-year of biologic-initiation. Patients with less severe impairment and shorter asthma duration at initiation had a greater chance of achieving remission post-biologic, indicating that biologic treatment should not be delayed if remission is the goal. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Clinical recovery of Macaca fascicularis infected with Plasmodium knowlesi.

BACKGROUND: Kra monkeys (Macaca fascicularis), a natural host of Plasmodium knowlesi, control parasitaemia caused by this parasite species and escape death without treatment. Knowledge of the disease progression and resilience in kra monkeys will aid the effective use of this species to study mechanisms of resilience to malaria. This longitudinal study aimed to define clinical, physiological and pathological changes in kra monkeys infected with P. knowlesi, which could explain their resilient phenotype. METHODS: Kra monkeys (n = 15, male, young adults) were infected intravenously with cryopreserved P. knowlesi sporozoites and the resulting parasitaemias were monitored daily. Complete blood counts, reticulocyte counts, blood chemistry and physiological telemetry data (n = 7) were acquired as described prior to infection to establish baseline values and then daily after inoculation for up to 50 days. Bone marrow aspirates, plasma samples, and 22 tissue samples were collected at specific time points to evaluate longitudinal clinical, physiological and pathological effects of P. knowlesi infections during acute and chronic infections. RESULTS: As expected, the kra monkeys controlled acute infections and remained with low-level, persistent parasitaemias without anti-malarial intervention. Unexpectedly, early in the infection, fevers developed, which ultimately returned to baseline, as well as mild to moderate thrombocytopenia, and moderate to severe anaemia. Mathematical modelling and the reticulocyte production index indicated that the anaemia was largely due to the removal of uninfected erythrocytes and not impaired production of erythrocytes. Mild tissue damage was observed, and tissue parasite load was associated with tissue damage even though parasite accumulation in the tissues was generally low. CONCLUSIONS: Kra monkeys experimentally infected with P. knowlesi sporozoites presented with multiple clinical signs of malaria that varied in severity among individuals. Overall, the animals shared common mechanisms of resilience characterized by controlling parasitaemia 3-5 days after patency, and controlling fever, coupled with physiological and bone marrow responses to compensate for anaemia. Together, these responses likely minimized tissue damage while supporting the establishment of chronic infections, which may be important for transmission in natural endemic settings. These results provide new foundational insights into malaria pathogenesis and resilience in kra monkeys, which may improve understanding of human infections.

International severe asthma registry (ISAR): protocol for a global registry.

BACKGROUND: Severe asthma exerts a disproportionately heavy burden on patients and health care. Due to the heterogeneity of the severe asthma population, many patients need to be evaluated to understand the clinical features and outcomes of severe asthma in order to facilitate personalised and targeted care. The International Severe Asthma Registry (ISAR) is a multi-country registry project initiated to aid in this endeavour. METHODS: ISAR is a multi-disciplinary initiative benefitting from the combined experience of the ISAR Steering Committee (ISC; comprising 47 clinicians and researchers across 29 countries, who have a special interest and/or experience in severe asthma management or establishment and maintenance of severe asthma registries) in collaboration with scientists and experts in database management and communication. Patients (≥18 years old) receiving treatment according to the 2018 definitions of the Global Initiative for Asthma (GINA) Step 5 or uncontrolled on GINA Step 4 treatment will be included. Data will be collected on a core set of 95 variables identified using the Delphi method. Participating registries will agree to provide access to and share standardised anonymous patient-level data with ISAR. ISAR is a registered data source on the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance. ISAR's collaborators include Optimum Patient Care, the Respiratory Effectiveness Group (REG) and AstraZeneca. ISAR is overseen by the ISC, REG, the Anonymised Data Ethics & Protocol Transparency Committee and the ISAR operational committee, ensuring the conduct of ethical, clinically relevant research that brings value to all key stakeholders. CONCLUSIONS: ISAR aims to offer a rich source of real-life data for scientific research to understand and improve disease burden, treatment patterns and patient outcomes in severe asthma. Furthermore, the registry will provide an international platform for research collaboration in respiratory medicine, with the overarching aim of improving primary and secondary care of adults with severe asthma globally.

Blood eosinophil count correlates with severity of respiratory failure in life-threatening asthma and predicts risk of subsequent exacerbations.

BACKGROUND: An elevated blood eosinophil count when asthma is stable predicts exacerbations and therapeutic response to corticosteroids or biologics targeting eosinophils. Few studies have examined the prognostic value of blood eosinophils measured at exacerbation. AIM: To elucidate the relationship between a spot blood eosinophil count-measured at the onset of a life-threatening asthma exacerbation-with indices of exacerbation severity and risk of subsequent exacerbations. METHODS: Real-world, retrospective review of all life-threatening asthma cases admitted at 4 public hospitals in Singapore between 2011-2015. We assessed the trends and correlations between blood eosinophil count on admission with arterial blood gas values, duration of mechanical ventilation, and risk of death, hypoxic ischemic encephalopathy or respiratory arrest. Risk of future exacerbations among survivors was modelled using Cox regression and survival curves. RESULTS: There were 376 index life-threatening exacerbations with median blood eosinophil count (5-95th percentiles) of 0.270 × 109 /L (0-1.410 × 109 /L). Arterial pH decreased and PCO2 increased with increasing eosinophil count. Duration of mechanical ventilation and risk of death, hypoxic ischaemic encephalopathy or respiratory arrest did not vary with eosinophils. Among 329 survivors who were followed-up over a median of 52 months, blood eosinophils ≥1.200 × 109 /L was associated with an increased hazard of emergency visits and/or admissions for asthma (hazard ratio 1.8, 95% confidence interval 1.1-2.9, P = .02). CONCLUSION: In this study of life-threatening asthma, we found that a spot blood eosinophil count correlates with severity of respiratory failure and predicts risk of subsequent exacerbations.

Treatable traits can be identified in a severe asthma registry and predict future exacerbations.

BACKGROUND AND OBJECTIVE: A new taxonomic and management approach, termed treatable traits, has been proposed for airway diseases including severe asthma. This study examined whether treatable traits could be identified using registry data and whether particular treatable traits were associated with future exacerbation risk. METHODS: The Australasian Severe Asthma Web-Based Database (SAWD) enrolled 434 participants with severe asthma and a comparison group of 102 participants with non-severe asthma. Published treatable traits were mapped to registry data fields and their prevalence was described. Participants were characterized at baseline and every 6 months for 24 months. RESULTS: In SAWD, 24 treatable traits were identified in three domains: pulmonary, extrapulmonary and behavioural/risk factors. Patients with severe asthma expressed more pulmonary and extrapulmonary treatable traits than non-severe asthma. Allergic sensitization, upper-airway disease, airflow limitation, eosinophilic inflammation and frequent exacerbations were common in severe asthma. Ten traits predicted exacerbation risk; among the strongest were being prone to exacerbations, depression, inhaler device polypharmacy, vocal cord dysfunction and obstructive sleep apnoea. CONCLUSION: Treatable traits can be assessed using a severe asthma registry. In severe asthma, patients express more treatable traits than non-severe asthma. Traits may be associated with future asthma exacerbation risk demonstrating the clinical utility of assessing treatable traits.

Global-scale Evaluation of SMAP, SMOS and ASCAT Soil Moisture Products using Triple Collocation.

Global-scale surface soil moisture products are currently available from multiple remote sensing platforms. Footprint-scale assessments of these products are generally restricted to limited number of densely-instrumented validation sites. However, by taking active and passive soil moisture products together with a third independent soil moisture estimates via land surface modeling, triple collocation (TC) can be applied to estimate the correlation metric of satellite soil moisture products (versus an unknown ground truth) over a quasi-global domain. Here, an assessment of Soil Moisture Active Passive (SMAP), Soil Moisture Ocean Salinity (SMOS) and Advanced SCATterometer (ASCAT) surface soil moisture retrievals via TC is presented. Considering the potential violation of TC error assumptions, the impact of active-passive and satellite-model error cross correlations on the TC-derived inter-comparison results is examined at in situ sites using quadruple collocation analysis. In addition, confidence intervals for the TC-estimated correlation metric are constructed from moving-block bootstrap sampling designed to preserve the temporal persistence of the original (unevenly-sampled) soil moisture time-series. This study is the first to apply TC to obtain a robust global-scale cross-assessment of SMAP, SMOS and ASCAT soil moisture retrieval accuracy in terms of anomaly temporal correlation. Our results confirm the overall advantage of SMAP (with a global average anomaly correlation of 0.76) over SMOS (0.66) and ASCAT (0.63) that has been established in several recent regional, ground-based studies. SMAP is also the best-performing product over the majority of applicable land pixels (52%), although SMOS and ASCAT each shows advantage in distinct geographic regions.

A Comparative Study of the SMAP Passive Soil Moisture Product With Existing Satellite-Based Soil Moisture Products.

The NASA Soil Moisture Active Passive (SMAP) satellite mission was launched on January 31, 2015 to provide global mapping of high-resolution soil moisture and freeze-thaw state every 2-3 days using an L-band (active) radar and an L-band (passive) radiometer. The Level 2 radiometer-only soil moisture product (L2_SM_P) provides soil moisture estimates posted on a 36-km Earth-fixed grid using brightness temperature observations from descending passes. This paper provides the first comparison of the validated-release L2_SM_P product with soil moisture products provided by the Soil Moisture and Ocean Salinity (SMOS), Aquarius, Advanced Scatterometer (ASCAT), and Advanced Microwave Scanning Radiometer 2 (AMSR2) missions. This comparison was conducted as part of the SMAP calibration and validation efforts. SMAP and SMOS appear most similar among the five soil moisture products considered in this paper, overall exhibiting the smallest unbiased root-mean-square difference and highest correlation. Overall, SMOS tends to be slightly wetter than SMAP, excluding forests where some differences are observed. SMAP and Aquarius can only be compared for a little more than two months; they compare well, especially over low to moderately vegetated areas. SMAP and ASCAT show similar overall trends and spatial patterns with ASCAT providing wetter soil moistures than SMAP over moderate to dense vegetation. SMAP and AMSR2 largely disagree in their soil moisture trends and spatial patterns; AMSR2 exhibits an overall dry bias, while desert areas are observed to be wetter than SMAP.

Precipitation Estimation Using L-Band and C-Band Soil Moisture Retrievals.

An established methodology for estimating precipitation amounts from satellite-based soil moisture retrievals is applied to L-band products from the Soil Moisture Active Passive (SMAP) and Soil Moisture and Ocean Salinity (SMOS) satellite missions and to a C-band product from the Advanced Scatterometer (ASCAT) mission. The precipitation estimates so obtained are evaluated against in situ (gauge-based) precipitation observations from across the globe. The precipitation estimation skill achieved using the L-band SMAP and SMOS datasets is higher than that obtained with the C-band product, as might be expected given that L-band is sensitive to a thicker layer of soil and thereby provides more information on the response of soil moisture to precipitation. The square of the correlation coefficient between the SMAP-based precipitation estimates and the observations (for aggregations to ~100 km and 5 days) is on average about 0.6 in areas of high rain gauge density. Satellite missions specifically designed to monitor soil moisture thus do provide significant information on precipitation variability, information that could contribute to efforts in global precipitation estimation.

Cation-dependent folding of 3' cap-independent translation elements facilitates interaction of a 17-nucleotide conserved sequence with eIF4G.

The 3'-untranslated regions of many plant viral RNAs contain cap-independent translation elements (CITEs) that drive translation initiation at the 5'-end of the mRNA. The barley yellow dwarf virus-like CITE (BTE) stimulates translation by binding the eIF4G subunit of translation initiation factor eIF4F with high affinity. To understand this interaction, we characterized the dynamic structural properties of the BTE, mapped the eIF4G-binding sites on the BTE and identified a region of eIF4G that is crucial for BTE binding. BTE folding involves cooperative uptake of magnesium ions and is driven primarily by charge neutralization. Footprinting experiments revealed that functional eIF4G fragments protect the highly conserved stem-loop I and a downstream bulge. The BTE forms a functional structure in the absence of protein, and the loop that base pairs the 5'-untranslated region (5'-UTR) remains solvent-accessible at high eIF4G concentrations. The region in eIF4G between the eIF4E-binding site and the MIF4G region is required for BTE binding and translation. The data support the model in which the eIF4F complex binds directly to the BTE which base pairs simultaneously to the 5'-UTR, allowing eIF4F to recruit the 40S ribosomal subunit to the 5'-end.

Proteomes of plasmodium knowlesi early and late ring-stage parasites and infected host erythrocytes.

The emerging malaria parasite Plasmodium knowlesi threatens the goal of worldwide malaria elimination due to its zoonotic spread in Southeast Asia. After brief ex-vivo culture we used 2D LC/MS/MS to examine the early and late ring stages of infected Macaca mulatta red blood cells harboring P. knowlesi. The M. mulatta clathrin heavy chain and T-cell and macrophage inhibitor ERMAP were overexpressed in the early ring stage; glutaredoxin 3 was overexpressed in the late ring stage; GO term differential enrichments included response to oxidative stress and the cortical cytoskeleton in the early ring stage. P. knowlesi clathrin heavy chain and 60S acidic ribosomal protein P2 were overexpressed in the late ring stage; GO term differential enrichments included vacuoles in the early ring stage, ribosomes and translation in the late ring stage, and Golgi- and COPI-coated vesicles, proteasomes, nucleosomes, vacuoles, ion-, peptide-, protein-, nucleocytoplasmic- and RNA-transport, antioxidant activity and glycolysis in both stages. SIGNIFICANCE: Due to its zoonotic spread, cases of the emerging human pathogen Plasmodium knowlesi in southeast Asia, and particularly in Malaysia, threaten regional and worldwide goals for malaria elimination. Infection by this parasite can be fatal to humans, and can be associated with significant morbidity. Due to zoonotic transmission from large macaque reservoirs that are untreatable by drugs, and outdoor biting mosquito vectors that negate use of preventive measures such as bed nets, its containment remains a challenge. Its biology remains incompletely understood. Thus we examine the expressed proteome of the early and late ex-vivo cultured ring stages, the first intraerythrocyte developmental stages after infection of host rhesus macaque erythrocytes. We used GO term enrichment strategies and differential protein expression to compare early and late ring stages. The early ring stage is characterized by the enrichment of P. knowlesi vacuoles, and overexpression of the M. mulatta clathrin heavy chain, important for clathrin-coated pits and vesicles, and clathrin-mediated endocytosis. The M. mulatta protein ERMAP was also overexpressed in the early ring stage, suggesting a potential role in early ring stage inhibition of T-cells and macrophages responding to P. knowlesi infection of reticulocytes. This could allow expansion of the host P. knowlesi cellular niche, allowing parasite adaptation to invasion of a wider age range of RBCs than the preferred young RBCs or reticulocytes, resulting in proliferation and increased pathogenesis in infected humans. Other GO terms differentially enriched in the early ring stage include the M. mulatta cortical cytoskeleton and response to oxidative stress. The late ring stage is characterized by overexpression of the P. knowlesi clathrin heavy chain. Combined with late ring stage GO term enrichment of Golgi-associated and coated vesicles, and enrichment of COPI-coated vesicles in both stages, this suggests the importance to P. knowlesi biology of clathrin-mediated endocytosis. P. knowlesi ribosomes and translation were also differentially enriched in the late ring stage. With expression of a variety of heat shock proteins, these results suggest production of folded parasite proteins is increasing by the late ring stage. M. mulatta endocytosis was differentially enriched in the late ring stage, as were clathrin-coated vesicles and endocytic vesicles. This suggests that M. mulatta clathrin-based endocytosis, perhaps in infected reticulocytes rather than mature RBC, may be an important process in the late ring stage. Additional ring stage biology from enriched GO terms includes M. mulatta proteasomes, protein folding and the chaperonin-containing T complex, actin and cortical actin cytoskeletons. P knowlesi biology also includes proteasomes, as well as nucleosomes, antioxidant activity, a variety of transport processes, glycolysis, vacuoles and protein folding. Mature RBCs have lost internal organelles, suggesting infection here may involve immature reticulocytes still retaining organelles. P. knowlesi parasite proteasomes and translational machinery may be ring stage drug targets for known selective inhibitors of these processes in other Plasmodium species. To our knowledge this is the first examination of more than one timepoint within the ring stage. Our results expand knowledge of both host and parasite proteins, pathways and organelles underlying P. knowlesi ring stage biology.

Exploring Definitions and Predictors of Response to Biologics for Severe Asthma.

BACKGROUND: Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging. OBJECTIVE: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response. METHODS: This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in four asthma outcome domains were assessed in the 1-year period before and after biologic initiation in patients with a predefined level of prebiologic impairment. Responder cutoffs were 50% or greater reduction in exacerbation rate, 50% or greater reduction in long-term oral corticosteroid daily dose, improvement in one or more category in asthma control, and 100 mL or greater improvement in FEV1. Responders were defined using single and multiple domains. The association between prebiologic characteristics and postbiologic initiation response was examined by multivariable analysis. RESULTS: A total of 2,210 patients were included. Responder rate ranged from 80.7% (n = 566 of 701) for exacerbation response to 10.6% (n = 9 of 85) for a four-domain response. Many responders still exhibited significant impairment after biologic initiation: 46.7% (n = 206 of 441) of asthma control responders with uncontrolled asthma before the biologic still had incompletely controlled disease postbiologic initiation. Predictors of response were outcome-dependent. Lung function responders were more likely to have higher prebiologic FeNO (odds ratio = 1.20 for every 25-parts per billion increase), and shorter asthma duration (odds ratio = 0.81 for every 10-year increase in duration). Higher blood eosinophil count and the presence of type 2-related comorbidities were positively associated with higher odds of meeting long-term oral corticosteroid, control, and lung function responder criteria. CONCLUSIONS: Our findings underscore the multimodal nature of response, showing that many responders experience residual symptoms after biologic initiation and that predictors of response vary according to the outcome assessed.

A review of psychological dysfunction in asthma: affective, behavioral and cognitive factors.

BACKGROUND: The research on psychological dysfunction in asthma is extensive but heterogeneous. We undertook a narrative review about the effects of psychological dysfunction on asthma. METHODS: Electronic searches of MEDLINE, EMBASE, CINAHL and the Cochrane Library were conducted, supplemented by hand-searching bibliographies and seeking expert opinion. RESULTS: The impact of psychological factors on asthma can be classified according to dysfunction in the domains of affect, behavior and cognition. Affective or emotional disturbance may lead to poor asthma control by directly modulating disease activity. Maladaptive behaviors may occur in asthma patients. These include maladaptive breathing behaviors, such as impaired voluntary drive to breathe and dysfunctional breathing, as well as impaired asthma health behaviors, that is, a coordinated range of activities performed to maintain good disease control. Dysfunctional cognitions (thoughts and beliefs) about asthma and impaired cognitive processing of the perception of dyspnea are associated with poorly controlled disease and asthma deaths, respectively. The three domains of psychological dysfunction are often closely intertwined, leading to vicious circles. CONCLUSIONS: We have conceptualized psychological dysfunction in asthma using a framework consisting of affect, behavior and cognition. Their influences are intertwined and complex. Future research should focus on the formulation of a psychological assessment tool based on this framework and evaluating its efficacy in improving asthma outcomes.

Impact of COVID-19 on perceived wellbeing, self-management and views of novel modalities of care among medically vulnerable patients in Singapore.

OBJECTIVES: This study aims to examine the impact of COVID-19 measures on wellbeing and self-management in medically vulnerable non-COVID patients and their views of novel modalities of care in Singapore. METHODS: Patients with cardiovascular disease (CVD), respiratory disease, chronic kidney disease, diabetes and cancer were recruited from the SingHealth cluster and national cohort of older adults. Data on demographics, chronic conditions and perceived wellbeing were collected using questionnaire. We performed multivariable regression to examine factors associated with perceived wellbeing. Qualitative interviews were conducted to elicit patient's experience and thematically analyzed. RESULTS: A total of 91 patients participated. Male patients compared with female patients perceived a lower impact of the pandemic on subjective wellbeing. Patients with CVD compared to those having conditions other than CVD perceived a lower impact. Impacts of the pandemic were primarily described in relation to emotional distress and interference in maintaining self-care. Hampering of physical activity featured prominently, but most did not seek alternative ways to maintain activity. Despite general willingness to try novel care modalities, lack of physical interaction and communication difficulties were perceived as main barriers. DISCUSSION: Findings underline the need to alleviate emotional distress and develop adaptive strategies to empower patients to maintain wellbeing and self-care.

[Epidemiological and clinical aspects of atrial fibrillation at the cardiology department of kati university hospital]. / Aspects epidemiologique et clinique de la fibrillation auriculaire au service de cardiologie du chu de kati.

Atrial fibrillation is the most frequent permanent rhythm disorder.Theaim of this work was to determine the epidemiological and clinical aspects of atrial fibrillation cases hospitalized in the cardiology department of the University Hospital of Kati. MATERIALS AND METHODS: We carried out a descriptive retrospective study, from January 2018 to December 2019.Patients of all ages and both sexes with clinical and EKG atrial fibrillation admitted to the department during the study period were included in the study.The variables studiedwere: socio-demographic characteristics, clinical signs, classification of atrial fibrillation, and comorbidities associated. RESULTS: A total of 52 patients were included in the studyof 203 cases hospitalized in the department, with a hospital prevalence of 25.61%, the female sex was predominant 69.23%. The main reason for consultation was heart failure syndrome (46.15%).Arterial hypertension (55.76%) was the mostassociatedcomorbidity. Permanent atrial fibrillation accounted for 63.46% of cases . CONCLUSION: Atrial fibrillation is the most frequent arrhythmia in our environment, preventive measures must be put in place for early detection and better management of comorbiditiesassociatedwith atrial fibrillation.

La fibrillation auriculaire est le trouble du rythme le plus fréquent. Le but de ce travail était de déterminer les aspects épidémiologiques et cliniques de la fibrillation atriale dans le service de cardiologie du CHU de Kati. MATÉRIELS ET MÉTHODES: Il s'agit d'une étude rétrospective descriptive menée de janvier 2018 à décembre 2019. Ont été inclus dans cette étude les patients de tout âge et des deux sexes ayant présenté une fibrillation atriale sur des critères cliniques et électrocardiographiques, admis dans le service pendant la période d'étude. Les variables étudiées étaient : les caractéristiques sociodémographiques, les signes cliniques et électriques, et les comorbidités associées. RÉSULTATS: Au total 52 patients ont été inclus dans l'étude sur 203 cas hospitalisés dans le service soit une prévalence hospitalière de 25,61%, le sexe féminin a été prédominant 69,23%. Le principal motif de consultation était le syndrome d'insuffisance cardiaque (46,15%). L'hypertension artérielle (55,76%) a été la comorbidité la plus associée. La fibrillation atriale permanente représentait 63,46% des cas. CONCLUSION: La fibrillation atriale est l'arythmie la plus fréquente dans notre milieu, des mesures préventives doivent être mise en place pour une détection précoce et une meilleure prise en charge des comorbidités associées.

Spillover Effects of COVID-19 on Essential Chronic Care and Ways to Foster Health System Resilience to Support Vulnerable Non-COVID Patients: A Multistakeholder Study.

OBJECTIVES: Little empirical research exists on how key stakeholders involved in the provision of care for chronic conditions and policy planning perceive the indirect or "spillover" effects of the COVID-19 on non-COVID patients. This study aims to explore stakeholder experiences and perspectives of the impact of COVID-19 on the provision of care for chronic conditions, evolving modalities of care, and stakeholder suggestions for improving health system resilience to prepare for future pandemics. DESIGN: Qualitative study design. SETTING AND PARTICIPANTS: This study was conducted during and after the COVID-19 lockdown period in Singapore. We recruited a purposive sample of 51 stakeholders involved in care of non-COVID patients and/or policy planning for chronic disease management. They included health care professionals (micro-level), hospital management officers (meso-level), and government officials (macro-level). METHODS: In-depth semi-structured interviews were conducted. All interviews were digitally recorded, transcribed verbatim, and thematically analyzed. RESULTS: Optimal provision of care for chronic diseases may be compromised through the following processes: lack of "direct" communication between colleagues on clinical cases resulting in rescheduling of patient visits; uncertainty in diagnostic decisions due to protocol revision and lab closure; and limited preparedness to handle non-COVID patients' emotional reactions. Although various digital innovations enhanced access to care, a digital divide exists due to uneven digital literacy and perceived data security risks, thereby hampering wider implementation. To build health system resilience, stakeholders suggested the need to integrate digital care into the information technology ecosystem, develop strategic public-private partnerships for chronic disease management, and give equal attention to the provision of holistic psychosocial and community support for vulnerable non-COVID patients. CONCLUSIONS AND IMPLICATIONS: Findings highlight that strategies to deliver quality chronic care for non-COVID patients in times of public health crisis should include innovative care practices and institutional reconfiguration within the broader health system context.

Plasmodium knowlesi Cytoadhesion Involves SICA Variant Proteins.

Plasmodium knowlesi poses a health threat throughout Southeast Asian communities and currently causes most cases of malaria in Malaysia. This zoonotic parasite species has been studied in Macaca mulatta (rhesus monkeys) as a model for severe malarial infections, chronicity, and antigenic variation. The phenomenon of Plasmodium antigenic variation was first recognized during rhesus monkey infections. Plasmodium-encoded variant proteins were first discovered in this species and found to be expressed at the surface of infected erythrocytes, and then named the Schizont-Infected Cell Agglutination (SICA) antigens. SICA expression was shown to be spleen dependent, as SICA expression is lost after P. knowlesi is passaged in splenectomized rhesus. Here we present data from longitudinal P. knowlesi infections in rhesus with the most comprehensive analysis to date of clinical parameters and infected red blood cell sequestration in the vasculature of tissues from 22 organs. Based on the histopathological analysis of 22 tissue types from 11 rhesus monkeys, we show a comparative distribution of parasitized erythrocytes and the degree of margination of the infected erythrocytes with the endothelium. Interestingly, there was a significantly higher burden of parasites in the gastrointestinal tissues, and extensive margination of the parasites along the endothelium, which may help explain gastrointestinal symptoms frequently reported by patients with P. knowlesi malarial infections. Moreover, this margination was not observed in splenectomized rhesus that were infected with parasites not expressing the SICA proteins. This work provides data that directly supports the view that a subpopulation of P. knowlesi parasites cytoadheres and sequesters, likely via SICA variant antigens acting as ligands. This process is akin to the cytoadhesive function of the related variant antigen proteins, namely Erythrocyte Membrane Protein-1, expressed by Plasmodium falciparum.

MaHPIC malaria systems biology data from Plasmodium cynomolgi sporozoite longitudinal infections in macaques.

Plasmodium cynomolgi causes zoonotic malarial infections in Southeast Asia and this parasite species is important as a model for Plasmodium vivax and Plasmodium ovale. Each of these species produces hypnozoites in the liver, which can cause relapsing infections in the blood. Here we present methods and data generated from iterative longitudinal systems biology infection experiments designed and performed by the Malaria Host-Pathogen Interaction Center (MaHPIC) to delve deeper into the biology, pathogenesis, and immune responses of P. cynomolgi in the Macaca mulatta host. Infections were initiated by sporozoite inoculation. Blood and bone marrow samples were collected at defined timepoints for biological and computational experiments and integrative analyses revolving around primary illness, relapse illness, and subsequent disease and immune response patterns. Parasitological, clinical, haematological, immune response, and -omic datasets (transcriptomics, proteomics, metabolomics, and lipidomics) including metadata and computational results have been deposited in public repositories. The scope and depth of these datasets are unprecedented in studies of malaria, and they are projected to be a F.A.I.R., reliable data resource for decades.

Determination of ranges for reporting pollen aeroallergen levels in the Washington, DC, metropolitan area.

BACKGROUND: Local aeroallergen monitoring provides useful information for the atopic patient and medical community. Currently, National Allergy Bureau (NAB) ranges are used for reporting pollen count levels in the Washington, DC, area. OBJECTIVE: To determine standard range criteria (low, moderate, high, and very high) for the reporting of specific tree, grass, and weed aeroallergens representative of the Washington, DC, metropolitan region. METHODS: Atmospheric sampling for pollen aeroallergens was performed using a volumetric rotating-arm impaction sampler (model 40 Rotorod, SDI Company, Plymouth Meeting, PA). The cumulative pollen count, over a 12-year period (1998-2009), was determined for specific pollen aeroallergens. Local ranges were developed using methodology previously employed to determine NAB ranges. A comparison was made between NAB and Washington, DC, area ranges. RESULTS: The local median count, and low and moderate range criteria, are markedly lower than NAB range counts for tree, grass, and weed pollen. The NAB 99th percentile (high) count is significantly higher for grass and weed pollen but lower for tree pollen. Using new local range criteria, an increase was seen in the number of high days recorded for weed pollen (1,300%), grass pollen (258.6%), and tree pollen (11.8%). Previously, using NAB range criteria, no very high days were reported for grass and weed pollen over the 12-year period. CONCLUSION: Washington, DC, ranges establish more relevant reporting standards for our local patient population and will allow for comparison with reporting levels developed for sampling locations nationwide as well as with other regional sites.

[Epidemiology of Covid-19 and high blood pressure association at Mali'shospital]. / Epidemiologie de l'association Covid-19 et hypertension arterielle a l'hopital du Mali.

INTRODUCTION: High blood pressure is a major cardiovascular risk factor. Patients with cardiovascular risk factors are at risk of developing COVID-19. The objective of this study was to determine epidemiology of Covid-19 infected in patients with high blood pressure. PATIENTS AND METHOD: Descriptive cross-sectional study from April 2020 to June 2020 about patients hospitalized for Covid 19 by PCR diagnosis at the Hopital du Mali Bamako and having high blood pressure. Admission registry and patient charts were used to collect data. RESULTS: We collected 78 out of 484 in patients which mean hospital frequency of 16.11%. The mean age was 55.21 +/- 14.61 years. Sex ratio M / F was 1.36. Patients were followed for high blood pressure in 59% of cases. Medical history was ischemic heart disease in 2.6% and dilated cardiomyopathy in 2.6%. Main functional signs were cough in 41.02% and lost of taste in 11.53%. High blood pressure on admission was grade 2 in 37.2% and grade 3 in 3.8%. Treatments received were calcium channel blockers 41.02%, inhibitors of the reninangiotensinaldosterone system 16.66% and combinations 15.38%. Hospital mortality was 10.3%. There was no statistically significant difference in mortality between known hypertensive patients and de novo hypertensive patients. There was also no statistically significant difference in mortality by grade of hypertension. CONCLUSION: High blood pressure can be associated to Covid 19. Treatment is based on calcium channel blockers and reninangiotensinaldosterone system inhibitors. It has an impact on the prognosis of the disease with significant mortality.

INTRODUCTION: L'hypertension artérielle (HTA) est un facteur de risque cardiovasculaire majeur. Dans la littérature elle est fréquemment retrouvée chez les patients atteints de la COVID-19.L'objectif de cette étude est de décrire l'épidémiologie de cette association chez les patients hospitalisés pour Covid-19. PATIENTS ET MÉTHODE: L'Etude est transversale et descriptive ; elle a été réalisée sur la période du 1erAvril 2020 au 30 Juin 2020. Elle a concerné les patients hospitalisés pour Covid 19 avec un test PCR positif à l'hôpital du Mali de Bamako et ayant une HTA. Les registres d'admission et les dossiers des patients ont servi pour la collecte des données. RÉSULTATS: Nous avons colligé 78 sur 484 patients hospitalisés soit une fréquence de 16,11%. L'âge moyen était de 55,21 +/- 14,61 ans. Le sex ratio H/F était de 1,36.Les patients étaient suivis pour HTA dans 59% des cas. Les antécédents médicaux étaient la cardiopathie ischémique chez 2,6% et la cardiomyopathie dilatée chez 2,6%. Les principaux signes fonctionnels étaient la toux chez 41,02% et l'agueusie chez 11,53%. L'HTA à l'admission était de grade 2 dans 37,2% des cas et de grade 3 dans 3,8% des cas. Les traitements reçus étaient les inhibiteurs calciques 41,02%, les inhibiteurs du système rénine angiotensine aldostérone 16,66% et les associations 15,38%. La mortalité hospitalière était de 10,3%. Il n'y avait pas de différence statistiquement significative concernant la mortalité entre les patients connus hypertendus et les patients hypertendus de novo. Il n'y avait pas non plus de différence statistiquement significative concernant la mortalité selon le grade de l'HTA. CONCLUSION: l'HTA peut être associée au Covid 19. Le traitement est basé sur les inhibiteurs calciques et sur les inhibiteurs du système rénine angiotensine aldostérone. Elle a un impact sur le pronostic de la maladie avec une mortalité importante.

Impact of Air Pollution and Trans-Boundary Haze on Nation-Wide Emergency Department Visits and Hospital Admissions in Singapore.

INTRODUCTION: Air pollution is associated with adverse health outcomes. However, its impact on emergency health services is less well understood. We investigated the impact of air pollution on nation-wide emergency department (ED) visits and hospital admissions to public hospitals in Singapore. MATERIALS AND METHODS: Anonymised administrative and clinical data of all ED visits to public hospitals in Singapore from January 2010 to December 2015 were retrieved and analysed. Primary and secondary outcomes were defined as ED visits and hospital admissions, respectively. Conditional Poisson regression was used to model the effect of Pollutant Standards Index (PSI) on each outcome. Both outcomes were stratified according to subgroups defined a priori based on age, diagnosis, gender, patient acuity and time of day. RESULTS: There were 5,791,945 ED visits, of which 1,552,187 resulted in hospital admissions. No significant association between PSI and total ED visits (Relative risk [RR], 1.002; 99.2% confidence interval [CI], 0.995-1.008; P = 0.509) or hospital admissions (RR, 1.005; 99.2% CI, 0.996-1.014; P = 0.112) was found. However, for every 30-unit increase in PSI, significant increases in ED visits (RR, 1.023; 99.2% CI, 1.011-1.036; P = 1.24 × 10-6 ) and hospital admissions (RR, 1.027; 99.2% CI, 1.010-1.043; P = 2.02 × 10-5 ) for respiratory conditions were found. CONCLUSION: Increased PSI was not associated with increase in total ED visits and hospital admissions, but was associated with increased ED visits and hospital admissions for respiratory conditions in Singapore.