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Microplastic exposure can cause a range of negative effects on the biochemistry, condition and ecology of freshwater fishes depending on aspects of the exposure and the exposed fish. However, fishes are typically exposed to microplastics and additional multiple stressors simultaneously, for which the combined effects are poorly understood and may have important management consequences. Additive effects are those where the combined effect is equal to the sum, antagonistic where combined effects are less than the sum and for synergistic effects the combined effect is greater to the sum of the individual effects. Here, we performed a meta-analysis of studies recording freshwater fish responses to microplastic-stressor exposures to test if interactions were primarily non-additive (synergistic or antagonistic), and factors impacting the net response. Individual responses were classified (antagonistic/additive/synergistic) and the fit of net responses to a null additive model determined for 838 responses (36 studies) split by categorical variables for the microplastic exposure (environmental relevance, interacting stressor, microplastic morphology and response category measured), as well as the exposed fish (lifestage, ecology and family). Most responses were classified as antagonistic (48 %) and additive (34 %), with synergistic effects least frequent (17 %). Net responses fitted null additive models for all levels of interacting stressor, fish family and microplastic morphology. In contrast, net antagonism was present for biochemical responses, embryo lifestages, environmentally relevant microplastic exposures and fish with benthopelagic ecology, while synergism was identified for fishes with demersal ecology. While substantial knowledge gaps remain and are discussed, the data thus far suggest microplastic-stressor responses in freshwater fishes are rarely synergistic and, therefore, addressing either or both stressors will likely result in positive management and biological outcomes.
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Peixes , Água Doce , Microplásticos , Poluentes Químicos da Água , Animais , Peixes/fisiologia , Poluentes Químicos da Água/toxicidade , Microplásticos/toxicidade , Estresse Fisiológico , Monitoramento AmbientalRESUMO
INTRODUCTION: Classification criteria aim to identify a homogenous population of patients for research. We aimed to quantify how well phase-III trials in connective tissue diseases (CTDs) represent a real-world cohort. METHODS: A comprehensive review of all major published phase-III trials in CTDs was performed (clinicaltrials.gov). Classification criteria utilised most commonly in clinical trials were applied to a multicentre unselected CTD cohort. RESULTS: There were 42 CTD trials identified, with no trials in mixed (MCTD) or undifferentiated CTD (UCTD). The majority of trials (N = 38, 90 %) required patients to meet classification criteria for their respective disease. Eight (19.0 %) excluded patients with overlapping CTDs and a further two (4.8 %) excluded specific overlapping features, such as pulmonary arterial hypertension. One study explicitly allowed overlap syndromes. Our real-world CTD cohort included 391 patients. Patients with UCTD or MCTD (91/391, 23.3 %) would be excluded from participation in clinical trials for not having an eligible diagnosis. Of patients with primary Sjögren's syndrome (pSS), SLE, systemic sclerosis (SSc) or idiopathic inflammatory myopathy (IIM), 211/300 (70.3 %) met the classification criteria for their respective diagnosis and 24/211 (11.4 %) met criteria for >1 CTD. In total, 187/391 (47.8 %) would be eligible for recruitment, based upon their physician diagnosis, and most stringent trial eligibility criteria. CONCLUSION: In an unselected, real-world CTD cohort, up to half of patients are ineligible for clinical trials due to not meeting classification criteria, overlapping features or a lack of trials within their primary disease. To address this inequality in access to novel therapies, clinical trial design should evolve eligibility criteria in CTDs.
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Doenças do Tecido Conjuntivo , Seleção de Pacientes , Humanos , Doenças do Tecido Conjuntivo/diagnóstico , Doenças do Tecido Conjuntivo/classificação , Feminino , Definição da Elegibilidade , Masculino , Ensaios Clínicos Fase III como Assunto , Estudos de Coortes , Pessoa de Meia-Idade , AdultoRESUMO
Biological invasions pose a rapidly expanding threat to the persistence, functioning and service provisioning of ecosystems globally, and to socio-economic interests. The stages of successful invasions are driven by the same mechanism that underlies adaptive changes across species in general-via natural selection on intraspecific variation in traits that influence survival and reproductive performance (i.e., fitness). Surprisingly, however, the rapid progress in the field of invasion science has resulted in a predominance of species-level approaches (such as deny lists), often irrespective of natural selection theory, local adaptation and other population-level processes that govern successful invasions. To address these issues, we analyse non-native species dynamics at the population level by employing a database of European freshwater macroinvertebrate time series, to investigate spreading speed, abundance dynamics and impact assessments among populations. Our findings reveal substantial variability in spreading speed and abundance trends within and between macroinvertebrate species across biogeographic regions, indicating that levels of invasiveness and impact differ markedly. Discrepancies and inconsistencies among species-level risk screenings and real population-level data were also identified, highlighting the inherent challenges in accurately assessing population-level effects through species-level assessments. In recognition of the importance of population-level assessments, we urge a shift in invasive species management frameworks, which should account for the dynamics of different populations and their environmental context. Adopting an adaptive, region-specific and population-focused approach is imperative, considering the diverse ecological contexts and varying degrees of susceptibility. Such an approach could improve and refine risk assessments while promoting mechanistic understandings of risks and impacts, thereby enabling the development of more effective conservation and management strategies.
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Espécies Introduzidas , Invertebrados , Dinâmica Populacional , Animais , Invertebrados/fisiologia , Europa (Continente) , Ecossistema , Água DoceRESUMO
BACKGROUND: Anti-C20 monoclonal antibodies (MAb), such as rituximab, are commonly used for the treatment of patients with severe or refractory systemic lupus erythematosus (SLE) but clinical outcomes are highly variable. We aimed to provide an update of a systematic review of predictive and prognostic factors of anti-CD20 MAb treatment in SLE. METHODS: A systematic literature search was undertaken to identify predictive and prognostic factors of clinical response following treatment with anti-CD20 therapies in SLE patients. Studies examining rituximab published prior to 2015 were excluded. Risk of bias was assessed for randomized controlled trials (RCTs) using the Cochrane Collaboration (RoB2) tool for RCTs and the Quality In Prognosis Studies Tool (QUIPS) for cohort studies. A narrative synthesis of the evidence was undertaken and quality of evidence (QoE) was assessed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: From 850 studies identified, 17 studies met the inclusion criteria. A further 8 studies were identified and included through search updates. There were two post-hoc analyses of RCTs of rituximab, one RCT of ocrelizumab and one of obinutuzumab; and 16 cohort studies examining rituximab treatment. The overall QoE was low or very low. There was wide heterogeneity in definitions of clinical disease activity and outcome measures, non-standardized laboratory cut-offs, failure to account for confounders and multiple subgroup analyses of differing outcomes. B cell depletion as well as novel biomarkers, such as S100 proteins, FCGR genotype, anti-vimentin and anti-drug antibodies showed some evidence of prognostic value but QoE was limited due to moderate to high risk of bias, early phase of investigation and imprecision of results. CONCLUSION: There has been no validation of previously identified prognostic factors to guide outcome in anti-CD20 treated lupus patients. Hypothesis-driven studies of several novel markers however, demonstrate prognostic value and require replication and validation to support their use in routine clinical practice. PROSPERO REGISTRATION NUMBER: CRD42020220339.
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Antineoplásicos , Lúpus Eritematoso Sistêmico , Humanos , Rituximab/uso terapêutico , Resultado do Tratamento , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/induzido quimicamenteRESUMO
Background: As management of chronic pain continues to be suboptimal, there is a need for tools that support frequent, longitudinal pain self-reporting to improve our understanding of pain. This study aimed to assess the feasibility and acceptability of daily pain self-reporting using a smartphone-based pain manikin. Methods: For this prospective feasibility study, we recruited adults with lived experience of painful musculoskeletal condition. They were asked to complete daily pain self-reports via an app for 30 days. We assessed feasibility by calculating pain report completion levels, and investigated differences in completion levels between subgroups. We assessed acceptability via an end-of-study questionnaire, which we analysed descriptively. Results: Of the 104 participants, the majority were female (n = 87; 84%), aged 45-64 (n = 59; 57%), and of white ethnic background (n = 89; 86%). The mean completion levels was 21 (± 7.7) pain self-reports. People who were not working (odds ratio (OR) = 1.84; 95% confidence interval (CI), 1.52-2.23) were more likely, and people living in less deprived areas (OR = 0.77; 95% CI, 0.62-0.97) and of non-white ethnicity (OR = 0.45; 95% CI, 0.36-0.57) were less likely to complete pain self-reports than their employed, more deprived and white counterparts, respectively. Of the 96 participants completing the end-of-study questionnaire, almost all participants agreed that it was easy to complete a pain drawing (n = 89; 93%). Conclusion: It is feasible and acceptable to self-report pain using a smartphone-based manikin over a month. For its wider adoption for pain self-reporting, the feasibility and acceptability should be further explored among people with diverse socio-economic and ethnic backgrounds.
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The microplastic loads in elvers of the critically endangered European eel Anguilla anguilla, sampled in the lower reaches of three English rivers, were very low (incidence: 3.3%, mean ± s.d.: 0.03 ± 0.18 particles) and did not vary with body length or between rivers. Particles were mostly black, polyolefins, fibres and fragments of size 101-200 µm. Current levels indicate a low contamination pressure locally and, consequently, management efforts might prioritise mitigating the effects of other stressors affecting the species.
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Anguilla , Animais , Microplásticos , Plásticos , Água Doce , InglaterraRESUMO
Microplastics (plastics <5 mm) are an environmental contaminant that can negatively impact the behaviour and physiology of aquatic biota. Although parasite infection can also alter the behaviour and physiology of their hosts, few studies have investigated how microplastic and parasite exposure interact to affect hosts. Accordingly, an interaction experiment tested how exposure to environmentally relevant microplastic concentrations and the trophically transmitted parasite Pomphorhynchus tereticollis affected the parasite load, condition metrics and feeding rate of the freshwater fish final host chub Squalius cephalus. Microplastic exposure was predicted to increase infection susceptibility, resulting in increased parasite loads, whereas parasite and microplastic exposure were expected to synergistically and negatively impact condition indices and feeding rates. Following chronic (≈170 day) dietary microplastic exposure, fish were exposed to a given number of gammarids (4/8/12/16/20), with half of the fish presented with parasite infected individuals, before a comparative functional response experiment tested differences in feeding rates on different live prey densities. Contrary to predictions, dietary microplastic exposure did not affect parasite abundance at different levels of parasite exposure, specific growth rate was the only condition index that was lower for exposed but unexposed fish, with no single or interactive effects of microplastic exposure detected. However, parasite infected fish had significantly lower feeding rates than unexposed fish in the functional response experiment, with exposed but unexposed fish also showing an intermediate decrease in feeding rates. Thus, the effects of parasitism on individuals were considerably stronger than microplastic exposure, with no evidence of interactive effects. Impacts of environmentally relevant microplastic levels might thus be relatively minor versus other stressors, with their interactive effects difficult to predict based on their single effects.
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Cyprinidae , Parasitos , Doenças Parasitárias , Poluentes Químicos da Água , Animais , Microplásticos , Plásticos/toxicidade , Interações Hospedeiro-Parasita , Água Doce/parasitologia , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Monitoramento AmbientalRESUMO
OBJECTIVES: Poor health-related quality of life (HRQoL) is well recognized in patients with CTD. We hypothesized that subgroups of patients across the spectrum of CTD experience different HRQoL patterns and aimed to determine patient-level characteristics associated with these different subgroups. METHODS: Using the eight continuous domains of the Medical Outcomes Study 36-item Short Form (SF-36) questionnaire we performed data-driven clustering to derive latent profiles (LPs) of patients with distinct HRQoL patterns. Multivariable ordinal logistic regression was used to determine patient-level characteristics associated with each HRQoL subgroup identified. RESULTS: A total of 309 CTD patients completed the SF-36 questionnaire. The most impaired SF-36 domains in each disease group were vitality, general health and bodily pain. The physical component of the SF-36 was consistently more impaired compared with the mental component, with similar scores across disease groups. Three LPs were identified with poor [n = 89 (29%)], average [n = 190 (61.4%)] and excellent [n = 30 (9.7%)] HRQoL. LPs were not associated with diagnostic grouping or autoantibody profiles. Black background [odds ratio (OR) 0.22 (95% CI 0.08, 0.63)], Indo-Asian background [OR 0.39 (95% CI 0.19, 0.78)], concomitant fibromyalgia [OR 0.40 (95% CI 0.20, 0.78)], sicca symptoms [OR 0.56 (95% CI 0.32, 0.98)] and multimorbidity [Charlson Comorbidity Index; OR 0.81 (95% CI 0.67, 0.97)] were associated with the 'poor' HRQoL LP. CONCLUSION: Distinct HRQoL subgroups exist that are not primarily driven by a specific diagnosis or autoantibody profiles. We identified a number of key demographic and clinical factors associated with poor HRQoL. These factors need to be addressed across the whole CTD spectrum as part of a holistic management approach aimed at improving overall patient outcomes.
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Doenças do Tecido Conjuntivo , Fibromialgia , Humanos , Qualidade de Vida , Lipopolissacarídeos , Inquéritos e Questionários , Fibromialgia/epidemiologia , Doenças do Tecido Conjuntivo/epidemiologiaRESUMO
OBJECTIVE: To phenotype SLE based on symptom burden (disease damage, system involvement and patient reported outcomes), with a specific focus on objective and subjective cognitive function. METHODS: SLE patients ages 18-65 years underwent objective cognitive assessment using the ACR Neuropsychological Battery (ACR-NB) and data were collected on demographic and clinical variables, disease burden/activity, health-related quality of life (HRQoL), depression, anxiety, fatigue and perceived cognitive deficits. Similarity network fusion (SNF) was used to identify patient subtypes. Differences between the subtypes were evaluated using Kruskal-Wallis and χ2 tests. RESULTS: Of the 238 patients, 90% were female, with a mean age of 41 years (s.d. 12) and a disease duration of 14 years (s.d. 10) at the study visit. The SNF analysis defined two subtypes (A and B) with distinct patterns in objective and subjective cognitive function, disease burden/damage, HRQoL, anxiety and depression. Subtype A performed worst on all significantly different tests of objective cognitive function (P < 0.03) compared with subtype B. Subtype A also had greater levels of subjective cognitive function (P < 0.001), disease burden/damage (P < 0.04), HRQoL (P < 0.001) and psychiatric measures (P < 0.001) compared with subtype B. CONCLUSION: This study demonstrates the complexity of cognitive impairment (CI) in SLE and that individual, multifactorial phenotypes exist. Those with greater disease burden, from SLE-specific factors or other factors associated with chronic conditions, report poorer cognitive functioning and perform worse on objective cognitive measures. By exploring different ways of phenotyping SLE we may better define CI in SLE. Ultimately this will aid our understanding of personalized CI trajectories and identification of appropriate treatments.
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Disfunção Cognitiva , Lúpus Eritematoso Sistêmico , Humanos , Feminino , Adulto , Masculino , Qualidade de Vida/psicologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Ansiedade , Aprendizado de MáquinaRESUMO
BACKGROUND: Patients with systemic lupus erythematosus (SLE) are at an increased risk of infection relative to the general population. We aimed to describe the frequency and risk factors for serious infections in patients with moderate-to-severe SLE treated with rituximab, belimumab, and standard of care therapies in a large national observational cohort. METHODS: The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a UK-based prospective register of patients with SLE. Patients were recruited by their treating physician as part of their scheduled care from 64 centres across the UK by use of a standardised case report form. Inclusion criteria for the BILAG-BR included age older than 5 years, ability to provide informed consent, a diagnosis of SLE, and starting a new biological therapy within the last 12 months or a new standard of care drug within the last month. The primary outcome for this study was the rate of serious infections within the first 12 months of therapy. Serious infections were defined as those requiring intravenous antibiotic treatment, hospital admission, or resulting in morbidity or death. Infection and mortality data were collected from study centres and further mortality data were collected from the UK Office for National Statistics. The relationship between serious infection and drug type was analysed using a multiple-failure Cox proportional hazards model. FINDINGS: Between July 1, 2010, and Feb 23, 2021, 1383 individuals were recruited to the BILAG-BR. 335 patients were excluded from this analysis. The remaining 1048 participants contributed 1002·7 person-years of follow-up and included 746 (71%) participants on rituximab, 119 (11%) participants on belimumab, and 183 (17%) participants on standard of care. The median age of the cohort was 39 years (IQR 30-50), 942 (90%) of 1048 patients were women and 106 (10%) were men. Of the patients with available ethnicity data, 514 (56%) of 911 were White, 169 (19%) were Asian, 161 (18%) were Black, and 67 (7%) were of multiple-mixed or other ethnic backgrounds. 118 serious infections occurred in 76 individuals during the 12-month study period, which included 92 serious infections in 58 individuals on rituximab, eight serious infections in five individuals receiving belimumab, and 18 serious infections in 13 individuals on standard of care. The overall crude incidence rate of serious infection was 117·7 (95% CI 98·3-141·0) per 1000 person-years. Compared with standard of care, the serious infection risk was similar in the rituximab (adjusted hazard ratio [HR] 1·68 [0·60-4·68]) and belimumab groups (1·01 [0·21-4·80]). Across the whole cohort in multivariate analysis, serious infection risk was associated with prednisolone dose (>10 mg; 2·38 [95%CI 1·47-3·84]), hypogammaglobulinaemia (<6 g/L; 2·16 [1·38-3·37]), and multimorbidity (1·45 [1·17-1·80]). Additional concomitant immunosuppressive use appeared to be associated with a reduced risk (0·60 [0·41-0·90]). We found no significant safety signals regarding atypical infections. Six infection-related deaths occurred at a median of 121 days (IQR 60-151) days from cohort entry. INTERPRETATION: In patients with moderate-to-severe SLE, rituximab, belimumab, and standard immunosuppressive therapy have similar serious infection risks. Key risk factors for serious infections included multimorbidity, hypogammaglobulinaemia, and increased glucocorticoid doses. When considering the risk of serious infection, we propose that immunosupppressives, rituximab, and belimumab should be prioritised as mainstay therapies to optimise SLE management and support proactive minimisation of glucocorticoid use. FUNDING: None.
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Agamaglobulinemia , Anticorpos Monoclonais Humanizados , Produtos Biológicos , Lúpus Eritematoso Sistêmico , Adulto , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glucocorticoides , Imunossupressores/efeitos adversos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/complicações , Rituximab/efeitos adversos , Estudos ProspectivosRESUMO
PURPOSE: Undifferentiated connective tissue disease (UCTD) encapsulates a broad range of conditions including incomplete forms of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), some of whom progress to a formal clinical diagnosis over time. This systematic review (SR) and meta-analysis aimed to identify clinical and laboratory features and biomarkers that can predict progression of UCTD. METHODS: A systematic literature search was carried out on MEDLINE, EMBASE and the Cochrane Central Register of Randomized Controlled Trials. Abstracts and full-text manuscripts were screened by two reviewers. Publications were included if they included at least 20 UCTD patients, a minimum of six months of follow up, and provided data on at least one risk factor for developing a defined CTD. The QUIPS tool was used to assess risk of bias (RoB) and GRADE for grading the quality of the evidence. The study is registered with PROSPERO (ID: CRD42021237725). RESULTS: Fifty-nine studies were included in the SR, and forty-one in the meta-analysis. The predictors for progression to SLE with the highest certainty of evidence included those with younger age (MD -5.96 [-11.05-0.87 years]), serositis (RR 2.69 [1.61-4.51]), or the presence of anti-dsDNA antibodies (RR 4.27 [1.92-9.51]). For SSc, the highest certainty of evidence included puffy fingers (RR [3.09 [1.48-6.43]), abnormal nailfold changes (NFC) (avascular areas [RR 5.71 (3.03-10.8)] or active or late SSc pattern [RR 2.24 (1.25-4.01)] and anti-topoisomerase-I (RR 1.83 [1.45-2.30]). No novel biomarkers were included in the meta-analysis; however HLA molecules, regulatory T cell shift, pro-inflammatory cytokines and complement activation products were identified as potential predictors for evolution of disease. CONCLUSIONS: Clinical and immunological parameters may predict which patients with UCTD progress to definitive disease; however, the heterogeneous nature and RoB in most studies limits the ability to apply these results in routine clinical practice. Limited data suggest that some novel biomarkers may provide additional predictive value but these will need larger well designed studies to fully delineate their clinical utility.
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Doenças do Tecido Conjuntivo , Lúpus Eritematoso Sistêmico , Escleroderma Sistêmico , Doenças do Tecido Conjuntivo Indiferenciado , Humanos , Doenças do Tecido Conjuntivo/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Biomarcadores , Progressão da DoençaRESUMO
Urban freshwaters, their sediments and resident biota are often highly susceptible to microplastic contamination from catchment-specific sources. Water velocity and spatiotemporal dynamics within the system can impact microplastic loads, while biological features may additionally impact levels within freshwater biota. Here, we investigated the spatiotemporal variations in microplastic loads collected from sediment, macroinvertebrate and fish samples from an urban watercourse (Bourne Stream) in Dorset, southwest England. Sediment particles were mostly fragments of colours (especially orange and purple) whereas microplastics in both macroinvertebrates and fishes were blue/green and fibres. Across all sample types, the dominant particle size class was ≤100 µm. Median (M) and range (R) of microplastic loads within each sample type were sediment: M = 0.06, R = 0-0.36 particles g-1; macroinvertebrates: M = 0, R = 0-4 particles per batch; and fishes: M = 1, R = 0-6 particles per individual. Sediment loads varied spatially, with the highest load in the most upstream site, whereas biotic loads did not vary across space and time. Macroinvertebrate batch loadings varied between taxa and feeding guild, with counts significantly higher in annelids but lower in herbivores. Fish counts were higher in species with true, differentiated stomachs, but with the effects of species, feeding guild and body size being non-significant. Within sites, mean microplastic loads did not correlate between sediment, macroinvertebrate and fish samples. These results suggest that sediment freshwater microplastic loadings may vary spatially but that these trends are not reflected by, or correlated to, those in the biota where ingestion varies with biological traits. Assessments of freshwater microplastic contamination must therefore consider sampling spatiotemporally and across different biotic communities to fully understand the scale of contamination, and to subsequently undertake effective mitigation steps.
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Microplásticos , Poluentes Químicos da Água , Animais , Biota , Monitoramento Ambiental , Peixes , Plásticos , Rios , Poluentes Químicos da Água/análiseRESUMO
Microplastics are a relatively new but important form of freshwater contamination that can be ingested by a range of different species, with particle counts thought to be predictable from species ecology and morphology. Here, we report levels of microplastics in a 26 µm-5 mm size range within the macroinvertebrate and fish community of a lowland river (Dorset Stour, SW England), and test the hypothesis that counts are predictable from characteristics such as feeding guild, body length and trophic position. Macroinvertebrates (n = 257, 12 taxa) and fish (n = 418, 9 species) were collected from distinct river reaches by kick sampling and rod and line angling, respectively. Batches of whole macroinvertebrates and individual fish gastrointestinal tracts were digested with 30% hydrogen peroxide before microplastic screening and FTIR polymer confirmation on a particle subset. Particles were found in 40% of pooled macroinvertebrate batches (taxa incidences: 14-75%) and 39% of fishes (species incidences: 29-47%). Dominant particle feature categories were ≤100 µm, blue/green, fragments and fibres identified as various polyolefins. Although particle counts in macroinvertebrates were highest in Ephemeroptera (mean of 0.74 particles per individual), the relationships between particle loads, batch number and guild were all non-significant. In fishes, particle counts were not significantly related to species, stomach structure, feeding guild or body length, with spatial differences also not apparent across the catchment. Individual fish particle counts were similarly not significantly associated with their trophic positions (calculated from bulk δ15N values for a subset of fishes) and parasite load of Pomphorhynchus tereticollis. Correlations between fish and macroinvertebrate particle counts within specific river reaches were also not significant. In entirety, these results indicated although loadings of microplastic particles were relatively consistent within the two communities, they were not predictable from any of their ecological or morphological characteristics.
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Microplásticos , Poluentes Químicos da Água , Animais , Monitoramento Ambiental , Peixes , Plásticos , Poluentes Químicos da Água/análiseRESUMO
Introduction: Although Black Americans are not substantially more likely to be diagnosed with COVID-19, hospitalization rates and death rates are considerably higher than for White Americans. The aim of this study was to assess the relationship between systemic racism generally, and residential segregation in particular, and racial/ethnic disparities in deaths due to COVID-19. Methods: To assess racial disparities in COVID-19 and systemic racism in US states, we calculated descriptive statistics and bivariate Pearson correlations. Using data on deaths through December 2020, we developed a weighted logistic mixed model to assess whether state-level systemic racism generally and residential segregation, in particular, predicted the probability of COVID-19 deaths among Americans, considering key sociodemographic factors. Results: Residential segregation is a stronger predictor of COVID-19 deaths among Black Americans, as compared to systemic racism more generally. Looking at the interaction between residential segregation and COVID-19 death rates by race, residential segregation is associated with negative outcomes for Black and White Americans, but disproportionately impacts Black state residents (P<.001), who have 2.14 times higher odds of dying from COVID-19 when residential segregation is increased. Conclusion: To understand and address disparities in infectious disease, researchers and public health practitioners should acknowledge how different forms of systemic racism shape health outcomes in the United States. More attention should be given to the mechanisms by which infectious disease pandemics exacerbate health disparities in areas of high residential segregation and should inform more targeted health policies. Such policy changes stand to make all American communities more resilient in the face of new and emerging infectious diseases.
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COVID-19 , Segregação Social , Humanos , Características de Residência , SARS-CoV-2 , Racismo Sistêmico , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES: Cognitive dysfunction (CD) and depression are interlinked comorbidities of SLE. They may be the result of altered brain mechanisms. This study aimed to examine SLE effects on functional connectivity (FC) within the default mode network (DMN) using resting state fMRI, and how depression may impact this. METHODS: Demographic, clinical and psychiatric data were collected from 19 SLE-active, 23 SLE-stable and 30 healthy controls (HC) participants. A T2*-weighted rsfMR scan was acquired and analysed using independent component analysis. Group z-scores for nodes associated with the DMN were tested. Significant nodes were entered into a factor analysis. The combined factor was used in correlations with factors of interest. Significant variables were used in a mediation analysis. RESULTS: 14 DMN nodes were defined using independent component analysis. In five nodes, the SLE groups had significantly reduced FC compared with the HC group (P < 0.01). Factor analysis generated one factor that only depression score correlated with for both the HC group (rs = -0.510) and SLE groups combined (rs = -0.390). Mediation analysis revealed depression score accounted for 22% of the altered FC in the DMN. Disease state accounted for the remaining 78%. CONCLUSIONS: Altered FC was evident in DMN nodes for SLE groups irrespective of disease activity. Depression accounts for some of this effect but SLE directly accounted for more. Further studies are needed to assess if these changes may be a precursor to CD in SLE. If so, rs-fMRI could be an early marker for CD in SLE and help in future CD in SLE treatment trials.
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Lúpus Eritematoso Sistêmico , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Cognição , Depressão/diagnóstico por imagem , Fadiga/etiologia , Humanos , Inflamação , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico por imagemRESUMO
OBJECTIVE: To quantify how well phase III randomised clinical trials in both SLE and lupus nephritis (LN) represents a real-world SLE cohort. METHODS: Literature reviews were performed of major published phase III SLE (n=12) and LN (n=6) clinical trials (ClinicalTrials.gov). Inclusion and exclusion criteria common across these trials were collated for non-renal SLE or LN trials, and applied to patients recruited to the British Isles Lupus Assessment Group-Biologics Register (BILAG-BR) starting either biological or standard-of-care (SOC) therapies. RESULTS: We recruited 837 patients to the BILAG-BR from September 2010 to June 2018, starting either SOC (n=125, 15%) or a biological medication (n=712, 85%). Active LN, defined as a BILAG A in the renal domain occurred in 20% (n=166). Overall, 530 (63%) patients were ineligible to participate in non-renal SLE clinical trials and 72 (43%) patients with active LN would be ineligible for LN trials. The most common reasons for ineligibility from the non-renal lupus trials included active renal involvement (n=166, 20%) and low disease activity (n=114, 15%). For LN trials, the most common exclusion met was pre-existing renal impairment (n=15, 9%). Patients with fewer comorbidities were more likely to be eligible to participate in non-renal SLE trials. CONCLUSIONS: In this national register of patients with moderate-to-severe SLE, nearly two-thirds would not be eligible for recruitment to key SLE clinical trials nor would almost half of those with active LN. Eligibility criteria may excessively constrain enrolment and thus, how we can generalise trial results in a real-world setting.