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BACKGROUND: Long COVID is highly heterogeneous, often debilitating, and may last for years after infection. The aetiology of long COVID remains uncertain. Examination of potential serological markers of long COVID, accounting for clinical covariates, may yield emergent pathophysiological insights. METHODS: In adherence to PRISMA guidelines, we carried out a rapid review of the literature. We searched Medline and Embase for primary observational studies that compared IgG response in individuals who experienced COVID-19 symptoms persisting ≥12 weeks post-infection with those who did not. We examined relationships between serological markers and long COVID status and investigated sources of inter-study variability, such as severity of acute illness, long COVID symptoms assessed and target antigen(s). RESULTS: Of 8018 unique records, we identified 29 as being eligible for inclusion in synthesis. Definitions of long COVID varied. In studies that reported anti-nucleocapsid (N) IgG (n = 10 studies; n = 989 participants in aggregate), full or partial anti-Spike IgG (i.e. the whole trimer, S1 or S2 subgroups, or receptor binding domain, n = 19 studies; n = 2606 participants), or neutralizing response (n = 7 studies; n = 1123 participants), we did not find strong evidence to support any difference in serological markers between groups with and without persisting symptoms. However, most studies did not account for severity or level of care required during acute illness, and other potential confounders. CONCLUSIONS: Pooling of studies would enable more robust exploration of clinical and serological predictors among diverse populations. However, substantial inter-study variations hamper comparability. Standardized reporting practices would improve the quality, consistency and comprehension of study findings.
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COVID-19 , Humanos , SARS-CoV-2 , Síndrome de COVID-19 Pós-Aguda , Doença Aguda , Imunoglobulina G , Anticorpos AntiviraisRESUMO
OBJECTIVES: Evaluate transcatheter heart valve (THV) geometry according to left ventricular outflow tract (LVOT) calcium degree and its impact on hemodynamics and outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) with a contemporary self-expanding THV. BACKGROUND: LVOT calcium remains challenging for contemporary THVs. LVOT calcium location and degree may affect THV deployment and impact flow patterns and shear stress, accelerating THV degeneration. METHODS: EPROMPT (CoreValve Evolut Pro Prospective Registry; NCT03423459) is a prospective, investigator-initiated, multicenter registry of patients undergoing TAVR using CoreValve Evolut PRO/PRO + THVs. A total of 107 patients were enrolled in EPROMPT's computed tomography (CT) cohort between January 2018 and October 2021. These patients underwent follow-up CT scan 30 days post-TAVR. We analyzed THV geometry and its interaction with the aortic root following deployment using 30-day post-TAVR CT in patients with none/mild versus moderate/severe LVOT calcium. RESULTS: Thirty-day THV inflows were less eccentric in the short axis in patients with none/mild versus moderate/severe LVOT calcium (1.16 ± 0.09 vs. 1.21 ± 0.12; p = 0.007). THV became more circular and was similar between both cohorts at the THV waist (1.08 ± 0.06 vs. 1.09 ± 0.11; p = 0.551), leaflet tips (1.03 ± 0.04 vs. 1.05 ± 0.09; p = 0.299), and THV outflow (1.04 ± 2.2 vs. 1.03 ± 2.7; p = 0.143). Thirty-day > mild paravalvular leak was low in both cohorts (1.5% vs. 2.4%; p = 0.724); mean gradients were similar (7.7 ± 3.6 vs. 7.7 ± 3.4 mmHg; p = 0.955). CONCLUSIONS: Despite inflow deformities observed in patients with moderate/severe LVOT calcium, Evolut PRO/PRO + conforms to elliptical aortic annuli, maintaining circularity and proper function at the leaflets and outflow, even in patients with moderate/severe LVOT calcium.
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Estenose da Valva Aórtica , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/etiologia , Estenose da Valva Aórtica/cirurgia , Cálcio , Humanos , Desenho de Prótese , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/métodos , Resultado do TratamentoRESUMO
Treatment of ß-hydroxy-α-p-methoxyphenoxy carboxylic acids derived from the asymmetric glycolate aldol addition reaction with p-nitrobenzenesulfonyl chloride yielded divergent results depending on the nature of the ß-substituent of the carboxylic acid. Substrates bearing either alkyl substituents (R = -n-butyl, -n-octyl, -benzyl, isopropyl, -tert-butyl) or aryl systems bearing electron-withdrawing substituents (R = -p-C6H4Cl, -p-C6H4Br, -p-C6H4NO2) yielded ß-lactones. In contrast, α-p-methoxyphenoxy-ß-hydroxycarboxylic acids bearing electron-donating aryl groups or the sterically demanding 2-naphthyl group formed (Z)-alkenes.
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Hidroxiácidos , Lactonas , Alcenos , Lactonas/química , EstereoisomerismoRESUMO
INTRODUCTION: Clinical trials data concerning use of nusinersen in older spinal muscular atrophy (SMA) patients is lacking. We describe our center's experience in using intrathecal nusinersen for older patients in the clinical setting. METHODS: Retrospective study. RESULTS: Twelve patients (12-52 years old) were treated with nusinersen. Mean follow-up duration was 17.4 months (range, 4-26 months). All patients had scoliosis; 10 had spinal fusion/instrumentation. All procedures (30 cervical and 57 lumbar punctures) were technically successful. The only side effects were postprocedural headache (9%) and site pain (5.7%). Functional assessments showed stability in 6/9 patients and improvement in 3/9 patients. Subjective improvements in endurance, hand strength, and bulbar functioning critical for activities of daily living were reported in 8/12 patients. None of the patients has discontinued treatment so far. DISCUSSION: Intrathecal nusinersen can be safely delivered in older SMA patients. Available functional outcome measures are not adequate to capture meaningful subjective improvements.
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Atrofia Muscular Espinal/tratamento farmacológico , Oligonucleotídeos/uso terapêutico , Atividades Cotidianas , Adolescente , Adulto , Criança , Estudos Transversais , Feminino , Seguimentos , Força da Mão , Humanos , Injeções Espinhais , Masculino , Pessoa de Meia-Idade , Oligonucleotídeos/administração & dosagem , Oligonucleotídeos/efeitos adversos , Resistência Física , Estudos Retrospectivos , Escoliose/complicações , Fusão Vertebral , Resultado do Tratamento , Adulto JovemRESUMO
Mesenchymal stem cells (MSCs) are useful in tissue repair but also possess immunomodulatory properties. Murine and uncontrolled human trials suggest efficacy of MSCs in treating lupus. Autologous cells are preferable; however, recent studies suggest that lupus-derived MSCs lack efficacy in treating disease. Thus, the optimum derivation of MSCs for use in lupus is unknown. It is also unknown which in vitro assays of MSC function predict in vivo efficacy. The objectives for this study were to provide insight into the optimum source of MSCs and to identify in vitro assays that predict in vivo efficacy. We derived MSCs from four umbilical cords, four healthy bone marrows (BMs), and four lupus BMs. In diseased MRL/lpr mice, MSCs from healthy BM and umbilical cords significantly decreased renal disease, whereas lupus BM MSCs only delayed disease. Current in vitro assays did not differentiate efficacy of the different MSCs. However, differences in MSC efficacy were observed in B cell proliferation assays. Our results suggest that autologous MSCs from lupus patients are not effective in treating disease. Furthermore, standard in vitro assays for MSC licensing are not predictive of in vivo efficacy, whereas inhibiting B cell proliferation appears to differentiate effective MSCs from ineffective MSCs.
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Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Adulto , Animais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Medula Óssea/imunologia , Medula Óssea/metabolismo , Medula Óssea/patologia , Diferenciação Celular , Citocinas/biossíntese , Modelos Animais de Doenças , Feminino , Expressão Gênica , Humanos , Imunofenotipagem , Mediadores da Inflamação/metabolismo , Rim/imunologia , Rim/patologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/mortalidade , Lúpus Eritematoso Sistêmico/patologia , Lúpus Eritematoso Sistêmico/terapia , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos MRL lpr , Fenótipo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Doadores de Tecidos , Resultado do TratamentoRESUMO
Palliative care has made great strides in improving the lives of people living with serious illness, with an empirical premise for increasing quality, and sometimes quantity of life. Yet in some cases, there exist gaps that impede the ability of palliative care clinicians to truly advocate, procure, and provide the comprehensive services needed for patients, family caregivers, and communities, particularly in the contexts of caring for marginalized populations and working in under-resourced practice settings. The end-of-life doula role has emerged over the last decade and the availability of trained doulas in the community has burgeoned. An end-of-life doula is a nonmedical, holistic support person who provides education, guidance, emotional, spiritual, and practical support to persons and families navigating serious and terminal illness, ideally early in the disease process, throughout the time surrounding death, and during bereavement. A pervasive Western culture of avoiding the subject of death means that we, as a society, often do not know or remember how to navigate the journey of end of life in a way that is caring, compassionate, skilled, holistic, and centered on the needs and worldview of the dying one. The ten tips provided here can guide palliative care clinicians to leverage collaboration with trusted, community-based end-of-life doulas to ensure comprehensive and people-centered palliative care.
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Introduction: More than 3 years into the pandemic, there is persisting uncertainty as to the etiology, biomarkers, and risk factors of Post COVID-19 Condition (PCC). Serological research data remain a largely untapped resource. Few studies have investigated the potential relationships between post-acute serology and PCC, while accounting for clinical covariates. Methods: We compared clinical and serological predictors among COVID-19 survivors with (n = 102 cases) and without (n = 122 controls) persistent symptoms ≥12 weeks post-infection. We selected four primary serological predictors (anti-nucleocapsid (N), anti-Spike, and anti-receptor binding domain (RBD) IgG titres, and neutralization efficiency), and specified clinical covariates a priori. Results: Similar proportions of PCC-cases (66.7%, n = 68) and infected-controls (71.3%, n = 87) tested positive for anti-N IgG. More cases tested positive for anti-Spike (94.1%, n = 96) and anti-RBD (95.1%, n = 97) IgG, as compared with controls (anti-Spike: 89.3%, n = 109; anti-RBD: 84.4%, n = 103). Similar trends were observed among unvaccinated participants. Effects of IgG titres on PCC status were non-significant in univariate and multivariate analyses. Adjusting for age and sex, PCC-cases were more likely to be efficient neutralizers (OR 2.2, 95% CI 1.11-4.49), and odds was further increased among cases to report deterioration in quality of life (OR 3.4, 95% CI 1.64-7.31). Clinical covariates found to be significantly related to PCC included obesity (OR 2.3, p = 0.02), number of months post COVID-19 (OR 1.1, p < 0.01), allergies (OR 1.8, p = 0.04), and need for medical support (OR 4.1, p < 0.01). Conclusion: Despite past COVID-19 infection, approximately one third of PCC-cases and infected-controls were seronegative for anti-N IgG. Findings suggest higher neutralization efficiency among cases as compared with controls, and that this relationship is stronger among cases with more severe PCC. Cases also required more medical support for COVID-19 symptoms, and described complex, ongoing health sequelae. More data from larger cohorts are needed to substantiate results, permit subgroup analyses of IgG titres, and explore for differences between clusters of PCC symptoms. Future assessment of IgG subtypes may also elucidate new findings.
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COVID-19 , Imunoglobulina G , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/sangue , COVID-19/diagnóstico , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Canadá/epidemiologia , Imunoglobulina G/sangue , SARS-CoV-2/imunologia , Adulto , Anticorpos Antivirais/sangue , Idoso , Fatores de Risco , Biomarcadores/sangue , Síndrome de COVID-19 Pós-Aguda , Glicoproteína da Espícula de Coronavírus/imunologiaRESUMO
Cell based therapies are of increasing interest in the treatment of systemic lupus due to their potential for long term suppression or cure of disease. Two methods for stem cell transplantation are currently being investigated/performed for treatment of lupus. Autologous hematopoetic stem cell transplantation is used in patients refractory to standard therapy. The morbidity and mortality of the procedure limit its use to select patients. Results indicate 50% long term disease free survival. The technical difficulty of the procedure requires it to be performed only in experienced centers. Mesenchymal stem cell transplants are a new emerging therapy for the treatment of lupus. Studies in murine models of lupus provide evidence of efficacy with safety. Limited uncontrolled trials in humans provide evidence of efficacy as well. Controlled trials are needed to assess the efficacy of both these therapies compared to standard therapy.
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Transplante de Células-Tronco Hematopoéticas , Lúpus Eritematoso Sistêmico/terapia , Transplante de Células-Tronco Mesenquimais , Animais , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/mortalidadeRESUMO
Suppressor of cytokine signaling 1-deficient (SOCS1(-/-)) mice, which are lymphopenic, die <3 wk after birth of a T cell-mediated autoimmune inflammatory disease characterized by leukocyte infiltration and destruction of vital organs. Notably, Foxp3(+) regulatory T cells (Tregs) have been shown to be particularly potent in inhibiting inflammation-associated autoimmune diseases. We observed that SOCS1(-/-) mice were deficient in peripheral Tregs despite enhanced thymic development. The adoptive transfer of SOCS1-sufficient Tregs, CD4(+) T lymphocytes, or administration of SOCS1 kinase inhibitory region (KIR), a peptide that partially restores SOCS1 function, mediated a statistically significant but short-term survival of SOCS1(-/-) mice. However, the adoptive transfer of SOCS1-sufficient CD4(+) T lymphocytes, combined with the administration of SOCS1-KIR, resulted in a significant increase in the survival of SOCS1(-/-) mice both short and long term, where 100% death occurred by day 18 in the absence of treatment. Moreover, the CD4(+)/SOCS1-KIR combined therapy resulted in decreased leukocytic organ infiltration, reduction of serum IFN-γ, and enhanced peripheral accumulation of Foxp3(+) Tregs in treated mice. These data show that CD4(+)/SOCS1-KIR combined treatment can synergistically promote the long-term survival of perinatal lethal SOCS1(-/-) mice. In addition, these results strongly suggest that SOCS1 contributes to the stability of the Foxp3(+) Treg peripheral population under conditions of strong proinflammatory environments.
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Doenças Autoimunes/imunologia , Homeostase/imunologia , Inflamação/imunologia , Proteínas Supressoras da Sinalização de Citocina/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Animais , Doenças Autoimunes/metabolismo , Separação Celular , Citometria de Fluxo , Fatores de Transcrição Forkhead/imunologia , Fatores de Transcrição Forkhead/metabolismo , Genótipo , Imuno-Histoquímica , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína 1 Supressora da Sinalização de Citocina , Proteínas Supressoras da Sinalização de Citocina/deficiência , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismoRESUMO
Although it is known that resident gut flora contribute to immune system function and homeostasis, their role in the progression of the autoimmune disease type 1 diabetes (T1D) is poorly understood. Comparison of stool samples isolated from Bio-Breeding rats, a classic model of T1D, shows that distinct bacterial populations reside in spontaneous Bio-Breeding diabetes-prone (BBDP) and Bio-Breeding diabetes-resistant animals. We have previously shown that the oral transfer of Lactobacillus johnsonii strain N6.2 (LjN6.2) from Bio-Breeding diabetes-resistant to BBDP rodents conferred T1D resistance to BBDP rodents, whereas Lactobacillus reuteri strain TD1 did not. In this study, we show that diabetes resistance in LjN6.2-fed BBDP rodents was correlated to a Th17 cell bias within the mesenteric lymph nodes. The Th17 bias was not observed in the non-gut-draining axillary lymph nodes, suggesting that the Th17 bias was because of immune system interactions with LjN6.2 within the mesenteric lymph node. LjN6.2 interactions with the immune system were observed in the spleens of diabetes-resistant, LjN6.2-fed BBDP rats, as they also possessed a Th17 bias in comparison with control or Lactobacillus reuteri strain TD1-fed rats. Using C57BL/6 mouse in vitro assays, we show that LjN6.2 directly mediated enhanced Th17 differentiation of lymphocytes in the presence of TCR stimulation, which required APCs. Finally, we show that footpad vaccination of NOD mice with LjN6.2-pulsed dendritic cells was sufficient to mediate a Th17 bias in vivo. Together, these data suggest an interesting paradigm whereby T1D induction can be circumvented by gut flora-mediated Th17 differentiation.
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Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/microbiologia , Interleucina-17/biossíntese , Lactobacillus/imunologia , Células Th17/imunologia , Células Th17/microbiologia , Animais , Diferenciação Celular/imunologia , Células Cultivadas , Diabetes Mellitus Tipo 1/patologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Limosilactobacillus reuteri/imunologia , Linfonodos/imunologia , Linfonodos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Ratos , Ratos Endogâmicos BB , Células Th17/patologiaRESUMO
The neonicotinoids have recently been identified as a potential contributing factor to the sudden decline in adult honeybee population, commonly known as colony collapse disorder (CCD). To protect the health of honeybees and other pollinators, a new, simple, and sensitive liquid chromatography-electrospray ionization mass spectrometry method was developed and validated for simultaneous determination of eight neonicotinoids, including acetamiprid, clothianidin, dinotefuran, flonicamid, imidacloprid, nitenpyram, thiacloprid, and thiamethoxam, in pollen and high-fructose corn syrup (HFCS). In this method, eight neonicotinoids, along with their isotope-labeled internal standards, were extracted from 2 g of pollen or 5 g of HFCS using an optimized quick, easy, cheap, effective, rugged, and safe extraction procedure. The method limits of detection in pollen and HFCS matrices were 0.03 ng/g for acetamiprid, clothianidin, dinotefuran, imidacloprid, thiacloprid, and thiamethoxam and ranged between 0.03 and 0.1 ng/g for nitenpyram and flonicamid. The precision and accuracy were well within the acceptable 20% range. Selectivity, linearity, lower limit of quantitation, matrix effect, recovery, and stability in autosampler were also evaluated during validation. This validated method has been used successfully in analyzing a set of pollen and HFCS samples collected for evaluating potential honeybee exposure to neonicotinoids.
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Resíduos de Praguicidas/química , Pólen/química , Espectrometria de Massas em Tandem/métodos , Zea mays/química , Frutose/análise , Nitrocompostos/química , Piridinas/química , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
Pyrethroid insecticides are applied in the residential environment, as well as in agricultural crops, for insect control purpose. We developed and validated an accurate, sensitive, and reproducible analytical method to simultaneously detect seven pyrethroid metabolites, namely, 3-(2,2-dichlorovinyl)-2,2-dimethyl-(1-cyclopropane) carboxylic acid, 3-(2,2-dibromovinyl)-2,2-dimethyl-(1-cyclopropane) carboxylic acid, 3-phenoxybenzoic acid, 4-fluoro-3-phenoxybenzoic acid, 2-methyl-3-phenylbenzoic acid, 4-chloro-α-isoproply benzeneacetic acid, and 3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethylcyclopropanecarboxylic acid, in human urine. This method employs deconjugation with enzyme, SPE using Agilent C18 cartridges on a RapidTrace SPE workstation, derivatization using hexafluoro isopropanol and N,N'-diisopropylcarbodiimide, and compounds separation and identification on GC-MS. The detection limits of seven metabolites were 0.02-0.08 ng/mL in urine. The recoveries of seven metabolites were 81-104%, 85-99%, and 83-99% in urine specimens fortified at 0.1, 0.4, and 3.2 ng/mL concentrations, respectively. The overall coefficient of variation was 4.3-10.8% in two quality control specimens which were repeatedly measured during a period of 2 months. This method was applied to urine samples collected from children living in Boston, MA. The median concentrations of six detected pyrethroid metabolites ranged from 0.06 to 0.86 ng/mL in urine.
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Cromatografia Gasosa-Espectrometria de Massas/métodos , Inseticidas/urina , Piretrinas/urina , Humanos , Inseticidas/metabolismo , Piretrinas/metabolismoRESUMO
Background: The risk of arterial thrombotic events (ATEs) is high among patients on systemic anticancer therapies. Despite the efficacy of anticoagulants in the prevention of cancer-associated venous thromboembolism, it is unknown whether anticoagulation is effective to prevent ATEs. Objectives: This study sought to examine the efficacy and safety of anticoagulants in ATE prevention among ambulatory cancer patients. Methods: We performed a systematic review using Medline, Embase, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to May 21, 2022, and included studies comparing oral or parenteral anticoagulation with no anticoagulation among ambulatory patients receiving systemic anticancer therapy with no other indication for anticoagulation. The primary outcome was ATE (myocardial infarction, ischemic stroke, intra-abdominal arterial embolism, or peripheral artery occlusion). The secondary outcomes were major and nonmajor bleeding and all-cause mortality. Results: Fourteen randomized trials involving low-molecular-weight heparins, direct oral anticoagulants, and warfarin were included. ATEs were captured as coefficacy endpoints or adverse events. Anticoagulant use was not associated with a reduction in ATEs compared with placebo or standard treatment (RR: 0.73, 95% CI: 0.50-1.04; P = 0.08; I2 = 0%). RRs of major and minor bleeding were 1.56 (95% CI: 1.12-2.17) and 2.25 (95% CI: 1.45-3.48) with anticoagulant use. In 13 trials that reported all-cause mortality, risk of death was not reduced with anticoagulants (RR: 0.99; 95% CI: 0.95-1.02; P = 0.38; I2 = 0%). Conclusions: Anticoagulants did not reduce ATE risk among ambulatory patients on systemic anticancer therapy and were associated with increased bleeding. Based on the current data, anticoagulants have a limited role in ATE prevention in this population as a whole.
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This review article summarizes the findings from the first virtual International End-of-Life Doula Symposium, held over 3 days on 25-27 April 2022. More than 40 people attended from seven countries, predominantly from Australia, Canada, the United States and the United Kingdom, and they were primarily experienced practitioners. In this article, we focus on participants' topics of conversations and experiences that were relevant across international boundaries, organized through the symposium themes of developments, disruptions, dilemmas and directions. All authors took de-identified handwritten notes across the 3 days of discussion, as well as reflexive notes about our own thoughts and perspectives on the topics discussed. We then collated our notes and abductively focussed our analysis on topics that generated significant conversation and/or came up repeatedly within the overall symposium themes, as well as trying to capture any unexpected issues and perspectives. We identify and summarize a wide range of interests and concerns within the development of the end-of-life doula (EOLD) role. We provide a model for integration pathways within existing health care systems, as well as an innovative conceptual framework synthesizing key intersecting developmental issues that are relevant across regional and national boundaries. The symposium was the first opportunity for EOLDs to collectively discuss their work and interests within an international context. Our findings indicate that there are fundamentally similar developmental issues across countries, along with some variations. As the first international event of its kind, our 'state of the field' summary review of the symposium holds significant insights relevant to both national and international contexts, and to a diversity of stakeholders interested in the development of this new care role and emerging transnational movement.
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BACKGROUND: Predictors of COVID-19 vaccine immunogenicity and the influence of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection require elucidation. METHODS: Stop the Spread Ottawa is a prospective cohort of individuals at-risk for or who have been infected with SARS-CoV-2, initially enrolled for 10 months beginning October 2020. This cohort was enriched for public-facing workers. This analysis focuses on safety and immunogenicity of the initial two doses of COVID-19 vaccine. RESULTS: Post-vaccination data with blood specimens were available for 930 participants. 22.8% were SARS-CoV2 infected prior to the first vaccine dose. Cohort characteristics include: median age 44 (IQR: 22-56), 66.6% women, 89.0% white, 83.2% employed. 38.1% reported two or more comorbidities and 30.8% reported immune compromising condition(s). Over 95% had detectable IgG levels against the spike and receptor binding domain (RBD) 3 months post second vaccine dose. By multivariable analysis, increasing age and high-level immune compromise predicted diminishing IgG spike and RBD titres at month 3 post second dose. IgG spike and RBD titres were higher immediately post vaccination in those with SARS-CoV-2 infection prior to first vaccination and spike titres were higher at 6 months in those with wider time intervals between dose 1 and 2. IgG spike and RBD titres and neutralisation were generally similar by sex, weight and whether receiving homogeneous or heterogeneous combinations of vaccines. Common symptoms post dose 1 vaccine included fatigue (64.7%), injection site pain (47.5%), headache (27.2%), fever/chills (26.2%) and body aches (25.3%). These symptoms were similar with subsequent doses. CONCLUSION: The initial two COVID-19 vaccine doses are safe, well-tolerated and highly immunogenic across a broad spectrum of vaccine recipients including those working in public facing environments.
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COVID-19 , Feminino , Humanos , Adulto , Masculino , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Formação de Anticorpos , SARS-CoV-2 , Estudos de Coortes , RNA Viral , Canadá/epidemiologia , Vacinação , Imunoglobulina G , Anticorpos AntiviraisRESUMO
The American Society of Bone and Mineral Research (ASBMR) Professional Practice Committee charged an ASBMR Task Force on Clinical Algorithms for Fracture Risk to review the evidence on whether current approaches for differentiating fracture risk based on race and ethnicity are necessary and valid. To help address these charges, we performed a systematic literature review investigating performance of calculators for predicting incident fractures within and across race and ethnicity groups in middle-aged and older US adults. We included English-language, controlled or prospective cohort studies that enrolled US adults aged >40 years and reported tool performance predicting incident fractures within individual race and ethnicity groups for up to 10 years. From 4838 identified references, six reports met eligibility criteria, all in women. Just three, all from one study, included results in non-white individuals. In these three reports, non-white women experienced relatively few major osteoporotic fractures (MOFs), especially hip fractures, and risk thresholds for predicting fractures in non-white women were derived from risks in the overall, predominantly white study population. One report suggested the Fracture Risk Assessment Tool (FRAX) without bone mineral density (BMD) overestimated hip fracture similarly across race and ethnicity groups (black, Hispanic, American Indian, Asian, white) but overestimated MOF more in non-white than White women. However, these three reports were inconclusive regarding whether discrimination of FRAX or the Garvan calculator without BMD or of FRAX with BMD for MOF or hip fracture differed between white versus black women. This uncertainty was at least partly due to imprecise hip fracture estimates in black women. No reports examined whether ratios of observed to predicted hip fracture risks within each race or ethnicity group varied across levels of predicted hip fracture risk. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
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Fraturas do Quadril , Fraturas por Osteoporose , Adulto , Pessoa de Meia-Idade , Humanos , Feminino , Idoso , Etnicidade , Estudos Prospectivos , Medição de Risco/métodos , Fraturas por Osteoporose/epidemiologia , Fraturas do Quadril/epidemiologia , Densidade Óssea , Algoritmos , Minerais , Fatores de RiscoRESUMO
BACKGROUND: It is evident that COVID-19 will remain a public health concern in the coming years, largely driven by variants of concern (VOC). It is critical to continuously monitor vaccine effectiveness as new variants emerge and new vaccines and/or boosters are developed. Systematic surveillance of the scientific evidence base is necessary to inform public health action and identify key uncertainties. Evidence syntheses may also be used to populate models to fill in research gaps and help to prepare for future public health crises. This protocol outlines the rationale and methods for a living evidence synthesis of the effectiveness of COVID-19 vaccines in reducing the morbidity and mortality associated with, and transmission of, VOC of SARS-CoV-2. METHODS: Living evidence syntheses of vaccine effectiveness will be carried out over one year for (1) a range of potential outcomes in the index individual associated with VOC (pathogenesis); and (2) transmission of VOC. The literature search will be conducted up to May 2023. Observational and database-linkage primary studies will be included, as well as RCTs. Information sources include electronic databases (MEDLINE; Embase; Cochrane, L*OVE; the CNKI and Wangfang platforms), pre-print servers (medRxiv, BiorXiv), and online repositories of grey literature. Title and abstract and full-text screening will be performed by two reviewers using a liberal accelerated method. Data extraction and risk of bias assessment will be completed by one reviewer with verification of the assessment by a second reviewer. Results from included studies will be pooled via random effects meta-analysis when appropriate, or otherwise summarized narratively. DISCUSSION: Evidence generated from our living evidence synthesis will be used to inform policy making, modelling, and prioritization of future research on the effectiveness of COVID-19 vaccines against VOC.
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COVID-19 , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , SARS-CoV-2 , Eficácia de Vacinas , Viés , Metanálise como AssuntoRESUMO
Anadromous fish experience physiological modifications necessary to migrate between vastly different freshwater and marine environments, but some species such as Oncorhynchus mykiss demonstrate variation in life history strategies with some individuals remaining exclusively resident in freshwater, whereas others undergo anadromous migration. Because there is limited understanding of genes involved in this life history variation across populations of this species, we evaluated the genomic difference between known anadromous (n = 39) and resident (n = 78) Oncorhynchus mykiss collected from the Klickitat River, WA, USA, with whole-genome resequencing methods. Sequencing of these collections yielded 5.64 million single-nucleotide polymorphisms that were tested for significant differences between resident and anadromous groups along with previously identified candidate gene regions. Although a few regions of the genome were marginally significant, there was one region on chromosome Omy12 that provided the most consistent signal of association with anadromy near two annotated genes in the reference assembly: COP9 signalosome complex subunit 6 (CSN6) and NACHT, LRR, and PYD domain-containing protein 3 (NLRP3). Previously identified candidate genes for anadromy within the inversion region of chromosome Omy05 in coastal steelhead and rainbow trout were not informative for this population as shown in previous studies. Results indicate that the significant region on chromosome Omy12 may represent a minor effect gene for male anadromy and suggests that this life history variation in Oncorhynchus mykiss is more strongly driven by other mechanisms related to environmental rearing such as epigenetic modification, gene expression, and phenotypic plasticity. Further studies into regulatory mechanisms of this trait are needed to understand drivers of anadromy in populations of this protected species.
RESUMO
PURPOSE: To investigate the robustness and longevity of SARS-CoV-2 immune responses conferred by natural infection and vaccination among priority populations such as immunocompromised individuals and people with post-acute sequelae of COVID-19 in a prospective cohort study (Stop the Spread Ottawa-SSO) in adults living in the Ottawa region. In this paper, we describe the study design, ongoing data collection and baseline characteristics of participants. PARTICIPANTS: Since October 2020, participants who tested positive for COVID-19 (convalescents) or at high risk of exposure to the virus (under surveillance) have provided monthly blood and saliva samples over a 10-month period. As of 2 November 2021, 1026 adults had completed the baseline survey and 976 had attended baseline bloodwork. 300 participants will continue to provide bimonthly blood samples for 24 additional months (ie, total follow-up of 34 months). FINDINGS TO DATE: The median age of the baseline sample was 44 (IQR 23, range: 18-79) and just over two-thirds (n=688; 67.1%) were female. 255 participants (24.9%) had a history of COVID-19 infection confirmed by PCR and/or serology. Over 600 participants (60.0%) work in high-risk occupations (eg, healthcare, teaching and transportation). 108 participants (10.5%) reported immunocompromising conditions or treatments at baseline (eg, cancer, HIV, other immune deficiency, and/or use of immunosuppressants). FUTURE PLANS: SSO continues to yield rich research potential, given the collection of pre-vaccine baseline data and samples from the majority of participants, recruitment of diverse subgroups of interest, and a high level of participant retention and compliance with monthly sampling. The 24-month study extension will maximise opportunities to track SARS-CoV-2 immunity and vaccine efficacy, detect and characterise emerging variants, and compare subgroup humoral and cellular response robustness and persistence.
Assuntos
COVID-19 , Adulto , Humanos , Feminino , Masculino , SARS-CoV-2 , Formação de Anticorpos , Estudos Prospectivos , Anticorpos , Vacinação , Imunidade Celular , Anticorpos AntiviraisRESUMO
Despite an expanding armamentarium of devices, many patients with mitral regurgitation referred for transcatheter mitral valve repair (TMVr) or replacement (TMVR) do not meet strict clinical trial inclusion and exclusion criteria. We sought to understand the rates that patients were excluded from transcatheter mitral valve therapies and reasons why. We retrospectively analyzed the medical charts and correspondence related to patients referred to our tertiary valve center for TMVr or TMVR between June 2016 and September 2019. Patients were screened for eligibility by our structural Heart Team for either TMVr or TMVR. If TMVr or TMVR was not offered, the reason for screen failure was recorded and categorized. Over the 3-year period, 564 patients were referred for TMVr and orTMVR. Out of these, 15.9% were determined to be eligible for, and underwent, surgical repair or replacement. Ninety-two patients (16.3%) underwent TMVr or TMVR. The majority of patients (343 of 564, 60.8%) ultimately did not undergo intervention. The primary reason for exclusion was clinical in 38.5%, issues related to patient preference of care delivery in 38.8%, anatomical in 13.7%, and futility in 9.0%. In contemporary real-world practice, the majority of patients with mitral regurgitation referred for transcatheter therapies are excluded. Clinical trials testing new transcatheter devices should be encouraged to record and report reasons for screen failure and follow these patients to better understand optimal timing of intervention, address challenging anatomies, and, ultimately, improve penetrance of these novel therapies.