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BACKGROUND: Mental health (MH) conditions are prevalent in adolescents with childhood-onset SLE (cSLE). Early identification is crucial in preventing poor patient outcomes; however, MH screening rates remain low. LOCAL PROBLEM: From July 2021-January 2022, only 15% of adolescents in a paediatric tertiary care cSLE clinic were being screened for depression and anxiety. By November 2023, we aimed to increase the percentage of patients with cSLE (≥12-18 years) screened for depression (Patient Health Questionnaire: PHQ-9) and anxiety (Generalised Anxiety Disorder-7: GAD-7) from 15% to 80%. METHODS: This quality improvement project employed the Model for Improvement framework. Stakeholders included the clinic team, patients and families, and MH providers. Statistical process control charts were used to analyse the outcome measure for percentage of screened patients with cSLE. Patient and caregiver satisfaction surveys were conducted at baseline and after screening as a balancing measure. INTERVENTIONS: MH screening workflow with a referral algorithm was developed with stakeholders. Additional interventions included two MH training workshops for healthcare providers and a preclinic reminder of eligible patients for screening. RESULTS: Over 21 months, 146 patients with cSLE completed 270 MH screens, increasing the screening rate from 15%, peaking at 100%, to a median of 56%. Sixty-six individuals (45%) reported symptoms of depression and/or anxiety on their initial screen. Of 270 screens, 44 individuals (17%) reported moderate to severe symptoms meeting the screening workflow criteria for referral to a MH service; 10% of patients screened were referred and seen by the MH service within 2-12 weeks. Patients and caregivers reported satisfaction with the MH screening process and quality of MH follow-up. CONCLUSION: Despite not sustainably meeting the target, MH screening rates increased in the cSLE clinic by nearly fourfold, demonstrating feasibility and acceptability. Patients expressed satisfaction with their mental health follow-up, emphasising its importance in their care.
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Ansiedade , Depressão , Lúpus Eritematoso Sistêmico , Programas de Rastreamento , Melhoria de Qualidade , Humanos , Adolescente , Feminino , Masculino , Ansiedade/diagnóstico , Ansiedade/etiologia , Criança , Programas de Rastreamento/métodos , Depressão/diagnóstico , Lúpus Eritematoso Sistêmico/psicologia , Lúpus Eritematoso Sistêmico/complicações , Saúde Mental , Serviços de Saúde Mental , Satisfação do Paciente , Cuidadores/psicologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Cognitive dysfunction (CD) is highly prevalent in systemic lupus erythematosus (SLE), yet the underlying mechanisms are poorly understood. Neuroimaging utilising advanced MRI metrics may yield mechanistic insights. We conducted a systematic review of neuroimaging studies to investigate the relationship between structural and diffusion MRI metrics and CD in SLE. METHODS: We systematically searched several databases between January 2000 and October 2023 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Retrospective and prospective studies were screened for search criteria keywords (including structural or diffusion MRI, cognitive function and SLE) to identify peer-reviewed articles reporting advanced structural MRI metrics and evaluating CD in human patients with SLE. RESULTS: Eighteen studies (8 structural MRI, 9 diffusion MRI and 1 with both modalities) were included; sample sizes ranged from 11 to 120 participants with SLE. Neurocognitive assessments and neuroimaging techniques, parameters and processing differed across articles. The most frequently affected cognitive domains were memory, psychomotor speed and attention; while abnormal structural and/or diffusion MRI metrics were found more consistently in the hippocampus, corpus callosum and frontal cortex of patients with SLE, with and without clinically diagnosed central nervous system involvement. CONCLUSION: Advanced structural MRI analysis can identify total and regional brain abnormalities associated with CD in patients with SLE, with potential to enhance clinical assessment. Future collaborative, longitudinal studies of neuroimaging in SLE are needed to better characterise CD, with focus on harmonised neurocognitive assessments, neuroimaging acquisitions and postprocessing analyses and improved clinical characterisation of SLE cohorts.
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Encéfalo , Disfunção Cognitiva , Lúpus Eritematoso Sistêmico , Imageamento por Ressonância Magnética , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/psicologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Masculino , Adulto , Testes NeuropsicológicosRESUMO
BACKGROUND AND OBJECTIVES: Neurological involvement associated with SARS-CoV-2 infection is increasingly recognized. However, the specific characteristics and prevalence in pediatric patients remain unclear. The objective of this study was to describe the neurological involvement in a multinational cohort of hospitalized pediatric patients with SARS-CoV-2. METHODS: This was a multicenter observational study of children <18 years of age with confirmed SARS-CoV-2 infection or multisystemic inflammatory syndrome (MIS-C) and laboratory evidence of SARS-CoV-2 infection in children, admitted to 15 tertiary hospitals/healthcare centers in Canada, Costa Rica, and Iran February 2020-May 2021. Descriptive statistical analyses were performed and logistic regression was used to identify factors associated with neurological involvement. RESULTS: One-hundred forty-seven (21%) of 697 hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Headache (n = 103), encephalopathy (n = 28), and seizures (n = 30) were the most reported. Neurological signs/symptoms were significantly associated with ICU admission (OR: 1.71, 95% CI: 1.15-2.55; p = 0.008), satisfaction of MIS-C criteria (OR: 3.71, 95% CI: 2.46-5.59; p < 0.001), fever during hospitalization (OR: 2.15, 95% CI: 1.46-3.15; p < 0.001), and gastrointestinal involvement (OR: 2.31, 95% CI: 1.58-3.40; p < 0.001). Non-headache neurological manifestations were significantly associated with ICU admission (OR: 1.92, 95% CI: 1.08-3.42; p = 0.026), underlying neurological disorders (OR: 2.98, 95% CI: 1.49-5.97, p = 0.002), and a history of fever prior to hospital admission (OR: 2.76, 95% CI: 1.58-4.82; p < 0.001). DISCUSSION: In this study, approximately 21% of hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Future studies should focus on pathogenesis and long-term outcomes in these children.
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COVID-19 , Criança Hospitalizada , Síndrome de Resposta Inflamatória Sistêmica , Humanos , Criança , COVID-19/complicações , SARS-CoV-2 , Hospitalização , Febre/epidemiologia , Febre/etiologia , Cefaleia/epidemiologia , Cefaleia/etiologia , SíndromeRESUMO
BACKGROUND: Paediatric inflammatory multisystem syndrome (PIMS) is a rare condition temporally associated with SARS-CoV-2 infection. Using national surveillance data, we compare presenting features and outcomes among children hospitalized with PIMS by SARS-CoV-2 linkage, and identify risk factors for intensive care (ICU). METHODS: Cases were reported to the Canadian Paediatric Surveillance Program by a network of >2800 pediatricians between March 2020 and May 2021. Patients with positive versus negative SARS-CoV-2 linkages were compared, with positive linkage defined as any positive molecular or serologic test or close contact with confirmed COVID-19. ICU risk factors were identified with multivariable modified Poisson regression. RESULTS: We identified 406 children hospitalized with PIMS, including 49.8% with positive SARS-CoV-2 linkages, 26.1% with negative linkages, and 24.1% with unknown linkages. The median age was 5.4 years (IQR 2.5-9.8), 60% were male, and 83% had no comorbidities. Compared to cases with negative linkages, children with positive linkages experienced more cardiac involvement (58.8% vs. 37.4%; p < 0.001), gastrointestinal symptoms (88.6% vs. 63.2%; p < 0.001), and shock (60.9% vs. 16.0%; p < 0.001). Children aged ≥6 years and those with positive linkages were more likely to require ICU. CONCLUSIONS: Although rare, 30% of PIMS hospitalizations required ICU or respiratory/hemodynamic support, particularly those with positive SARS-CoV-2 linkages. IMPACT: We describe 406 children hospitalized with paediatric inflammatory multisystem syndrome (PIMS) using nationwide surveillance data, the largest study of PIMS in Canada to date. Our surveillance case definition of PIMS did not require a history of SARS-CoV-2 exposure, and we therefore describe associations of SARS-CoV-2 linkages on clinical features and outcomes of children with PIMS. Children with positive SARS-CoV-2 linkages were older, had more gastrointestinal and cardiac involvement, and hyperinflammatory laboratory picture. Although PIMS is rare, one-third required admission to intensive care, with the greatest risk amongst those aged ≥6 years and those with a SARS-CoV-2 linkage.
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COVID-19 , SARS-CoV-2 , Humanos , Masculino , Criança , Pré-Escolar , Feminino , COVID-19/epidemiologia , COVID-19/terapia , Canadá/epidemiologia , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/epidemiologiaRESUMO
Background: Direct comparisons of paediatric hospitalizations for acute coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) can inform health system planning. We describe the absolute and relative hospital burden of acute paediatric COVID-19 and MIS-C in Canada. Methods: This national prospective study was conducted via the Canadian Paediatric Surveillance Program from March 2020-May 2021. Children younger than 18 years old and hospitalized for acute COVID-19 or MIS-C were included in the analysis. Outcomes included supplemental oxygen (low-flow oxygen or high-flow nasal cannula), ventilation (non-invasive or conventional mechanical), vasopressors, paediatric intensive care unit (PICU) admission, or death. Adjusted risk differences (aRD) and 95% confidence intervals (CI) were calculated to identify factors associated with each diagnosis. Results: Overall, we identified 330 children hospitalized for acute COVID-19 (including five deaths) and 208 hospitalized for MIS-C (including zero deaths); PICU admission was required for 49.5% of MIS-C hospitalizations versus 18.2% of acute COVID-19 hospitalizations (aRD 20.3; 95% CI, 9.9-30.8). Resource use differed by age, with children younger than one year hospitalized more often for acute COVID-19 (aRD 43.4% versus MIS-C; 95% CI, 37.7-49.1) and more children 5-11 years hospitalized for MIS-C (aRD 38.9% vs. acute COVID-19; 95% CI, 31.0-46.9). Conclusion: While there were more hospitalizations and deaths from acute paediatric COVID-19, MIS-C cases were more severe, requiring more intensive care and vasopressor support. Our findings suggest that both acute COVID-19 and MIS-C should be considered when assessing the overall burden of severe acute respiratory syndrome coronavirus 2 in hospitalized children.
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OBJECTIVE: To identify risk factors for severe disease in children hospitalised for SARS-CoV-2 infection. DESIGN: Multicentre retrospective cohort study. SETTING: 18 hospitals in Canada, Iran and Costa Rica from 1 February 2020 to 31 May 2021. PATIENTS: Children<18 years of age hospitalised for symptomatic PCR-positive SARS-CoV-2 infection, including PCR-positive multisystem inflammatory syndrome in children (MIS-C). MAIN OUTCOME MEASURE: Severity on the WHO COVID-19 Clinical Progression Scale was used for ordinal logistic regression analyses. RESULTS: We identified 403 hospitalisations. Median age was 3.78 years (IQR 0.53-10.77). At least one comorbidity was present in 46.4% (187/403) and multiple comorbidities in 18.6% (75/403). Eighty-one children (20.1%) met WHO criteria for PCR-positive MIS-C. Progression to WHO clinical scale score ≥6 occurred in 25.3% (102/403). In multivariable ordinal logistic regression analyses adjusted for age, chest imaging findings, laboratory-confirmed bacterial and/or viral coinfection, and MIS-C diagnosis, presence of a single (adjusted OR (aOR) 1.90, 95% CI 1.13 to 3.20) or multiple chronic comorbidities (aOR 2.12, 95% CI 1.19 to 3.79), obesity (aOR 3.42, 95% CI 1.76 to 6.66) and chromosomal disorders (aOR 4.47, 95% CI 1.25 to 16.01) were independent risk factors for severity. Age was not an independent risk factor, but different age-specific comorbidities were associated with more severe disease in age-stratified adjusted analyses: cardiac (aOR 2.90, 95% CI 1.11 to 7.56) and non-asthma pulmonary disorders (aOR 3.07, 95% CI 1.26 to 7.49) in children<12 years old and obesity (aOR 3.69, 1.45-9.40) in adolescents≥12 years old. Among infants<1 year old, neurological (aOR 10.72, 95% CI 1.01 to 113.35) and cardiac disorders (aOR 10.13, 95% CI 1.69 to 60.54) were independent predictors of severe disease. CONCLUSION: We identified risk factors for disease severity among children hospitalised for PCR-positive SARS-CoV-2 infection. Comorbidities predisposing children to more severe disease may vary by age. These findings can potentially guide vaccination programmes and treatment approaches in children.
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COVID-19 , Adolescente , COVID-19/complicações , COVID-19/diagnóstico , Teste para COVID-19 , Criança , Criança Hospitalizada , Pré-Escolar , Humanos , Lactente , Obesidade/epidemiologia , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/genética , Síndrome de Resposta Inflamatória SistêmicaRESUMO
BACKGROUND: SARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We sought to investigate risk factors for admission to the intensive care unit (ICU) and explored changes in disease severity over time. METHODS: We obtained data from chart reviews of children younger than 18 years with confirmed or probable MIS-C who were admitted to 15 hospitals in Canada, Iran and Costa Rica between Mar. 1, 2020, and Mar. 7, 2021. Using multivariable analyses, we evaluated whether admission date and other characteristics were associated with ICU admission or cardiac involvement. RESULTS: Of 232 children with MIS-C (median age 5.8 yr), 130 (56.0%) were male and 50 (21.6%) had comorbidities. Seventy-three (31.5%) patients were admitted to the ICU but none died. We observed an increased risk of ICU admission among children aged 13-17 years (adjusted risk difference 27.7%, 95% confidence interval [CI] 8.3% to 47.2%), those aged 6-12 years (adjusted risk difference 25.2%, 95% CI 13.6% to 36.9%) or those with initial ferritin levels greater than 500 µg/L (adjusted risk difference 18.4%, 95% CI 5.6% to 31.3%). Children admitted to hospital after Oct. 31, 2020, had numerically higher rates of ICU admission (adjusted risk difference 12.3%, 95% CI -0.3% to 25.0%) and significantly higher rates of cardiac involvement (adjusted risk difference 30.9%, 95% CI 17.3% to 44.4%). At Canadian sites, the risk of ICU admission was significantly higher for children admitted to hospital between December 2020 and March 2021 than those admitted between March and May 2020 (adjusted risk difference 25.3%, 95% CI 6.5% to 44.0%). INTERPRETATION: We observed that age and higher ferritin levels were associated with more severe MIS-C. We observed greater severity of MIS-C later in the study period. Whether emerging SARS-CoV-2 variants pose different risks of severe MIS-C needs to be determined.
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COVID-19 , Doenças do Tecido Conjuntivo , COVID-19/complicações , COVID-19/epidemiologia , Canadá/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Ferritinas , Humanos , Masculino , SARS-CoV-2 , Síndrome de Resposta Inflamatória SistêmicaRESUMO
OBJECTIVE: Treat to target (T2T) is a strategy of adjusting treatment until a target is reached. An international task force recommended T2T for juvenile idiopathic arthritis (JIA) treatment. Implementing T2T in a standard and reliable way in clinical practice requires agreement on critical elements of (1) target setting, (2) T2T strategy, (3) identifying barriers to implementation, and (4) patient eligibility. A consensus conference was held among Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) stakeholders to inform a statement of understanding regarding the PR-COIN approach to T2T. METHODS: PR-COIN stakeholders including 16 healthcare providers and 4 parents were invited to form a voting panel. Using the nominal group technique, 2 rounds of voting were held to address the above 4 areas to select the top 10 responses by rank order. RESULTS: Incorporation of patient goals ranked most important when setting a treatment target. Shared decision making (SDM), tracking measurable outcomes, and adjusting treatment to achieve goals were voted as the top elements of a T2T strategy. Workflow considerations, and provider buy-in were identified as key barriers to T2T implementation. Patients with JIA who had poor prognostic factors and were at risk for high disease burden were leading candidates for a T2T approach. CONCLUSION: This consensus conference identified the importance of incorporating patient goals as part of target setting and of the influence of patient stakeholder involvement in drafting treatment recommendations. The network approach to T2T will be modified to address the above findings, including solicitation of patient goals, optimizing SDM, and better workflow integration.
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Artrite Juvenil , Reumatologia , Artrite Juvenil/tratamento farmacológico , Criança , Consenso , Efeitos Psicossociais da Doença , Humanos , Participação do Paciente , Reumatologia/métodosRESUMO
Age is the most important determinant of COVID-19 severity. Infectious disease severity by age is typically J-shaped, with infants and the elderly carrying a high burden of disease. We report on the comparative disease severity between infants and older children in a multicenter retrospective cohort study of children 0 to 17 years old admitted for acute COVID-19 from February 2020 through May 2021 in 17 pediatric hospitals. We compare clinical and laboratory characteristics and estimate the association between age group and disease severity using ordinal logistic regression. We found that infants comprised one-third of cases, but were admitted for a shorter period (median 3 days IQR 2-5 versus 4 days IQR 2-7), had a lower likelihood to have an increased C-reactive protein, and had half the odds of older children of having severe or critical disease (OR 0.50 (95% confidence interval 0.32-0.78)). Conclusion: When compared to older children, there appeared to be a lower threshold to admit infants but their length of stay was shorter and they had lower odds than older children of progressing to severe or critical disease. What is Known: ⢠A small proportion of children infected with SARS-CoV-2 require hospitalization for acute COVID-19 with a subgroup needing specialized intensive care to treat more severe disease. ⢠For most infectious diseases including viral respiratory tract infections, disease severity by age is J-shaped, with infants having more severe disease compared to older children. What is New: ⢠One-third of admitted children for acute COVID-19 during the first 14 months of the pandemic were infants. ⢠Infants had half the odds of older children of having severe or critical disease.
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COVID-19 , Adolescente , COVID-19/terapia , Criança , Pré-Escolar , Estudos de Coortes , Hospitalização , Humanos , Lactente , Recém-Nascido , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de DoençaAssuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , COVID-19 , Criança , Infecções por Coronavirus/terapia , Humanos , Pandemias , Pneumonia Viral/terapia , SARS-CoV-2 , Avaliação de Sintomas , Síndrome de Resposta Inflamatória Sistêmica/terapiaRESUMO
Several common degenerative mechanisms and mediators underlying the neuronal injury pathways characterize several neurodegenerative diseases including Alzheimer's, Parkinson's, and Huntington's disease, as well as brain neurotrauma. Such common ground invites the emergence of new approaches and tools to study the altered pathways involved in neural injury alongside with neuritogenesis, an intricate process that commences with neuronal differentiation. Achieving a greater understanding of the impaired pathways of neuritogenesis would significantly help in uncovering detailed mechanisms of axonal regeneration. Among the several agents involved in neuritogenesis are the Rho and Rho kinases (ROCKs), which constitute key integral points in the Rho/ROCK pathway that is known to be disrupted in multiple neuropathologies such as spinal cord injury, traumatic brain injury, and Alzheimer's disease. This in turn renders ROCK inhibition as a promising candidate for therapeutic targets for treatment of neurodegenerative diseases. Among the novel tools to investigate the mechanisms involved in a specific disorder is the use of neuroproteomics/systems biology approach, a growing subfield of bioinformatics aiming to study and establishing a global assessment of the entire neuronal proteome, addressing the dynamic protein changes and interactions. This review aims to examine recent updates regarding how neuroproteomics aids in the understanding of molecular mechanisms of activation and inhibition in the area of neurogenesis and how Rho/ROCK pathway/ROCK inhibitors, primarily Y-27632 and Fasudil compounds, are applied in biological settings, promoting neuronal survival and neuroprotection that has direct future implications in neurotrauma.