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BACKGROUND: Early control of elevated blood pressure is the most promising treatment for acute intracerebral haemorrhage. We aimed to establish whether implementing a goal-directed care bundle incorporating protocols for early intensive blood pressure lowering and management algorithms for hyperglycaemia, pyrexia, and abnormal anticoagulation, implemented in a hospital setting, could improve outcomes for patients with acute spontaneous intracerebral haemorrhage. METHODS: We performed a pragmatic, international, multicentre, blinded endpoint, stepped wedge cluster randomised controlled trial at hospitals in nine low-income and middle-income countries (Brazil, China, India, Mexico, Nigeria, Pakistan, Peru, Sri Lanka, and Viet Nam) and one high-income country (Chile). Hospitals were eligible if they had no or inconsistent relevant, disease-specific protocols, and were willing to implement the care bundle to consecutive patients (aged ≥18 years) with imaging-confirmed spontaneous intracerebral haemorrhage presenting within 6 h of the onset of symptoms, had a local champion, and could provide the required study data. Hospitals were centrally randomly allocated using permuted blocks to three sequences of implementation, stratified by country and the projected number of patients to be recruited over the 12 months of the study period. These sequences had four periods that dictated the order in which the hospitals were to switch from the control usual care procedure to the intervention implementation of the care bundle procedure to different clusters of patients in a stepped manner. To avoid contamination, details of the intervention, sequence, and allocation periods were concealed from sites until they had completed the usual care control periods. The care bundle protocol included the early intensive lowering of systolic blood pressure (target <140 mm Hg), strict glucose control (target 6·1-7·8 mmol/L in those without diabetes and 7·8-10·0 mmol/L in those with diabetes), antipyrexia treatment (target body temperature ≤37·5°C), and rapid reversal of warfarin-related anticoagulation (target international normalised ratio <1·5) within 1 h of treatment, in patients where these variables were abnormal. Analyses were performed according to a modified intention-to-treat population with available outcome data (ie, excluding sites that withdrew during the study). The primary outcome was functional recovery, measured with the modified Rankin scale (mRS; range 0 [no symptoms] to 6 [death]) at 6 months by masked research staff, analysed using proportional ordinal logistic regression to assess the distribution in scores on the mRS, with adjustments for cluster (hospital site), group assignment of cluster per period, and time (6-month periods from Dec 12, 2017). This trial is registered at Clinicaltrials.gov (NCT03209258) and the Chinese Clinical Trial Registry (ChiCTR-IOC-17011787) and is completed. FINDINGS: Between May 27, 2017, and July 8, 2021, 206 hospitals were assessed for eligibility, of which 144 hospitals in ten countries agreed to join and were randomly assigned in the trial, but 22 hospitals withdrew before starting to enrol patients and another hospital was withdrawn and their data on enrolled patients was deleted because regulatory approval was not obtained. Between Dec 12, 2017, and Dec 31, 2021, 10 857 patients were screened but 3821 were excluded. Overall, the modified intention-to-treat population included 7036 patients enrolled at 121 hospitals, with 3221 assigned to the care bundle group and 3815 to the usual care group, with primary outcome data available in 2892 patients in the care bundle group and 3363 patients in the usual care group. The likelihood of a poor functional outcome was lower in the care bundle group (common odds ratio 0·86; 95% CI 0·76-0·97; p=0·015). The favourable shift in mRS scores in the care bundle group was generally consistent across a range of sensitivity analyses that included additional adjustments for country and patient variables (0·84; 0·73-0·97; p=0·017), and with different approaches to the use of multiple imputations for missing data. Patients in the care bundle group had fewer serious adverse events than those in the usual care group (16·0% vs 20·1%; p=0·0098). INTERPRETATION: Implementation of a care bundle protocol for intensive blood pressure lowering and other management algorithms for physiological control within several hours of the onset of symptoms resulted in improved functional outcome for patients with acute intracerebral haemorrhage. Hospitals should incorporate this approach into clinical practice as part of active management for this serious condition. FUNDING: Joint Global Health Trials scheme from the Department of Health and Social Care, the Foreign, Commonwealth & Development Office, and the Medical Research Council and Wellcome Trust; West China Hospital; the National Health and Medical Research Council of Australia; Sichuan Credit Pharmaceutic and Takeda China.
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Hipotensão , Pacotes de Assistência ao Paciente , Humanos , Adolescente , Adulto , Pressão Sanguínea , Resultado do Tratamento , Hemorragia Cerebral/tratamento farmacológico , Cuidados Críticos , Anticoagulantes/uso terapêuticoRESUMO
Altered autonomic balance is a hallmark of numerous cardiovascular diseases, including myocardial infarction (MI). Although device-based vagal stimulation is cardioprotective during chronic disease, a non-invasive approach to selectively stimulate the cardiac parasympathetic system immediately after an infarction does not exist and is desperately needed. Cardiac vagal neurons (CVNs) in the brainstem receive powerful excitation from a population of neurons in the paraventricular nucleus (PVN) of the hypothalamus that co-release oxytocin (OXT) and glutamate to excite CVNs. We tested if chemogenetic activation of PVN-OXT neurons following MI would be cardioprotective. The PVN of neonatal rats was transfected with vectors to selectively express DREADDs within OXT neurons. At 6 weeks of age, an MI was induced and DREADDs were activated with clozapine-N-oxide. Seven days following MI, patch-clamp electrophysiology confirmed the augmented excitatory neurotransmission from PVN-OXT neurons to downstream nuclei critical for parasympathetic activity with treatment (43.7 ± 10 vs 86.9 ± 9 pA; MI vs. treatment), resulting in stark improvements in survival (85% vs. 95%; MI vs. treatment), inflammation, fibrosis assessed by trichrome blue staining, mitochondrial function assessed by Seahorse assays, and reduced incidence of arrhythmias (50% vs. 10% cumulative incidence of ventricular fibrillation; MI vs. treatment). Myocardial transcriptomic analysis provided molecular insight into potential cardioprotective mechanisms, which revealed the preservation of beneficial signaling pathways, including muscarinic receptor activation, in treated animals. These comprehensive results demonstrate that the PVN-OXT network could be a promising therapeutic target to quickly activate beneficial parasympathetic-mediated cellular pathways within the heart during the early stages of infarction.
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Infarto do Miocárdio , Ocitocina , Ratos , Animais , Ocitocina/farmacologia , Ocitocina/metabolismo , Ratos Sprague-Dawley , Hipotálamo , Infarto do Miocárdio/metabolismo , Neurônios/metabolismo , Arritmias Cardíacas/metabolismoRESUMO
BACKGROUND: To update and internally validate a model to predict children and young people (CYP) most likely to experience long COVID (i.e. at least one impairing symptom) 3 months after SARS-CoV-2 PCR testing and to determine whether the impact of predictors differed by SARS-CoV-2 status. METHODS: Data from a nationally matched cohort of SARS-CoV-2 test-positive and test-negative CYP aged 11-17 years was used. The main outcome measure, long COVID, was defined as one or more impairing symptoms 3 months after PCR testing. Potential pre-specified predictors included SARS-CoV-2 status, sex, age, ethnicity, deprivation, quality of life/functioning (five EQ-5D-Y items), physical and mental health and loneliness (prior to testing) and number of symptoms at testing. The model was developed using logistic regression; performance was assessed using calibration and discrimination measures; internal validation was performed via bootstrapping and the final model was adjusted for overfitting. RESULTS: A total of 7139 (3246 test-positives, 3893 test-negatives) completing a questionnaire 3 months post-test were included. 25.2% (817/3246) of SARS-CoV-2 PCR-positives and 18.5% (719/3893) of SARS-CoV-2 PCR-negatives had one or more impairing symptoms 3 months post-test. The final model contained SARS-CoV-2 status, number of symptoms at testing, sex, age, ethnicity, physical and mental health, loneliness and four EQ-5D-Y items before testing. Internal validation showed minimal overfitting with excellent calibration and discrimination measures (optimism-adjusted calibration slope: 0.96575; C-statistic: 0.83130). CONCLUSIONS: We updated a risk prediction equation to identify those most at risk of long COVID 3 months after a SARS-CoV-2 PCR test which could serve as a useful triage and management tool for CYP during the ongoing pandemic. External validation is required before large-scale implementation.
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COVID-19 , SARS-CoV-2 , Criança , Humanos , Adolescente , SARS-CoV-2/genética , COVID-19/diagnóstico , Qualidade de Vida , Reação em Cadeia da Polimerase , Síndrome de COVID-19 Pós-AgudaRESUMO
In parallel with advances in the synthesis of solid-state ionic conductors, there is a need to understand the underlying mechanisms behind their improved ionic conductivities. This can be achieved by obtaining an atomic level picture of the interplay between the structure of materials and the resultant ionic diffusion processes. To this end, the structure and dynamics of Mg2+-stabilized rotor phase material γ-Na3PO4, characterized by neutron scattering, are detailed in this work. The Mg2+-stabilized rotor phase is found to be thermally stable from 4 to 650 K. However, signatures of orientational disorder of the phosphate anions are also evident in the average structure. Long-range Na+ self-diffusion was probed by quasi-elastic neutron scattering and subsequently modeled via a jump diffusion matrix with consideration of the phosphate anion rotations. The resultant diffusion model points directly to coupled anion-cation dynamics. Our approach highlights the importance of considering the whole system when developing an atomic level picture of structure and dynamics, which is critical in the rational design and optimization of energy materials.
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Pediatric obstructive sleep apnea has significant negative effects on health and behavior in childhood including depression, failure to thrive, neurocognitive impairment, and behavioral issues. It is strongly associated with an increased risk for chronic adult disease such as obesity and diabetes, accelerated atherosclerosis, and endothelial dysfunction. Accumulating evidence suggests that adult-onset non-communicable diseases may originate from early life through a process by which an insult applied at a critical developmental window causes long-term effects on the structure or function of an organism. In recent years, there has been increased interest in the role of epigenetic mechanisms in the pathogenesis of adult disease susceptibility. Epigenetic mechanisms that influence adaptive variability include histone modifications, non-coding RNAs, and DNA methylation. This review will highlight what is currently known about the phenotypic associations of epigenetic modifications in pediatric obstructive sleep apnea and will emphasize the importance of epigenetic changes as both modulators of chronic disease and potential therapeutic targets.
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Metilação de DNA , Epigênese Genética , Histonas , Processamento de Proteína Pós-Traducional , RNA não Traduzido , Síndromes da Apneia do Sono , Criança , Doença Crônica , Epigenômica , Histonas/genética , Histonas/metabolismo , Humanos , RNA não Traduzido/biossíntese , RNA não Traduzido/genética , Síndromes da Apneia do Sono/genética , Síndromes da Apneia do Sono/metabolismo , Síndromes da Apneia do Sono/patologiaRESUMO
Recruitment of poliovirus (PV) RNA to the human ribosome requires the coordinated interaction of the viral internal ribosome entry site (IRES) and several host cellular initiation factors and IRES trans-acting factors (ITAFs). Attenuated PV Sabin strains contain point mutations in the PV IRES domain V (dV) that inhibit viral translation. Remarkably, attenuation is most apparent in cells of the central nervous system, but the molecular basis to explain this is poorly understood. The dV contains binding sites for eukaryotic initiation factor 4G (eIF4G) and polypyrimidine tract-binding protein (PTB). Impaired binding of these proteins to the mutant IRESs has been observed, but these effects have not been quantitated. We used a fluorescence anisotropy assay to reveal that the Sabin mutants reduce the equilibrium dissociation constants of eIF4G and PTB to the PV IRES by up to 6-fold. Using the most inhibitory Sabin 3 mutant, we used a real-time fluorescence helicase assay to show that the apparent affinity of an active eIF4G/4A/4B helicase complex for the IRES is reduced by 2.5-fold. The Sabin 3 mutant did not alter the maximum rate of eIF4A-dependent helicase activity, suggesting that this mutant primarily reduces the affinity, rather than activity, of the unwinding complex. To confirm this affinity model of attenuation, we show that eIF4G overexpression in HeLa cells overcomes the attenuation of a Sabin 3 mutant PV-luciferase replicon. Our study provides a quantitative framework for understanding the mechanism of PV Sabin attenuation and provides an explanation for the previously observed cell type-specific translational attenuation.
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Fator de Iniciação Eucariótico 4G/genética , Mutação , Vacina Antipólio Oral/genética , Poliovirus/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Biossíntese de Proteínas , Animais , Baculoviridae/genética , Baculoviridae/imunologia , Sequência de Bases , Clonagem Molecular , Escherichia coli/genética , Escherichia coli/imunologia , Fator de Iniciação 4A em Eucariotos/genética , Fator de Iniciação 4A em Eucariotos/imunologia , Fator de Iniciação Eucariótico 4G/imunologia , Expressão Gênica , Genes Reporter , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Células HeLa , Humanos , Sítios Internos de Entrada Ribossomal , Luciferases/genética , Luciferases/metabolismo , Conformação de Ácido Nucleico , Poliovirus/imunologia , Vacina Antipólio Oral/biossíntese , Vacina Antipólio Oral/imunologia , Proteína de Ligação a Regiões Ricas em Polipirimidinas/imunologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Alinhamento de Sequência , Células Sf9 , Spodoptera , Vacinas AtenuadasRESUMO
The recent advancements in radiotherapy technologies have made delivery of the highly conformal dose to the target volume possible. With the increasing popularity of delivering high dose per fraction in modern radiotherapy schemes such as in stereotactic body radiotherapy and stereotactic body ablative therapy, high degree of treatment precision is essential. In order to achieve this, we have to overcome the potential difficulties caused by patient instability due to immobilization problems; patient anxiety and random motion due to prolonged treatment time; tumor deformation and baseline shift during a treatment course. This is even challenging for patients receiving radiotherapy in the chest and abdominal regions because it is affected by the patient's respiration which inevitably leads to tumor motion. Therefore, monitoring of intrafractional motion has become increasingly important in modern radiotherapy. Major intrafractional motion management strategies including integration of respiratory motion in treatment planning; breath-hold technique; forced shallow breathing with abdominal compression; respiratory gating and dynamic real-time tumor tracking have been developed. Successful intrafractional motion management is able to reduce the planning target margin and ensures planned dose delivery to the target and organs at risk. Meanwhile, the emergency of MRI-linear accelerator has facilitated radiation-free real-time monitoring of soft tissue during treatment and could be the future modality in motion management. This review article summarizes the various approaches that deal with intrafractional target, organs or patient motion with discussion of their advantages and limitations. In addition, the potential future advancements including MRI-based tumor tracking are also discussed.
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Movimento (Física) , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Humanos , Imageamento por Ressonância Magnética , Neoplasias/radioterapia , Aceleradores de Partículas , Radioterapia Guiada por Imagem , RespiraçãoRESUMO
Pediatric obstructive sleep apnea poses a significant health risk, with potential long-term consequences on cardiovascular health. This study explores the dichotomous nature of neonatal cardiac response to chronic intermittent hypoxia (CIH) between males and females, aiming to fill a critical knowledge gap in the understanding of sex-specific cardiovascular consequences of sleep apnea in early life. Neonates were exposed to CIH until p28 and underwent comprehensive in vivo physiological assessments, including whole-body plethysmography, treadmill stress-tests, and echocardiography. Results indicated that male CIH rats weighed 13.7% less than age-matched control males (p = 0.0365), while females exhibited a mild yet significant increased respiratory drive during sleep (93.94 ± 0.84 vs. 95.31 ± 0.81;p = 0.02). Transcriptomic analysis of left ventricular tissue revealed a substantial sex-based difference in the cardiac response to CIH, with males demonstrating a more pronounced alteration in gene expression compared to females (5986 vs. 3174 genes). The dysregulated miRNAs in males target metabolic genes, potentially predisposing the heart to altered metabolism and substrate utilization. Furthermore, CIH in males was associated with thinner left ventricular walls and dysregulation of genes involved in the cardiac action potential, possibly predisposing males to CIH-related arrhythmia. These findings emphasize the importance of considering sex-specific responses in understanding the cardiovascular implications of pediatric sleep apnea.
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Animais Recém-Nascidos , Caracteres Sexuais , Transcriptoma , Masculino , Feminino , Animais , Ratos , Síndromes da Apneia do Sono/genética , Síndromes da Apneia do Sono/metabolismo , Síndromes da Apneia do Sono/fisiopatologia , Ratos Sprague-Dawley , Hipóxia/metabolismo , Hipóxia/genética , Hipóxia/fisiopatologia , MicroRNAs/genética , MicroRNAs/metabolismo , Fatores Sexuais , Coração/fisiopatologiaRESUMO
Background: Although Cognitive Behavioural Therapy (CBT) is effective for 60% of adolescents with anxiety disorders, only 36% are in remission post-intervention. This indicates that more effective treatments are needed which should be reflected in the NICE guidelines. We hypothesised that Single-case experimental designs (SCEDs) may provide a framework for accelerating the development of novel interventions. The primary purpose of this review was to investigate whether SCEDs are currently followed by randomised controlled trials (RCTs) of CBT intervention for adolescent anxiety disorders named in the NICE guidelines. The secondary objective was to investigate whether using SCEDs prior to RCTs could be a helpful approach. Method: For the primary search of SCEDs five databases were used (PsycINFO, PubMed, PsycArticles, Web of Science and ProQuest). Nineteen articles met eligibility criteria including a total of 107 participants. For the secondary search of RCTs named in the NICE guidelines for adolescent anxiety disorders 53 articles met inclusion criteria and were included in the systematic review. Results: The 19 SCED studies included in the review were conducted with participants with a diverse range of anxiety disorders and across a range of CBT formats. Two of the SCEDs were followed by RCTs, but neither of these were named in the NICE guidelines for anxiety disorders. All of the SCEDs identified were rated as low quality with none meeting the criteria for the highest or second highest quality rating. From the secondary searches, none of the RCTs named in the NICE guide were preceded by SCEDs. Conclusions: It was concluded that currently SCEDs were not followed by RCTs of CBT interventions named in the NICE guidelines for adolescent anxiety disorders. However, it was suggested that SCEDs may provide an important framework for the development of more effective interventions for adolescents with anxiety.
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BACKGROUND: Obstructive sleep apnea is a prevalent and poorly treated cardiovascular disease that leads to hypertension and autonomic imbalance. Recent studies that restore cardiac parasympathetic tone using selective activation of hypothalamic oxytocin neurons have shown beneficial cardiovascular outcomes in animal models of cardiovascular disease. This study aimed to determine if chemogenetic activation of hypothalamic oxytocin neurons in animals with existing obstructive sleep apnea-induced hypertension would reverse or blunt the progression of autonomic and cardiovascular dysfunction. METHODS: Two groups of rats were exposed to chronic intermittent hypoxia (CIH), a model of obstructive sleep apnea, for 4 weeks to induce hypertension. During an additional 4 weeks of exposure to CIH, 1 group was treated with selective activation of hypothalamic oxytocin neurons while the other group was untreated. RESULTS: Hypertensive animals exposed to CIH and treated with daily hypothalamic oxytocin neuron activation had lower blood pressure, faster heart rate recovery times after exercise, and improved indices of cardiac function compared with untreated hypertensive animals. Microarray analysis suggested that, compared with treated animals, untreated animals had gene expression profiles associated with cellular stress response activation, hypoxia-inducible factor stabilization, and myocardial extracellular matrix remodeling and fibrosis. CONCLUSIONS: In animals already presenting with CIH-induced hypertension, chronic activation of hypothalamic oxytocin neurons blunted the progression of hypertension and conferred cardioprotection after an additional 4 weeks of CIH exposure. These results have significant clinical translation for the treatment of cardiovascular disease in patients with obstructive sleep apnea.
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Doenças Cardiovasculares , Cardiopatias , Hipertensão , Apneia Obstrutiva do Sono , Ratos , Animais , Ocitocina/farmacologia , Ratos Sprague-Dawley , Doenças Cardiovasculares/complicações , Modelos Animais de Doenças , Apneia Obstrutiva do Sono/complicações , Hipóxia/metabolismo , Neurônios/metabolismoRESUMO
OBJECTIVES: To describe the physical and mental health of children and young people (CYP) 6 months after infection with SARS-CoV-2 and explore whether this varies by COVID-19 vaccination. DESIGN: A non-hospitalised, national cohort of people aged 11-17 years old with PCR-confirmed SARS-CoV-2 infection and PCR negatives matched at study invitation, by age, sex, region and date of testing who completed questionnaires 6 months after PCR testing. The questionnaire included 21 symptoms and standardised scales (eg, EQ-5D-Y and Chalder Fatigue Scale). RESULTS: 6407 test-positive and 6542 test-negative CYP completed the 6-month questionnaire: 60.9% of test-positive vs 43.2% of test-negative CYP reported at least one symptom 6 months post-test; 27.6% of test-positive vs 15.9% of test-negative CYP reported 3+ symptoms. Common symptoms at 6 months were tiredness and shortness of breath among both test-positive and test-negative CYP; however, the prevalence of both was higher in test-positive (38.4% and 22.8%, respectively) compared with test-negative CYP (26.7% and 10.9%, respectively). 24.5% test-positive vs 17.8% test-negative CYP met the Delphi research definition of long COVID. Mental health, well-being, fatigue and health-related quality of life scores were similar among test-positive and test-negative CYP 6 months post-test. Similarly, symptomatology was similar among COVID-19-vaccinated and COVID-19-unvaccinated test-positive and test-negative CYP. CONCLUSIONS: Six-months post-PCR testing, CYP who tested positive for SARS-CoV-2 had similar symptoms to those who tested negative, but test-positive CYP had higher symptom prevalence. Mental health, well-being, fatigue and health-related quality of life were similar among test-positive and test-negative CYP, and symptoms at 6 months were similar in COVID-19 vaccinated and unvaccinated. TRIAL REGISTRATION NUMBER: ISRCTN 34804192.
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COVID-19 , Humanos , Criança , Adolescente , Lactente , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Síndrome de COVID-19 Pós-Aguda , Qualidade de Vida , SARS-CoV-2 , Vacinação , Fadiga/epidemiologia , Fadiga/etiologiaRESUMO
PURPOSE: This study describes long COVID symptomatology in a national sample of 18- to 20-year-olds with Polymerase Chain Reaction (PCR)-confirmed Severe acute respiratory syndrome coronavirus 2 (SARSCoV2) and matched test-negative controls in England. Symptoms in 18- to 20-year-olds were compared to symptoms in younger adolescents (aged 11-17 years) and all adults (18+). METHODS: A national database was used to identify SARS-CoV-2 PCR-positive 18- to 20-year-olds and test-negative controls matched by time of test, age, gender, and geographical region. Participants were invited to complete a questionnaire about their health retrospectively at time of test and also when completing the questionnaire. Comparison cohorts included children and young people with long COVID and REal-time Assessment of Community Transmission studies. RESULTS: Of 14,986 people invited, 1,001 were included in the analysis (562 test-positive; 440 test-negative). At testing, 46.5% of test-positives and 16.4% of test-negatives reported at least one symptom. At the time of questionnaire completion (median 7 months post-testing), 61.5% of test-positives and 47.5% of test-negatives reported one or more symptoms. The most common symptoms were similar amongst test-positives and test-negatives and included tiredness (44.0%; 35.7%), shortness of breath (28.8%; 16.3%), and headaches (13.7%; 12.0%). Prevalence rates were similar to those reported by 11-17-year-olds (66.5%) and higher than those reported in all adults (37.7%). For 18- to 20-year-olds, there was no significant difference in health-related quality of life and well-being (p > .05). However, test-positives reported being significantly more tired than test-negatives (p = .04). DISCUSSION: Seven months after PCR test, a high proportion of test-positive and test-negative 18- to 20-year-olds reported similar symptoms to each other and to those experienced by younger and older counterparts.
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COVID-19 , Criança , Adolescente , Humanos , Adulto Jovem , SARS-CoV-2 , Estudos Transversais , Síndrome de COVID-19 Pós-Aguda , Estudos Retrospectivos , Qualidade de Vida , Inglaterra/epidemiologiaRESUMO
OBJECTIVE: The aim of this study was to derive a research definition for 'Long COVID (post-COVID-19 condition)' in children and young people (CYP) to allow comparisons between research studies. DESIGN: A three-phase online Delphi process was used, followed by a consensus meeting. Participants were presented with 49 statements in each phase and scored them from 1 to 9 based on how important they were for inclusion in the research definition of Long COVID in CYP. The consensus meeting was held to achieve representation across the stakeholder groups. Statements agreed at the consensus meeting were reviewed by participants in the Patient and Public Involvement (PPI) Research Advisory Group. SETTING: The study was conducted remotely using online surveys and a virtual consensus meeting. PARTICIPANTS: 120 people with relevant expertise were divided into three panels according to their area of expertise: Service Delivery, Research (or combination of research and service delivery) and Lived Experience. The PPI Research Advisory group consisted of CYP aged 11-17 years. MAIN OUTCOME MEASURES: Consensus was defined using existing guidelines. If consensus was achieved in two or more panels or was on the border between one and two panels, those statements were discussed and voted on at the consensus meeting. RESULTS: Ten statements were taken forward for discussion in the consensus meeting and five statements met threshold to be included in the research definition of Long COVID among CYP. The research definition, aligned to the clinical case definition of the WHO, is proposed as follows: Post-COVID-19 condition occurs in young people with a history of confirmed SARS-CoV-2 infection, with at least one persisting physical symptom for a minimum duration of 12 weeks after initial testing that cannot be explained by an alternative diagnosis. The symptoms have an impact on everyday functioning, may continue or develop after COVID infection, and may fluctuate or relapse over time. The positive COVID-19 test referred to in this definition can be a lateral flow antigen test, a PCR test or an antibody test. CONCLUSIONS: This is the first research definition of Long COVID (post-COVID-19 condition) in CYP and complements the clinical case definition in adults proposed by the WHO.
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COVID-19 , Adolescente , Adulto , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/epidemiologia , Criança , Consenso , Técnica Delphi , Humanos , SARS-CoV-2 , Inquéritos e Questionários , Síndrome de COVID-19 Pós-AgudaRESUMO
Pattern reversal visual evoked potentials have been used to study optic neuritis. Although smaller check size in the central fields are more sensitive, larger check sizes can be advantageous for patient fixation and in poor vision. We compared sectorial central and peripheral hemisurround stimulus with commonly used full- and half- field stimulus using large check sizes (65') in the context of optic neuritis and multiple sclerosis. Of 19 female and 16 male control subjects studied, females had shorter P100 latencies and larger amplitudes than males. In 9 of the 18 patients with VEP abnormalities, the central field abnormalities were greater than those recorded with the full field response. The results confirm for the first time that central field stimulation using large checks can show a greater extent of abnormality than can be appreciated with large check full field stimulation alone, and could be commonly employed to improve yield in the investigation of optic neuritis. The data suggest that it is necessary to collect separate gender-specific laboratory normal values using this check size.
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Potenciais Evocados Visuais/fisiologia , Esclerose Múltipla/fisiopatologia , Neurite Óptica/fisiopatologia , Estimulação Luminosa/métodos , Campos Visuais/fisiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico , Neurite Óptica/diagnóstico , Adulto JovemRESUMO
The modified technology acceptance model was used to predict actual Blackboard usage (a web-based information system) in a sample of 57 Hong Kong student teachers whose mean age was 27.8 yr. (SD = 6.9). While the general form of the model was supported, Application-specific Self-efficacy was a more powerful predictor of system use than Behavioural Intention as predicted by the theory of reasoned action. Thus in this cultural and educational context, it has been shown that the model does not fully mediate the effect of Self-efficacy on System Use. Also, users' Enjoyment exerted considerable influence on the component variables of Usefulness and Ease of Use and on Application-specific Self-efficacy, thus indirectly influencing system usage. Consequently, efforts to gain students' acceptance and, therefore, use of information systems such as Blackboard must pay adequate attention to users' Self-efficacy and motivational variables such as Enjoyment.
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Povo Asiático/psicologia , Atitude Frente aos Computadores , Instrução por Computador , Computadores , Comparação Transcultural , Internet , Interface Usuário-Computador , Adulto , Alfabetização Digital , Difusão de Inovações , Feminino , Hong Kong , Humanos , Intenção , Motivação , Autoeficácia , Inquéritos e Questionários , EnsinoAssuntos
Potenciais de Ação , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Nervos Periféricos/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios Motores/fisiologia , Esclerose Múltipla Recidivante-Remitente/patologia , Nervos Periféricos/patologiaRESUMO
The optimal timing for renal replacement therapy initiation in septic acute kidney injury (AKI) remains controversial. This study investigates the impact of early versus late initiation of continuous renal replacement therapy (CRRT) on organ dysfunction among patients with septic shock and AKI. Patients were dichotomized into "early" (simplified RIFLE Risk) or "late" (simplified RIFLE Injury or Failure) CRRT initiation. Patients with chronic kidney disease stage 5 or those on long-term dialysis were excluded. Organ dysfunction was quantified by Sequential Organ Failure Assessment (SOFA) score. From January 2008 to June 2011, 120 patients fulfilled the inclusion criteria. Thirty-one (26%) underwent "early" while 89 (74%) had "late" CRRT. No significant difference was noted between groups on improvement of total SOFA/non-renal SOFA score or noradrenaline equivalent in the first 24 and 48 h after CRRT initiation. Dialysis requirement and mortality (at 28 days, 3 months and 6 months) did not differ. In conclusion, improvement of non-renal SOFA score 48 h after CRRT correlated with SOFA score on CRRT initiation (P = 0.040) and APACHE IV risk of death (P = 0.000), but not estimated glomerular filtration rate on CRRT initiation (P = 0.377). Improvement of non-renal SOFA score correlated with SOFA score on CRRT initiation and APACHE IV risk of death. However, this retrospective review cannot identify any significant clinical benefit of early CRRT initiation in patients presenting with septic shock and AKI.
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Injúria Renal Aguda/terapia , Terapia de Substituição Renal/métodos , Choque Séptico/terapia , APACHE , Injúria Renal Aguda/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Diálise Renal/métodos , Estudos Retrospectivos , Choque Séptico/complicações , Fatores de TempoRESUMO
Generalized anxiety disorder (GAD) is understudied in Asian communities. There were 3,304 Chinese subjects (aged 15-60 years) randomly drawn from the general population of Hong Kong and successfully interviewed. The participation rate was 65.8%. The six-month prevalence of DSM-IV GAD was 4.1%. Over half of the GAD subjects reported palpitations and bowel symptoms. Comorbid depressive mood (65%) and substance use (35%) were common. Forty-one percent of GAD subjects sought help, usually from general practitioners who prescribed tranquilizers after negative physical investigations. Telephone-based surveys have limitations but provide an affordable and destigmatizing alternative to face-to-face surveys for communities with limited mental health resources.