The objective of this study was to evaluate the clinical safety of intravenous gadolinium-based contrast media used in patients who underwent MRI at a single institution. Acute adverse reactions to ...intravenous gadolinium-based contrast media used for MRI at the Princess Margaret Hospital, Hong Kong, SAR, from January 1999 to November 2004 were recorded in an incidence log book. The medical records of patients' demographics were retrospectively reviewed and the nature, frequency and severity of the adverse reactions were investigated and documented. The incidence of acute adverse reactions to intravenous gadolinium-based contrast media was 0.48% (45 patients with 46 adverse reactions). The severity of these adverse reactions were 96% mild, 2% moderate (one patient developed shortness of breath that required oxygen supplementation and intravenous steroidal management) and 2% severe (one patient developed an anaphylactoid reaction, but successfully recovered through timely resuscitation). No patients were recorded as having contrast extravasation and none died as a result of any adverse reaction. Among the 45 patients who developed adverse reactions, three patients (6.7%) had prior adverse reactions to iodinated contrast media, three (6.7%) had prior reactions to a different gadolinium-based contrast agent, one (2%) had asthma and nine (20%) had a history of drug/food allergy. Overall, 41% of the adverse reactions were not documented in the final MRI report or the clinical medical records. Gadolinium-based contrast media are safe and well tolerated by the vast majority of patients. In our study, the adverse reaction rate (0.48%) and the incidence of severe anaphylactoid reaction (0.01%) concur with those reported in the literature. Although most of the symptoms are mild and transient, these adverse reactions must be accurately documented and managed.
The caliber of the retinal vessels has been shown to be associated with stroke events. However, the consistency and magnitude of association, and the changes in predicted risk independent of ...traditional risk factors, are unclear. To determine the association between retinal vessel caliber and the risk of stroke events, the investigators combined individual data from 20,798 people, who were free of stroke at baseline, in 6 cohort studies identified from a search of the Medline (National Library of Medicine, Bethesda, Maryland) and EMBASE (Elsevier B.V., Amsterdam, the Netherlands) databases. During follow-up of 5–12 years, 945 (4.5%) incident stroke events were recorded. Wider retinal venular caliber predicted stroke (pooled hazard ratio = 1.15, 95% confidence interval: 1.05, 1.25 per 20-μm increase in caliber), but the caliber of retinal arterioles was not associated with stroke (pooled hazard ratio = 1.00, 95% confidence interval: 0.92, 1.08). There was weak evidence of heterogeneity in the hazard ratio for retinal venular caliber, which may be attributable to differences in follow-up strategies across studies. Inclusion of retinal venular caliber in prediction models containing traditional stroke risk factors reassigned 10.1% of people at intermediate risk into different, mostly lower, risk categories.
Children with special educational needs (SEN) are more vulnerable during the COVID-19 pandemic with risk of poor mental wellbeing and child maltreatment.
To examine the impact of COVID-19 on the ...mental health of children with SEN and their maltreatment risk.
417 children with SEN studying at special schools and 25,427 children with typical development (TD) studying at mainstream schools completed an online survey in April 2020 in Hong Kong during school closures due to COVID-19.
Emotional/behavioural difficulties, quality of life and parental stress of children with SEN were compared with typically developed children using mixed effect model. Linear regression analyses were performed to explore factors associated with child emotional/behavioural difficulties and parental stress during the pandemic. Chi-square test was performed to detect the differences in maltreatment risk before and during COVID-19.
Children with SEN had significantly poorer overall quality of life (68.05 vs 80.65, p < 0.01). 23.5% of children had at least one episode of severe physical assault and 1.9% experienced very severe physical assault during COVID-19. Rates of physical assault increased significantly (59.8% vs. 71.2% p < 0.001) while children with mental disorders had increased risk of severe physical assault comparing to those without mental disorders (RR = 1.58, ꭓ2 = 5.19 p = 0.023).
Children with SEN had poorer mental health than typically developed children during the COVID-19 pandemic. Maltreatment risk for children with SEN is higher in comparison to pre-COVID-19 era. Surveillance of child maltreatment, continuity of medical and rehabilitation care to support children with SEN are essential during a disease pandemic.
•Child maltreatment risk increased in children with SEN during the COVID-19 pandemic.•Over 80% of children with SEN were victims of psychological aggression.•Over 20% of children with SEN had at least one episode of severe physical assault.•Children with mental disorders were vulnerable to severe physical abuse.•Higher parental stress led to higher risk of maltreatment for children with SEN.
According to the dual stream model of auditory language processing, the dorsal stream is responsible for mapping sound to articulation and the ventral stream plays the role of mapping sound to ...meaning. Most researchers agree that the arcuate fasciculus (AF) is the neuroanatomical correlate of the dorsal steam; however, less is known about what constitutes the ventral one. Nevertheless, two hypotheses exist: one suggests that the segment of the AF that terminates in middle temporal gyrus corresponds to the ventral stream, and the other suggests that it is the extreme capsule that underlies this sound-to-meaning pathway. The goal of this study was to evaluate these two competing hypotheses. We trained participants with a sound-to-word learning paradigm in which they learned to use a foreign phonetic contrast for signaling word meaning. Using diffusion tensor imaging, a brain-imaging tool to investigate white matter connectivity in humans, we found that fractional anisotropy in the left parietal-temporal region positively correlated with the performance in sound-to-word learning. In addition, fiber tracking revealed a ventral pathway, composed of the extreme capsule and the inferior longitudinal fasciculus, that mediated auditory comprehension. Our findings provide converging evidence supporting the importance of the ventral steam, an extreme capsule system, in the frontal-temporal language network. Implications for current models of speech processing are also discussed.
Retinal microvasculature changes are associated with vascular events including stroke in healthy populations. It is not known whether retinal microvascular changes predict recurrent vascular events ...after ischemic stroke. We examined the relationship between retinal microvascular signs and subsequent vascular events in a prospective cohort of 652 acute ischemic stroke patients admitted to a tertiary hospital in Singapore from 2005 to 2007.
Retinal photographs taken within 1 week of stroke onset were assessed in a masked manner for quantitative and qualitative measures. Follow-up data over 2-4 years were obtained by standardized telephone interview and then were verified from medical records. Predictors of recurrent vascular events (cerebrovascular, coronary, vascular death, and composite vascular events) were determined using Cox regression models.
Follow-up data over a median of 29 months were obtained for 89% (652 patients) of the cohort. After adjustment for covariates including traditional risk factors and index stroke etiology, patients with severe arteriovenous nicking (AVN) were more likely to have a recurrent cerebrovascular event (hazard ratio HR 2.28, 95% confidence interval CI 1.20-4.33) compared with those without AVN. Patients with severe focal arteriolar narrowing (FAN) were more likely to have a recurrent cerebrovascular event (HR 2.75, 95% CI 1.14-6.63) or subsequent composite vascular event (HR 2.77, 95% CI 1.31-5.86) compared to those without FAN.
Retinal microvascular changes predicted subsequent vascular events after ischemic stroke, independent of traditional risk factors and stroke subtype. Thus, retinal imaging has a potential role in predicting the risk of recurrent vascular events after ischemic stroke and in understanding novel vascular risk factors.
Ponatinib is a potent oral tyrosine kinase inhibitor of unmutated and mutated BCR-ABL, including BCR-ABL with the tyrosine kinase inhibitor-refractory threonine-to-isoleucine mutation at position 315 ...(T315I). We conducted a phase 2 trial of ponatinib in patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL).
We enrolled 449 heavily pretreated patients who had CML or Ph-positive ALL with resistance to or unacceptable side effects from dasatinib or nilotinib or who had the BCR-ABL T315I mutation. Ponatinib was administered at an initial dose of 45 mg once daily. The median follow-up was 15 months.
Among 267 patients with chronic-phase CML, 56% had a major cytogenetic response (51% of patients with resistance to or unacceptable side effects from dasatinib or nilotinib and 70% of patients with the T315I mutation), 46% had a complete cytogenetic response (40% and 66% in the two subgroups, respectively), and 34% had a major molecular response (27% and 56% in the two subgroups, respectively). Responses were observed regardless of the baseline BCR-ABL kinase domain mutation status and were durable; the estimated rate of a sustained major cytogenetic response of at least 12 months was 91%. No single BCR-ABL mutation conferring resistance to ponatinib was detected. Among 83 patients with accelerated-phase CML, 55% had a major hematologic response and 39% had a major cytogenetic response. Among 62 patients with blast-phase CML, 31% had a major hematologic response and 23% had a major cytogenetic response. Among 32 patients with Ph-positive ALL, 41% had a major hematologic response and 47% had a major cytogenetic response. Common adverse events were thrombocytopenia (in 37% of patients), rash (in 34%), dry skin (in 32%), and abdominal pain (in 22%). Serious arterial thrombotic events were observed in 9% of patients; these events were considered to be treatment-related in 3%. A total of 12% of patients discontinued treatment because of an adverse event.
Ponatinib had significant antileukemic activity across categories of disease stage and mutation status. (Funded by Ariad Pharmaceuticals and others; PACE ClinicalTrials.gov number, NCT01207440 .).
Summary
Background
Patients with non‐alcoholic steatohepatitis (NASH) have increased intestinal permeability and small intestine bacterial overgrowth.
Aims
To test the hypothesis that endotoxemia is ...associated with non‐alcoholic fatty liver disease (NAFLD) in the general population, and to study dietary factors associated with endotoxemia.
Methods
Nine hundred and twenty adults were randomly selected from the government's census database and underwent proton‐magnetic resonance spectroscopy to assess hepatic steatosis. Endotoxemia was assessed using the limulus amebocyte lysate, lipopolysaccharide‐binding protein (LBP) and EndoCab immunoglobulin G (IgG) assays.
Results
Two hundred and sixty‐three (29%) subjects had NAFLD. Subjects with NAFLD had slightly higher LBP (P < 0.001) and EndoCab IgG (P = 0.013) levels. EndoCab IgG remained an independent factor associated with intrahepatic triglycerides after adjusting for other metabolic factors. Among 565 subjects without NAFLD at baseline who had repeated assessment at a median interval of 47 months, 78 (13.8%) developed incident NAFLD and they also had higher LBP (P = 0.016). Moreover, LBP was associated with insulin resistance and dyslipidaemia, and modestly increased with the cytokeratin‐18 fragment level but not liver stiffness measurement by transient elastography. Although total energy consumption and individual macronutrients were not associated with endotoxemia, current drinkers (mostly <140 g/week) had lower endotoxin, EndoCab IgG and fetuin‐A levels than nondrinkers.
Conclusions
Endotoxin markers are associated with NAFLD in the general population, but do not have a major effect on NASH and fibrosis. People with modest alcohol consumption have lower serum endotoxin. This may partly explain the lower risk of NAFLD and NASH in modest drinkers in previous observational studies.
Background and Aims: Severe acute respiratory syndrome (SARS) is a virulent viral infection that affects a number of organs and systems. This study examined if SARS may result in cardiovascular ...complications. Methods and Results: 121 patients (37.5 (SD13.2) years, 36% male) diagnosed to have SARS were assessed continuously for blood pressure, pulse, and temperature during their stay in hopsital. Hypotension occurred in 61 (50.4%) patients in hospital, and was found in 28.1%, 21.5%, and 14.8% of patients during the first, second, and third week, respectively. Only one patient who had transient echocardiographic evidence of impaired left ventricular systolic function required temporary inotropic support. Tachycardia was present in 87 (71.9%) patients, and was found in 62.8%, 45.4%, and 35.5% of patients from the first to third week. It occurred independent of hypotension, and could not be explained by the presence of fever. Tachycardia was also present in 38.8% of patients at follow up. Bradycardia only occurred in 18 (14.9%) patients as a transient event. Reversible cardiomegaly was reported in 13 (10.7%) patients, but without clinical evidence of heart failure. Transient atrial fibrillation was present in one patient. Corticosteroid therapy was weakly associated with tachycardia during the second (χ2 = 3.99, p = 0.046) and third week (χ2 = 6.53, p = 0.01), although it could not explain tachycardia during follow up. Conclusions: In patients with SARS, cardiovascular complications including hypotension and tachycardia were common but usually self limiting. Bradycardia and cardiomegaly were less common, while cardiac arrhythmia was rare. However, only tachycardia persisted even when corticosteroid therapy was withdrawn.
Abstract
Aims
Brief measurements of the subjective experience of stress with good predictive capability are important in a range of community mental health and research settings. The potential for ...large-scale implementation of such a measure for screening may facilitate early risk detection and intervention opportunities. Few such measures however have been developed and validated in epidemiological and longitudinal community samples. We designed a new single-item measure of the subjective level of stress (SLS-1) and tested its validity and ability to predict long-term mental health outcomes of up to 12 months through two separate studies.
Methods
We first examined the content and face validity of the SLS-1 with a panel consisting of mental health experts and laypersons. Two studies were conducted to examine its validity and predictive utility. In study 1, we tested the convergent and divergent validity as well as incremental validity of the SLS-1 in a large epidemiological sample of young people in Hong Kong (
n
= 1445). In study 2, in a consecutively recruited longitudinal community sample of young people (
n
= 258), we first performed the same procedures as in study 1 to ensure replicability of the findings. We then examined in this longitudinal sample the utility of the SLS-1 in predicting long-term depressive, anxiety and stress outcomes assessed at 3 months and 6 months (
n
= 182) and at 12 months (
n
= 84).
Results
The SLS-1 demonstrated good content and face validity. Findings from the two studies showed that SLS-1 was moderately to strongly correlated with a range of mental health outcomes, including depressive, anxiety, stress and distress symptoms. We also demonstrated its ability to explain the variance explained in symptoms beyond other known personal and psychological factors. Using the longitudinal sample in study 2, we further showed the significant predictive capability of the SLS-1 for long-term symptom outcomes for up to 12 months even when accounting for demographic characteristics.
Conclusions
The findings altogether support the validity and predictive utility of the SLS-1 as a brief measure of stress with strong indications of both concurrent and long-term mental health outcomes. Given the value of brief measures of mental health risks at a population level, the SLS-1 may have potential for use as an early screening tool to inform early preventative intervention work.
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