Mental health symptoms in children and adolescents during COVID-19 in Australia

OBJECTIVE: COVID-19 has led to disruptions to the lives of Australian families through social distancing, school closures, a temporary move to home-based online learning, and effective lockdown. Understanding the effects on child and adolescent mental health is important to inform policies to support communities as they continue to face the pandemic and future crises. This paper sought to report on mental health symptoms in Australian children and adolescents during the initial stages of the pandemic (May to November 2020) and to examine their association with child/family characteristics and exposure to the broad COVID-19 environment. METHODS: An online baseline survey was completed by 1327 parents and carers of Australian children aged 4 to 17 years. Parents/carers reported on their child’s mental health using five measures, including emotional symptoms, conduct problems, hyperactivity/inattention, anxiety symptoms and depressive symptoms. Child/family characteristics and COVID-related variables were measured. RESULTS: Overall, 30.5%, 26.3% and 9.5% of our sample scored in the high to very high range for emotional symptoms, conduct problems and hyperactivity/inattention, respectively. Similarly, 20.2% and 20.4% of our sample scored in the clinical range for anxiety symptoms and depressive symptoms, respectively. A child’s pre-existing mental health diagnosis, neurodevelopmental condition and chronic illness significantly predicted parent-reported child and adolescent mental health symptoms. Parental mental health symptoms, having a close contact with COVID-19 and applying for government financial assistance during COVID-19, were significantly associated with child and adolescent mental health symptoms. CONCLUSION: Our findings show that Australian children and adolescents experienced considerable levels of mental health symptoms during the initial phase of COVID-19. This highlights the need for targeted and effective support for affected youth, particularly for those with pre-existing vulnerabilities

Influence of ischemic core muscle fibers on surface depolarization potentials in superfused cardiac tissue preparations: a simulation study

Thin-walled cardiac tissue samples superfused with oxygenated solutions are widely used in experimental studies. However, due to decreased oxygen supply and insufficient wash out of waste products in the inner layers of such preparations, electrophysiological functions could be compromised. Although the cascade of events triggered by cutting off perfusion is well known, it remains unclear as to which degree electrophysiological function in viable surface layers is affected by pathological processes occurring in adjacent tissue. Using a 3D numerical bidomain model, we aim to quantify the impact of superfusion-induced heterogeneities occurring in the depth of the tissue on impulse propagation in superficial layers. Simulations demonstrated that both the pattern of activation as well as the distribution of extracellular potentials close to the surface remain essentially unchanged. This was true also for the electrophysiological properties of cells in the surface layer, where most relevant depolarization parameters varied by less than 5.5 %. The main observed effect on the surface was related to action potential duration that shortened noticeably by 53 % as hypoxia deteriorated. Despite the known limitations of such experimental methods, we conclude that superfusion is adequate for studying impulse propagation and depolarization whereas repolarization studies should consider the influence of pathological processes taking place at the core of tissue sample

Automatic Filtering and Substantiation of Drug Safety Signals

Drug safety issues pose serious health threats to the population and constitute a major cause of mortality worldwide. Due to the prominent implications to both public health and the pharmaceutical industry, it is of great importance to unravel the molecular mechanisms by which an adverse drug reaction can be potentially elicited. These mechanisms can be investigated by placing the pharmaco-epidemiologically detected adverse drug reaction in an information-rich context and by exploiting all currently available biomedical knowledge to substantiate it. We present a computational framework for the biological annotation of potential adverse drug reactions. First, the proposed framework investigates previous evidences on the drug-event association in the context of biomedical literature (signal filtering). Then, it seeks to provide a biological explanation (signal substantiation) by exploring mechanistic connections that might explain why a drug produces a specific adverse reaction. The mechanistic connections include the activity of the drug, related compounds and drug metabolites on protein targets, the association of protein targets to clinical events, and the annotation of proteins (both protein targets and proteins associated with clinical events) to biological pathways. Hence, the workflows for signal filtering and substantiation integrate modules for literature and database mining, in silico drug-target profiling, and analyses based on gene-disease networks and biological pathways. Application examples of these workflows carried out on selected cases of drug safety signals are discussed. The methodology and workflows presented offer a novel approach to explore the molecular mechanisms underlying adverse drug reactions

Atrial arrhythmogenicity of KCNJ2 mutations in short QT syndrome: Insights from virtual human atria

Gain-of-function mutations in KCNJ2-encoded Kir2.1 channels underlie variant 3 (SQT3) of the short QT syndrome, which is associated with atrial fibrillation (AF). Using biophysically-detailed human atria computer models, this study investigated the mechanistic link between SQT3 mutations and atrial arrhythmogenesis, and potential ion channel targets for treatment of SQT3. A contemporary model of the human atrial action potential (AP) was modified to recapitulate functional changes in IK1 due to heterozygous and homozygous forms of the D172N and E299V Kir2.1 mutations. Wild-type (WT) and mutant formulations were incorporated into multi-scale homogeneous and heterogeneous tissue models. Effects of mutations on AP duration (APD), conduction velocity (CV), effective refractory period (ERP), tissue excitation threshold and their rate-dependence, as well as the wavelength of re-entry (WL) were quantified. The D172N and E299V Kir2.1 mutations produced distinct effects on IK1 and APD shortening. Both mutations decreased WL for re-entry through a reduction in ERP and CV. Stability of re-entrant excitation waves in 2D and 3D tissue models was mediated by changes to tissue excitability and dispersion of APD in mutation conditions. Combined block of IK1 and IKr was effective in terminating re-entry associated with heterozygous D172N conditions, whereas IKr block alone may be a safer alternative for the E299V mutation. Combined inhibition of IKr and IKur produced a synergistic anti-arrhythmic effect in both forms of SQT3. In conclusion, this study provides mechanistic insights into atrial proarrhythmia with SQT3 Kir2.1 mutations and highlights possible pharmacological strategies for management of SQT3-linked AF

Ventricular Dysrhythmias Associated with Poisoning and Drug Overdose: A 10-Year Review of Statewide Poison Control Center Data from California

Background: Ventricular dysrhythmias are a serious consequence associated with drug overdose and chemical poisoning. The risk factors for the type of ventricular dysrhythmia and the outcomes by drug class are not well documented. Objective: The aim of this study was to determine the most common drugs and chemicals associated with ventricular dysrhythmias and their outcomes. Methods: We reviewed all human exposures reported to a statewide poison control system between 2002 and 2011 that had a documented ventricular dysrhythmia. Cases were differentiated into two groups by type of arrhythmia: (1) ventricular fibrillation and/or tachycardia (VT/VF); and (2) torsade de pointes (TdP). Results: Among the 300 potential cases identified, 148 cases met the inclusion criteria. Of these, 132 cases (89 %) experienced an episode of VT or VF, while the remaining 16 cases (11 %) had an episode of TdP. The most commonly involved therapeutic classes of drugs associated with VT/VF were antidepressants (33/132, 25 %), stimulants (33/132, 25 %), and diphenhydramine (16/132, 12.1 %). Those associated with TdP were antidepressants (4/16, 25 %), methadone (4/16, 25 %), and antiarrhythmics (3/16, 18.75 %). Drug exposures with the greatest risk of death in association with VT/VF were antidepressant exposure [odds ratio (OR) 1.71; 95 % confidence interval (CI) 0.705–4.181] and antiarrhythmic exposure (OR 1.75; 95 % CI 0.304–10.05), but neither association was statistically significant. Drug exposures with a statistically significant risk for TdP included methadone and antiarrhythmic drugs. Conclusions: Antidepressants and stimulants were the most common drugs associated with ventricular dysrhythmias. Patients with suspected poisonings by medications with a high risk of ventricular dysrhythmia warrant prompt ECG monitoring

Parent-child interactions in children with asthma and anxiety

© 2017 Elsevier Ltd Anxiety disorders are highly prevalent in children with asthma yet very little is known about the parenting factors that may underlie this relationship. The aim of the current study was to examine observed parenting behaviours – involvement and negativity - associated with asthma and anxiety in children using the tangram task and the Five Minute Speech Sample (FMSS). Eighty-nine parent-child dyads were included across four groups of children (8–13 years old): asthma and anxiety, anxiety only, asthma only and healthy controls. Overall, results from both tasks showed that parenting behaviours of children with and without asthma did not differ significantly. Results from a subcomponent of the FMSS indicated that parents of children with asthma were more overprotective, or self-sacrificing, or non-objective than parents of children without asthma, and this difference was greater in the non-anxious groups. The results suggest that some parenting strategies developed for parents of children with anxiety may be useful for parents of children with asthma and anxiety (e.g. strategies targeting involvement), however, others may not be necessary (e.g. those targeting negativity)

Benefits and Pitfalls of the Perceval Sutureless Bioprosthesis

Objective: To highlight the main target points covered by clinical studies on the Perceval sutureless valve for surgical aortic valve replacement (SAVR) and raise a point of discussion for further expansion of its use when compared with stented bioprostheses (SB) and transcatheter aortic valve replacement (TAVR).Methods: We reviewed clinical trials and retrospective studies published up to date and compared the outcomes in terms of mortality, myocardial infarction (MI) stroke, paravalvular leak (PVL), permanent pacemaker implantation (PPI), bleeding and long-term outcomes.Results: Clinical studies showed that 30-day mortality ranged from 0-4% for Perceval and 2.9-7% for TAVR. The incidence of PVL (Perceval 1.9-19.4 vs. TAVR 9-53.5%), PPI (Perceval 2-11.2 vs. TAVR 4.9-25.5%), stroke (Perceval 0 vs. TAVR 0-2.8%), MI (Perceval 0 vs. TAVR 0-3.5%), were all higher in the TAVR group. Compared to other SB, mortality ranged from 0-6.4% for Perceval and 0-5.9% for SB. The incidence of PVR (Perceval 1-19.4 vs. SB 0-1%), PPI (Perceval 2-10.7 vs. SB 1.8-8.5%), stroke (Perceval 0-3.7 vs. SB 1.8-7.3%) and MI (Perceval 0-7.8 vs. SB 0-4.3%) were comparable among the groups. In patients with a bicuspid aortic valve, mortality rate was (0-4%) and PVL incidence was (0-2.3%). However, there was a high incidence of PPI (0-20%), and stroke (0-8%). Long-term survival ranged between 96.7-98.6%.Conclusions: The Perceval bioprosthesis has proved to be a reliable prosthesis for surgical aortic valve replacement due to its implantation speed, the reduced cardiopulmonary bypass time, the reduced aortic cross-clamp time and the shorter intensive care unit and hospital length of stay

Benefits and Pitfalls of the Perceval Sutureless Bioprosthesis

Objective: To highlight the main target points covered by clinical studies on the Perceval sutureless valve for surgical aortic valve replacement (SAVR) and raise a point of discussion for further expansion of its use when compared with stented bioprostheses (SB) and transcatheter aortic valve replacement (TAVR). Methods: We reviewed clinical trials and retrospective studies published up to date and compared the outcomes in terms of mortality, myocardial infarction (MI) stroke, paravalvular leak (PVL), permanent pacemaker implantation (PPI), bleeding and long-term outcomes. Results: Clinical studies showed that 30-day mortality ranged from 0–4% for Perceval and 2.9–7% for TAVR. The incidence of PVL (Perceval 1.9–19.4 vs. TAVR 9–53.5%), PPI (Perceval 2–11.2 vs. TAVR 4.9–25.5%), stroke (Perceval 0 vs. TAVR 0–2.8%), MI (Perceval 0 vs. TAVR 0–3.5%), were all higher in the TAVR group. Compared to other SB, mortality ranged from 0–6.4% for Perceval and 0–5.9% for SB. The incidence of PVR (Perceval 1–19.4 vs. SB 0–1%), PPI (Perceval 2–10.7 vs. SB 1.8–8.5%), stroke (Perceval 0–3.7 vs. SB 1.8–7.3%) and MI (Perceval 0–7.8 vs. SB 0–4.3%) were comparable among the groups. In patients with a bicuspid aortic valve, mortality rate was (0–4%) and PVL incidence was (0–2.3%). However, there was a high incidence of PPI (0–20%), and stroke (0–8%). Long-term survival ranged between 96.7–98.6%. Conclusions: The Perceval bioprosthesis has proved to be a reliable prosthesis for surgical aortic valve replacement due to its implantation speed, the reduced cardiopulmonary bypass time, the reduced aortic cross-clamp time and the shorter intensive care unit and hospital length of stay