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1.
Heart Lung Circ ; 33(6): 773-827, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38749800

RESUMO

Transthoracic echocardiography (TTE) is the most widely available and utilised imaging modality for the screening, diagnosis, and serial monitoring of all abnormalities related to cardiac structure or function. The primary objectives of this document are to provide (1) a guiding framework for treating clinicians of the acceptable indications for the initial and serial TTE assessments of the commonly encountered cardiovascular conditions in adults, and (2) the minimum required standard for TTE examinations and reporting for imaging service providers. The main areas covered within this Position Statement pertain to the TTE assessment of the left and right ventricles, valvular heart diseases, pericardial diseases, aortic diseases, infective endocarditis, cardiac masses, pulmonary hypertension, and cardiovascular diseases associated with cancer treatments or cardio-oncology. Facilitating the optimal use and performance of high quality TTEs will prevent the over or under-utilisation of this resource and unnecessary downstream testing due to suboptimal or incomplete studies.


Assuntos
Ecocardiografia , Doenças das Valvas Cardíacas , Humanos , Ecocardiografia/métodos , Ecocardiografia/normas , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/diagnóstico por imagem , Adulto , Sociedades Médicas , Cardiologia/métodos , Cardiologia/normas
2.
J Cardiovasc Electrophysiol ; 34(5): 1286-1295, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37186322

RESUMO

BACKGROUND: Intravenous magnesium (IV Mg), a commonly utilized therapeutic agent in the management of atrial fibrillation (AF) with rapid ventricular response, is thought to exert its influence via its effect on cellular automaticity and prolongation of atrial and atrioventricular nodal refractoriness thus reducing ventricular rate. We sought to undertake a systematic review and meta-analysis of the effectiveness of IV Mg versus placebo in addition to standard pharmacotherapy in the rate and rhythm control of AF in the nonpostoperative patient cohort given that randomized control trials (RCTs) have shown conflicting results. METHODS: Randomized controlled trials comparing IV Mg versus placebo in addition to standard of care were identified via electronic database searches. Nine RCTs were returned with a total of 1048 patients. Primary efficacy endpoints were study-defined rate control and rhythm control/reversion to sinus rhythm. The secondary endpoint was patient experienced side effects. RESULTS: Our analysis found IV Mg in addition to standard care was successful in achieving rate control (odd ratio [OR] 1.87, 95% confidence interval [CI] 1.13-3.11, p = .02) and rhythm control (OR 1.45, 95% CI 1.04-2.03, p = .03). Although not well reported among studies, there was no significant difference between groups regarding the likelihood of experiencing side effects. CONCLUSIONS: IV Mg, in addition to standard-of-care pharmacotherapy, increases the rates of successful rate and rhythm control in nonpostoperative patients with AF with rapid ventricular response and is well tolerated.


Assuntos
Fibrilação Atrial , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/induzido quimicamente , Antiarrítmicos/uso terapêutico , Magnésio/efeitos adversos , Administração Intravenosa , Ventrículos do Coração
3.
PLoS Comput Biol ; 17(11): e1009477, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34793435

RESUMO

Over the past decade, biomarker discovery has become a key goal in psychiatry to aid in the more reliable diagnosis and prognosis of heterogeneous psychiatric conditions and the development of tailored therapies. Nevertheless, the prevailing statistical approach is still the mean group comparison between "cases" and "controls," which tends to ignore within-group variability. In this educational article, we used empirical data simulations to investigate how effect size, sample size, and the shape of distributions impact the interpretation of mean group differences for biomarker discovery. We then applied these statistical criteria to evaluate biomarker discovery in one area of psychiatric research-autism research. Across the most influential areas of autism research, effect size estimates ranged from small (d = 0.21, anatomical structure) to medium (d = 0.36 electrophysiology, d = 0.5, eye-tracking) to large (d = 1.1 theory of mind). We show that in normal distributions, this translates to approximately 45% to 63% of cases performing within 1 standard deviation (SD) of the typical range, i.e., they do not have a deficit/atypicality in a statistical sense. For a measure to have diagnostic utility as defined by 80% sensitivity and 80% specificity, Cohen's d of 1.66 is required, with still 40% of cases falling within 1 SD. However, in both normal and nonnormal distributions, 1 (skewness) or 2 (platykurtic, bimodal) biologically plausible subgroups may exist despite small or even nonsignificant mean group differences. This conclusion drastically contrasts the way mean group differences are frequently reported. Over 95% of studies omitted the "on average" when summarising their findings in their abstracts ("autistic people have deficits in X"), which can be misleading as it implies that the group-level difference applies to all individuals in that group. We outline practical approaches and steps for researchers to explore mean group comparisons for the discovery of stratification biomarkers.


Assuntos
Biomarcadores/análise , Biologia Computacional/educação , Transtorno Autístico/diagnóstico , Estudos de Casos e Controles , Biologia Computacional/estatística & dados numéricos , Simulação por Computador , Humanos , Individualidade , Transtornos Mentais/diagnóstico , Transtornos do Neurodesenvolvimento/diagnóstico , Neuropsiquiatria/estatística & dados numéricos , Neuropsicologia/estatística & dados numéricos , Distribuição Normal , Tamanho da Amostra
5.
Cereb Cortex ; 30(10): 5204-5217, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32427284

RESUMO

Two important theories in cognitive neuroscience are predictive coding (PC) and the global workspace (GW) theory. A key research task is to understand how these two theories relate to one another, and particularly, how the brain transitions from a predictive early state to the eventual engagement of a brain-scale state (the GW). To address this question, we present a source-localization of EEG responses evoked by the local-global task-an experimental paradigm that engages a predictive hierarchy, which encompasses the GW. The results of our source reconstruction suggest three phases of processing. The first phase involves the sensory (here auditory) regions of the superior temporal lobe and predicts sensory regularities over a short timeframe (as per the local effect). The third phase is brain-scale, involving inferior frontal, as well as inferior and superior parietal regions, consistent with a global neuronal workspace (GNW; as per the global effect). Crucially, our analysis suggests that there is an intermediate (second) phase, involving modulatory interactions between inferior frontal and superior temporal regions. Furthermore, sedation with propofol reduces modulatory interactions in the second phase. This selective effect is consistent with a PC explanation of sedation, with propofol acting on descending predictions of the precision of prediction errors; thereby constraining access to the GNW.


Assuntos
Encéfalo/fisiologia , Estado de Consciência/fisiologia , Potenciais Evocados Auditivos/fisiologia , Aceleração , Adulto , Compreensão/fisiologia , Humanos , Masculino , Lobo Parietal/fisiologia , Lobo Temporal/fisiologia , Adulto Jovem
6.
Heart Lung Circ ; 29(9): 1347-1355, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32359870

RESUMO

BACKGROUND: Patients admitted to hospital with acute heart failure (AHF) are at increased risk of readmission and mortality post-discharge. The aim of the study was to examine health service utilisation within 30 days post-discharge from an AHF hospitalisation. METHODS: This was a prospective, observational, non-randomised study of consecutive patients hospitalised with acute HF to one of 16 Victorian hospitals over a 30-day period each year and followed up for 30 days post-discharge. The project was conducted annually over three consecutive years from 2015 to 2017. RESULTS: Of the 1,197 patients, 56.3% were male with an average age of 77±13.23 years. Over half of the patients (711, 62.5%) were referred to an outpatient clinic and a third (391, 34.4%) to a HF disease management program. In-hospital mortality was 5.1% with 30 day-mortality of 9% and readmission rate of 24.4%. Patients who experienced a subsequent readmission less than 10 days post-discharge and between 11 and 20 days post-discharge had a five- to six-fold increase in risk of mortality (adjusted OR 5.02, 95% CI 2.11-11.97; OR 6.45, 95% CI 2.69-15.42; respectively) compared to patients who were not readmitted to hospital. An outpatient appointment within 30 days post-discharge significantly reduced the risk of 30-day mortality by 81% (95% CI 0.09-0.43). CONCLUSION: Patients admitted to hospital with AHF who experience a subsequent readmission within 20 days post-discharge are at increased risk of dying. However, early follow-up post-discharge may reduce this risk. Early post-discharge follow-up is vital to address this vulnerable period after a HF admission.


Assuntos
Insuficiência Cardíaca/terapia , Pacientes Internados , Readmissão do Paciente/tendências , Cuidado Transicional/organização & administração , Doença Aguda , Idoso , Feminino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Mortalidade Hospitalar/tendências , Humanos , Masculino , Morbidade/tendências , Estudos Prospectivos , Fatores de Risco , Volume Sistólico/fisiologia , Taxa de Sobrevida/tendências , Vitória/epidemiologia
7.
Heart Lung Circ ; 29(10): 1440-1448, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31843365

RESUMO

BACKGROUND: Bioresorbable scaffolds (BRS) are a novel technology in coronary intervention. However, recent trials demonstrate higher rates of device failure compared to contemporary drug-eluting stents. This study sought to utilise a clinical quality registry to assess the medium-term safety of the Abbott Absorb BRS (Abbott Vascular, Santa Clara, CA, USA), in an Australian context. METHODS: A prospective, observational study of 192 BRS percutaneous coronary interventions (PCI) compared to 31,773 non-BRS PCIs entered in the Victorian Cardiac Outcomes Registry from 2013 to 2017. The main outcome measure was patient-oriented composite endpoint (POCE) events comprising all-cause mortality, any myocardial infarction (MI), and any revascularisation. RESULTS: Bioresorbable scaffolds patients (mean age 61.6±10.5 years, 79% male) were younger, had less comorbidity, less prior PCI, fewer ST elevation myocardial infarction (STEMI) presentations, lower rates of multi-lesion disease and more adjuvant devices compared to non-BRS PCI (all p<0.01). All-cause mortality was 2.1%, myocardial infarction (MI) 2.1%, scaffold thrombosis 3.1% and any revascularisation 14.1% (mean follow-up 27.4±8.9 months). POCE events occurred in 11.5% at 1 year and 16.9% at 2 years, comparable to pooled-trial data. Multivariate predictors of POCE were >1 scaffold used (odds ratio [OR] 4.6, 95% confidence interval [CI] 1.9-11.4, p<0.01) and scaffold diameter ≤2.5 mm (OR 3.3, 95% CI 1.4-7.6, p=0.02). Over 95% guideline adherence was achieved in six of eight patient selection criteria and four of six device deployment criteria. CONCLUSION: In an Australian setting, BRS were used in non-complex patients. Most guidelines for use were adhered to and outcomes were comparable to pooled trial data. Clinical quality registries are effective in assessing novel treatments and technologies when potential safety concerns develop.


Assuntos
Implantes Absorvíveis , Intervenção Coronária Percutânea/normas , Melhoria de Qualidade , Sistema de Registros/estatística & dados numéricos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Alicerces Teciduais , Idoso , Austrália/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Desenho de Prótese , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Fatores de Tempo , Resultado do Tratamento
8.
J Electrocardiol ; 52: 47-52, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30476638

RESUMO

INTRODUCTION: Several ECG markers are postulated to represent underlying atrial remodelling and have been associated with ischemic stroke. P-wave terminal force in lead V1 (PTFV1) is one such marker. We examined the factors that contribute to the reliability of PTFV1 and its association with ischemic stroke. MATERIAL AND METHODS: Four hundred and thirty-five patients that presented with an ischemic stroke or transient ischemic attack (TIA) were identified through a prospectively maintained multi-site institutional stroke database. Control group consisted of age matched patients without prior history of an ischemic stroke or TIA. All patients underwent a 12-lead ECG and 24-hour Holter monitoring during the study period to exclude atrial fibrillation. RESULTS: Morphology consistent with PTFV1 occurred commonly in both the stroke/TIA and control groups. There was no significant difference in the median PTFV1 value between the stroke 3.96 mV ms [Interquartile range (IQR) 2.78-5.58] and control 4.23 mV ms [IQR 2.91-5.57] groups. Measurements of PTFV1 demonstrated excellent intra-observer reliability on assessment of the same P-wave (Intra class correlation (ICC) 0.91, p < 0.001) with narrow limits of agreement 2.21 to -2.95 mV ms. A change in the P wave assessed led to a significant reduction in reliability (ICC 0.79, p < 0.001). Inter-observer, inter P-wave assessment demonstrated further reduction in reliability (ICC 0.68, p < 0.002) with wide limits of agreement 6.17 to -5.78 mV ms, indicating significant under and overestimation of PTFV1. CONCLUSION: The utility of PTFV1 as a clinical marker for ischemic stroke is limited by the reduction in reliability associated with inter-observer and inter P-wave measurements.


Assuntos
Remodelamento Atrial , Isquemia Encefálica/fisiopatologia , Eletrocardiografia , Ataque Isquêmico Transitório/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Idoso , Estudos de Casos e Controles , Eletrocardiografia Ambulatorial , Feminino , Humanos , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Risco
9.
Am Heart J ; 205: 149-153, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30195576

RESUMO

Despite the appeal of smartphone-based electrocardiograms (ECGs) for arrhythmia screening, a paucity of data exists on the accuracy of primary care physicians' and cardiologists' interpretation of tracings compared with the device's automated diagnosis. Using 408 ECGs in 51 patients, we demonstrate a variable accuracy in clinician interpretation of smartphone-based ECGs, with only cardiologists demonstrating satisfactory agreement when referenced against a 12-lead ECG. Combining the device automated diagnostic algorithm with cardiologist interpretation of only uninterpretable traces yielded excellent results and provides an efficient, cost-effective workflow for the utilization of a smartphone-based ECG in clinical practice.


Assuntos
Arritmias Cardíacas/diagnóstico , Cardiologistas/normas , Competência Clínica , Eletrocardiografia/métodos , Smartphone , Telemedicina/métodos , Humanos , Estudos Prospectivos , Curva ROC
10.
Conscious Cogn ; 63: 123-142, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30005277

RESUMO

While many studies have linked prediction errors and event related potentials at a single processing level, few consider how these responses interact across levels. In response, we present a factorial analysis of a multi-level oddball task - the local-global task - and we explore it when participants are sedated versus recovered. We found that the local and global levels in fact interact. This is of considerable current interest, since it has recently been argued that the MEEG response evoked by the global effect corresponds to a distinct processing mode that moves beyond predictive coding. This interaction suggests that the two processing modes are not distinct. Additionally, we observed that sedation modulates this interaction, suggesting that conscious awareness may not be completely restricted to a single (global) processing level.


Assuntos
Estado de Consciência , Estimulação Acústica , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Sedação Consciente , Estado de Consciência/efeitos dos fármacos , Estado de Consciência/fisiologia , Eletroencefalografia/efeitos dos fármacos , Potenciais Evocados Auditivos/efeitos dos fármacos , Potenciais Evocados Auditivos/fisiologia , Humanos , Hipnóticos e Sedativos/farmacologia , Propofol/farmacologia , Teoria Psicológica , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologia
11.
Intern Med J ; 48(5): 587-591, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29722189

RESUMO

The accuracy of photoplethysmography (PPG) for heart rate (HR) estimation in cardiac arrhythmia is unknown. PPG-HR was evaluated in 112 hospitalised inpatients (cardiac arrhythmias (n = 60), sinus rhythm (n = 52)) using a continuous electrocardiogram monitoring as a reference standard. Strong agreement was observed in sinus rhythm HR < 100 and atrial flutter (bias 1 beat), modest agreement in sinus tachycardia (bias 24 beats) and complete heart block (bias -6 beats) and weak agreement with significant HR underestimation was seen in atrial fibrillation (bias 23 beats). Routine utilisation of PPG for HR estimation may delay early recognition of clinical deterioration in certain arrhythmias and sinus tachycardia.


Assuntos
Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Frequência Cardíaca/fisiologia , Hospitalização , Fotopletismografia/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Eletrocardiografia/métodos , Eletrocardiografia/tendências , Feminino , Hospitalização/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Fotopletismografia/métodos , Fotopletismografia/tendências
12.
BMC Musculoskelet Disord ; 19(1): 238, 2018 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-30025540

RESUMO

BACKGROUND: To examine whether number of physical therapy (PT) visits or amount of use of an internet-based exercise training (IBET) program is associated with differential improvement in outcomes for participants with knee osteoarthritis (OA). METHODS: A secondary analysis was performed using data from participants in 2 arms of a randomized control trial for individuals with symptomatic knee OA: PT (N = 135) or IBET (N = 124). We examined associations of number of PT visits attended (up to 8) or number of days the IBET website was accessed during the initial 4-month study period with changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total, pain and function subscales, as well as a 2-min Step Test, at 4-month and 12-month follow-up. RESULTS: Participants with more PT visits experienced greater improvement in WOMAC total score (estimate per additional visit = - 1.18, CI 95% = - 1.91, 0.46, p <  0.001) and function subscore (estimate = - 0.80, CI 95% = - 1.33, - 0.28, p <  0.001) across follow-up periods. For WOMAC pain subscale, the association with number of PT visits varied significantly between 4- and 12-month follow-up, with a stronger relationship at 4-months. There was a non-significant trend for more PT visits to be associated with greater improvement in 2-min Step Test. More frequent use of the IBET website was not associated with greater improvement for any outcome, at either time point. CONCLUSION: Increased number of PT visits was associated with improved outcomes, and some of this benefit persisted 8 months after PT ended. This provides guidance for PT clinical practice and policies. TRIAL REGISTRATION: NCT02312713 , posted 9/25/2015.


Assuntos
Exercício Físico/fisiologia , Osteoartrite do Joelho/reabilitação , Participação do Paciente/tendências , Modalidades de Fisioterapia/tendências , Terapia Assistida por Computador/tendências , Idoso , Exercício Físico/psicologia , Feminino , Seguimentos , Humanos , Internet/tendências , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/psicologia , Participação do Paciente/métodos , Participação do Paciente/psicologia , Modalidades de Fisioterapia/psicologia , Autoeficácia , Terapia Assistida por Computador/métodos , Resultado do Tratamento
13.
Brain ; 136(Pt 5): 1488-507, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23587805

RESUMO

Tripeptidyl peptidase 1 (TPP1) deficiency causes CLN2 disease, late infantile (or classic late infantile neuronal ceroid lipofuscinosis), a paediatric neurodegenerative disease of autosomal recessive inheritance. Patients suffer from blindness, ataxia, epilepsy and cognitive defects, with MRI indicating widespread brain atrophy, and profound neuron loss is evident within the retina and brain. Currently there are no effective therapies for this disease, which causes premature death in adolescence. Zebrafish have been successfully used to model a range of neurological and behavioural abnormalities. The aim of this study was to characterize the pathological and functional consequences of Tpp1 deficiency in zebrafish and to correlate these with human CLN2 disease, thereby providing a platform for drug discovery. Our data show that homozygous tpp1(sa0011) mutant (tpp1(sa0011)(-/-)) zebrafish display a severe, progressive, early onset neurodegenerative phenotype, characterized by a significantly small retina, a small head and curved body. The mutant zebrafish have significantly reduced median survival with death occurring 5 days post-fertilization. As in human patients with CLN2 disease, mutant zebrafish display storage of subunit c of mitochondrial ATP-synthase, hypertrophic lysosomes as well as localized apoptotic cell death in the retina, optic tectum and cerebellum. Further neuropathological phenotypes of these mutants provide novel insights into mechanisms of pathogenesis in CLN2 disease. Secondary neurogenesis in the retina, optic tectum and cerebellum is impaired and axon tracts within the spinal cord, optic nerve and the posterior commissure are disorganized, with the optic nerve failing to reach its target. This severe neurodegenerative phenotype eventually results in functional motor impairment, but this is preceded by a phase of hyperactivity that is consistent with seizures. Importantly, both of these locomotion phenotypes can be assayed in an automated manner suitable for high-throughput studies. Our study provides proof-of-principle that tpp1(sa0011)(-/-) mutants can utilize the advantages of zebrafish for understanding pathogenesis and drug discovery in CLN2 disease and other epilepsies.


Assuntos
Aminopeptidases/deficiência , Proliferação de Células , Dipeptidil Peptidases e Tripeptidil Peptidases/deficiência , Progressão da Doença , Lipofuscinoses Ceroides Neuronais/enzimologia , Lipofuscinoses Ceroides Neuronais/patologia , Serina Proteases/deficiência , Aminopeptidases/genética , Aminopeptidases/fisiologia , Animais , Animais Geneticamente Modificados , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Dipeptidil Peptidases e Tripeptidil Peptidases/fisiologia , Modelos Animais de Doenças , Inibidores do Crescimento/deficiência , Inibidores do Crescimento/genética , Inibidores do Crescimento/fisiologia , Humanos , Atividade Motora/fisiologia , Doenças Neurodegenerativas/enzimologia , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , Lipofuscinoses Ceroides Neuronais/genética , Serina Proteases/genética , Serina Proteases/fisiologia , Tripeptidil-Peptidase 1 , Peixe-Zebra
14.
PeerJ ; 12: e17508, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38854796

RESUMO

Objectives: Low back pain (LBP) is common in elite athletes. Several peripheral and central factors have been identified to be altered in non-athletic LBP populations, however whether these alterations also exist in elite athletes with LBP is unknown. The aim of this study was to determine whether elite basketballers with a history of persistent LBP perform worse than those without LBP at a lumbar muscle endurance task, a lumbar extension peak-torque task, and a lumbar motor imagery task. Method: An observational pilot study. Twenty junior elite-level male basketballers with (n = 11) and without (n = 9) a history of persistent LBP were recruited. Athletes completed a lumbar extensor muscle endurance (Biering-Sorensen) task, two lumbar extensor peak-torque (modified Biering-Sorensen) tasks and two motor imagery (left/right lumbar and hand judgement) tasks across two sessions (48 hours apart). Performance in these tasks were compared between the groups with and without a history of LBP. Results: Young athletes with a history of LBP had reduced lumbar extensor muscle endurance (p < 0.001), reduced lumbar extension peak-torque (p < 0.001), and were less accurate at the left/right lumbar judgement task (p = 0.02) but no less accurate at a left/right hand judgement task (p = 0.59), than athletes without a history of LBP. Response times for both left/right judgement tasks did not differ between groups (lumbar p = 0.24; hand p = 0.58). Conclusions: Junior elite male basketballers with a history of LBP demonstrate reduced lumbar extensor muscle endurance and lumbar extension peak-torque and are less accurate at a left/right lumbar rotation judgement task, than those without LBP.


Assuntos
Basquetebol , Dor Lombar , Região Lombossacral , Resistência Física , Humanos , Dor Lombar/fisiopatologia , Basquetebol/fisiologia , Masculino , Projetos Piloto , Adolescente , Resistência Física/fisiologia , Torque , Atletas , Músculo Esquelético/fisiopatologia , Músculo Esquelético/fisiologia
15.
Eur J Med Genet ; 66(6): 104770, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37085014

RESUMO

Phelan-McDermid syndrome is a rare genetic condition caused by a deletion encompassing the 22q13.3 region or a pathogenic variant of the gene SHANK3. The clinical presentation is variable, but main characteristics include global developmental delay/intellectual disability (ID), marked speech impairment or delay, along with other features like hypotonia and somatic or psychiatric comorbidities. This publication delineates mental health, developmental and behavioural themes across the lifetime of individuals with PMS as informed by parents/caregivers, experts, and other key professionals involved in PMS care. We put forward several recommendations based on the available literature concerning mental health and behaviour in PMS. Additionally, this article aims to improve our awareness of the importance of considering developmental level of the individual with PMS when assessing mental health and behavioural issues. Understanding how the discrepancy between developmental level and chronological age may impact concerning behaviours offers insight into the meaning of those behaviours and informs care for individuals with PMS, enabling clinicians to address unmet (mental health) care needs and improve quality of life.


Assuntos
Transtornos Cromossômicos , Saúde Mental , Humanos , Consenso , Qualidade de Vida , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/psicologia , Deleção Cromossômica , Cromossomos Humanos Par 22/genética
16.
Front Mol Neurosci ; 16: 1191323, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37441676

RESUMO

Multiple molecular pathways and cellular processes have been implicated in the neurobiology of autism and other neurodevelopmental conditions. There is a current focus on synaptic gene conditions, or synaptopathies, which refer to clinical conditions associated with rare genetic variants disrupting genes involved in synaptic biology. Synaptopathies are commonly associated with autism and developmental delay and may be associated with a range of other neuropsychiatric outcomes. Altered synaptic biology is suggested by both preclinical and clinical studies in autism based on evidence of differences in early brain structural development and altered glutamatergic and GABAergic neurotransmission potentially perturbing excitatory and inhibitory balance. This review focusses on the NRXN-NLGN-SHANK pathway, which is implicated in the synaptic assembly, trans-synaptic signalling, and synaptic functioning. We provide an overview of the insights from preclinical molecular studies of the pathway. Concentrating on NRXN1 deletion and SHANK3 mutations, we discuss emerging understanding of cellular processes and electrophysiology from induced pluripotent stem cells (iPSC) models derived from individuals with synaptopathies, neuroimaging and behavioural findings in animal models of Nrxn1 and Shank3 synaptic gene conditions, and key findings regarding autism features, brain and behavioural phenotypes from human clinical studies of synaptopathies. The identification of molecular-based biomarkers from preclinical models aims to advance the development of targeted therapeutic treatments. However, it remains challenging to translate preclinical animal models and iPSC studies to interpret human brain development and autism features. We discuss the existing challenges in preclinical and clinical synaptopathy research, and potential solutions to align methodologies across preclinical and clinical research. Bridging the translational gap between preclinical and clinical studies will be necessary to understand biological mechanisms, to identify targeted therapies, and ultimately to progress towards personalised approaches for complex neurodevelopmental conditions such as autism.

17.
Eur J Med Genet ; 66(7): 104771, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37120079

RESUMO

Phelan-McDermid syndrome (PMS) is a rare neurodevelopmental disorder characterised by hypotonia, speech problems, intellectual disability and mental health issues like regression, autism and mood disorders. In the development, implementation and dissemination of a new clinical guideline for a rare genetic disorder like PMS, the parental experienced perspective is essential. As information from literature is scarce and often conflicting the European Phelan-McDermid syndrome guideline consortium created a multi-lingual survey for parents of individuals with PMS to collect their lived experiences with care needs, genotypes, somatic issues, mental health issues and parental stress. In total, we analysed 587 completed surveys from 35 countries worldwide. Based on parental reporting, PMS appeared to be caused by a deletion of chromosome 22q13.3 in 78% (379/486) of individuals and by a variant in the SHANK3 gene in 22% (107/486) of the individuals. Parents reported a wide variety of developmental, neurological, and other clinical issues in individuals with PMS. The most frequently experienced issues were related to speech and communication, learning disabilities/intellectual disability, and behaviour. While most reported issues were present across all age groups and genotypes, the prevalence of epilepsy, lymphoedema, and mental health issues do appear to vary with age. Developmental regression also appeared to begin earlier in this cohort than described in literature. Individuals with PMS due to a 22q13.3 deletion had a higher rate of kidney issues and lymphoedema compared to individuals with SHANK3 variants. Parental stress was high, with specific contributing factors being child and context related in accordance with the PMS phenotype. The survey results led to various validated recommendations in the European PMS guideline including an age specific surveillance scheme, specific genetic counselling, structured healthcare evaluations on sleep and communication and a focus on family well-being.


Assuntos
Transtornos Cromossômicos , Deficiência Intelectual , Humanos , Deficiência Intelectual/genética , Transtornos Cromossômicos/genética , Deleção Cromossômica , Pais , Cromossomos Humanos Par 22/genética
18.
Front Neurosci ; 16: 806990, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250452

RESUMO

Synaptic gene conditions, i.e., "synaptopathies," involve disruption to genes expressed at the synapse and account for between 0.5 and 2% of autism cases. They provide a unique entry point to understanding the molecular and biological mechanisms underpinning autism-related phenotypes. Phelan-McDermid Syndrome (PMS, also known as 22q13 deletion syndrome) and NRXN1 deletions (NRXN1ds) are two synaptopathies associated with autism and related neurodevelopmental disorders (NDDs). PMS often incorporates disruption to the SHANK3 gene, implicated in excitatory postsynaptic scaffolding, whereas the NRXN1 gene encodes neurexin-1, a presynaptic cell adhesion protein; both are implicated in trans-synaptic signaling in the brain. Around 70% of individuals with PMS and 43-70% of those with NRXN1ds receive a diagnosis of autism, suggesting that alterations in synaptic development may play a crucial role in explaining the aetiology of autism. However, a substantial amount of heterogeneity exists between conditions. Most individuals with PMS have moderate to profound intellectual disability (ID), while those with NRXN1ds have no ID to severe ID. Speech abnormalities are common to both, although appear more severe in PMS. Very little is currently known about the neurocognitive underpinnings of phenotypic presentations in PMS and NRXN1ds. The Synaptic Gene (SynaG) study adopts a gene-first approach and comprehensively assesses these two syndromic forms of autism. The study compliments preclinical efforts within AIMS-2-TRIALS focused on SHANK3 and NRXN1. The aims of the study are to (1) establish the frequency of autism diagnosis and features in individuals with PMS and NRXN1ds, (2) to compare the clinical profile of PMS, NRXN1ds, and individuals with 'idiopathic' autism (iASD), (3) to identify mechanistic biomarkers that may account for autistic features and/or heterogeneity in clinical profiles, and (4) investigate the impact of second or multiple genetic hits on heterogeneity in clinical profiles. In the current paper we describe our methodology for phenotyping the sample and our planned comparisons, with information on the necessary adaptations made during the global COVID-19 pandemic. We also describe the demographics of the data collected thus far, including 25 PMS, 36 NRXN1ds, 33 iASD, and 52 NTD participants, and present an interim analysis of autistic features and adaptive functioning.

19.
Stress Health ; 38(3): 544-555, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34775683

RESUMO

Postnatal post-traumatic stress disorder (PTSD) affects 3%-4% of women who give birth. It is underdiagnosed and undertreated. Thus far, no studies have investigated doctors' perceptions of PTSD in postnatal women. We investigated whether GPs and psychiatrists perceive PTSD symptoms after birth to indicate pathology and what diagnosis and management they would offer. Semi-structured interviews were conducted with six GPs and seven psychiatrists using a fictional vignette featuring a woman experiencing PTSD following a traumatic birth. A framework analysis approach was used. Despite half the GPs recognizing trauma-related features in the vignette their most common diagnosis was postnatal depression whereas six of the seven psychiatrists identified PTSD. Management plans reflected this. Both GPs and psychiatrists lacked trust in timeliness of referrals to psychological services. Both suggested referral to specialist perinatal mental health teams. Results suggest women are unlikely to get a PTSD diagnosis during initial GP consultations, however the woman-centred care proposed by GPs means that a trauma-focussed diagnosis later in the care pathway was not ruled out. Further research is needed to confirm these findings, which suggest that an evidence base around best management for women with postnatal PTSD is sorely needed, especially to inform GP training.


Assuntos
Depressão Pós-Parto , Médicos , Psiquiatria , Transtornos de Estresse Pós-Traumáticos , Feminino , Humanos , Gravidez , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/psicologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-36612621

RESUMO

BACKGROUND: In high-performance sport, athlete performance health encompasses a state of optimal physical, mental, and social wellbeing related to an athlete's sporting success. The aim of this study was to identify the priority areas for achieving athlete performance health in Australia's high-performance sport system (HPSS). METHODS: Participants across five socioecological levels of Australia's HPSS were invited to contribute to this study. Concept mapping, a mixed-methods approach incorporating qualitative and quantitative data collection, was used. Participants brainstormed ideas for what athlete performance health requires, sorted the ideas into groups based on similar meaning and rated the importance, and ease of achieving each idea on a scale from 1 (not important/easiest to overcome) to 5 (extremely important/hardest to overcome). RESULTS: Forty-nine participants generated 97 unique statements that were grouped into 12 clusters following multidimensional scaling and hierarchical cluster analysis. The three clusters with highest mean importance rating were (mean importance rating (1-5), mean ease of overcoming (1-5)): 'Behavioral competency' (4.37, 2.30); 'Collaboration and teamwork' (4.19, 2.65); 'Valuing athlete wellbeing' (4.17, 2.77). The 12 clusters were grouped into five overarching domains: Domain one-Performance health culture; Domain two-Integrated strategy; Domain three-Operational effectiveness; Domain four-Skilled people; Domain five-Leadership. CONCLUSION: A diverse sample of key stakeholders from Australia's HPSS identified five overarching domains that contribute to athlete performance health. The themes that need to be addressed in a strategy to achieve athlete performance health in Australia's HPSS are 'Leadership', 'Skilled people', 'Performance health culture', 'Operational effectiveness', and 'Integrated strategy'.


Assuntos
Atletas , Desempenho Atlético , Humanos , Análise por Conglomerados , Liderança
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