Treatment of hypoplastic left heart syndrome: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: This meta-analysis aimed to consolidate existing data from randomised controlled trials on hypoplastic left heart syndrome. METHODS: Hypoplastic left heart syndrome specific randomised controlled trials published between January 2005 and September 2021 in MEDLINE, EMBASE, and Cochrane databases were included. Regardless of clinical outcomes, we included all randomised controlled trials about hypoplastic left heart syndrome and categorised them according to their results. Two reviewers independently assessed for eligibility, relevance, and data extraction. The primary outcome was mortality after Norwood surgery. Study quality and heterogeneity were assessed. A random-effects model was used for analysis. RESULTS: Of the 33 included randomised controlled trials, 21 compared right ventricle-to-pulmonary artery shunt and modified Blalock-Taussig-Thomas shunt during the Norwood procedure, and 12 regarded medication, surgical strategy, cardiopulmonary bypass tactics, and ICU management. Survival rates up to 1 year were superior in the right ventricle-to-pulmonary artery shunt group; this difference began to disappear at 3 years and remained unchanged until 6 years. The right ventricle-to-pulmonary artery shunt group had a significantly higher reintervention rate from the interstage to the 6-year follow-up period. Right ventricular function was better in the modified Blalock-Taussig-Thomas shunt group 1-3 years after the Norwood procedure, but its superiority diminished in the 6-year follow-up. Randomised controlled trials regarding medical treatment, surgical strategy during cardiopulmonary bypass, and ICU management yielded insignificant results. CONCLUSIONS: Although right ventricle-to-pulmonary artery shunt appeared to be superior in the early period, the two shunts applied during the Norwood procedure demonstrated comparable long-term prognosis despite high reintervention rates in right ventricle-to-pulmonary artery shunt due to pulmonary artery stenosis. For medical/perioperative management of hypoplastic left heart syndrome, further randomised controlled trials are needed to deliver specific evidence-based recommendations.

Fat mass: a novel digital biomarker for remote monitoring that may indicate risk for malnutrition and new complications in decompensated cirrhosis.

BACKGROUND: Cirrhosis is associated with sarcopaenia and fat wasting, which drive decompensation and mortality. Currently, nutritional status, through body composition assessment, is not routinely monitored in outpatients. Given the deleterious outcomes associated with poor nutrition in decompensated cirrhosis, there is a need for remotely monitoring this to optimise community care. METHODS: A retrospective analysis was conducted on patients monitored remotely with digital sensors post hospital discharge, to assess outcomes and indicators of new cirrhosis complications. 15 patients had daily fat mass measurements as part of monitoring over a median 10 weeks, using a Withing's bioimpedance scale. The Clinical Frailty Score (CFS) was used to assess frailty and several liver disease severity scores were assessed. RESULTS: 73.3% (11/15) patients were male with a median age of 63 (52-68). There was a trend towards more severe liver disease based on CLIF-Consortium Acute Decompensation (CLIF-C AD) scores in frail patients vs. those not frail (53 vs 46, p = 0.072). When the cohort was split into patients who gained fat mass over 8 weeks vs. those that lost fat mass, the baseline CLIF-C AD scores and WBC were significantly higher in those that lost fat (58 vs 48, p = 0.048 and 11.2 × 109 vs 4.7 × 109, p = 0.031). CONCLUSIONS: This proof-of-principle study shows feasibility for remote monitoring of fat mass and nutritional reserve in decompensated cirrhosis. Our results suggest fat mass is associated with greater severity of acute decompensation and may serve as an indicator of systemic inflammatory response. Further prospective studies are required to validate this digital biomarker.

A phase 1, single centre, open label, escalating dose study to assess the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) for HPV-associated head and neck cancer (HNC).

BACKGROUND: We conducted a phase 1 dose escalation study (ACTRN12618000140257 registered on 30/01/2018) to evaluate the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) in subjects previously treated for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Eligible subjects had to have no evidence of recurrent and/or metastatic disease at least 12 weeks following the completion of treatment. Three dosing cohorts each consisted of four subjects: group 1: 0.25 mg/dose, group 2: 1 mg/dose, group 3: 4 mg/dose. AMV002 was delivered intradermally on days 0, 28 and 56. Incidence and severity of treatment-emergent adverse events (TEAE) including local reaction at the injection site, and vaccination compliance were recorded. T cell and antibody responses to HPV16 E6 and E7 were measured by interferon gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assay and enzyme-linked immunosorbent assay (ELISA). RESULTS: All subjects completed the vaccination programme and experienced mild discomfort at the injection site(s). Pre-immunisation, cell-mediated responses to HPV16 E6 and E7 were evident in all subjects, and E7-specific antibodies were detected in 11 (91.7%), reflecting previous exposure to HPV. Post-vaccination, 10 of 12 (83.3%) subjects responded to one or more of the E6 and/or E7 peptide pools, while 2 (16.7%) did not show additional vaccine-induced cell-mediated responses. Vaccination resulted in a ≥ 4-fold increase in anti-HPV16 E7 antibody titre in one subject in group 3. CONCLUSIONS: AMV002 was well tolerated at all dose levels and resulted in enhanced specific immunity to virus-derived tumour-associated antigens in subjects previously treated for HPV-associated OPSCC.

A targeted response to the COVID-19 pandemic: analysing effectiveness of remote consultations for triage and management of routine dermatology referrals.

During the UK's COVID-19 pandemic lockdown there was national guidance to suspend routine dermatology work. As a consequence, over 800 patient appointments in a district general dermatology department were temporarily suspended. Remote consultations were carried out to triage and manage referrals, via telephone or video consultations. Data were prospectively recorded on 488 patient interactions. Outcomes included advice/treatment, discharge, surgery or clinic review; 25% of patients were either uncontactable or their problem had resolved. Over a third of referrals were discharged with advice/treatment initiated remotely; 56% of referred dermatoses required further clinical review; 25% of lesion referrals were booked directly to surgery. This process was time-intensive for the clinicians involved, and triage mechanisms could be improved. Sufficient referral information allows remote diagnosis; implementation of management plans and appropriate discharge of patients. This process has been shown to be feasible, and may be a temporary solution for other COVID-19 impacted dermatology departments.

Single-channel blind separation using L1-sparse complex non-negative matrix factorization for acoustic signals.

An innovative method of single-channel blind source separation is proposed. The proposed method is a complex-valued non-negative matrix factorization with probabilistically optimal L1-norm sparsity. This preserves the phase information of the source signals and enforces the inherent structures of the temporal codes to be optimally sparse, thus resulting in more meaningful parts factorization. An efficient algorithm with closed-form expression to compute the parameters of the model including the sparsity has been developed. Real-time acoustic mixtures recorded from a single-channel are used to verify the effectiveness of the proposed method.

Underdetermined reverberant acoustic source separation using weighted full-rank nonnegative tensor models.

In this paper, a fusion of K models of full-rank weighted nonnegative tensor factor two-dimensional deconvolution (K-wNTF2D) is proposed to separate the acoustic sources that have been mixed in an underdetermined reverberant environment. The model is adapted in an unsupervised manner under the hybrid framework of the generalized expectation maximization and multiplicative update algorithms. The derivation of the algorithm and the development of proposed full-rank K-wNTF2D will be shown. The algorithm also encodes a set of variable sparsity parameters derived from Gibbs distribution into the K-wNTF2D model. This optimizes each sub-model in K-wNTF2D with the required sparsity to model the time-varying variances of the sources in the spectrogram. In addition, an initialization method is proposed to initialize the parameters in the K-wNTF2D. Experimental results on the underdetermined reverberant mixing environment have shown that the proposed algorithm is effective at separating the mixture with an average signal-to-distortion ratio of 3 dB.

Cochleagram-based audio pattern separation using two-dimensional non-negative matrix factorization with automatic sparsity adaptation.

An unsupervised single channel audio separation method from pattern recognition viewpoint is presented. The proposed method does not require training knowledge and the separation system is based on non-uniform time-frequency (TF) analysis and feature extraction. Unlike conventional research that concentrates on the use of spectrogram or its variants, the proposed separation algorithm uses an alternative TF representation based on the gammatone filterbank. In particular, the monaural mixed audio signal is shown to be considerably more separable in this non-uniform TF domain. The analysis of signal separability to verify this finding is provided. In addition, a variational Bayesian approach is derived to learn the sparsity parameters for optimizing the matrix factorization. Experimental tests have been conducted, which show that the extraction of the spectral dictionary and temporal codes is more efficient using sparsity learning and subsequently leads to better separation performance.

EEG Interchannel Causality to Identify Source/Sink Phase Connectivity Patterns in Developmental Dyslexia.

While the brain connectivity network can inform the understanding and diagnosis of developmental dyslexia, its cause-effect relationships have not yet enough been examined. Employing electroencephalography signals and band-limited white noise stimulus at 4.8 Hz (prosodic-syllabic frequency), we measure the phase Granger causalities among channels to identify differences between dyslexic learners and controls, thereby proposing a method to calculate directional connectivity. As causal relationships run in both directions, we explore three scenarios, namely channels' activity as sources, as sinks, and in total. Our proposed method can be used for both classification and exploratory analysis. In all scenarios, we find confirmation of the established right-lateralized Theta sampling network anomaly, in line with the assumption of the temporal sampling framework of oscillatory differences in the Theta and Gamma bands. Further, we show that this anomaly primarily occurs in the causal relationships of channels acting as sinks, where it is significantly more pronounced than when only total activity is observed. In the sink scenario, our classifier obtains 0.84 and 0.88 accuracy and 0.87 and 0.93 AUC for the Theta and Gamma bands, respectively.

Low-Rank Tensor Completion Based on Self-Adaptive Learnable Transforms.

The tensor nuclear norm (TNN), defined as the sum of nuclear norms of frontal slices of the tensor in a frequency domain, has been found useful in solving low-rank tensor recovery problems. Existing TNN-based methods use either fixed or data-independent transformations, which may not be the optimal choices for the given tensors. As the consequence, these methods cannot exploit the potential low-rank structure of tensor data adaptively. In this article, we propose a framework called self-adaptive learnable transform (SALT) to learn a transformation matrix from the given tensor. Specifically, SALT aims to learn a lossless transformation that induces a lower average-rank tensor, where the Schatten- p quasi-norm is used as the rank proxy. Then, because SALT is less sensitive to the orientation, we generalize SALT to other dimensions of tensor (SALTS), namely, learning three self-adaptive transformation matrices simultaneously from given tensor. SALTS is able to adaptively exploit the potential low-rank structures in all directions. We provide a unified optimization framework based on alternating direction multiplier method for SALTS model and theoretically prove the weak convergence property of the proposed algorithm. Experimental results in hyperspectral image (HSI), color video, magnetic resonance imaging (MRI), and COIL-20 datasets show that SALTS is much more accurate in tensor completion than existing methods. The demo code can be found at https://faculty.uestc.edu.cn/gaobin/zh_ CN/lwcg/153392/list/index.htm.

Gait analysis in neurological populations: Progression in the use of wearables.

Gait assessment is an essential tool for clinical applications not only to diagnose different neurological conditions but also to monitor disease progression as it contributes to the understanding of underlying deficits. There are established methods and models for data collection and interpretation of gait assessment within different pathologies. This narrative review aims to depict the evolution of gait assessment from observation and rating scales to wearable sensors and laboratory technologies and provide limitations and possible future directions in the field of gait assessment. In this context, we first present an extensive review of current clinical outcomes and gait models. Then, we demonstrate commercially available wearable technologies with their technical capabilities along with their use in gait assessment studies for various neurological conditions. In the next sections, a descriptive knowledge for existing inertial and EMG based algorithms and a sign based guide that shows the outcomes of previous neurological gait assessment studies are presented. Finally, we state a discussion for the use of wearables in gait assessment and speculate the possible research directions by revealing the limitations and knowledge gaps in the literature.

An expedited stroke triage pathway: the key to shortening the door-to-needle time in delivery of thrombolysis.

OBJECTIVES: To assess time management of stroke thrombolysis triage and functional outcomes in patients receiving recombinant tissue plasminogen activator for hyperacute stroke, and identify bottlenecks in delivery of the treatment. DESIGN: Prospective study. SETTING: A university teaching hospital in Hong Kong. PATIENTS: Patients with suspected hyperacute stroke referred to the stroke thrombolysis team during October 2008 to September 2009. MAIN OUTCOME MEASURES: Time performance records including door-to-stroke team, door-to-needle, and onset-to-thrombolysis times. Functional outcomes by modified Rankin Scale score at 3 months, and thrombolysis-related complications including haemorrhagic transformations and mortality. RESULTS: During the 12-month period, 95 thrombolysis calls were received; recombinant tissue plasminogen activator was given intravenously to 17 (18%) of the patients and intra-arterially to 11 (12%). The mean (standard deviation) door-to-stroke team and the door-to-needle times for intravenous recombinant tissue plasminogen activator patients were 33 (25) and 80 (25) minutes, respectively; both were about 20 minutes longer than that recommended by the National Institute of Neurological Disorders and Stroke. The mean National Institute of Health Stroke Scale score for patients received intravenous recombinant tissue plasminogen activator was 16 (standard deviation, 7). The mean (standard deviation) onset-to-treatment time was 144 (42) minutes. Nine (53%) patients who received intravenous recombinant tissue plasminogen activator achieved favourable outcomes at 3 months, with a modified Rankin Scale score of 0 to 1. Symptomatic haemorrhage and mortality occurred in one (6%) patient. CONCLUSION: A dedicated stroke triage pathway is essential to ensure efficient and safe delivery of thrombolysis therapy. Improvements in door-to-stroke team time through integration with emergency medicine staff and neuroradiologists may improve thrombolysis eligibility.

Stacking Fault Energy Analyses of Additively Manufactured Stainless Steel 316L and CrCoNi Medium Entropy Alloy Using In Situ Neutron Diffraction.

Stacking fault energies (SFE) were determined in additively manufactured (AM) stainless steel (SS 316 L) and equiatomic CrCoNi medium-entropy alloys. AM specimens were fabricated via directed energy deposition and tensile loaded at room temperature. In situ neutron diffraction was performed to obtain a number of faulting-embedded diffraction peaks simultaneously from a set of (hkl) grains during deformation. The peak profiles diffracted from imperfect crystal structures were analyzed to correlate stacking fault probabilities and mean-square lattice strains to the SFE. The result shows that averaged SFEs are 32.8 mJ/m2 for the AM SS 316 L and 15.1 mJ/m2 for the AM CrCoNi alloys. Meanwhile, during deformation, the SFE varies from 46 to 21 mJ/m2 (AM SS 316 L) and 24 to 11 mJ/m2 (AM CrCoNi) from initial to stabilized stages, respectively. The transient SFEs are attributed to the deformation activity changes from dislocation slip to twinning as straining. The twinning deformation substructure and atomic stacking faults were confirmed by electron backscatter diffraction (EBSD) and transmission electron microscopy (TEM). The significant variance of the SFE suggests the critical twinning stress as 830 ± 25 MPa for the AM SS 316 L and 790 ± 40 MPa for AM CrCoNi, respectively.

HIV- and HCV-specific markers and echocardiographic pulmonary artery systolic pressure among United States veterans.

Hepatitis C virus (HCV) may increase pulmonary hypertension (PH) risk among people living with HIV (PLWH). Prior studies on this topic have been relatively small and examined selected populations. We determine whether HIV/HCV coinfection is associated with higher pulmonary artery systolic pressure (PASP) and prevalent echocardiographic PH. We performed a cross-sectional analysis of 6032 (16% HIV/HCV coinfected) Veterans Aging Cohort Study participants enrolled 4/1/2003-9/30/2012 with echocardiographic PASP measures. We performed multiple linear and logistic regression analyses to determine whether HIV/HCV mono- or co-infection were associated with PASP and PH compared to uninfected individuals. Individuals with HIV/HCV coinfection displayed a higher PASP than uninfected individuals ([Formula: see text]=1.10, 95% CI 0.01, 2.20) but there was no association between HIV/HCV coinfection and prevalent PH. Subset analyses examined HIV and HCV disease severity markers separately and jointly. Among PLWH, HCV coinfection ([Formula: see text]=1.47, 95% CI 0.26, 2.67) and CD4 + cell count ([Formula: see text]= - 0.68, 95% CI - 1.10, - 0.27), but not HIV viral load nor ART regimen, were associated with PASP. Among people with HCV, neither HIV coinfection nor HCV biomarkers were associated with PASP. Among US veterans referred for echocardiography, HIV/HCV coinfection was not associated with a clinically significant elevation in pulmonary pressure. Lower absolute CD4 + T-cell count was inversely associated with PASP which warrants further investigation in prospective studies.

Oral paracetamol and/or ibuprofen for treating pain after soft tissue injuries: Single centre double-blind, randomised controlled clinical trial.

BACKGROUND: Soft tissue injuries commonly present to the emergency department (ED), often with acute pain. They cause significant suffering and morbidity if not adequately treated. Paracetamol and ibuprofen are commonly used analgesics, but it remains unknown if either one or the combination of both is superior for pain control. OBJECTIVES: To investigate the analgesic effect of paracetamol, ibuprofen and the combination of both in the treatment of soft tissue injury in an ED, and the side effect profile of these drugs. METHODS: Double-blind, double dummy, placebo-controlled randomised controlled trial. 782 adult patients presenting with soft tissue injury without obvious fractures attending the ED of a university hospital in the New Territories of Hong Kong were recruited. Patients were randomised using a random number table into three parallel arms of paracetamol only, ibuprofen only and a combination of paracetamol and ibuprofen in a 1:1:1 ratio. The primary outcome measure was pain score at rest and on activity in the first 2 hours and first 3 days. Data was analysed on an intention to treat basis. RESULTS: There was no statistically significant difference in pain score in the initial two hours between the three groups, and no clinically significant difference in pain score in the first three days. CONCLUSION: There was no difference in analgesic effects or side effects observed using oral paracetamol, ibuprofen or a combination of both in patients with mild to moderate pain after soft tissue injuries attending the ED. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov (no. NCT00528658).