Abstract
Purpose To quantify and understand how to assess the quality of life and health-related QoL of parents with children with congenital abnormalities. Methods We conducted a systematic review with meta-analysis. The search was carried out in 5 bibliographic databases and in ClinicalTrials.gov. No restriction on language or date of publication was applied. This was complemented by references of the studies found and studies of evidence synthesis, manual search of abstracts of relevant congresses/scientific meetings and contact with experts. We included primary studies (observational, quasi-experimental and experimental studies) on parents of children with CA reporting the outcome quality of life (primary outcome) of parents, independently of the intervention/exposure studied. Results We included 75 studies (35 observational non-comparatives, 31 observational comparatives, 4 quasi-experimental and 5 experimental studies). We identified 27 different QoL instruments. The two most frequently used individual QoL instruments were WHOQOL-Bref and SF-36. Relatively to family QoL tools identified, we emphasized PedsQL FIM, IOFS and FQOL. Non-syndromic congenital heart defects were the CA most frequently studied. Through the analysis of comparative studies, we verified that parental and familial QoL were impaired in this population. Conclusions This review highlights the relevance of assessing QoL in parents with children with CA and explores the diverse QoL assessment tools described in the literature. Additionally, results indicate a knowledge gap that can help to draw new paths to future research. It is essential to assess QoL as a routine in healthcare providing and to implement strategies that improve it.

Abstract
Introduction Type 2 diabetes mellitus (T2DM) is a major cause of blindness, kidney failure, myocardial infarction, stroke and lower limb amputation. We are still unable, however, to accurately predict or identify which patients are at a higher risk of deterioration. Most risk stratification tools do not account for novel factors such as sociodemographic determinants, self-management ability or access to healthcare. Additionally, most tools are based in clinical trials, with limited external generalisability. Objective The aim of this work is to design and validate a machine learning-based tool to identify patients with T2DM at high risk of clinical deterioration, based on a comprehensive set of patient-level characteristics retrieved from a population health linked dataset. Sample and design Retrospective cohort study of patients with diagnosis of T2DM on 1 January 2015, with a 5-year follow-up. Anonymised electronic healthcare records from the Whole System Integrated Care (WSIC) database will be used. Preliminary outcomes Outcome variables of clinical deterioration will include retinopathy, chronic renal disease, myocardial infarction, stroke, peripheral arterial disease or death. Predictor variables will include sociodemographic and geographic data, patients' ability to self-manage disease, clinical and metabolic parameters and healthcare service usage. Prognostic models will be defined using multidependence Bayesian networks. The derivation cohort, comprising 80% of the patients, will be used to define the prognostic models. Model parameters will be internally validated by comparing the area under the receiver operating characteristic curve in the derivation cohort with those calculated from a leave-one-out and a 10 times twofold cross-validation. Ethics and dissemination The study has received approvals from the Information Governance Committee at the WSIC. Results will be made available to people with T2DM, their caregivers, the funders, diabetes care societies and other researchers.

Abstract
Data is a major asset in today's healthcare scenery. Hospitals are one of the primary producers of healthcare-related data and the value this data can provide is enormous. However, to use this to improve healthcare practice and push science forward, it is necessary to safeguard the patient's privacy and the ethical use of the data. The ethical and legal requirements are vast and complex. Synthetic data appears as a tool to overcome these hurdles and provide fast and reliable access to data without compromising utility nor privacy. Even though Generative Adversarial Networks (GANs) are receiving a lot of attention lately, the application of most common models and architectures are not suited to tabular data - the most prevalent healthcare-related data. This study surveys the current GAN implementations tailored to this scenario. The analysis was focused mainly on the models employed, datasets used, and metrics reported regarding the quality of the generated data in terms of utility, privacy and how they compare among themselves. We aim to help institutions and investigators get a grasp of the tools to facilitate access to healthcare data, as well as recommendations for testing data synthesizers with privacy concerns.

Abstract
The emergency department (ED) crowding is a critical healthcare issue worldwide that leads to long waits and poorer healthcare outcomes. Goldratt's theory of constraints (TOC) has been used effectively to improve such problematic environments for more than three decades. While most TOC solutions are simple, with many viewing them as purely common sense, they represent paradigm shifts in how to manage complex, uncertain, and silo environments. Goldratt used a simple dice game with a straight flow (I-shape) to illustrate the impact of dependent resources and statistical fluctuations in managing resources. Additionally, games help to overcome resistance to change and gain ownership by having participants develop their solutions. This new cooperative game illustrates an ED environment where patients may follow different care pathways according to their clinical needs, timeliness of care is measured in minutes, the demand is highly uncertain, and treatment must frequently start almost immediately. A Monte Carlo simulation validated the TOC solution to this ED game, achieving results similar to the real TOC's implementations. Moreover, this article provides a thorough process to Socratically introduce TOC to healthcare professionals and others to recognize that the EDs' (like other healthcare systems') core problem is the traditional approach to managing them.

Abstract
Background Stratifying patients with sepsis was the basis of the predisposition, infection, response and organ dysfunction (PIRO) concept, an attempt to resolve the heterogeneity in treatment response. The purpose of this study is to perform an independent validation of the PIRO staging system in an international cohort and explore its utility in the identification of patients in whom time to antibiotic treatment is particularly important. Methods Prospective international cohort study, conducted over a 6-month period in five Portuguese hospitals and one Australian institution. All consecutive adult patients admitted to selected wards or the intensive care, with infections that met the CDC criteria for lower respiratory tract, urinary, intra-abdominal and bloodstream infections were included. Results There were 1638 patients included in the study. Patients who died in hospital presented with a higher PIRO score (10 +/- 3 vs 8 +/- 4, p < 0.001). The observed mortality was 3%, 15%, 24% and 34% in stage I, II, III and IV, respectively, which was within the predicted intervals of the original model, except for stage IV patients that presented a lower mortality. The hospital survival rate was 84%. The application of the PIRO staging system to the validation cohort resulted in a positive predictive value of 97% for stage I, 91% for stage II, 85% for stage III and 66% for stage IV. The area under the receiver operating characteristics curve (AUROC) was 0.75 for the all cohort and 0.70 if only patients with bacteremia were considered. Patients in stage III and IV who did not have antibiotic therapy administered within the desired time frame had higher mortality rate than those who have timely administration of antibiotic. Conclusions To our knowledge, this is the first external validation of this PIRO staging system and it performed well on different patient wards within the hospital and in different types of hospitals. Future studies could apply the PIRO system to decision-making about specific therapeutic interventions and enrollment in clinical trials based on disease stage.

Abstract
Congenital heart disease (CHD) is the most common congenital malformation and has high morbidity and mortality related to late diagnosis. Screening protocols are lacking and only 1% of murmurs are associated with CHD. The decline in auscultation skills highlights the need for better screening. This study aims to create and evaluate models for the detection of CHD using clinical data and sound features. These features were extracted using pure conventional MFCC and selected MFCC through matrix profiling and motif search. Four combinations of data were used to train decision trees (DT) and artificial neural networks (ANN), and the area under the curve (AUC) was compared. Posteriorly, models were also trained for the detection of any cardiac pathology. In both pathologies, the ANN model using clinical data and conventional MFCC showed the highest performance with AUC of 0.761 for CHD and 0.791 for any cardiac pathology. However, this is only a slight improvement when compared with the ANN models using only clinical data (0.747 and 0.789, respectively. Additionally, the inclusion of motif selected MFCC seems to worsen the model performance. Although further research is still needed, this is a potential improvement in CHD screening, particularly for primary care physicians. © 2021 Copyright for this paper by its authors.