Abstract
Missing data can pose severe consequences in critical contexts, such as clinical research based on routinely collected healthcare data. This issue is usually handled with imputation strategies, but these tend to produce poor and biased results under the Missing Not At Random (MNAR) mechanism. A recent trend that has been showing promising results for MNAR is the use of generative models, particularly Variational Autoencoders. However, they have a limitation: the imputed values are the result of a single sample, which can be biased. To tackle it, an extension to the Variational Autoencoder that uses a partial multiple imputation procedure is introduced in this work. The proposed method was compared to 8 state-of-the-art imputation strategies, in an experimental setup with 34 datasets from the medical context, injected with the MNAR mechanism (10% to 80% rates). The results were evaluated through the Mean Absolute Error, with the new method being the overall best in 71% of the datasets, significantly outperforming the remaining ones, particularly for high missing rates. Finally, a case study of a classification task with heart failure data was also conducted, where this method induced improvements in 50% of the classifiers.

Abstract
Background: American Academy of Sleep Medicine guidelines suggest that clinical prediction algorithms can be used to screen patients with obstructive sleep apnea (OSA) without replacing polysomnography, the gold standard.Objective: We aimed to identify, gather, and analyze existing machine learning approaches that are being used for disease screening in adult patients with suspected OSA. Methods: We searched the MEDLINE, Scopus, and ISI Web of Knowledge databases to evaluate the validity of different machine learning techniques, with polysomnography as the gold standard outcome measure and used the Prediction Model Risk of Bias Assessment Tool (Kleijnen Systematic Reviews Ltd) to assess risk of bias and applicability of each included study. Results: Our search retrieved 5479 articles, of which 63 (1.15%) articles were included. We found 23 studies performing diagnostic model development alone, 26 with added internal validation, and 14 applying the clinical prediction algorithm to an independent sample (although not all reporting the most common discrimination metrics, sensitivity or specificity). Logistic regression was applied in 35 studies, linear regression in 16, support vector machine in 9, neural networks in 8, decision trees in 6, and Bayesian networks in 4. Random forest, discriminant analysis, classification and regression tree, and nomogram were each performed in 2 studies, whereas Pearson correlation, adaptive neuro-fuzzy inference system, artificial immune recognition system, genetic algorithm, supersparse linear integer models, and k-nearest neighbors algorithm were each performed in 1 study. The best area under the receiver operating curve was 0.98 (0.96-0.99) for age, waist circumference, Epworth Somnolence Scale score, and oxygen saturation as predictors in a logistic regression. Conclusions: Although high values were obtained, they still lacked external validation results in large cohorts and a standard OSA criteria definition. Trial Registration: PROSPERO CRD42021221339; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=221339(J Med Internet Res 2022;24(9):e39452) doi: 10.2196/39452

Abstract

Abstract
Introduction: Evidence shows most patients are not recognised by their attending healthcare professionals as having palliative needs. This feasibility study aimed to aid healthcare professionals identify hospital patients with palliative needs. Material and Methods: Mixed-methods, cross-sectional, observational study. The patient inclusion criteria comprised: age over 18 years old, being mentally capable to give consent judged as such by participating healthcare professionals, and if unable, having a legal substitute to consent, having a diagnosis of an incurable, potentially life-threatening illness. Field notes were taken for reflexive purposes. Outcome measures included: Integrated Palliative Care Outcome scale, surprise question, phase of illness, referral request status, The Eastern Cooperative Oncology Group Performance Status and social needs assessment. An interim data collection period meeting assessed implementation outcomes in each context. A web-based survey was sent to all participating healthcare professionals at the end of data collection period to explore overall experiences of participation and implementation outcomes. Results: Forty-two departments in four hospitals were contacted. The study was presented in nine departments. The field notes were vital to understand the recruitment process and difficulties experienced: time constraints, fear of additional work, department dynamics and organisation, relationships between departments and need of training in palliative care and research. One department agreed to participate. There were six participating healthcare professionals and only 45 patients included. Three participating healthcare professionals responded to the web-based survey. Discussion: The response rate was very low. Legislating palliative care is not enough, and an integrated palliative care plan needs to be implemented at country and institution level. Conclusion: There is an urgent need to provide generalist palliative care training to clinicians.

Abstract

Abstract
Background: Approximately 62% of patients with breast cancer with a pathogenic variant (BRCA1 or BRCA2) undergo primary breast-conserving therapy. Objective: The study aims to develop a personalized risk management decision support tool for carriers of a pathogenic variant (BRCA1 or BRCA2) who underwent breast-conserving therapy for unilateral early-stage breast cancer. Methods: We developed a Bayesian network model of a hypothetical cohort of carriers of BRCA1 or BRCA2 diagnosed with stage I/II unilateral breast cancer and treated with breast-conserving treatment who underwent subsequent second primary cancer risk–reducing strategies. Using event dependencies structured according to expert knowledge and conditional probabilities obtained from published evidence, we predicted the 40-year overall survival rate of different risk-reducing strategies for 144 cohorts of women defined by the type of pathogenic variants (BRCA1 or BRCA2), age at primary breast cancer diagnosis, breast cancer subtype, stage of primary breast cancer, and presence or absence of adjuvant chemotherapy. Results: Absence of adjuvant chemotherapy was the most powerful factor that was linked to a dramatic decline in survival. There was a negligible decline in the mortality in patients with triple-negative breast cancer, who received no chemotherapy and underwent any secondary risk–reducing strategy, compared with surveillance. The potential survival benefit from any risk-reducing strategy was more modest in patients with triple-negative breast cancer who received chemotherapy compared with patients with luminal breast cancer. However, most patients with triple-negative breast cancer in stage I benefited from bilateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy or just risk-reducing salpingo-oophorectomy. Most patients with luminal stage I/II unilateral breast cancer benefited from bilateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy. The impact of risk-reducing salpingo-oophorectomy in patients with luminal breast cancer in stage I/II increased with age. Most older patients with the BRCA1 and BRCA2 pathogenic variants in exons 12-24/25 with luminal breast cancer may gain a similar survival benefit from other risk-reducing strategies or surveillance. Conclusions: Our study showed that it is mandatory to consider the complex interplay between the types of BRCA1 and BRCA2 pathogenic variants, age at primary breast cancer diagnosis, breast cancer subtype and stage, and received systemic treatment. As no prospective study results are available at the moment, our simulation model, which will integrate a decision support system in the near future, could facilitate the conversation between the health care provider and patient and help to weigh all the options for risk-reducing strategies leading to a more balanced decision. ©Jelena Maksimenko, Pedro Pereira Rodrigues, Miki Nakazawa-Miklaševica, David Pinto, Edvins Miklaševics, Genadijs Trofimovics, Janis Gardovskis, Fatima Cardoso, Maria João Cardoso.