Record linkage of routine and cohort data of children in Portugal: challenges and opportunities when using record linkage as a tool for scientific research.

Linking records could serve as a useful tool for scientific research and as a facilitator for local policymaking. This article examines the challenges and opportunities for researchers to lawfully link routinely collected health and education data with cohort data of children when using it as a tool for scientific research in Portugal. Such linking can be lawfully conducted in Portugal if three requirements are met. First, data processing pursues a legitimate purpose, such as scientific research. Secondly, data linking complies with the legal obligations of research entities and researchers, acting as data controllers or processors, and it respects the rights of children as data subjects. Finally, data linking is based on the explicit written consent of those with parental responsibility for the child. So far, the implementation of the General Data Protection Regulation in Portugal has not facilitated record linkage. It is argued that further harmonised implementation of that Regulation across European Union and European Economic Area Member States, establishing a minimum shared denominator for record linkage in scientific research for the common good, including without explicit consent, is needed.

Geoprivacy in Neighbourhoods and Health Research: A Mini-Review of the Challenges and Best Practices in Epidemiological Studies.

Neighbourhood and health research often relies on personal location data (e.g., home address, daily itineraries), despite the risks of geoprivacy breaches. Thus, geoprivacy is an important emerging topic, contemplated in international regulations such as the General Data Protection Regulation. In this mini-review, we briefly assess the potential risks associated with the usage of personal location data and provide geoprivacy-preserving recommendations to be considered in epidemiological research. Risks include inference of personal information that the individual does not wish to disclose, reverse-identification and security breaches. Various measures should be implemented at different stages of a project (pre-data collection, data processing, data analysis/publication and data sharing) such as informed consent, pseudo-anonymization and geographical methods.

Joint controllers in large research consortia: a funnel model to distinguish controllers in the sense of the GDPR from other partners in the consortium.

Large European research consortia in the health sciences face challenges regarding the governance of personal data collected, generated and/or shared during their collective research. A controller in the sense of the GDPR is the entity which decides about purposes and means of the data processing. Case law of the Court of Justice of the European Union (CJEU) and Guidelines of the European Data Protection Board (EDPB) indicate that all partners in the consortium would be joint controllers. This paper summarises the case law, the Guidelines and literature on joint controllership, gives a brief account of a webinar organised on the issue by Lygature and the MLC Foundation. Participants at the webinar agreed in large majority that it would be extreme if all partners in the consortium would become joint controllers. There was less agreement how to disentangle partners who are controllers of a study from those who are not. In order to disentangle responsibilities, we propose a funnel model with consecutive steps acting as sieves in the funnel. It differentiates between two types of partners: all partners who are involved in shaping the project as a whole versus those specific partners who are more closely involved in a sub-study following from the DoA or the use of the data Platform. If the role of the partner would be comparable to that of an outside advisor, that partner would not be a data controller even though the partner is part of the consortium. We propose further nuances for the disentanglement which takes place in various steps. Uncertainty about formal controllership under the GDPR can stifle collaboration in consortia due to concerns over (shared) responsibility and liability. Data subjects' ability to exercise their right can also be affected by this. The funnel model proposes a way out of this conundrum.

Sharing Biomedical Data: Strengthening AI Development in Healthcare.

Artificial intelligence (AI)-based solutions have revolutionized our world, using extensive datasets and computational resources to create automatic tools for complex tasks that, until now, have been performed by humans. Massive data is a fundamental aspect of the most powerful AI-based algorithms. However, for AI-based healthcare solutions, there are several socioeconomic, technical/infrastructural, and most importantly, legal restrictions, which limit the large collection and access of biomedical data, especially medical imaging. To overcome this important limitation, several alternative solutions have been suggested, including transfer learning approaches, generation of artificial data, adoption of blockchain technology, and creation of an infrastructure composed of anonymous and abstract data. However, none of these strategies is currently able to completely solve this challenge. The need to build large datasets that can be used to develop healthcare solutions deserves special attention from the scientific community, clinicians, all the healthcare players, engineers, ethicists, legislators, and society in general. This paper offers an overview of the data limitation in medical predictive models; its impact on the development of healthcare solutions; benefits and barriers of sharing data; and finally, suggests future directions to overcome data limitations in the medical field and enable AI to enhance healthcare. This perspective is dedicated to the technical requirements of the learning models, and it explains the limitation that comes from poor and small datasets in the medical domain and the technical options that try or can solve the problem related to the lack of massive healthcare data.

Record linkage of population-based cohort data from minors with national register data: a scoping review and comparative legal analysis of four European countries.

Background: The GDPR was implemented to build an overarching framework for personal data protection across the EU/EEA. Linkage of data directly collected from cohort participants, potentially serving as a prominent tool for health research, must respect data protection rules and privacy rights. Our objective was to investigate law possibilities of linking cohort data of minors with routinely collected education and health data comparing EU/EEA member states. Methods: A legal comparative analysis and scoping review was conducted of openly accessible published laws and regulations in EUR-Lex and national law databases on GDPR's implementation in Portugal, Finland, Norway, and the Netherlands and its connected national regulations purposing record linkage for health research that have been implemented up until April 30, 2021. Results: The GDPR does not ensure total uniformity in data protection legislation across member states offering flexibility for national legislation. Exceptions to process personal data, e.g., public interest and scientific research, must be laid down in EU/EEA or national law. Differences in national interpretation caused obstacles in cross-national research and record linkage: Portugal requires written consent and ethical approval; Finland allows linkage mostly without consent through the national Social and Health Data Permit Authority; Norway when based on regional ethics committee's approval and adequate information technology safeguarding confidentiality; the Netherlands mainly bases linkage on the opt-out system and Data Protection Impact Assessment. Conclusions: Though the GDPR is the most important legal framework, national legislation execution matters most when linking cohort data with routinely collected health and education data. As national interpretation varies, legal intervention balancing individual right to informational self-determination and public good is gravely needed for health research. More harmonization across EU/EEA could be helpful but should not be detrimental in those member states which already opened a leeway for registries and research for the public good without explicit consent.

Predictors of In-Hospital Mortality after Recovered Out-of-Hospital Cardiac Arrest in Patients with Proven Significant Coronary Artery Disease: A Retrospective Study.

INTRODUCTION: Recovered Out-of-Hospital Cardiac Arrest (rOHCA) population is heterogenous. Few studies focused on outcomes in the rOHCA subgroup with proven significant coronary artery disease (SigCAD). We aimed to characterize this subgroup and study the determinants of in-hospital mortality. METHODS: Retrospective study of consecutive rOHCA patients submitted to coronary angiography. Only patients with SigCAD were included. RESULTS: 60 patients were studied, 85% were male, mean age was 62.6 ± 12.1 years. In-hospital mortality rate was 43.3%. Patients with diabetes and history of stroke were less likely to survive. Significant univariate predictors of in-hospital mortality were further analysed separately, according to whether they were present at hospital admission or developed during hospital evolution. At hospital admission, initial non-shockable rhythm, low-flow time>12min, pH<7.25mmol/L and lactates >4.75mmol/L were the most relevant predictors and therefore included in a score tested by Kaplan-Meyer. Patients who had 0/4 criteria had 100% chance of survival till hospital discharge, 1/4 had 77%, 2/4 had 50%, 3/4 had 25%. Patients with all 4 criteria had 0% survival. During in-hospital evolution, a pH<7.35 at 24h, lactates>2mmol/L at 24h, anoxic brain injury and persistent hemodynamic instability proved significant. Patients who had 0/4 of these in-hospital criteria had 100% chance of survival till hospital discharge, 1/4 had 94%, 2/4 had 47%, 3/4 had 25%. Patients with all 4 criteria had 0% survival. Contrarily, CAD severity and ventricular dysfunction didn't significantly correlate to the outcome. CONCLUSION: Classic prehospital variables retain their value in predicting mortality in the specific group of OHCA with SigCAD. In-hospital evolution variables proved to add value in mortality prediction. Combining these simple variables in risk scores might help refining prognostic prediction in these patients's subset.

Lack of Benefit of Ischemic Postconditioning After Routine Thrombus Aspiration During Reperfusion: Immediate and Midterm Results.

OBJECTIVES: The underutilization of manual thrombus aspiration (MTA) may have reduced the benefits of ischemic postconditioning (PostCon), as it reduces thrombus embolization. We aimed to assess the benefits of PostCon in patients with ST-segment elevation myocardial infarction (STEMI) after the systematic utilization of MTA. METHODS: A total of 87 patients were enrolled in a prospective, randomized trial (43 PostCon and 44 controls). After MTA, PostCon was performed on the treatment group by applying 4 cycles of alternate reperfusion and reocclusion (60 seconds each) using the angioplasty balloon. The primary end point was infarct size assessed by the area under the curve (AUC) of troponin T (TnT) activity. The secondary end points were left ventricle ejection fraction (LVEF) and major cardiac events (new myocardial infarction or cardiac death) both at discharge and at follow-up. RESULTS: The AUC for TnT was no different with respect to study arms (median [interquartile range]): PostCon = 8.9 (10.6) versus control = 8.2 (10.6), P = .68. Left ventricle ejection fraction improved from in-hospital to follow-up (9 ± 3 months) for the entire cohort (46.3% ± 7.3% vs 52.2% ± 10.7%, P < .001), with no differences between PostCon and controls (51.6% ± 9.5% vs 52.7% ± 11.9%, P = .89); major cardiac events at 14 ± 4 months of follow-up were also no different (PostCon = 1.0 (2.3%) vs control = 0, P = .49). CONCLUSION: In patients with STEMI treated with MTA, PostCon offered no benefits to infarct size, LVEF, or major cardiac events.

Role of quetiapine beyond its clinical efficacy in bipolar disorder: From neuroprotection to the treatment of psychiatric disorders (Review).

The aim of the present review was to discuss the following aspects of treatment with quetiapine in psychiatric disorders: i) Neurocognition and functional recovery in bipolar disorder (BD); ii) neuroprotective profile in different models; and iii) potential off-label indications. A PubMed search was conducted of articles published in English between 2000 and 2012 on quetiapine, cross-referenced with the terms 'anxiety', 'attention deficit disorder', 'borderline personality disorder', 'dementia', 'insomnia', 'major depressive disorder' (MDD), 'obsessive-compulsive disorder', 'post-traumatic stress disorder', 'remission', 'cognition', 'neurobiology', 'neuroprotection', 'efficacy' and 'effectiveness'. Articles were selected from meta-analyses, randomized clinical trials and open trials, and the results were summarized. Quetiapine, when studied in off-label conditions, has shown efficacy as a monotherapy in MDD and general anxiety disorder. Quetiapine also appears to exhibit a small beneficial effect in dementia. The review of other conditions was affected by methodological limitations that precluded any definitive conclusions on the efficacy or safety of quetiapine. Overall, the present review shows evidence supporting a potential role for quetiapine in improving cognition, functional recovery and negative symptoms in a cost-effective manner in BD. These benefits of quetiapine are potentially associated with its well-described neuroprotective effects; however, further studies are clearly warranted.

Body position and oxygenation: An intriguing relationship.

Dyspnea and hypoxemia are among the most common symptoms and signs that need to be assessed in clinical practice. This case illustrates how simple steps in history taking and physical examination can be crucial for diagnosis. We present a patient with intermittent hypoxemia, initially attributed to a pulmonary infection. However, the hypoxemia persisted even after successful treatment of the infection. Computed tomography angiography of the chest and ventilation/perfusion lung scan excluded pulmonary embolism. We then observed that the hypoxemia and dyspnea were triggered by orthostatism. An echocardiogram with a bubble test showed a patent foramen ovale, with a right-to-left shunt, without pulmonary hypertension. After percutaneous closure of the foramen ovale, the symptoms completely resolved. This is a case of platypnea-orthodeoxia syndrome, which is usually associated with patent foramen ovale or atrial septal defect and is typically observed in the elderly. The features and causes of this curious syndrome are discussed.

Vulnerability to stress, anxiety and depressive symptoms and metabolic control in type 2 diabetes.

BACKGROUND: Vulnerability to stress has been associated to distress, emotional distress symptoms and metabolic control in type 2 diabetes mellitus (T2DM) patients as well. Furthermore some conflicting results were noticed. We aimed to evaluate the effect over metabolic control in what concerns vulnerability to stress beyond depressive and anxiety symptoms. FINDINGS: This cross-sectional study assessed 273 T2DM patients with depressive and anxiety symptoms using the Hospital Anxiety Depression Scale (HADS) and the 23 Questions to assess Vulnerability to Stress (23QVS), along with demographic and clinical diabetes-related variables. Hierarchical logistic regression models were used to investigate predictors of poor glycemic control. The results showed an association of depressive symptoms (odds ratio = 1.12, 95%CI = 1.01-1.24, P = 0.030) with increased risk of poor glycemic control. Anxiety symptoms and vulnerability to stress on their own were not predictive of metabolic control, respectively (odds ratio = 0.92, 95%CI = 0.84-1.00, P = 0.187 and odds ratio = 0.98, 95%CI = 0.95-1.01, P = 0.282). CONCLUSIONS: Our data suggested that vulnerability to stress was not predictive of poor glycemic control in T2DM, but depressive symptoms were.

The impact of a history of psychotic symptoms on cognitive function in euthymic bipolar patients: a comparison with schizophrenic patients and healthy controls.

BACKGROUND: About two-thirds of patients with bipolar disorder (BD) have a lifetime history of at least one psychotic symptom. OBJECTIVE: To compare the neurocognitive performance of four groups: BD patients with and without a history of psychotic symptoms (BD HPS+ and BD HPS-, respectively); patients with schizophrenia (SZ); and healthy control (HC) subjects. METHOD: In this cross-sectional study, 35 stabilized patients with SZ, 79 euthymic (44 HPS+ and 35 HPS-) patients with BD, and 50 HC were administered a comprehensive battery of neuropsychological tests. RESULTS: There was worse neurocognitive functioning in both BD and SZ patients compared to HC. Overall, data from both groups of BD patients did not differ on sociodemographic, clinical, or neurocognitive variables. However, BD HPS+ patients had significantly more negative symptoms, as measured by the Positive and Negative Syndrome Scale (PANSS), and showed a trend toward worse performance on executive functions compared to BD HPS- patients. Moreover, both BD groups had better performance on all neurocognitive tests compared to SZ group. CONCLUSIONS: Neurocognitive dysfunction may be more marked in SZ than in BD, yet qualitatively similar. A history of past psychotic symptoms in BD was not associated with more severe cognitive impairment during euthymia. Therefore, BD with psychotic symptoms does not appear to be a distinct neurocognitive phenotype.

The impact of a history of psychotic symptoms on cognitive function in euthymic bipolar patients: a comparison with schizophrenic patients and healthy controls / O impacto da história de sintomas psicóticos na função cognitiva de doentes bipolares eutímicos: comparação com doentes esquizofrênicos e controles saudáveis

BACKGROUND: About two-thirds of patients with bipolar disorder (BD) have a lifetime history of at least one psychotic symptom. Objective: To compare the neurocognitive performance of four groups: BD patients with and without a history of psychotic symptoms (BD HPS+ and BD HPS-, respectively); patients with schizophrenia (SZ); and healthy control (HC) subjects. METHOD: In this cross-sectional study, 35 stabilized patients with SZ, 79 euthymic (44 HPS+ and 35 HPS-) patients with BD, and 50 HC were administered a comprehensive battery of neuropsychological tests. RESULTS: There was worse neurocognitive functioning in both BD and SZ patients compared to HC. Overall, data from both groups of BD patients did not differ on sociodemographic, clinical, or neurocognitive variables. However, BD HPS+ patients had significantly more negative symptoms, as measured by the Positive and Negative Syndrome Scale (PANSS), and showed a trend toward worse performance on executive functions compared to BD HPS- patients. Moreover, both BD groups had better performance on all neurocognitive tests compared to SZ group. CONCLUSIONS: Neurocognitive dysfunction may be more marked in SZ than in BD, yet qualitatively similar. A history of past psychotic symptoms in BD was not associated with more severe cognitive impairment during euthymia. Therefore, BD with psychotic symptoms does not appear to be a distinct neurocognitive phenotype.

INTRODUÇÃO: Cerca de dois terços dos pacientes com Transtorno Bipolar (TB) apresentam sintomas psicóticos ao longo da vida. OBJETIVO: Comparar o desempenho neurocognitivo de quatro grupos: pacientes com TB, com e sem histórico de sintomas psicóticos (HPS+ ou HPS-, respectivamente); pacientes esquizofrénicos; e grupo controle (GC) com indivíduos saudáveis. MÉTODOS: Estudo transversal no qual 35 pacientes com esquizofrenia (EZ), 79 pacientes com TB na fase eutímica (44 HPS+ e 35 HPS-) e 50 GC foram submetidos a extensa avaliação neuropsicológica. RESULTADOS: Observou-se pior funcionamento neurocognitivo em pacientes com TB e com EZ quando comparados ao GC. Os dois grupos de pacientes TB não diferiram em dados demográficos, clínicos ou variáveis neurocognitivas. Entretanto o grupo HPS+ teve mais sintomas negativos mensurados pela Positive and Negative Syndrome Scale (PANSS) e apresentou uma tendência a pior performance nas funções executivas comparativamente aos pacientes HPS-. Além disso ambos os grupos de pacientes TB tiveram melhor desempenho em todos testes neurocognitivos quando comparados aos pacientes com EZ. CONCLUSÕES: A disfunção neurocognitiva é mais marcada nos pacientes com EZ do que com TB, apesar de ser qualitativamente similar. Um histórico de sintomas psicóticos no TB não associou esta amostra de pacientes eutímicos a um maior prejuízo neurocognitivo. Assim sendo, o TB com sintomas psicóticos parece não possuir um fenótipo neurocognitivo diferenciado.

Hyponatremia--an unusual trigger of Takotsubo cardiomyopathy.

Takotsubo cardiomyopathy is an acute cardiac entity with clinical manifestations similar to myocardial infarction, accounting for 1-2% of acute coronary syndrome admissions. Its underlying pathophysiology is not yet well established. It is usually associated with acute physical or emotional stress, but the list of potential triggers has grown as the condition attracts the attention of the medical community. In order to diagnose the condition correctly and to gain new insights into it, we need to know its potential triggers as well as its clinical presentation and diagnostic criteria. We report a case of takotsubo cardiomyopathy triggered by hyponatremia.

Successful management of Listeria monocytogenes pericarditis: case report and review of the literature.

Listeria monocytogenes, although an uncommon cause of illness in the general population, is feared principally because of the morbidity and mortality associated with CNS infections. Cardiovascular involvement with L. monocytogenes is very rare, and has been limited to endocarditis. We describe a case of Listeria pericarditis, which occurred in a 60-year-old man with Child-Pugh B cirrhosis who presented to the emergency department with asthenia, anorexia, and respiratory distress. The echocardiogram showed severe pericardial effusion and after pericardiocentesis, L. monocytogenes was isolated in the culture of pericardial fluid. After surgical pericardiectomy with draining of the pericardial effusion and antibiotic treatment with ampicillin, the patient experienced a slow, but full recovery. Documentation of L. monocytogenes pericarditis is an extremely rare entity with very scarce reports in medical literature, and is usually associated with a very poor prognosis. A case report is presented together with a review of the literature.

Creativity and executive function across manic, mixed and depressive episodes in bipolar I disorder.

INTRODUCTION: Creativity is a complex construct involving affective and cognitive components. Bipolar Disorder (BD) has been associated with creativity and is characterized by a wide range of affective and cognitive symptoms. Although studies of creativity in BD have tended to focus on creativity as a trait variable in medicated euthymic patients, it probably fluctuates during symptomatic states of BD. Since creativity is known to involve key affective and cognitive components, it is plausible to speculate that cognitive deficits and symptoms present in symptomatic BD could interfere with creativity. MATERIAL AND METHODS: Sixty-seven BD type I patients medication free, age 18-35 years and experiencing a maniac, mixed, or depressive episodes, were assessed for creativity, executive functioning, and intelligence. RESULTS: Manic and mixed state patients had higher creativity scores than depressive individuals. Creativity was influenced by executive function measures only in manic patients. Intelligence did not influence creativity for any of the mood episode types. CONCLUSION: We propose that creativity in BD might be linked to the putative hyperdopaminergic state of mania and be dependent on intact executive function. Future studies should further explore the role of dopaminergic mechanisms in creativity in BD.

The importance of measuring psychosocial functioning in schizophrenia.

BACKGROUND: Schizophrenia is among the most disabling of mental illnesses and frequently causes impaired functioning. We explore issues of definition and terminology, and the relationship between social functioning, cognition, and psychopathology considering relevant research findings. METHODS: The present article describes measures of social functioning and outlines their psychometric properties. It considers their usefulness in research and clinical settings. Treatment aims and objectives are explored in the context of cognitive and social functioning. Finally, we identify areas for developing research and refining the measurement of social functioning. RESULTS: The definition and measurement of social functioning in schizophrenia remains a complex and disputed area. The relationships between symptoms, cognitive functioning and social functioning are complex but we are beginning to understand them better. Scales for measuring functioning in clinical practice must be brief and sensitive to change and the Personal and Social Performance (PSP) scale may offer several advantages in these regards. Brief cognitive assessments focusing upon the domains most commonly affected in schizophrenia, such as verbal memory and executive functions, should be coadministered with measures of functioning. CONCLUSIONS: The use of validated scales for schizophrenia that are sensitive to change over the course of the illness and its treatment, should allow for a better understanding of patients' functional disabilities, enabling better and more comprehensive monitoring and evaluation of both pharmacological and non-pharmacological treatment strategies.