Background: To investigate whether vaccination against SARS-CoV-2 is associated with the onset of retinal vascular occlusive disease (RVOD). Methods: In this multicentre study, data from patients with central and branch retinal vein occlusion (CRVO and BRVO), central and branch retinal artery occlusion (CRAO and BRAO), and anterior ischaemic optic neuropathy (AION) were retrospectively collected during a 2-month index period (1 June–31 July 2021) according to a defined protocol. The relation to any previous vaccination was documented for the consecutive case series. Numbers of RVOD and COVID-19 vaccination were investigated in a case-by-case analysis. A case– control study using age- and sex-matched controls from the general population (study participants from the Gutenberg Health Study) and an adjusted conditional logistic regression analysis was conducted. Results: Four hundred and twenty-one subjects presenting during the index period (61 days) were enrolled: one hundred and twenty-one patients with CRVO, seventy-five with BRVO, fifty-six with CRAO, sixty-five with BRAO, and one hundred and four with AION. Three hundred and thirty-two (78.9%) patients had been vaccinated before the onset of RVOD. The vaccines given were BNT162b2/BioNTech/Pfizer (n = 221), followed by ChadOx1/AstraZeneca (n = 57), mRNA- 1273/Moderna (n = 21), and Ad26.COV2.S/Johnson & Johnson (n = 11; unknown n = 22). Our case–control analysis integrating population-based data from the GHS yielded no evidence of an increased risk after COVID-19 vaccination (OR = 0.93; 95% CI: 0.60–1.45, p = 0.75) in connection with a vaccination within a 4-week window. Conclusions: To date, there has been no evidence of any association between SARS-CoV-2 vaccination and a higher RVOD risk.

This thesis discusses the design and the utilization of the artificial neural networks as ECG classifiers and the detectors of heart diseases in ECG signal especially myocardial ischaemia. The changes of ST-T complexes are the important indicator of ischaemia in ECG signal. Different types of ischaemia are expressed particularly by depression or elevation of ST segments and changes of T wave. The first part of this thesis is orientated towards the theoretical knowledges and describes changes in the ECG signal rising close to different types of ischaemia. The second part deals with to the ECG signal pre-processing for the classification by neural network, filtration, QRS detection, ST-T detection, principal component analysis. In the last part there is described design of detector of myocardial ischaemia based on artificial neural networks with utilisation of two types of neural networks back – propagation and self-organizing map and the results of used algorithms. The appendix contains detailed description of each neural networks, description of the programme for classification of ECG signals by ANN and description of functions of programme. The programme was developed in Matlab R2007b.

Infants with hypoxic-ischaemic encephalopathy (birth asphyxia) have a high risk of death or disability. Those with poor prognosis are sometimes allowed to die after withdrawal of intensive care. In recent years, doctors have used new types of brain scan, magnetic resonance imaging (MRI), to predict the type and severity of impairment if the infant survives and to help with such decisions. In this thesis, I analyse the issues arising from the use of MRI for prognostication and decision-making in newborn infants. I argue that previous prognostic research has been hampered by a failure to identify and focus on the most important practical question and that this contributes to uncertainty in practice. I outline recommendations for improving research. I then look at existing guidelines about withdrawal of life-sustaining treatment. I identify several problems with these guidelines; they are vague and fail to provide practical guidance, they provide little or no genuine scope for parental involvement in decisions, and they give no weight to the interests of others. I argue that parental interests should be given some weight in decisions for newborn infants. I develop a new model of decision-making that, using the concept of a Restricted Life, attempts to set out clearly the boundaries of parental discretion in decision-making. I argue that where infants are predicted to have severe cognitive or very severe physical impairment parents should be permitted to request either withdrawal or continuation of treatment. I justify this model on the basis of overlapping interests, (prognostic, experiential and moral) uncertainty, asymmetrical harms, and the burden of care. In the conclusion, I set out a guideline for the use of MRI in newborn infants with hypoxic-ischaemic encephalopathy. I suggest that this guideline would provide a more robust, coherent and practical basis for decision-making in newborn intensive care.

Acute myocardial infarction (AMI), caused by ischaemic heart disease (IHD), is a leading cause of death in both men and women in the western society. Hypertension, diabetes, and smoking are examples of well-known risk factors of IHD, but also there are psychosocial factors, such as stress, vital exhaustion (unusual fatigue, irritability, and demoralization) and depression that have been associated with an increased risk in both genders. After an AMI, however, women are more likely than men to be psychosocially impaired resulting in suffering and a presumed increase in the risk of recurrent cardiac events. Psychosocial factors may be targeted in secondary prevention, complementary to drug treatment and conventional lifestyle advice. There is some evidence of beneficial effects on both psychosocial well-being and cardiac outcomes by psychosocial interventions in men. Far fewer women have been studied and the results have been inconsistent. It is not clear how psychosocial factors convey the increased risk of cardiac events, but many possible psychopathological mechanisms, including biochemical and physiological links, have been suggested. In the Women’s Hearts study we have, in a randomised controlled trial, evaluated a one-year cognitive-behavioural stress management programme designed specifically for women with IHD. We included 198 women with IHD, with a mean age of 61 years and from the county of Västerbotten in Northern Sweden, who were randomised to either conventional treatment and follow-up, or to stress management in addition to conventional care. Extensive questionnaires, blood samplings, and biomedical and physiologic data were obtained before randomisation, as well as at follow-ups approximately one and two years after randomisation. Two groups of healthy controls were included for comparisons with women with IHD. Compared to women without IHD, women with IHD reported more stress behaviour and vital exhaustion. Women with IHD also had a lower heart rate variability (HRV) than the healthy controls, possibly reflecting a dysfunctional autonomic nervous regulation of the heart. Reduced HRV has been shown to increase the risk of cardiac arrhythmias and sudden death. At the first follow-up, performed at the end of the one-year stress management programme, women who had participated in the programme had reduced the stress behaviour and vital exhaustion, compared to the women in the conventional care group. We could not find any evidence of a direct cause-effect relationship between stress management and biological cardiovascular risk indicators, or HRV; the intervention and control groups did not differ in insulin resistance, inflammatory, haemostatic and fibrinolytic factors, or HRV. At second follow-up one year later, several additional psychosocial domains were studied. The stress management programme had accelerated psychosocial recovery at the first follow-up over and above that observed in the control group. At the second follow-up, there was further marked improvement in the control group, so the differences in psychosocial variables between the intervention and control groups were no longer significant. In conclusion, a cognitive-behavioural stress management programme could accelerate psychosocial improvement in women with IHD, and thus reduce the amount of psychological and psychosocial suffering. We could not find any evidence that the stress management programme was associated with a concomitant improvement in biological cardiovascular risk indicators, or HRV. Our results suggest that the women with the greatest psychosocial burden should be identified and targeted in new clinical trials of cognitive-behavioural interventions in women with IHD. Future studies within the Women’s Hearts project will evaluate the psychosocial effects at a five-year follow-up, as well as investigations of other possible pathways by which psychosocial interventions might mediate beneficial effects on cardiac events.

In ischaemic stroke a disruption of cerebral blood flow leads to impaired metabolism and the formation of an ischaemic penumbra in which tissue at risk of infarction is sought for clinical intervention. In stroke trials, therapeutic intervention has largely been based on perfusion-weighted measures, but these have not been shown to be good predictors of tissue outcome. The aim of this thesis was to develop analysis techniques for magnetic resonance imaging (MRI) of chemical exchange saturation transfer (CEST) in order to quantify metabolic signals associated with tissue fate in patients with acute ischaemic stroke. This included addressing robustness for clinical application, and developing quantitative tools that allow exploration of the in-vivo complexity. Tissue-level analyses were performed on a dataset of 12 patients who had been admitted to the John Radcliffe Hospital in Oxford with acute ischaemic stroke and recruited into a clinical imaging study. Further characterisation of signals was performed on stroke models and tissue phantoms. A comparative study of CEST analysis techniques established a model-based approach, Bloch-McConnell model analysis, as the most robust for measuring pH-weighted signals in a clinical setting. Repeatability was improved by isolating non-CEST effects which attenuate signals of interest. The Bloch-McConnell model was developed further to explore whether more biologically-precise quantification of CEST effects was both possible and necessary. The additional model complexity, whilst more reflective of tissue biology, diminished contrast that distinguishes tissue fate, implying the biology is more complex than pH alone. The same model complexity could be used reveal signal patterns associated with tissue outcome that were otherwise obscured by competing CEST processes when observed through simpler models. Improved quantification techniques were demonstrated which were sufficiently robust to be used on clinical data, but also provided insight into the different biological processes at work in ischaemic tissue in the early stages of the disease. The complex array of competing processes in pathological tissue has underscored a need for analysis tools adequate for investigating these effects in the context of human imaging. The trends herein identified at the tissue level support the use of quantitative CEST MRI analysis as a clinical metabolic imaging tool in the investigation of ischaemic stroke.

Background: Patients with carotid artery dissection (CAD) have been reported to have different vascular risk factor profiles and clinical outcomes to those with vertebral artery dissection (VAD). However, there are limited data from recent, large international studies comparing risk factors and clinical features in patients with cervical artery dissection (CeAD) with other TIA or ischemic stroke (IS) patients of similar age and sex. Methods: We analysed demographic, clinical and risk factor profiles in TIA and IS patients ≤ 55 years of age with and without CeAD in the large European, multi-centre, Stroke In young FAbry Patients 1 (sifap1) study. Patients were further categorised according to age (younger: 18–44 years; middle-aged: 45–55 years), sex, and site of dissection. Results: Data on the presence of dissection were available in 4,208 TIA and IS patients of whom 439 (10.4%) had CeAD: 196 (50.1%) had CAD, 195 (49.9%) had VAD, and 48 had multiple artery dissections or no information regarding the dissected artery. The prevalence of CAD was higher in women than in men (5.9 vs. 3.8%, p < 0.01), whereas the prevalence of VAD was similar in women and men (4.6 vs. 4.7%, n.s.). Patients with VAD were younger than patients with CAD (median = 41 years (IQR = 35–47 years) versus median = 45 years (IQR = 39–49 years); p < 0.01). At stroke onset, about twice as many patients with either CAD (54.0 vs. 23.1%, p < 0.001) or VAD (63.4 vs. 36.6%, p < 0.001) had headache than patients without CeAD and stroke in the anterior or posterior circulation, respectively. Compared to patients without CeAD, hypertension, concomitant cardiovascular diseases and a patent foramen ovale were significantly less prevalent in both CAD and VAD patients, whereas tobacco smoking, physical inactivity, obesity and a family history of cerebrovascular diseases were found less frequently in CAD patients, but not in VAD patients. A history of migraine was observed at a similar frequency in patients with CAD (31%), VAD (27.8%) and in those without CeAD (25.8%). Conclusions: We identified clinical features and risk factor profiles that are specific to young patients with CeAD, and to subgroups with either CAD or VAD compared to patients without CeAD. Therefore, our data support the concept that certain vascular risk factors differentially affect the risk of CAD and VAD.