/library/oar/handle/123456789/29421 2026-05-26T09:55:14Z /library/oar/handle/123456789/135034 Title: Coronary risk reduction intervention for siblings and offspring of patients with premature coronary heart disease : the CRISO project Abstract: This work and its abstract are both under embargo until the restriction is lifted. Description: Ph.D.(Melit.) 2024-01-01T00:00:00Z /library/oar/handle/123456789/108077 Title: Impact of outdoor and indoor air quality in secondary schools and homes on children’s respiratory health in Malta Abstract: Background: As seen in the International Study of Asthma and Allergies in Childhood (ISAAC) studies, children in Malta have a very high prevalence of symptoms pertaining to asthma and allergies. It is also one of the most densely populated countries in the world, with a high vehicular density, a central industrial and maritime hub and two coastal power stations running on heavy fuel oil. One of the main risk factors for asthma remains air pollution, known to worsen asthma prevalence and its control, particularly amongst children. Particulate matter (PM) of aerodynamic diameter of less than 2.5 micrometres (PM2.5), has quickly become known as one of the most ubiquitous and dangerous air pollutants of our times, able to penetrate deeply within the lung, due to its small size. Malta has often reported very high outdoor concentrations of PM2.5, yet we know little about the local respiratory morbidity caused by this PM. In Malta, indoor PM2.5 concentrations has been even less well studied, yet schoolchildren spend the majority of their times indoors, either at school or at home. Recently the SINPHONIE study looked into the respiratory effects of indoor air pollution at primary schools in Malta. However, there are no studies on the effects of outdoor and indoor PM2.5 concentrations amongst our Maltese adolescents, at their schools and homes. The primary aim of the present research study was to look at the effects of analysed PM2.5 levels and its components, on the respiratory symptoms in Malta amongst adolescent school children; comparing the indoor and outdoor levels at the schools they attended and the homes they live in. The assessment was performed in two ways: Associations of PM exposures with asthma cases and controls, as well as children living in the different geographical locations in Malta. Finally, the results of this research were compared with the closest neighbouring country Sicily, with whom as a population, there are similarities in climate and culture, and with whom the RESPIRA study collaborated. Particulate matter remains the most heterogenous and complex air pollutant, differing in its composition depending on the sources present, as well as with its interplay with weather and seasonality. Thus, its main components were studied by collecting PM2.5 was analysing its constituent elements (anions, cations, metal oxides), and its elemental and organic carbon content. We also studied variations in its concentrations in accordance with weather changes and various dwelling characteristics. Method: The study was started during the scholastic years of 2012 and 2013, with six secondary schools included from the north, south and central localities of Malta. Using a validated RESPIRA questionnaire, based on the ISAAC questionnaire, an assessment of the current prevalence of respiratory symptoms, asthma and allergies amongst the Maltese adolescents was preformed, together with information on their school and home environment, in order to identify children who are symptomatic cases from asymptomatic controls. Within the same time period, the indoor and outdoor PM2.5 was collected at the schools and homes of the case / control cohort. PM2.5 was collected by gravimetric impaction onto teflon and quartz filters for both quantitative and qualitative analysis, allowing for the identification of the PM2.5 components (i.e., sea, crustal, secondary inorganics, traffic and organic PM components). Further data was obtained from the two Environment and Resource Authority (ERA) PM2.5 monitoring stations in Malta, with accompanying weather data from the Luqa airport meteorological office, for the study period held in 2012. At the schools, traffic counts of passenger cars and heavy vehicles were also collected. For both schools and homes, specific building characteristics were noted, which could affect their outdoor and indoor air quality. Results:1075 secondary schoolchildren and 862 parents participated in the study by completing the questionnaires: 380 males; 482 females (male to female ratio of 1:1.3); mean age of 12.5 years; mean BMI of 21.5 kg/m2. There was a high prevalence of asthma and allergies in Malta, which was consistent with previous ISAAC studies: cumulative and current wheezing at 32% and 13% respectively; doctor diagnosed asthma at 18%; cumulative and current rhinitis at 31% and 27% respectively. This current research found elevated outdoor PM2.5, Elemental Carbon (EC) and Organic Carbon (OC) concentrations, above the WHO, US-EPA and EU safety thresholds for PM. The indoor PM2.5 was significantly higher than the outdoors, particularly during the colder months due to insulation and domestic heating. Outdoor organic PM components were found to be associated with increased respiratory morbidity amongst secondary schoolchildren, including chronic cough, dry and irritative cough, sore throat and wheezing on exercise. The highest prevalence for asthma and allergies was found in the central area of Ħamrun, which is highly urbanised and contains the industrial and maritime-hub, together with a local power-station. The highest indoor and outdoor PM2.5, traffic and organic components were recorded in the central area of Ħamrun. There were no significant differences in pollutant levels between schools and homes, and minimal differences between cases and controls. However, there were some important building characteristics which effected the PM2.5, EC and OC concentrations including dwelling type (i.e., flats), smaller living spaces and lesser window apertures, the use of fireplaces for domestic heating and indoor smoking. Description: Ph.D.(Melit.) 2022-01-01T00:00:00Z /library/oar/handle/123456789/106677 Title: A study focused on the biological effects of pleural fluid in mesothelioma, and an analysis of the feasibility of a personalised bench-to-bedside pathway for mesothelioma treatment Abstract: Background and aims: Malignant pleural mesothelioma (MPM) carries a poor prognosis and more than half MPM patients do not show disease response to cancer drugs. A more personalised effective approach to MPM treatment is desirable, and the timely development of personalised MPM cell cultures and analysis of drug response/resistance profiles may help guide clinical management of MPM. MPM or pleural metastases often present with malignant pleural effusion (MPE). There is early pre-clinical evidence of potential biological properties of MPE fluid that may contribute to cancer cell proliferation. Current management of MPE is symptomatic. Should pleural fluid have biological properties, management of MPE may shift towards a more aggressive approach in order to impact on patient survival. This study aimed to: a) Analyse a database of MPM patients to explore associations between pleural fluid and survival. b) Develop patient-derived MPM cell cultures from MPE fluid, with high success rate; develop cell cultures from the same patient at different time points. c) Analyse the effects of pleural fluid on cancer cells in vitro. d) Provide a description of potential future directions of research. e) Conduct drug screening assays on MPM cell cultures, to assess feasibility of a bench-to-bedside pathway from MPM MPE fluid to drug resistance/response profiles which would be clinically relevant and useful. Methodology: a) Data on MPM patients (in 3 UK pleural units) were collected and analysed. b) MPM cell cultures were established from MPE samples. c) Cells from established, patient-derived, cancer cell cultures were seeded in pleural fluid, and cell proliferation monitored. Primary MPM cell culture was attempted in 100% MPE fluid, with primary MPM cell culture in complete medium as a control. d) A literature review of animal models studying MPE and MPM, and an experimental model I was involved in the development of, were used to design animal models utilising indwelling pleural catheters to investigate the effects of MPE on pleural tumour growth and on chemotherapy response in vivo. e) DNA sequencing and drug screening were performed on MPM cell cultures. Discussion and conclusions: Pleurodesis success appears to be associated with improved survival. It is unclear whether prolonged exposure to MPE affects MPM tumour proliferation in humans. This data serves to highlight the need for prospective data and can be used to guide the direction of future study designs. MPM cell cultures were established from MPE fluid samples with a high success rate, had recognisable malignant features on cytology, included cancer stem cells, and had similar variant profile to MPM tumours. The cell cultures were used to perform quality drug screening assays and DNA sequencing, and the feasibility of a bench to bedside pathway was shown, with the cell cultures as potential tools to refine patient management in MPM. Cancer cells proliferate strongly in 100% pleural fluid, and to our knowledge this is the first demonstration of this effect, which potentially reflects the intrapleural environment in vivo. Although the mechanism is unclear, any form of human pleural fluid (malignant, nonmalignant, transudate, exudate) appears to have this effect, and this has potentially significant mechanistic and clinical implications. Moreover, this is the first time that primary cancer cell culture has been performed using pleural fluid alone. Description: Ph.D.(Melit.) 2022-01-01T00:00:00Z /library/oar/handle/123456789/33205 Title: Development of a prediction model for the diagnosis of suspected acute poisoning Abstract: The diagnosis of acute poisoning is based on clinical assessment, electrocardiography and laboratory investigations. Diagnosis of acute poisoning in patients with altered mental status is challenging because an accurate history may be unavailable or unreliable and clinicians rely on clinical assessment, whilst the role of screening toxicology tests in such patients is not clear. The aim of the project was to develop a prediction model derived from clinical risk factors that would help in the diagnosis of suspected acute poisoning. In the first phase of the project, reliability of a history of poisoning and characteristics of patients with suspected acute poisoning presenting to Mater Dei Hospital, Malta were investigated. The second phase of the project involved development, validation and testing of a prediction model for the diagnosis of acute poisoning in patients with altered mental status. The reliability of a history of poisoning was measured by a meta-analysis of studies comparing history of poisoning with diagnosis, showing that history was moderately reliable and varied with different drugs. Pooled kappa for the reliability of a history of paracetamol poisoning was 0.67 (95%CI 0.64-0.71) whilst history of drugs of abuse was less reliable with a pooled kappa ranging from 0.35 (95%CI 0.14-0.56) for MDMA to 0.48 (95%CI 0.41-0.54) for opiates. Features of patients with suspected acute poisoning referred for toxicology investigations were evaluated by comparing clinical features with toxicology laboratory results evaluating demographics, differential diagnosis, range of ingested drugs and diagnostic yield. 51.7% (350/677) had confirmed acute poisoning, classified as primary alcohol intoxication and drug overdose in 28.3% (99/350) and 69.7% (244/350)' respectively. Toxicology testing was carried out on 677 patients of which 464/677 (68.5%) were positive. Univariate analysis identified significant diagnostic factors for acute poisoning and although individual parameters had limited prognostic value, composite clinical scores were accurate predictors of poisoning severity. Based on these results, it was determined that a prediction model would be suitable for diagnosis of poisoning in patients with altered mental status. In the second phase of the project, clinical data were gathered on patients presenting with altered mental state and their characteristics were studied. Mean age was 54 years and 55.4% (484/873) were males. Age and gender distribution varied according to diagnosis. Drug overdose and isolated alcohol intoxication was present in 21.4% (187/873) and 14.4% (126/873) respectively. A history of overdose was present in 17.1% (149/873) whilst 15.8% (138/873) had a history of alcohol ingestion. 45.5% of patients with AMS had a toxicology investigation of which 66% had a detectable drug result. Univariate analysis identified significant diagnostic variables. A prediction model based on significant clinical risk factors was developed for use in stratifying risk of acute poisoning in patients with altered mental status. The model was validated internally and externally and a decision rule for use of screening tests was derived and tested. A simplified risk score was derived from the model and was found to have a negative predictive value of 94.2%. In this project the diagnostic value of clinical factors in suspected acute poisoning was investigated and a prediction model based on selected predictive factors was developed, validated and applied into a decision rule that was simple to calculate and may be of value in a pre-hospital environment or at triage. Description: PH.D. 2017-01-01T00:00:00Z