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Many blood markers have been associated with stroke. I set out to determine whether blood markers can be applied to: (i) improve the accuracy of the clinical diagnosis of stroke or TIA, and/or (ii) improve the prediction of poor outcome in patients who are still symptomatic at the time of admission with stroke or TIA. I systematically reviewed the existing literature on the diagnostic performance of a range of blood markers measured soon after stroke onset, to inform the choice of markers for my subsequent prospective studies in this thesis. Many studies had deficiencies in their design, which may have explained the apparently – and perhaps spuriously - impressive diagnostic performance of several markers. In the light of these data I was able to improve the design of my own studies and suggest how future studies of diagnostic markers could be improved. In order to define an appropriate comparator test for assessing the diagnostic accuracy of blood markers, I first examined the performance of emergency room nurses and doctors. I assessed the accuracy of their diagnosis of TIA or stroke (‘acute cerebrovascular disease’) in patients presenting with symptoms of suspected stroke, and compared them with a number of stroke diagnostic scales. In the 405 patients recruited to the study, the sensitivity of emergency department staff was 77% and specificity 58%. Each stroke diagnostic scale had a slightly better sensitivity, though worse specificity, than an emergency department clinician. I decided to use the diagnosis by an emergency department clinician of ‘probable or definite acute cerebrovascular disease’ as the best clinical performance reference standard. In blood taken from the same cohort of 405 patients, accredited research laboratories measured markers of inflammation, thrombosis, thrombolysis, cardiac strain and cerebral damage. Tissue plasminogen activator and loge N-terminal pro brain natriuretic peptide were associated positively with a diagnosis of acute cerebrovascular disease, though each marker did not add diagnostic value to the diagnosis of an emergency department doctor or nurse. I systematically reviewed the literature examining the association between the levels of blood markers with poor outcome (i.e. death or dependency) after stroke. I found that although almost all markers studied had a positive association with poor outcome, there were methodological problems with many studies, chiefly small sample size, publication bias or within study reporting biases, and lack of adjustment for important confounders such as age or stroke severity. With data from the Edinburgh Stroke Study, I examined the association between circulating markers of the inflammatory response (white cell count, interleukin-6, Creactive protein and fibrinogen) and poor outcome after stroke. After adjustment for age, whether the patient lived alone, was independent of activities of daily living, was orientated, able to lift both arms and able to walk, I found that higher levels of interleukin-6, white cell count and glucose were associated with poor outcome. The relevant test of a biological marker is not its predictive ability alone, but whether, when added to a validated predictive model based on clinical variables, it improves the prediction of outcome. No individual marker improved the prediction of poor outcome when added to a validated prognostic model based on clinical variables alone. From my cohort of 405 patients with suspected stroke 285 patients had a confirmed diagnosis. Follow up of these 285 patients with confirmed acute cerebrovascular disease showed that, after adjustment for neurological impairment and age, only interleukin-6 and N-terminal pro brain natriuretic peptide were significantly associated with death or disability at 3 months. Neither marker improved the predictions of a model to predict poor outcome based on clinical variables alone. To examine the relationship between circulating markers of the inflammatory response and recurrent stroke, myocardial infarction, and vascular death (‘recurrent vascular events’), again I used data from the Edinburgh Stroke Study. After adjustment for clinical predictors (age, prior MI, stroke, or TIA and AF) I found that higher levels of interleukin-6, C-reactive protein and fibrinogen remained significantly associated with an increased risk of recurrent vascular events. However, the relationship with deaths from all causes was somewhat stronger for each marker, perhaps suggesting that higher marker levels were associated with debility rather than vascular events per se. In conclusion, I found no marker measured could improve on the diagnostic accuracy of an emergency department clinician for acute cerebrovascular disease, nor improve the prediction of poor outcome by a prognostic model based upon clinical variables. The work of this thesis does not support the routine use of blood markers as an aid to the diagnosis of, or the prediction of outcome of, acute stroke.

The use of exercise is a valuable tool in the healthcare management of young patients with chronic chest diseases (CCD). Indeed, exercise testing yields important prognostic data which are a strong predictor of survival. Such information can indicate to the clinician to increase drug therapy treatment, and functional capacity of the patient can be monitored over time with repeated testing. Exercise training has been shown to improve both aerobic and anaerobic fitness and quality of life in patients with lung disease. The use of exercise testing and training in the healthcare of patients with lung disease in the UK, however, has not been investigated. In order for recommendations for exercise testing and training based on scientific evidence to be implemented, they should relate to current standards and resources. Therefore, the first study of the present thesis sought to characterise the use of both exercise testing and training in UK Cystic fibrosis (CF) clinics through a nationwide audit. Data from the audit showed that exercise testing and training are underused despite recognition of the importance of each in the healthcare of the patient by clinicians and other healthcare providers. Indeed, resources for exercise testing in UK CF clinics are limited. A patient over the age of 8 y will only have a 41.1 % chance of receiving an exercise test of any type over a 12 month period, and the exercise test will be quite crude. Exercise training is frequently discussed with the patient; however, there is a strong likelihood (72.9 %) that the advice given will only be general encouragement. The prognostic value of exercise testing is becoming increasingly recognised. Indeed, peak oxygen uptake (VO2peak) derived through maximal cardiopulmonary exercise testing (CPET) has been reported to be equal or superior to that of resting spirometric lung function tests in the prognostic evaluation of patients with CCD. Furthermore, a high correlation between VO2peak and long term survival in both adults and children with CF has been reported. Other physiological data from CPET, such as oxygen uptake (VO2) recovery following CPET, has not been investigated in young patients with CCD and may provide an additional physiological marker of patient health. The aim of study two, therefore, was to investigate recovery following CPET in young patients with CCD, and determine if any significant relationships exist between VO2 recovery and measures of disease severity in these patients. Data from study two showed that young patients with CCD compared to healthy controls had significantly reduced aerobic fitness (t52 = - 2.64, P = 0.011), and the fast component of the VO2 recovery following CPET, analysed by a mono-exponential model, is significantly prolonged (t52 = 2.63, P = 0.011). Furthermore, the fast component of the VO2 recovery is significantly related to disease severity, as assessed by the Shwachman score (SS), in the CF subgroup (r = - 0.75, P < 0.001), and as assessed by forced expiratory volume in 1 s (FEV1), in the young patients with CCD (r = - 0.49, P = 0.009). Thus, indicating that greater disease severity is associated with a longer VO2 recovery following CPET. A significant relationship between VO2peak and VO2 recovery was shown in the young patients with CCD (r = - 0.45, P = 0.018). Although the relationship is significant, however, it is still quite weak, and, therefore, indicates that the VO2 recovery is not closely related to the VO2peak in these patients. Quality of life and likelihood of survival are greater in patients with CCD with higher levels of aerobic fitness, and regular exercise has been shown to improve both lung function and exercise capacity in these patients. Indeed, exercise training programmes tailored to the individual patient are recommended in the standards of patient healthcare in the UK. Whilst the chronic effects of regular exercise have been investigated, the acute physiological responses to exercise training have not been studied in young patients with CCD. In study three young patients with CCD and healthy controls performed intermittent exercise (IE) designed to replicate the typical activity and exercise patterns of young people. Following IE, in the healthy controls the VO2 required to sustain moderate steady-state exercise fell significantly from 3 min to 1 h and 1 h to 24 h, however, in the young patients with CCD VO2 during moderate steady-state exercise increased significantly from 3 min to 1 h and then decreased significantly from 1 h to 24 h (main effect for time: F1.5,79.2 = 22.82, P < 0.001). A significant time × group interaction between young patients with CCD and controls in VO2 during moderate steady-state exercise 3 min, 1 h and 24 h following IE (interaction: F1.5,79.4 = 30.01, P < 0.001) may suggest that metabolic stress is still evident over this time period, which may be indicative of fatigue. Data from the present thesis shows that exercise is underused in UK CF clinics, with the availability of equipment and personnel both being limiting factors. Furthermore, a lack of standardisation in the provision of exercise between clinics is evident. In studies two and three, data shows different physiological responses following CPET and IE, respectively, between children with CCD and controls. The present thesis has advanced our understanding of the provision of exercise in the healthcare of CF in the UK, and furthered knowledge in how young patients with CCD respond physiologically to exercise.

Cone beam computed tomography (CBCT) is the recommended imaging modality of choice for evaluating previous endodontic treatment (1). The aim of this study was to compare treatment planning decisions made when evaluating previous endodontic treatment to determine if treatment planned and projected prognosis differs when digital radiography is used alone or in combination with CBCT. A retrospective chart review was conducted. Patients for whom a CBCT was taken were included in the study. Twenty-eight patients qualified. Patient’s periapical digital radiographs (Dexis©) were evaluated by 2 calibrated endodontists, a treatment plan was identified and a prognosis was projected. Later the same radiographs were viewed with CBCT scan. The CBCT provided significant information 75% of the time. CBCT provided the only information for an accurate diagnosis 17% of the time. Prognosis changed 38% of the time when CBCT was added. An unfavorable or questionable prognosis changed to favorable 30% of the time.

No description available.

Introdução: Os neuroblastomas apresentam grande diversidade de comportamento clínico, evoluindo desde remissão espontânea à rápida progressão e morte. Heterogeneidade clínica e biológica tem implicado em grande variedade de respostas terapêuticas, inclusive em crianças maiores de 1 ano e em estádios avançados. Objetivo: estudar quadro clínico, aspectos epidemiológicos, características laboratoriais, genéticas e histológicas em crianças maiores de 1 ano portadoras de neuroblastoma disseminado, correlacionando-os com a evolução clínica e tentando definir fatores de risco que possam influir na sobrevida e na possibilidade da indicação do transplante de medula óssea (TMO). Casuística e Métodos: as informações foram obtidas de 53 pacientes admitidos na Unidade de Oncologia (ITACI) do Instituto da Criança do HC-FMUSP no período de 1997 a 2007. Os pacientes foram estudados quanto aos seguintes fatores: sexo, idade, raça, estado nutricional, DHL, Hb, ferritina, VMA, características tumorais (tamanho, localização, metástases, histologia, MYCN), terapêutica utilizada e evolução clínica. Estudamos separadamente também os fatores preditivos para TMO. Resultados: devem ser destacados: 1) crianças submetidas à cirurgia retardada completa apresentam 5 vezes menor chance de óbito do que as demais; 2) pacientes submetidos a TMO apresentam maior sobrevida total e livre de eventos em relação ao grupo não submetido a essa modalidade terapêutica 3) a utilização de retinóides gera 14 vezes menor chance de óbito em relação ao grupo que não os utiliza. 4) surpreendentemente, pacientes com ferritina abaixo de 334 n/ug/l apresentam 8 vezes maior chance de óbito. Conclusões: Não identificamos parâmetros clínicos e laboratoriais, práticos e facilmente disponíveis, de prognóstico para subpopulações de neuroblastomas de prognóstico avançado, sendo o estudo de fatores de ordem molecular e biológicos essenciais, apesar das dificuldades em realizá-lo / Introduction: Neuroblastomas (NB) have widely diverse clinical behavior, moving from spontaneous remission to progression and death. Clinical and biological heterogeneity factors determine different survival, even with children older than 1 year in advanced stages. Objective: to study the clinical presentation, epidemiology, laboratory findings, genetics and histopathologic characteristics in children older than 1 year with advanced neuroblastoma and their correlation with the survival. Also defining prognostic variables for bone marrow transplantation (BMT) indication. Casuistic and Methods: 53 selected medical records from patients older than 1 year with advanced NB admitted to the Instituto da Criança do HC-FMUSP from 1997 to 2007 were reviewed. The following risk factors were analyzed: age, sex, race, nutritional status, LDH, hemoglobin level, ferritin level, urinary VMA, tumor characteristics such as: site, histology, size, metastases, MYCN, treatment and clinical course. Results: it should be mentioned that: 1) possibility of death in children who underwent complete second look is 5 times lower than remaining ones; 2) patients who underwent BMT have better overall survival and event-free survival in comparison to the group not receiving this treatment modality. 3) the use of retinoids generates 14 times less chance of death in comparison to the group not receiving them. 4) patients whose ferritin level was below 334 n/ug/l had surprisingly 8 times more chances to die from diseases Conclusions: no simple and easily obtainable prognostic variables in a subpopulation of patients with advanced stage neuroblastoma, suitable to be widely employed in a country as ours, were identified. The study of molecular and biologics factors remains essential for precise characterization of these patients

by Anthony Tak Cheung Chan. / "March 1998." / Thesis (M.D.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (p. 200-242). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstract in Chinese.