High-dose therapy and autologous stem cell transplantation in first relapse for diffuse large B cell lymphoma in the rituximab era:an analysis based on data from the European Blood and Marrow Transplantation Registry

Autologous stem cell transplantation (ASCT) consolidation remains the treatment of choice for patients with relapsed diffuse large B cell lymphoma. The impact of rituximab combined with chemotherapy in either first- or second-line therapy on the ultimate results of ASCT remains to be determined, however. This study was designed to evaluate the benefit of ASCT in patients achieving a second complete remission after salvage chemotherapy by retrospectively comparing the disease-free survival (DFS) after ASCT for each patient with the duration of the first complete remission (CR1). Between 1990 and 2005, a total of 470 patients who had undergone ASCT and reported to the European Blood and Bone Transplantation Registry with Medical Essential Data Form B information were evaluated. Of these 470 patients, 351 (74%) had not received rituximab before ASCT, and 119 (25%) had received rituximab before ASCT. The median duration of CR1 was 11 months. The median time from diagnosis to ASCT was 24 months. The BEAM protocol was the most frequently used conditioning regimen (67%). After ASCT, the 5-year overall survival was 63% (95% confidence interval, 58%-67%) and 5-year DFS was 48% (95% confidence interval, 43%-53%) for the entire patient population. Statistical analysis showed a significant increase in DFS after ASCT compared with duration of CR1 (median, 51 months versus 11 months; P < .001). This difference was also highly significant for patients with previous exposure to rituximab (median, 10 months versus not reached; P < .001) and for patients who had experienced relapse before 1 year (median, 6 months versus 47 months; P < .001). Our data indicate that ASCT can significantly increase DFS compared with the duration of CR1 in relapsed diffuse large B cell lymphoma and can alter the disease course even in patients with high-risk disease previously treated with rituximab.

Comorbidity in severe asthma requiring systemic corticosteroid therapy: cross-sectional data from the Optimum Patient Care Research Database and the British Thoracic Difficult Asthma Registry

Objective: To determine the prevalence of systemic corticosteroid-induced morbidity in severe asthma.
Design: Cross-sectional observational study.Setting The primary care Optimum Patient Care Research Database and the British Thoracic Society Difficult Asthma Registry.
Participants: Optimum Patient Care Research Database (7195 subjects in three age- and gender-matched groups)—severe asthma (Global Initiative for Asthma (GINA) treatment step 5 with four or more prescriptions/year of oral corticosteroids, n=808), mild/moderate asthma (GINA treatment step 2/3, n=3975) and non-asthma controls (n=2412). 770 subjects with severe asthma from the British Thoracic Society Difficult Asthma Registry (442 receiving daily oral corticosteroids to maintain disease control).
Main outcome measures: Prevalence rates of morbidities associated with systemic steroid exposure were evaluated and reported separately for each group.
Results: 748/808 (93%) subjects with severe asthma had one or more condition linked to systemic corticosteroid exposure (mild/moderate asthma 3109/3975 (78%), non-asthma controls 1548/2412 (64%); p<0.001 for severe asthma versus non-asthma controls). Compared with mild/moderate asthma, morbidity rates for severe asthma were significantly higher for conditions associated with systemic steroid exposure (type II diabetes 10% vs 7%, OR=1.46 (95% CI 1.11 to 1.91), p<0.01; osteoporosis 16% vs 4%, OR=5.23, (95% CI 3.97 to 6.89), p<0.001; dyspeptic disorders (including gastric/duodenal ulceration) 65% vs 34%, OR=3.99, (95% CI 3.37 to 4.72), p<0.001; cataracts 9% vs 5%, OR=1.89, (95% CI 1.39 to 2.56), p<0.001). In the British Thoracic Society Difficult Asthma Registry similar prevalence rates were found, although, additionally, high rates of osteopenia (35%) and obstructive sleep apnoea (11%) were identified.

Conclusions: Oral corticosteroid-related adverse events are common in severe asthma. New treatments which reduce exposure to oral corticosteroids may reduce the prevalence of these conditions and this should be considered in cost-effectiveness analyses of these new treatments.

Myopia, spectacle wear, and risk of bicycle accidents among rural Chinese secondary school students: the Xichang Pediatric Refractive Error Study report no. 7.

OBJECTIVE: To study the effect of myopia and spectacle wear on bicycle-related injuries in rural Chinese students. Myopia is common among Chinese students but few studies have examined its effect on daily activities. METHODS: Data on visual acuity, refractive error, current spectacle wear, and history of bicycle use and accidents during the past 3 years were sought from 1891 students undergoing eye examinations in rural Guangdong province. RESULTS: Refractive and accident data were available for 1539 participants (81.3%), among whom the mean age was 14.6 years, 52.5% were girls, 26.8% wore glasses, and 12.9% had myopia of less than -4 diopters in both eyes. More than 90% relied on bicycles to get to school daily. A total of 2931 accidents were reported by 423 participants, with 68 requiring medical attention. Male sex (odds ratio, 1.55; P < .001) and spectacle wear (odds ratio, 1.38; P = .04) were associated with a higher risk of accident, but habitual visual acuity and myopia were unassociated with the crash risk, after adjusting for age, sex, time spent riding, and risky riding behaviors. CONCLUSION: These results may be consistent with data on motor vehicle accidents implicating peripheral vision (potentially compromised by spectacle wear) more strongly than central visual acuity in mediating crash risk.

Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study)

AIMS: Rheumatic heart disease (RHD) accounts for over a million premature deaths annually; however, there is little contemporary information on presentation, complications, and treatment.

METHODS AND RESULTS: This prospective registry enrolled 3343 patients (median age 28 years, 66.2% female) presenting with RHD at 25 hospitals in 12 African countries, India, and Yemen between January 2010 and November 2012. The majority (63.9%) had moderate-to-severe multivalvular disease complicated by congestive heart failure (33.4%), pulmonary hypertension (28.8%), atrial fibrillation (AF) (21.8%), stroke (7.1%), infective endocarditis (4%), and major bleeding (2.7%). One-quarter of adults and 5.3% of children had decreased left ventricular (LV) systolic function; 23% of adults and 14.1% of children had dilated LVs. Fifty-five percent (n = 1761) of patients were on secondary antibiotic prophylaxis. Oral anti-coagulants were prescribed in 69.5% (n = 946) of patients with mechanical valves (n = 501), AF (n = 397), and high-risk mitral stenosis in sinus rhythm (n = 48). However, only 28.3% (n = 269) had a therapeutic international normalized ratio. Among 1825 women of childbearing age (12-51 years), only 3.6% (n = 65) were on contraception. The utilization of valvuloplasty and valve surgery was higher in upper-middle compared with lower-income countries.

CONCLUSION: Rheumatic heart disease patients were young, predominantly female, and had high prevalence of major cardiovascular complications. There is suboptimal utilization of secondary antibiotic prophylaxis, oral anti-coagulation, and contraception, and variations in the use of percutaneous and surgical interventions by country income level.

Urinary thrombomodulin levels were significantly higher following occupational exposure to chemicals, in the presence of dipstick protein, but not in the presence of dipstick blood

Currently, there are no biomarkers which can identify patients with an increased risk of developing urothelial cancer as a result of occupational chemical exposure. The aim of this study was to evaluate the relationships between final diagnosis and 22 biomarkers measured in urine, serum and plasma collected from 156 hematuric patients. Fourteen of the 80 patients (17.5%) with urothelial cancer and 13/76 (17.1%) of the controls were deemed to have a history of chemical exposure. We applied Fisher's exact tests to explore associations between chemical exposure and final diagnosis, and tumor stage and grade, where applicable; ANOVA and t-test to compare age across patients with and without chemical exposure; and Zelen's exact test to evaluate relationships across final diagnosis, chemical exposure and smoking. Following pre-selection of biomarkers using Lasso, we identified biomarkers with differential levels across patients with and without chemical exposure using Welch's t-test. Using a one-sided t-test and considering multiple testing using FDR, we observed that TM levels in urine were significantly higher in samples from patients with a history of chemical exposure regardless of their diagnosis as control or urothelial cancer (one-sided t-test, p_UC = 0.014 and p_CTL = 0.043); in the presence of dipstick protein and when urinary pH levels ≤ 6 (p = 0.003), but not in the presence of dipstick blood (p = 0.115). Urothelial cancer patients with a history of chemical exposure were significantly younger (64.1 years) than those without chemical exposure (70.2 years) (one-sided t-test p-value = 0.012); and their tumors were higher grade (Fisher's exact test; p = 0.008). There was a strong association between a history of chemical exposure and smoking in urothelial cancer patients (Zelen's exact test; p = 0.025). Elevated urinary thrombomodulin levels could have the potential to identify chemical exposure in hematuric patients at high risk of developing urothelial cancer.

Selection and combination of biomarkers to control and prevent the risk of occupational exposure to the mixture of lead, arsenic and manganese

Tese de doutoramento, Farmácia (Toxicologia), Universidade de Lisboa, Faculdade de Farmácia, 2014

Bridging the Divide in Work and Occupational Psychology: Evidence From Practice

This study explores the extent to which work and organizational (W&O) psychology practitioners use evidence, how they apply it to the everyday contexts in which they work and the types of barriers they encounter in so doing. It adopts a mixed methods approach involving the administration of a survey to a UK sample (N=163) of W&O psychologists and a series of semi-structured interviews (N=25) exploring in greater depth how evidence is applied in practice. Findings reveal that practitioners consult a wide range of different types of evidence which they employ at various stages of engagement with client organisations and that this evidence is pressed into service in the pursuit of solutions which are both acceptable from the client perspective and consistent with the scientific standards underpinning professional knowledge and expertise in W&O psychology. Barriers to evidence-use were mainly practical in nature, concerning issues around managing the client-consultant relationship and the particularities of implementation context, both of which were shown to influence evidence utilisation. The study contributes to current debate on the extent to which W&O psychologists adopt an evidence-based approach and provides a valuable and much called-for empirical insight into the enactment of the scientist-practitioner model in W&O psychology

The First Year Experience of Occupational Therapy Students at an Australian Regional University: Promoting Student Retention and Developing a Regional and Remote Workforce

Abstract Objective: Student retention at regional universities is important in addressing regional and remote workforce shortages. Students attending regional universities are more likely to work in regional areas. First year experience at university plays a key role in student retention. This study aimed to explore factors influencing the first year experience of occupational therapy students at a regional Australian university. Design: Surveys were administered to 58 second year occupational therapy students in the first week of second year. Data were analysed using descriptive statistics, inferential statistics (Pearson χ2; Spearman rho) and summarising descriptive responses. Setting: An Australian regional university. Participants: Second year undergraduate occupational therapy students. Main outcome measures: Factors influencing students’ decisions to study and continue studying occupational therapy; factors enhancing first year experience of university. Results: Fifty-four students completed the survey (93.1%). A quarter (25.9%) of students considered leaving the course during the first year. The primary influence for continuing was the teaching and learning experience. Most valued supports were orientation week (36.7%) and the first year coordinator (36.7%). Conclusion: The importance of the first year experience in retaining occupational therapy students is highlighted. Engagement with other students and staff and academic support are important factors in facilitating student retention. It is important to understand the unique factors influencing students’ decisions, particularly those from regional and remote areas, to enter and continue in tertiary education to assist in implementing supports and strategies to improve student retention.

The brain-sex theory of occupational choice: a counterexample

The brain-sex theory of occupational choice suggests that males and females in male-typical careers show a male pattern of cognitive ability in terms of better spatial than verbal performance on cognitive tests with the reverse pattern for females and males in female-typical careers, These differences are thought to result from patterns of cerebral functional lateralisation. This study Sought Such occupationally related effects using synonym generation (verbal ability) and mental rotation (spatial ability) tasks used previously. It also used entrants to these careers as participants to examine whether patterns of cognitive abilities might predate explicit training and practice. Using a population of entrants to sex-differentiated University Courses, a moderate occupational effect on the synonym generation task was found, along with a weak (p<.10) sex effect on the mental rotation task. Highest performance on the mental rotation task was by female Students in fashion design, a female-dominated occupation which makes substantial visuospatial demands and attracts many students with literacy problems such as dyslexia. This group then appears to be a counterexample to the brain-sex theory. However, methodological issues Surrounding previous Studies are highlighted: the simple synonym task appears to show limited discrimination of the sexes, leading to questions concerning the legitimacy of inferences about lateralisation based on scores from that test. Moreover, the human figure-based mental rotation task appears to tap the wrong aspect of visuospatial skill, likely to be needed for male-typical courses such as engineering, Since the fashion-clesign career is also one that attracts disproportionately many male students whose sexual orientation is homosexual, data were examined for evidence of female-typical patterns of cognitive performance among that subgroup. This was not found. This study therefore provides Do evidence for the claim that female-pattern cerebral functional lateralisation is likely in gay males.

Occupational exposure to environmental tobacco smoke in hospitality venues: are genetic- or proteomics-based biomarkers predictive of respiratory diseases?

Environmental tobacco smoke (ETS) is recognized as an occupational hazard in the hospitality industry. Although Portuguese legislation banned smoking in most indoor public spaces, it is still allowed in some restaurants/bars, representing a potential risk to the workers’ health, particularly for chronic respiratory diseases. The aims of this work were to characterize biomarkers of early genetic effects and to disclose proteomic signatures associated to occupational exposure to ETS and with potential to predict respiratory diseases development. A detailed lifestyle survey and clinical evaluation (including spirometry) were performed in 81 workers from Lisbon restaurants. ETS exposure was assessed through the level of PM 2.5 in indoor air and the urinary level of cotinine. The plasma samples were immunodepleted and analysed by 2D-SDSPAGE followed by in-gel digestion and LC-MS/MS. DNA lesions and chromosome damage were analysed innlymphocytes and in exfoliated buccal cells from 19 cigarette smokers, 29 involuntary smokers, and 33 non-smokers not exposed to tobacco smoke. Also, the DNA repair capacity was evaluated using an ex vivo challenge comet assay with an alkylating agent (EMS). All workers were considered healthy and recorded normal lung function. Interestingly, following 2D-DIGE-MS (MALDI-TOF/TOF), 61 plasma proteins were found differentially expressed in ETS-exposed subjects, including 38 involved in metabolism, acute-phase respiratory inflammation, and immune or vascular functions. On the other hand, the involuntary smokers showed neither an increased level of DNA/chromosome damage on lymphocytes nor an increased number of micronuclei in buccal cells, when compared to non-exposed non-smokers. Noteworthy, lymphocytes challenge with EMS resulted in a significantly lower level of DNA breaks in ETS-exposed as compared to non-exposed workers (P<0.0001) suggestive of an adaptive response elicited by the previous exposure to low levels of ETS. Overall, changes in proteome may be promising early biomarkers of exposure to ETS. Likewise, alterations of the DNA repair competence observed upon ETS exposure deserves to be further understood. Work supported by Fundação Calouste Gulbenkian, ACSS and FCT/Polyannual Funding Program.

Occupational exposure to particulate matter and respiratory symptoms in Portuguese swine barn workers

Certain environmental conditions in animal and plant production have been associated with increased frequency in respiratory illnesses, including asthma, chronic bronchitis, and hypersensitivity pneumonitis, in farmers occupationally exposed in swine production. The aim of this study was to characterize particulate matter (PM) contamination in seven Portuguese swine farms and determine the existence of clinical symptoms associated with asthma and other allergy diseases, utilizing the European Community Respiratory Health Survey questionnaire. Environmental assessments were performed with portable direct-reading equipment, and PM contamination including five different sizes (PM0.5, PM1.0, PM2.5, PM5.0, PM10) was determined. The distribution of particle size showed the same trend in all swine farms, with high concentrations of particles with PM5 and PM10. Results from the questionnaire indicated a trend such that subjects with diagnosis of asthma were exposed to higher concentrations of PM with larger size (PM2.5, PM5, and PM10) while subjects with sneezing, runny nose, or stuffy nose without a cold or flu were exposed to higher concentrations of PM with smaller size (PM0.5 and PM1). Data indicate that inhalation of PM in swine farm workers is associated with increased frequency of respiratory illnesses.

Identificação de perigos e avaliação de riscos na indústria alimentar : comparação de métodos

Dissertação de Mestrado em Ambiente, Saúde e Segurança.

Instrumentação e monitorização na avaliação do comportamento de maciços e estruturas envolventes: caso de poços em meio urbano

Atualmente, a escavação de poços em locais densamente ocupados requer medidas severas para reduzir riscos e possíveis influências quer na própria obra quer em estruturas próximas. Neste campo, a instrumentação geotécnica e a sua monitorização tem um papel determinante na execução de obras geotécnicas, sendo que neste trabalho é dado um especial realce à instrumentação utilizada, às atividades de observação geotécnica, bem como à análise e interpretação das leituras para o controlo de movimentos induzidos no terreno pelas escavações. Este acompanhamento é baseado num plano de instrumentação, sendo descrito de uma forma transversal a importância do projeto e em particular das fases do processo de investigação geotécnica. O acompanhamento da execução dos poços para a futura Estação da Reboleira, permitiu validar as soluções de projeto para um determinado método construtivo, determinadas através de métodos numéricos e semi-empíricos, e abordados neste trabalho. A monitorização sistemática desde o início das escavações até ao revestimento secundário, permitiu tecer apreciações sobre os valores obtidos, apresentando-se alguns registos. Todas estas ações visam controlar e antecipar riscos de acidentes provocados pela execução de escavações, pelo que nesta tese é também realçada a importância da segurança e higiene no trabalho na prevenção dos riscos profissionais, independentemente da sua origem.