Dissertations / Theses on the topic 'Population screening'

Despite significant improvements in therapy, ovarian cancer continues to be a leading cause of death amongst women with gynaecological malignancies. Advanced stage at diagnosis is thought to be a major contributor to mortality. Hence, there is considerable interest in early detection through screening. In the 1990s, Professor Jacobs pioneered the development of a multimodal ovarian cancer screening (OCS) strategy using serum CA125 as the first line screen and pelvic ultrasound as the second line test. This thesis summarises the next steps in the journey with refining of the screening algorithm, feasibility testing in a pilot randomised control trial (RCT) and finally setting up and recruiting 200,000 women into the largest ever RCT . The risk of ovarian cancer in postmenopausal women with elevated CA125 levels was established through a detailed analysis of 1219 pelvic scans from 741 women with raised CA125 levels in the completed trial of 22,000 women. Based on this, the multimodal 'Risk of Ovarian Cancer' (ROC) algorithm was refined and morphology instead of volume was used to interpret the ovarian scans. The refined ROC algorithm was then prospectively evaluated in a pilot RCT of 13,582 postmenopausal women. The trial established that screening using the ROC algorithm was feasible and could achieve high specificity and positive predictive value. The improved performance characteristics of the screening strategy and the experience accumulated in running and organising the pilot trial led to the design and successful implementation of a RCT - the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) - to assess the impact of early detection on disease mortality. The trial commenced in 2001 with recruitment of 202,638 postmenopausal women by September 2005. The issues involved in setting up the trial, recruitment of 202,000 women and the baseline characteristics of this population are described.

Disparity in access to health care and preventive services places a heavier burden of morbidity on those with limited access and resources. Underserved populations with decreased access to appropriate health screening and therapeutic interventions often present with increased risks for peripheral arterial disease. Some patients with peripheral arterial disease are asymptomatic and may defer treatment while others present with occlusive disease requiring immediate therapy. Delaying diagnosis and treatment reduces quality of life and functional status. The prevalence of peripheral arterial disease has been extensively studied in the elderly population but the prevalence in the high-risk underserved population is unknown. The purpose of this study was to identify the prevalence of peripheral arterial disease in an underserved, high-risk, predominantly African American population and to determine if providers using an electronic blood pressure machine could accurately measure the ankle-brachial index. The sample population of forty adult residents at a homeless shelter in northeast Florida was screened for peripheral arterial disease. Inclusion criteria consisted of a diagnosis of hypertension, hyperlipidemia, diabetes or a history of smoking. The ankle-brachial index was assessed using the vascular Doppler method and an electronic blood pressure machine though the latter was found to be an insensitive screening tool. The ankle-brachial index, the San Diego Claudication Questionnaire and a physical assessment were used in this crosssectional study to determine the prevalence of peripheral arterial disease. An abnormal ankle-brachial index value (≤ 0.90), indicating a high suspicion of peripheral arterial disease, was assessed in 22.5% of the sample population, all of whom were found to have a history of smoking crack cocaine.

The purpose of this study was to compare thirty-two childrens' performances on the Daberon-2 Screening for School Readiness and the Early Screening Inventory , as well as determine whether there was a correlation between the tests. This study responded to the needs of the local Portland, Oregon area schools, some of which use these tests, to investigate the tests, and explore the possibility of using the shorter ESI over the longer Daberon. The reasoning behind the goal of the study was to determine that if the two tests showed a strong, positive correlation and identified the same children as needing further assessment, then perhaps the test which was shorter to administer could be used with confidence as a faster, but equally reliable 2 pre-kindergarten screening tool. In other words, if a child "passes" the Daberon, one could assume that the child would most likely "pass" the ESI as well. Based on the results of this study, one can make this assumption with a reasonable amount of confidence. The subjects in this study included 16 males and 16 females. All were preschool students, ranging in age from 4-6 to 5-6 with a mean age of 5-1 years. The subjects were given the two tests in a counterbalanced order, which also varied as to sex so that not all of one sex received one test first. The standard scores and whether or not each subject "passed" or "failed" each screen was determined. The correlation between the two tests was also determined. The Pearson product moment correlation coefficient was used to determine the degree of relatedness between the tests. A high positive correlation of .73 was found between the Daberon and the ESI, with a shared variance

Colorectal cancer (CRC) is a primary cause of cancer-related mortality in the United States. Asian Americans have the highest CRC mortality rates. CRC screening tests can reduce CRC incidence, yet Asian Americans, specifically the subgroup of Vietnamese Americans, underuse CRC screening. The purpose of this phenomenological study was to understand why Vietnamese Americans, ages 50 to 75, underuse CRC screening. The health belief model constructs of susceptibility, severity, benefits, barriers, and self-efficacy were the framework for understanding this population's health-related behaviors. Three research questions focused on how knowledge, language, and cultural beliefs and perceptions affect Vietnamese Americans' CRC screening decisions. Interviews were conducted with 11 participants, and transcribed interview responses were input into NVivo 11 software to maintain a reliable database and to identify emerging themes. Key study findings revealed knowledge and English language gaps as well as adverse cultural perceptions of fear and doubt that influenced CRC screening choices among these 11 Vietnamese Americans. Future researchers might focus on cultural-tailored strategies to minimize these barriers for Vietnamese Americans. An understanding of this study population's perspectives offers the promise of positive social change for health services and public health administrations to develop cultural-tailored interventions that promote healthy lifestyles, prevention, early CRC detection and, consequently, reduce mortality rates and associated health care costs.

The aim of this study was to adapt the Kessler Psychological Distress Scale (K10) for Argentinean population. We conducted a linguistic adaptation of the instrument and an analysis of its psychometric properties. To assess the reliability of the scale, analysis of internal consis- tency was made through Cronbach’s alpha and temporal stability of the items was examined in two different subsamples. In addition, the scale’s validity was assessed, taking into account convergent validity, criterion validity by contrasting groups and factorial composition of the K10. Receiver Operating Characteristic (ROC) analysis was carried out to assess sensitivity, specificity and the area under the curve (AUC). The results of the present study indicate that the K10 is an adequate instrument presenting strong psychometric properties for screeningpsychological distress in our environment.
El objetivo del presente trabajo fue realizar la adaptación argentina de la Escala de Malestar Psicológico de Kessler (Kessler Psychological Distress Scale-K10). Para esto, se llevó a cabo una adaptación lingüística del instrumento y un análisis de sus propiedades psicométricas. Para evaluar la confiabilidad de la escala, se efectuó un análisis de la consistencia interna y se examinó la estabilidad temporal de los ítems. La validez del instrumento fue evaluada teniendoen consideración diferentes indicadores de la misma. Se calcularon, a través de las curvas ROC, los niveles de sensibilidad, especificidad y el área bajo la curva (ABC) de la prueba. Los resultados indican que se puede contar con la K10 como un instrumento de despistaje de malestar psicológico que reúne los requisitos psicométricos necesarios para ser utilizado en población argentina.

Globally, there is an alarming increase in the incidence of Type II diabetes mellitus (T2DM). It is well recognized that women who develop gestational diabetes (GDM) in their pregnancies are at increased risk of T2DM in later life. In addition, poor glycaemic control in pregnancy impacts adversely on the neonatal outcome, as well as the long term disease risks of that child. The risk of these outcomes increases continuously as maternal fasting plasma glucose levels increases. Several adverse outcomes have been associated with DM during pregnancy. These include pre-eclampsia, polyhydramnios, fetal macrosomia, fetal hepatomegaly and cardiomegaly, birth trauma, operative delivery, perinatal mortality and neonatal respiratory problems and metabolic complications such as hypoglycaemia, hyperbilirubinaemia, hypocalcaemia and polycythaemia. Despite five decades of research there is little consensus regarding the optimal approach to screening for GDM. Recently most international organisations have recommended that all women should be screened for GDM. South Africa is a diverse multi-racial society with an increasing burden of non-communicable diseases. The health system is already overburdened, and the optimal approach to screening for GDM remains unclear. A prospective cohort observational study was conducted at the Eyethu Yarona clinic (Lion Park Clinic), in Johannesburg, South Africa (SA). One thousand (1000) consecutive non-diabetic women who were less than 26 weeks pregnant were recruited. At recruitment the women completed a demographic questionnaire, and had a random glucose and glycated haemoglobin (HbA1c) drawn. A fasting blood glucose was assessed within 2 weeks, and a serum specimen was frozen at -40°C for further testing at a later stage. Patients had a 75 g 2-hour oral glucose tolerance test (OGTT) and HbA1c between 24 – 28 weeks gestation. All glucose measurements were done at the laboratory using standardized tests (venous blood) and on a Roche Accuchek Active® glucometer (Roche Diagnostics, Mannheim, Germany) (capillary blood). GDM was diagnosed according to the International Federation of Gynecology and Obstetrics (FIGO) criteria, i.e. any one abnormal reading was diagnostic of GDM: 0-hour ≥5.1 mmol/l, 1-hour ≥10 mmol/l, or 2-hour ≥8.5 mmol/l. Thereafter a nested cohort study of HIV negative patients was conducted to investigate the association between the concentrations of biomarkers associated with glucose homeostasis and GDM in a South African population. C-reactive protein (CRP), adiponectin, and fasting insulin were measured on the stored serum samples. The Insulin Sensitivity Index (HOMA-IR = fasting insulin (microU/L) x fasting glucose (mmol/L) / 22.5), and Quantitative Insulin Sensitivity Check Index (QUICKI = 1 / [log (I0) + log (G0)]) were calculated for further evaluation of markers of insulin sensitivity. The significance of this research was to assess the burden of disease of GDM in a South African population. The different diagnostic criteria were also compared, as well as the universal versus the traditional risk-factor based screening approach to GDM. Screening methods were compared so as to propose a simple, effective, cost efficient screening and diagnostic tool that may be implemented at primary health care level, which will in turn identify those pregnant women who warrant referral to a high care obstetric unit, thus improving both maternal and neonatal outcomes in our population.
Thesis (PhD) - University of Pretoria, 2017.
SEMDSA
SASA
Roche
Obstetrics and Gynaecology
PhD
Unrestricted

The interaction between a human's genes and their environment is dynamic, producing phenotypes that are subject to variance among individuals and across time. Metabolic interpretation of phenotypes, including the elucidation of underlying biochemical causes and effects for physiological or pathological processes, allows for the potential discovery of biomarkers and diagnostics which are important in understanding human health and disease. The study of large cohorts has been pursued in hopes of gaining sufficient statistical power to observe subtle biochemical processes relevant to human phenotypes. In order to minimise the effects of analytical variance in metabolic profiling and maximise extractable information, it is necessary to develop a refined analytical approach to large scale metabolic profiling that allows for efficient and high quality collection of data, facilitating analysis on a scale appropriate for molecular epidemiology applications. The analytical methods used for the multidimensional separation and detection of metabolic content from complex biofluids must be made fit for this purpose, deriving data with unprecedented reproducibility for direct comparison of metabolic profiles across thousands of individuals. Furthermore, computational methods must be established for collating this data into a form that is suitable for analysis and interpretation without compromising the quality achieved in the raw data. These developments together constitute a pipeline for large scale analysis, the components of which are explored and refined herein with a common thread of improving laboratory efficiency and measurement precision. Complimentary chromatographic methods are developed and implemented in the separation of human urine samples, and further mated to separation and detection by mass spectrometry to provide information rich metabolic maps. This system is optimised to derive precision from sustained analysis, with emphasis on minimisation of sample batching thereby allowing the development of metabolite collation tools that leverage the chromatographic reproducibility. Finally, the challenge of metabolite identification in molecular profiling is conceptually addressed in a manner that does not preclude the further reinvention of the analytical approaches established within this thesis. In summary, the thesis offers a novel and practical analytical pipeline suitable for achieving high quality population phenotyping and metabolome wide association studies.

In the interest of early identification and prevention of dissociative disorders, this author has contributed to the research history of various screening instruments and has commented on the degree to which such instruments are appropriate for screening subjects in a college population. The Dissociative Experiences Scale (DES; Bernstein & Putnam & Putnam, 1986) was administered to approximately 2500 college freshmen. Subjects from various levels of the distribution of DES scores were recalled to the laboratory for further testing on the abbreviated version of the Structured Clinical Interview for Dissociative Disorders (Mini-SCID-D) (Steinberg, Rounsaville & Cicchetti, 1987) to determine how many of these subjects might actually qualify for a diagnosis of dissociative disorder. The results of this study supported the factor structure of the DES as reported by Ross, Joshi, and Currie (1991). In addition, the DES evidenced a significant predictive relationship with the Mini SCID-D. The research was designed to screen a population at large for dissociative tendencies, the results of which will be useful to people who wish to identify ostensibly normal individuals who may be at risk for dissociative disorders. This research was supported in part by Grant #MH35856 from the National Institute of Mental Health to John F. Kihlstrom.

Background: Muscle, joint and bone injuries affect mobility and stability, which in turn limits physical activity. Screening tests such as the Functional Movement Screen (FMS) are used to assess an individual’s mobility and stability to determine whether any movement dysfunctions exist. Screening tests aim to establish an individual’s injury risk with the goal of guiding an intervention program. The Evaluation of Mobility Screen (EMS) is a screening test that has been developed at the Sports Science Institute of South Africa. The EMS has been adapted from the FMS by exchanging the Rotatory Stability test for the Seated Rotation test. The current use of screening tools is limited because of the lack of normative data sets that represent the diversity of age, gender and physical activity levels in the general population. Most current published data represent athletes or younger populations. By establishing the relationship between screening outcomes and variables such as age, gender and physical activity level, the effectiveness of screening tests may be improved. Aim: To describe associations between EMS scores for males and females across different age groups and levels of physical activity. Objective: To evaluate and compare differences in EMS scores relating to age, gender and physical activity levels. Methods: This was a quantitative study, with a descriptive, correlational design. The sample consisted of 135 males and 127 females between the ages of 18 and 60. The EMS data were collected at the HighPerformance Centre, in the Sports Science Institute of South Africa, Cape Town. Results: There was no difference between the total scores of males and females (median = 17). The two youngest groups (20-30 and 31-40 years) scored the highest (median = 17), while the oldest group (51-60 years) scored the lowest (median = 15). Gender had a significant effect (p < 0.05) on five subtests (Single Leg Hurdle, Shoulder Mobility, Asymmetric Leg Raise, Stability Push Up and Seated Rotation). Age had a significant effect (p < 0.05) on three subtests (Overhead Squat, Single Leg, Hurdle Split Squat). Physical activity level had a significant effect (p < 0.05) with two subtests (Single leg Hurdle and Stability Push Up). Conclusion: Gender, Age and Physical Activity are associated with changes in EMS scores. EMS total scores declined as age increased. While the total scores remain similar between genders, there were clear variations within the different subtests. The oldest participants (51-60 year) scored the lowest throughout all subtests. Males scored higher in the strength components, while females scored higher in the flexibility components. Physical activity levels did not have a clear pattern as expected but still demonstrated association with two subtests. The results add to the sentiment that the focus should move away from the composite scoring system, and towards analyzing individual subtest scores. Future studies should also investigate if subtest scores can be improved by targeted intervention programs.

If it is clearly demonstrated that eradicating Helicobacter pylori (H pylori) in asymptomatic subjects would lead to a reduction in morbidity and mortality, population screening may become justified. It must also, however, be shown that prevalence of infection can be effectively reduced; these studies addressed the hypothesis that this can be achieved through community screening and eradication. A serological screening test for infection with H. pylori was offered in two community programmes in Market Harborough and Belgrave. Those testing positive were offered a prescription for eradication therapy and successful eradication was assessed by urea breath testing. Consideration was given to compliance at each stage, also to the association between dyspepsia and H. pylori and to risk factors for infection. For possible long-term follow-up regarding health benefits, subjects in Market Harborough were randomised to be offered screening or to a matched control group not invited. The feasibility of community screening and eradication was demonstrated. Compliance with medication (100% in Market Harborough, 95% in Belgrave) and eradication rates (95%, 92%) were good in those who accepted therapy. Uptake of screening (39%, 26%) and therapy (79%, 81%) were however limited, with men and younger people less likely to attend. In Belgrave, low uptake was influenced by the inaccuracy of the mailing list, but attendance was similar in Asians and non-Asians and was not improved by the use of Asian Language materials. No correlation was found between infection with H. pylori and overall symptoms of dyspepsia (P=0.626 after adjustments). Using logistic regression, the association between the infection and childhood living conditions was confirmed. Intrafamilial transmission was suggested by an association between H. pylori status of self and spouse in married couples (odds ratio 2.65 after adjustments). Asian ethnicity was not a risk factor for infection in Belgrave (X2=0.31, P=0.611).

The reported incidence of self-harm is much higher among prisoners than in the general population. Along with the general increased risk among prisoners, there are also specific times of heightened vulnerability, such as on first reception into the prison environment. Currently in the UK, if an act of self-harm is carried out by a prisoner, if intent to do so is expressed, or if a prisoner is deemed vulnerable by a member of staff or a fellow prisoner, then this prisoner will be subject to a self-harm and suicide monitoring process known as an ACCT (Assessment, Care in Custody and Teamwork). As part of the ACCT process, a member of prison staff will carry out a prisoner assessment to ascertain the risk level of the prisoner, and whether the ACCT needs to remain open. However, there is currently no standardised risk assessment or clinical decision aid used as part of the ACCT process, which is perhaps largely owing to the paucity of validated risk assessment tools or clinical decision aids that are available to identify risk of self-harm in prisoner populations. The primary aim of the study was therefore to determine whether any pre-existing, standardised instrument would be suitable to use for the purpose of assessing the risk of self-harm among the specific ACCT population. This thesis describes various different elements of the study. Firstly, a scoping exercise was carried out in order to select the most appropriate pre-existing instruments that had the potential to predict self-harm events. A pilot study was then carried out to test the study process and to refine the instrument selection. Following this, a prospective cohort study was undertaken to assess the predictive validity of the selected instruments, where a six month follow-up determined self-harm occurrence since baseline, and area-under-the-curve (AUC) analysis examined the ability of the instruments to predict future self-harm. Alongside this, a thorough psychometric analysis of each of the instruments was carried out, in order to validate them among the specified ACCT population. Utilising the study dataset, an exploratory logistic regression analysis was carried out in order to identify individual background and instrument items that may prove effective in predicting future self-harm. Finally, structural equation modelling (SEM) was used to explore the relationships between some of the factors that influence self-harm, in order to contribute towards an understanding of the complexity of the issue of self-harm in prisons. The key findings from this programme of work can be summarised as follows: i. Self-harm is a common occurrence among the prison ACCT population, with 29.1% of the study participants deliberately self-harming during the follow up period, although this varied considerably across gender and participating prisons. ii. Four of the five selected instruments did display a certain level of psychometric validity among the study population; therefore validating the cut-points for the predictive analysis. However, all instruments required some refinement to meet the strict measurement criteria of the Rasch model. iii. Of the five pre-existing instruments that were selected for the study, none of these displayed a meaningful predictive validity. iv. Logistic regression analysis did reveal gender-specific item sets, producing predictive algorithms which were statistically significant in predicting future self-harm; however, the operational functionality of these item sets may be limited. v. Structural equation modelling revealed an insightful explanatory model of the process that may be involved in the culmination of self-harm in prison. Path analysis models supported the view that self-harm capacity and self-harm propensity are integral elements to the self-harm pathway, although the complete explanatory model is likely to be more complex.

A series of studies were carried out to assess the impact of guaiac faecal occult blood test (gFOBT) screening on colorectal cancer (CRC) mortality and associated outcomes in a true population based screening programme. Using data from the Scottish arm of the UK demonstration pilot of gFOBT screening for CRC, all residents in the three Scottish pilot NHS board areas invited for gFOBT screening were compared to controls individually matched by age, gender and deprivation and resident in one of the remaining Scottish NHS boards where screening had not been introduced. A reduction in CRC mortality was shown for those invited for screening and a further reduction in those who completed the test. Screening participants also benefited from reductions in emergency admissions to hospital, length of hospital stay and stoma formation. It was estimated that nine people had died during the pre-clinical stage of disease from a cause which may have been associated with the process initiated by the screening test. In additional studies, a randomised controlled trial (RCT) showed that a pre-notification letter was an effective method of increasing participation in gFOBT screening. In an examination of national trends in CRC survival in Scotland, an effect of gFOBT was apparent even in an all age cohort. An impact of gFOBT screening on all cause mortality could not be assessed due to a biased study cohort. In conclusion, the reduction in CRC mortality with gFOBT screening previously demonstrated in RCTs can be matched at the population level and these results justify the introduction of gFOBT screening to all four UK countries following the successful completion of the demonstration pilot. However, the studies showed that the benefits of screening were limited to those who participated. It is likely that a greater impact of screening would be realised with greater participation and increasing this is a priority.

Introducció: S'ha demostrat que el cribratge mamogràfic redueix la mortalitat per càncer de mama. Seguint les recomanacions de la Comissió Europea, els països europeus han establert programes poblacionals de cribratge que ofereixen mamografies biennals a dones d'entre 50 i 69 anys d'edat. No obstant això, el cribratge de càncer de mama no està lliure de controvèrsia ja que existeix un debat en relació a l'equilibri entre la reducció de la mortalitat i els efectes adversos. Per a millorar aquest equilibri, l'evidència científica actual dóna suport al cribratge personalitzat. Els estudis de modelització han demostrat que modificar l'interval de cribratge, la prova de cribratge o el rang d'edat de la població objectiu en funció del risc individual de les dones produeix un major benefici que les estratègies convencionals. Per tant, és necessari ampliar la informació actual sobre els factors de risc d'aquesta malaltia i crear models de predicció del risc individual mitjançant l'anàlisi de grans bases de dades poblacionals. Objectiu: L'objectiu general d'aquesta tesi és aprofundir en l'anàlisi del cribratge poblacional del càncer de mama. En concret, aquesta tesi pretén avaluar diferents factors de risc de càncer de mama per a desenvolupar i validar un model de predicció de risc individual d'aquesta malaltia. Es va analitzar com la densitat mamària afecta als diferents indicadors del cribratge en el context de la mamografia digital. A continuació, es van avaluar les diferències en el risc de càncer de mama en funció de si una lesió benigna de mama es va diagnosticar en un cribratge prevalent o un cribratge incident. També es va analitzar la interacció entre la densitat mamària i les lesions benignes en el risc de desenvolupar càncer de mama. Posteriorment, es va realitzar una revisió sistemàtica per a actualitzar l'evidència existent, dur a terme una valoració crítica i una avaluació del risc de biaix i resumir els resultats dels models de risc individualitzats que s'utilitzen per a estimar el risc de càncer de mama en les dones de la població general. Finalment, es va dissenyar un model de predicció individual del risc de càncer de mama i es va validar internament, a partir d'informació fàcilment accessible en un episodi de cribratge. Conclusions: i) Els diferents indicadors de cribratge es veuen afectats negativament per la densitat mamària, disminuint la sensibilitat i el valor predictiu positiu de la prova a mesura que augmenta la densitat mamària. ii) El risc de càncer de mama conferit per una lesió benigna difereix segons la mena de cribratge (prevalent o incident). Fins on sabem, aquest és el primer estudi que analitza l'impacte del tipus de cribratge en el pronòstic de la lesió benigna. iii) El risc de càncer de mama augmenta de manera independent amb la presència d'una lesió benigna i amb una major densitat mamària i es manté elevat durant més de 15 anys. iv) Els models de predicció són eines prometedores per a implementar polítiques de cribratge basades en el risc individualitzat. No obstant això, és un repte recomanar qualsevol d'ells per a la personalització del cribratge ja que necessiten millorar la seva qualitat i capacitat discriminatòria. v) Es va dissenyar i validar internament un model de predicció de risc capaç d'estimar el risc de càncer de mama a curt i llarg termini utilitzant la informació recollida de manera rutinària en el cribratge mamogràfic. El model inclou edat, antecedents familiars de càncer de mama, antecedents de lesió benigna i patrons mamogràfics previs, que van resultar estar relacionats amb un augment del risc de càncer de mama. El model ha de ser validat externament i actualitzat amb noves variables.
Introducción: Se ha demostrado que el cribado mamográfico reduce la mortalidad por cáncer de mama. Siguiendo las recomendaciones de la Comisión Europea, los países europeos han establecido programas poblacionales de cribado que ofrecen mamografías bienales a mujeres de entre 50 y 69 años de edad. Sin embargo, el cribado de cáncer de mama no está libre de controversia ya que existe un debate en cuanto al equilibrio entre la reducción de la mortalidad y los efectos adversos. Para mejorar este equilibrio, la evidencia científica actual apoya el cribado personalizado. Los estudios de modelización han demostrado que modificar el intervalo de cribado, la prueba de cribado o el rango de edad de la población objetivo en función del riesgo individual de las mujeres produce un mayor beneficio que las estrategias convencionales. Por lo tanto, es necesario ampliar la información actual sobre los factores de riesgo de esta enfermedad y crear modelos de predicción del riesgo individual mediante el análisis de grandes bases de datos poblacionales. Objetivo: El objetivo general de esta tesis es profundizar en el análisis del cribado poblacional del cáncer de mama. En concreto, esta tesis pretende evaluar diferentes factores de riesgo de cáncer de mama para desarrollar y validar un modelo de predicción de riesgo individual de esta enfermedad. Se analizó cómo la densidad mamaria afecta a los distintos indicadores de cribado en el contexto de la mamografía digital. A continuación, se evaluaron las diferencias en el riesgo de cáncer de mama en función de si una lesión benigna de mama se diagnosticó en un cribado prevalente o un cribado incidente. También se analizó la interacción entre la densidad mamaria y las lesiones benignas en el riesgo de cáncer de mama. Posteriormente, se realizó una revisión sistemática para actualizar la evidencia existente, llevar a cabo una valoración crítica y una evaluación del riesgo de sesgo y resumir los resultados de los modelos de riesgo individualizados que se utilizan para estimar el riesgo de cáncer de mama en las mujeres de la población general. Por último, se diseñó un modelo de predicción individual del riesgo de cáncer de mama y se validó internamente, basado en información fácilmente accesible en un episodio de cribado. Conclusiones: i) Los distintos indicadores de cribado se ven afectados negativamente por la densidad mamaria, disminuyendo la sensibilidad y el valor predictivo positivo de la prueba a medida que aumenta la densidad mamaria. ii) El riesgo de cáncer de mama conferido por una lesión benigna difiere según el tipo de cribado (prevalente o incidente). Hasta donde sabemos, este es el primer estudio que analiza el impacto del tipo de cribado en el pronóstico de la lesión benigna. iii) El riesgo de cáncer de mama aumenta de forma independiente con la presencia de una lesión benigna y con una mayor densidad mamaria y se mantiene elevado durante más de 15 años. iv) Los modelos de predicción son herramientas prometedoras para implementar políticas de cribado basadas en el riesgo individualizado. Sin embargo, es un reto recomendar cualquiera de ellos para la personalización del cribado ya que necesitan mejorar su calidad y capacidad discriminatoria. v) Diseñamos y validamos internamente un modelo de predicción de riesgo capaz de estimar el riesgo de cáncer de mama a corto y largo plazo utilizando la información recogida de forma rutinaria en el cribado mamográfico. El modelo incluye edad, antecedentes familiares de cáncer de mama, antecedentes de lesión benigna y patrones mamográficos previos, que resultaron estar relacionados con un aumento del riesgo de cáncer de mama. El modelo debe ser validado externamente y actualizado con nuevas variables.
Background: Mammographic screening has been shown to reduce mortality from breast cancer. Following the recommendations of the European Council, European countries have started population-based screening programs that offer biennial mammograms to women aged between 50 and 69 years. The results of the effectiveness of population-based screening are controversial in terms of the balance between mortality reduction and adverse effects. To improve this balance, current evidence supports personalized screening. Modeling studies have shown that modifying the screening interval, screening modality, or age range of the target population based on women's individual risk yields a greater benefit than conventional standard strategies. Several risk models have been designed to estimate women's individual breast cancer risk based on their personal characteristics. However, most of these models have not been specifically developed to estimate the risk of women targeted for breast cancer screening. There is therefore a need to broaden current information on risk factors for breast cancer and the estimation of individual risk prediction models through the analysis of large population-based databases. Aims: The general objective of the thesis is to deepen the analysis of population-based breast cancer screening. Specifically, the aim of this thesis is to assess different breast cancer risk factors in order to develop and validate an individualized breast cancer risk prediction model. We evaluated how breast density affects screening performance indicators in a digital mammography context. Then, we assessed differences in breast cancer risk across benign breast disease diagnosed at prevalent or incident screens. To our knowledge, this is the first time that such an approach has been used. We also evaluated the interaction between breast density and benign breast disease. Subsequently, we performed a systematic review to update the existing evidence, conduct a critical appraisal and risk of bias assessment and summarize the results of the individualized risk models that are used to estimate the risk of breast cancer in women in the general population. Finally, a breast cancer risk prediction model was designed and internally validated, based on information easily accessible at screening. Conclusions: i) Performance screening measures are negatively affected by breast density, with sensitivity and positive predictive value decreasing as breast density increases. ii) The risk of breast cancer conferred by benign breast disease differed according to type of screen (prevalent or incident). To our knowledge, this is the first study to analyze the impact of screening type on the prognosis of benign breast disease. iii) The risk of breast cancer independently increased with the presence of benign breast disease and with greater breast density and remained elevated for over 15 years. iv) Individualized risk prediction models are promising tools for implementing risk-based screening policies. However, it is a challenge to recommend any of them since they need further improvement in their quality and discriminatory capacity. v) We designed and internally validated a risk prediction model able to estimate short- and long-term breast cancer risk using information routinely reported at screening participation. The model included age, family history of breast cancer, benign breast disease and previous mammographic findings, which were found to be related to an increase in breast cancer risk. The model should be externally validated and updated with new variables.
Universitat Autònoma de Barcelona. Programa de Doctorat en Metodologia de la Recerca Biomèdica i Salut Pública

Psychological assessment of mentally disordered offenders requires a systematic consideration of response styles, including malingering and defensiveness. Important components of these evaluations are standardized diagnostic interviews. However, the ability of offenders to feign mental disorders on such measures to achieve such external incentives as treatment, placement on safer units, or possible release from jail remains uninvestigated. With a known-groups comparison with the data from the Structured Interview of Reported Symptoms as a criterion, 24 suspected malingerers were compared to 64 genuine patients on the Schedule of Affective Disorders and Schizophrenia (SADS), the abbreviated SADS-C, the Suicide Probability Scale, and the Referral Decision Scale.

BACKGROUND: Sudden cardiac death (SCD) in any young person is a tragic event with a significant number of life-years lost. Previous data from Italy suggest that pre-participation screening using an electrocardiogram (ECG) reduces the incidence of SCD in competitive athletes. However, the majority of SCD occurs in non-athletes within the general population. In the United Kingdom, state sponsored screening for cardiac disorders is confined to symptomatic individuals or those with a family history of inherited cardiac conditions or premature cardiac death. AIMS: To assess the feasibility and efficacy of screening, incorporating an ECG and point-ofcare echocardiography, in young individuals from the general population for cardiovascular conditions associated with SCD. METHODS: Between 2008-2012, 10,359 young individuals aged 14-35 years underwent screening by an attending cardiologist comprising a health questionnaire, physical examination and ECG. ECGs were analysed in accordance with the European Society of Cardiology (ESC} recommendations for ECG interpretation in athletes for Group-1 (trainingrelated) and Group-2 (potentially pathological) patterns. Group-2 ECG patterns warrant further cardiac evaluation. Individuals with findings raising suspicion of cardiomyopathy underwent on-site echocardiography. Individuals with abnormalities from the screening episode were referred for further evaluation for conditions associated with SCD and followed up annually to assess outcomes. Based on these data comparisons of the efficacy of different screening strategies were made and costs and cost effectiveness were calculated. RESULTS: Symptoms of a cardiovascular nature were reported in 44.2% of individuals, a family history of SCD or condition associated with SCD was reported in 3.8% and an abnormal physical examination occurred in 0.3% of individuals. ECG patterns suggestive of cardiac pathology were identified in 22.4% of individuals, predominantly due to abnormalities of QTc measurement. Male gender and black ethnicity demonstrated the strongest association with ESC Group-2 ECG patterns. Point-of-care echocardiography for individuals with suspicion of cardiomyopathy significantly reduced the number of patients requiring further evaluation as only 14.8% of these individuals demonstrated abnormal echocardiographic findings. Positive diagnosis of a cardiovascular condition associated with SCD was identified in 0.3% of individual;; (cardiomyopathy, n=6; primary electrical disease, n=17; Marfan syndrome, n=4). This screening strategy demonstrated a sensitivity of 100%, specificity of 93.2% and false-positive rate of 6.8% with an estimated cost of £106,141 per diagnosis made. CONCLUSIONS: Screening for conditions associated with SCD in the general population is feasible. A screening strategy incorporating the ECG and point-of-care echocardiography is associated with a high sensitivity and specificity and low false-positive rate as well as favourable cost analyses.

Background: Recent research is revealing the high rate of false-positive screening results for IEMs in the NICU population. No study published to date has specifically studied the possible relationship between nutrition and newborn screening in this population. Objective: It is suspected that NICU infants who receive PN are more likely to have abnormal newborn screening results than infants who receive EN. An understanding of the role of nutrition will assist in developing protocols for screening in the NICU and decrease false-positives. Design: Infants admitted to the NICU between January 1-June 30, 2009 were included in this retrospective chart review study (n=339). The type of nutrition and timing of its initiation was recorded and compared to newborn screening results to identify correlations with false-positives. Statistical analysis included means, percentages, Fisher's exact test, Chi-square test, and the Cochran-Mantel-Haenszel test. Results: Nutrition type was significantly associated with newborn screening (p<0.001); those who received parenteral nutrition were more likely to have a false-positive. For infants who also received PN, EN of breast milk exclusively increased risk of an abnormal screen more than formula exclusively or breast milk plus formula. The timing of parenteral nutrition had no effect on screening. Premature infants who received PN exclusively had a higher percentage of false-positives than those who received EN Conclusions: Although the hypothesis could not be statistically supported, PN appears to contribute to false-positive newborn screens. More research is needed to ascertain the role of EN and GA in newborn screening and to develop standardized protocols.
Master of Science

Background: Cervical cancer may be fatal to women if not identified and treated early. In Iraq, cervical cancer ranks as the 10th most frequent cancer among women between 15-44 years of age, with about 291 new cervical cancer cases diagnosed annually. Cervical cancer can be prevented in two ways: primary prevention aimed at preventing HPV infection through prophylactic HPV vaccinations; and secondary prevention aimed at preventing precancerous lesions from progressing into invasive lesions through screening. Cervical cancer screening is under researched in Iraq. It is clear that Iraq’s years of isolation and disorder has resulted in a loss of research capacity. Aim: To provide evidence–based strategies to establish population based cervical cancer screening services in Iraq. Methods: A mixed methods sequential exploratory design was used; an iterative mixed method approach which included the triangulation of qualitative, quantitative and systematic review methods. Results of all phases were used to develop an emergent theory around the barriers for establishing cervical screening programme and to provide evidence to enhance cervical cancer screening services to be established in Iraq. Findings: The findings from the systematic review indicated significant health inequalities for Arab Muslim women, in that no population-based cervical cancer screening programmes have been implemented in most of Western Asian and Middle Eastern Arab countries. Findings from the qualitative phase revealed gap in theoretical and practical knowledge among the health care professionals regarding cervical cancer screening programmes with a lack of the capacity and infrastructure to establish population based cervical screening programme in Kirkuk, Iraq. Also, results suggest that the health behaviour of women living in Kirkuk is influenced by cultural ‘stigma’ around the word ‘cancer’, in addition to women’s lack of awareness in relation to smear test and cervical screening. Conclusion: Women in Iraq are more likely to be diagnosed at an advanced, rather than early stage of cervical cancer. These women should be targeted by cervical cancer screening and health education programmes. Policy makers need to improve the cervical screening infrastructure and make the cervical screening service more accessible to women. The current opportunistic cervical screening services are insufficient; there is an urgent need to developing cervical cancer intervention programmes.

Type 2 diabetes mellitus (T2DM) is a major international health challenge which has a great worldwide impact on morbidity. Increased fasting plasma glucose (FPG) level is characterised as an independent risk factors for T2DM development and the development of predictive biomarkers for increased FPG level are crucial in Predictive, Preventive and Personalised medicine (PPPM) of T2DM. Established diagnostic tools for T2DM includes the oral glucose tolerance test (OGTT), fasting blood glucose (FBG) and glycated haemoglobin (HbA1c). These tests, however, provide “retrospective” markers for the diagnosis and prognosis of the disease, and therefore cannot be applied as predictive markers for from the perspectives of PPPM. A deeper understanding of the disease pathogenesis is urgently needed. Since blood is in direct contact with all tissues, pathological changes of T2DM are likely to be reflected in the genomic, proteomic and glycomic profiles of serum. With a multi-omics design, Study I combined genomics and glycomics factors to investigate the candidate genes and the glycosylation patterns of IgG that lead to increased FPG level among Chinese populations. Study I identified 9 new SNPs located in 5 genetic loci (RPL7AP27, SNX30, SLC39A12, BACE2 and IGFL2), which considerably affect the increase of FPG level. Moreover, out of 24 glycan peaks (GPs), GPs 2, 8 and 11 were found present positive trends with increased FPG level, while GPs 4 and 14 presented negative trends. Study I implied the feasibility of our current multi-omics study design for T2DM and potential application of multi-omics approaches T2DM biomarkers screening at DNA and glycan levels, which led to Study II, the serumbased proteomic biomarkers research for T2DM at protein level. In Study II, we analysed differences in serum peptide between T2DM patients and healthy controls, using magnetic bead-based fractionation, coupled with MALDI-TOF MS. Diagnostic models for T2DM based on a set of potential specific serum peptide biomarkers generated from a training cohort were further tested using an independent validation set of samples. Study II have found 6 peptides (peaks m/z 1452.9, 1692.8, 1946, 2115.1, 2211.0 and 4053.6) to be novel candidate biomarkers for T2DM diagnosis. The diagnostic performance of this peptide model indicated a high discriminatory power for T2DM, with an accuracy of 82.20%, sensitivity 82.50%, specificity 77.80% and an AUC value of 0.864. By combining Study I and Study II, we identified multiple biomarkers for T2DM across genomic, glycomic and proteomic level. Hence, it was necessary to complement it with robust subjective markers, and this led to Study III and Study IV. Study III is a community-based, real-life environment, prospective study to investigate whether suboptimal health status (SHS), along with life-style and other socio-economic factors, contributes to the incidence of chronic disease in Chinese adults. Furthermore, Study III affords the opportunity to longitudinally analyse the genetic, lifestyle and environmental factors that may determine onset and etiology of targeted chronic disease. Based on Study III, we further investigated the relationship between SHS and the onset of T2DM during the follow-up in Study IV. The main result of Study IV was that participants with higher levels of SHS had a considerably higher risk of T2DM. This finding in Study IV indicated that the risk will increase with the increasing SHS performance of an individual. These results provide the potential application of SHS as dynamic monitoring index for the development of T2DM. In conclusion, 1) We found significant associations of 9 genetic loci located in 5 genes (RPL7AP27, SNX30, SLC39A12, BACE2 and IGFL2) with increased FPG level. We also found that IgG GPs 3, 8 and 11 presented positive trends with increased FPG level, whereas GPs 4 and 14 showed negative trends with increased FPG level. 2) We have characterised 6 peptides (peaks m/z 1452.9, 1692.8, 1946, 2115.1, 2211.0 and 4053.6) to be novel candidate biomarkers for T2DM diagnosis. 3) SHS is a novel predictive factor for T2DM onset, and a higher SHS score is associated with a higher incidence of T2DM. The evaluation of SHS combined with the analysis of modifiable risk factors for SHS allows the risk stratification of T2DM, which might consequently contribute to the prevention of T2DM.

The aims of the study were:

To assess the risk for adverse obstetrical outcome in women where the EDD had been postponed more than 14 days with ultrasound.

To evaluate the mortality and morbidity of conservatively managed post-term pregnancies (gestation 294 days and beyond).

To assess the sensitivity for detecting fetal congenital anomalies with routine mid second trimester ultrasound performed in a routine clinical setting.

To estimate the random or biologic uncertainty of gestational age based on LMP and on routine ultrasound.

To compare the performance of the new Norwegian reference values for BPD measurement with the old reference values.

Paper IV is reprinted with kind permission of Elsevier, sciencedirect.com

Introduction: Central nervous system (CNS) tumours and leukaemia in children are associated with detrimental neurocognitive outcomes across a wide range of cognitive domains. It is recommended these children receive regular neuropsychological assessment to screen for deficits that may affect their long term outcomes. Barriers to this include time constraints and practice effects associated with traditional neuropsychological assessment. CogState is a brief computerised neuropsychological battery which assesses the neurocognitive domains at risk in this population. This study aimed to evaluate the construct validity of the battery in this population through convergent validity with standardised neuropsychological measures. A secondary aim was to investigate the relationship between time since diagnosis and performance on the CogState battery. Method: A cross-sectional within subject correlation design was used to assess the construct validity in a sample of 37 children aged 8-16 years treated for leukaemia or CNS tumours. Partial correlation was used to assess the relationship between overall performance on the battery and time since diagnosis controlling for IQ and emotional distress. Results: One subtest of the CogState battery correlated significantly with the standard measure assessing the same cognitive domain, showing a large effect size. Four further subtests showed small to medium correlations, however these were not significant and confidence intervals were large. One subtest showed no clear correlation. No significant correlation was found between overall performance on the battery and time since diagnosis, however there was also no relationship between time since diagnosis and IQ in this sample. Conclusion: This study provides some evidence for the construct validity of sections of the CogState battery in a paediatric oncology population. Sample characteristics and methodological limitations which may have affected the scope and reliability of results are discussed. Further research in larger samples is needed before it can be recommended as a standard follow up assessment.

Autism spectrum disorder (ASD) has a global prevalence of approximately one percent of all new births. There is a lack of literature on autism in South Africa. South African children are waiting years for diagnoses, despite the fact that early diagnosis and subsequent intervention appear to have a positive effect on the outcomes of the intervention. A screening device to detect ASD could be used to speed up the diagnostic process. This study tested the viability of using the Social Communication Questionnaire (SCQ) in a Western Cape state-funded hospital. This thesis describes Phase 1 of a larger study. The 40 item SCQ was adapted and translated into Afrikaans and isiXhosa. The English, Afrikaans and isiXhosa versions of the SCQ were administered to parents of very young children attending the Red Cross Children?s Hospital?s developmental clinic (N = 228, age range of children = 3.00-5.97 years). Positive results were that no relationship was found between age and SCQ score, or between SCQ language version and SCQ score were found. However there was a relationship between SCQ score and socioeconomic status, indicating a possible bias in the SCQ. Internal reliability of the SCQ versions was analysed and was satisfactory. The factor structure of the English SCQ was examined. Two and four factor solutions were explored, with the two factor solution proving the best fit with good internal reliability. This two factor solution reflected the recent changes to the Diagnostic and Statistical Manual of Mental Disorders, as well as previous findings on the SCQ and the ADI-R, the diagnostic instrument on which the SCQ was based. Preliminary results of Phase 2 of the larger study were analysed. Eighteen children received an Autism Diagnostic Observation Schedule (ADOS) assessment;; the current gold standard for diagnosing ASD. SCQ scores proved to be a good predictor of ASD diagnosis, predicting 17 out of 18 individuals correctly. Further research on isiXhosa and Afrikaans versions of the SCQ as well as the predictive power, sensitivity and specificity and cut-off scores for the SCQ is recommended.

Inledning:Oral cancer är ett allvarligt tillstånd med hög dödlighet, särskilt vid sen diagnostisering. Brasilien är ett av de länder i världen som har högst prevalens och dödlighet i oral cancer och det är den femte vanligaste cancerformen I landet. Ett hjälpmedel för tidig diagnostisering är önskvärd.Syfte:Att utvärdera skillnaden i diagnostisk tillförlitlighet mellan konventionell oral undersökning och användning av multispektralt ljus (Identafi®) som en metod för tidig upptäckt av potentiellt maligna och maligna lesioner i munslemhinnan i en brasiliansk befolkning.Material och metod:Screening av en befolkning med förhöjd risk för att utveckla oral cancer i Goiânia, Goiás, Brasilien, för att upptäcka potentiellt maligna (PML) eller maligna lesioner (ML). Patienter med misstänkta PML eller ML upptäckta under screeningen undersöktes med multispektralt ljus (Identafi®). Tre oberoende observatörer genomförde bedömning med Identafi® och slutgiltig beslut avseende PML/ML togs i konsensus. Biopsier användes som diagnostisk referensstandard. Interobservatörs överensstämmelse beräknades som procentuell överensstämmelse och kappa-värde (κ).Resultat:Undersökning med Identafi® genererade tolv biopsier. Resultaten blev tre sant positiva, fem falskt positiva, två sant negativa och noll falskt negativa. Sensitiviteten beräknades till 0,29. Specificiteten var inte möjlig att beräkna, då det inte fanns några falska negativa resultat. Interobservatörs överensstämmelse för par av observatörer varierade mellan 78-86% och κ-värden mellan 0,46-0,60.Slutsats:Slutsatsen är att multispektralt ljus, Identafi® inte har inga fördelar jämfört med konventionell klinisk undersökning i fråga om diagnostisk träffsäkerhet för PML eller ML. Dock kan det vara till hjälp för en tandläkare eller oral kirurg som stöd i sitt beslutsfattande. Det kan också hjälpa kirurgen att ta en biopsi från det mest misstänkta delen av lesionen. Det finns inte tillräckligt publicerade studier som tyder på att Identafi® kan skilja mellan normal slemhinna och PML eller ML och denna studie bekräftar detta. Användning av Identafi® som ett hjälpmedel vid screening och undersökning för PML eller ML behöver utredas ytterligare, men baserat på denna studie kan Identafi® inte rekommenderas.
Introduction: Oral cancer is a severe condition with high mortality rate, in particular if diagnosed late. Brazil is one of the countries in the world with high prevalence and mortality from oral cancer and it is the fifth most common cancer there. An aid in early detection of oral cancer as an adjunct to health promotion is desirable.Purpose:The aim of this study was to evaluate the diagnostic accuracy of conventional oral examination and the use of multi spectral light (Identafi®) as an approach for early detection of potentially malignant or malignant lesions in the oral mucosa in a Brazilian population.Material and method:Screening of high-risk population in Goiania, Goias, Brazil, for oral potentially malignant lesions (PML) or malignant lesions (ML) as a selection phase. Patients collected from the screening were examined with multi spectral light (Identafi®) to evaluate diagnostic accuracy. Three observers independently assessed all lesions with Identafi® and the final decision if a lesion was present was taken in consensus. Inter observer agreement was calculated as overall agreement and as kappa value (κ). Biopsies were used as diagnostic reference standard.Results:Identafi® generated, from twelve biopsies, three true positive, five false positive, two true negative and zero false negative. Sensitivity was calculated to 0.29 and specificity was not possible to calculate since there were no false negative results.Inter observer agreement for the use of Identafi® was calculated as overall agreement and as kappa value (κ). The overall agreement for the three pairs of observers varied between 78-86% and κ-values between 0.46 and 0.60.Conclusion:The conclusion of this study is that Identafi® does not have any benefits over conventional oral examination in diagnostic accuracy for potentially malignant or malignant lesions in the oral mucosa. It might, however, be an aid for a dentists or oral surgeons that are unsure whether to take a biopsy or not. It can also aid the surgeon when taking a biopsy to take the most suspicious part of the lesion. There are not enough published evidence that Identafi® can discriminate between normal mucosa and PML or ML, and this study confirms previous results. The use of Identafi® as an aid in screening and examination for PML or ML needs further investigation.

Hepatitis C is the most common chronic bloodbourne infection in the United States, with an estimated prevalence of 2.7 million. The total cost of care for this patient population was estimated to be $6.5 billion in 2013. Since 1998, the Centers for Disease Control (CDC) have recommended hepatitis C screening for specific high risk populations, but until recently there was no recommendation for age-based screening. The recent advent of new, more efficacious therapies for hepatitis C have made early identification significantly more important. Consequently, the CDC updated its recommendations in 2012 based on recent evidence to include one-time screening for all individuals born between 1945 and 1965. In 2013, the US Preventive Services Task Force (USPSTF) also incorporated this recommendation into their hepatitis C screening guidelines. In spite of this, there is some debate in the medical community regarding cohort screening for hepatitis C, and some data indicates widespread misunderstanding of current screening recommendations among primary care providers. The purpose of this project was to evaluate current knowledge and understanding of hepatitis C screening guidelines among a group of family medicine residents at East Tennessee State University, and to improve their knowledge in order to promote more appropriate screening practices in their patient population. To accomplish this, 13 question surveys were administered to residents to assess their current knowledge. Following these surveys, residents attended an education session covering current recommendations from the CDC and USPSTF. The 13 question survey was administered again in the post-intervention period. A t-test revealed that post-intervention survey scores increased significantly on 8 out of 13 questions. The intervention was successful at improving knowledge of current hepatitis C screening recommendations in the target population. Future research should be directed at broadening the intervention to include a variety of other providers, and at assessing the impact on execution of screening in the patient population, particularly regarding application to people born in the specified birth cohort.

Colorectal cancer (CRC) is the second leading cause of death in the United States and has the highest death rate among Blacks. Whereas studies have targeted patients to increase CRC adherence in the general population few studies have focused on improving providers’ adherence to screening guidelines. Also, CRC screening studies among HIV-positive patients consistently show lower screening rates compared to screening rates among HIV negative persons. Results of screening colonoscopy studies among HIV positive patients show higher prevalence of neoplastic lesions and colon cancer is diagnosed at advanced cancer stages; these patients have shorter disease-free survival compared to HIV-negative patients. The aim of this transdisciplinary retrospective–prospective and randomized control study is to examine providers’ adherence to screening colonoscopy guidelines before and after screening reminders, evaluate the impact of an educational screening video and review of colonoscopy decisions tree plus usual care on patient adherence compared to usual care only. Results showed that providers’ adherence to screening colonoscopy guidelines significantly increased after reminders to refer patients were placed in medical records. The randomized trial showed that patients in the intervention group were more adherent to screening colonoscopy appointments compared to patients in the usual care arm. Also, patients with little or no social support in the intervention arm were more likely to keep appointments. This is the first reported study of a Transdisciplinary prevention model integrating evidence-based medicine, behavioral medicine and human factors decision support through a multi-faceted intervention to increase screening colonoscopy adherence in the HIV population. We integrated a provider reminder system, patient informed decision support of colonoscopy educational video and decision tree review in addition to patient provider communication to promote increased provider and patient screening behavior. Further studies are needed to elucidate the impact of patient centered intervention strategies and social support on screening colonoscopy behavior.

Thesis (Ph. D.)--Ohio State University, 2003.
Title from first page of PDF file. Document formatted into pages; contains xi, 86 p.; also includes graphics. Includes abstract and vita. Advisor: Antoinette Miranda, College of Education. Includes bibliographical references (p. 82-86).

Biomarker testing, wherein the concentration of a biochemical marker is measured to predict the presence or absence of a certain binary characteristic (e.g., a disease) in a subject, is an essential component of public health screening. For many diseases, the concentration of disease-related biomarkers may exhibit a wide range, particularly among the disease positive subjects, in part due to variations caused by external and/or subject-specific factors. Further, a subject's actual biomarker concentration is not directly observable by the decision maker (e.g., the tester), who has access only to the test's measurement of the biomarker concentration, which can be noisy. In this setting, the decision maker needs to determine a classification scheme in order to classify each subject as test negative or test positive. However, the inherent variability in biomarker concentrations and the noisy test measurements can increase the likelihood of subject misclassification. We develop an optimal data-driven framework, which integrates optimization and data analytics methodologies, for subject classification in disease screening, with the aim of minimizing classification errors. In particular, our framework utilizes data analytics methodologies to estimate the posterior disease risk of each subject, based on both subject-specific and external factors, coupled with robust optimization methodologies to derive an optimal robust subject classification scheme, under uncertainty on actual biomarker concentrations. We establish various key structural properties of optimal classification schemes, show that they are easily implementable, and develop key insights and principles for classification schemes in disease screening. As one application of our framework, we study newborn screening for cystic fibrosis in the United States. Cystic fibrosis is one of the most common genetic diseases in the United States. Early diagnosis of cystic fibrosis can substantially improve health outcomes, while a delayed diagnosis can result in severe symptoms of the disease, including fatality. We demonstrate our framework on a five-year newborn screening data set from the North Carolina State Laboratory of Public Health. Our study underscores the value of optimization-based approaches to subject classification, and show that substantial reductions in classification error can be achieved through the use of the proposed framework over current practices.
Doctor of Philosophy

One thousand three hundred and sixty subjects without a prior diagnosis of heart failure of left ventricular systolic dysfunction were randomly selected from a general population in Leicestershire. All subjects had a transthoracic echocardiogram performed as well as a standard 12 lead electrocardiogram (ECG). Serum levels of N-ANP, BNP and N-BNP were analyzed. There were twenty-eight cases (2.1% of the population) of left ventricular systolic dysfunction (LVSD), defined as a wall motion score index of >1.8. Serum levels of all three cardiac peptides were significantly elevated in subjects with LVSD. The prevalence of electrocardiographic abnormalities was also higher in the LVSD population. Using multivariate logistic regression analysis, ECG abnormalities, including a prolonged QRS duration, as well as N-ANP, BNP and N-BNP independently predicted LVSD. I then analyzed the performance of cardiac peptides and the ECG in diagnosing LVSD. All three cardiac peptides had high negative predictive values but low positive predictive values. The ECG performed less well as compared to cardiac peptides in diagnosing LVSD. BNP consistently performed better than N-ANP and N-BNP. Combining the ECG to any of the three cardiac peptides improved the diagnostic utility for LVSD.

Osteoporosis is a common health problem and it is increasing in prevalence due to the increase in the aging population. The interest to treat osteoporosis has increased in recent years, due to availability of screening modalities, advances in medications that may prevent osteoporotic fractures. Many studies have showed the high medical and economic burden of the disease on the patients, their caregivers and on the health system. Clinical practice guidelines for management of osteoporosis varied nationally and internationally, and the adherence of physicians to guidelines were always reported as suboptimal, though most studies were for after fragility fracture care gap and vert few looked at the primary screening to identify patients at risk before the occurrence of fractures. This thesis is composed of two manuscripts research project assessing the development and impact of screening for osteoporosis guidelines. The first chapter is an overview of osteoporosis, definition, risk factors, diagnosis and treatment. A follow up discussion of the literature on adherence of physicians to the osteoporosis guidelines, which ends up with the rational for this thesis. The first paper is a systematic review to identify guidelines for screening for osteoporosis from 2002-2016 (Chapter 2). We assessed the quality of these guidelines using the AGREE II and IOM standards, compared between the two tools, and assessed if the quality has changed over time. We extracted recommendations in key areas with summary of the systems that were used to assign the level of evidence and strength of recommendations. We found that the quality of guidelines has varied greatly between different countries with no significant change over time. The recommendations and systems for level of evidence were variable and all this may create confusion to clinicians. In the second paper, we used an interrupted time series design to assess the effect of three clinical practice guidelines for screening for osteoporosis in Ontario on the baseline bone mineral density (BMD) testing for older adults 65 years of age and above using administrative data by ICES from 1998-2006. All three guidelines recommend baseline BMD testing for this age population. In addition, we analyzed the pattern of repeated testing in accordance with the latest guideline. We have found low rates of baseline BMD testing with a decreasing pattern of testing. The last guideline in 2010 had gradually increased the trend of BMD testing, though it was a very small change. Stratified analyses by sex showed that the decrease in the total BMD testing is due to decrease in the testing for female population while there is an increasing trend of BMD testing in male population. CPG by Osteoporosis Canada in 2010 caused an immediate reduction in the BMD testing for female, yet, over a period of time, the guideline increased the BMD testing. For male population; the 2002 CPG had immediately increased the BMD testing, while over time this trend has decreased. Despite the low baseline BMD testing by physicians, there is an over use of repeated BMD testing in the low risk population, especially the annual and the 2 yearly BMD repeats. In conclusion: This research project found a varied quality of guideline development and reporting of guidelines for osteoporosis screening, and no improvement in the quality over time (2002-2016). Several systems were used to assign the level of evidence and strength of recommendations with conflicting recommendations between different health organizations in the same country such as in Canada. Many tools are available to appraise the quality of guidelines, however, comparing between two tools (AGREE II & IOM standards) showed that they may give conflicting results for guidelines quality. There is no effect of guidelines for screening for osteoporosis on the ordering of BMD testing to screen adults 65 years and above living in Ontario between 1998- 2016. A small increase the rate of baseline BMD testing followed the release of the 2010 guideline. For male population the 2002 guideline showed an evident immediate and gradual effect over time on the rate of baseline BMD testing ordering for male population. Despite the low baseline BMD testing rates for adults 65 years and above, there is an unnecessary repeated BMD testing for low risk population in Ontario between 2011-2016 which is not in compliance to the latest guideline for screening for osteoporosis.

Les stress ont un impact majeur sur l'agriculture. Les études réalisées jusqu'à présent portent majoritairement sur des stress simples, appliqués indépendamment dans des conditions de culture idéales. Cependant, les combinaisons de stress sont la norme dans les champs et la réponse aux combinaisons de stress ne peut être extrapolée à partir de l'addition des réponses aux stress simples. Une analyse bioinformatique de banques de données de transcriptomique a permis d’identifier un gène (HSFA2) répondant a de multiple stress, isolés ou combinés. La présente thèse a pour but de découvrir les mécanismes contrôlant l'expression d’HSFA2. Deux stratégies ont alors été mise en oeuvre. Dans un premier temps, les facteurs capables de fixer une région promotrice d’HSFA2 ont été étudiés par système de « simple hybride levure ». Dans un second temps, une lignée transgénique biosenseur de l’activité d’HSFA2 a été produite et mutagénéisée. De nombreux mutants ont été sélectionnés sur la base d’une expression constitutive du biosenseur. La capacité des mutants sélectionnés à résister à une combinaison de stress chaleur et de stress lumière a ensuite été analysée. L’identification des mutations causales par séquençage du génome entier a permis, dans certains cas, de déterminer quels étaient les loci responsables des résistances observées. En particulier, deux mutations conférant une large résistance seront discutées
Stresses represent the major cause of yield loss in modern agriculture. Previously, the majority of studies concern simplified, single stress situations, whereas in the field, stresses are complex and most often occurring in combinations. However, multiple stress response cannot be extrapolated from single stress responses added together. Bioinformatic analysis of transcriptomic data banks allowed us to identify a gene (HSFA2) involved in multiple stress responses. The work presented here aimed at discovering the mechanisms controlling HSFA2 expression. Two strategies were used.First, factors able to bind a region of HSFA2 promoter were studied through a “yeast one hybrid” system. Secondly, a transgenic biosensor of HSFA2 activity line was produced and mutagenized. A great number of mutants were selected on the basis of showing a constitutive activation of the biosensor. Resistance potentials to a combination of heat and high light stresses were then determined. Causal mutations identification through whole genome sequencing allowed, in some cases, to determine which were the loci responsible for the resistance traits. In particular, two mutations confering broad spectrum stress resistance will be discussed

Screening, Brief Intervention, and Referral to Treatment (SBIRT) for alcohol use has been shown to reduce rates of alcohol use across multiple clinical settings, and is routinely recommended by the United States Preventative Services Task Force (USPSTF). In 2005 the National Institute on Alcohol Abuse and Alcoholism (NIAAA) recommended implementing a single item screening question (SISQ) for this purpose. Since then the SISQ has been well validated compared to other tools, such as the Alcohol Use Disorders Identification Test (AUDIT). It has not, however, been well studied in particular populations, such as those with comorbid anxiety and/or depressive disorders. Medicare Annual Wellness Visits present a unique opportunity to study the SISQ because while they do inquire about alcohol use, they do not routinely include a SISQ. Our study seeks to investigate the efficacy of implementation of a SISQ during Medicare Annual Wellness Visits in a residency clinic population with anxiety and/or depressive disorders. Data collection is ongoing and will measure rates of referral to treatment before and after the SISQ is implemented, as well as rates of brief interventions given.

Colorectal cancer (CRC) is the second most common cancer among males and third among females across the world. In Australia it is the second most prevalent and the second leading cause of cancer-related mortality with the number of CRC incidences doubling over the last decade. While there has been a reduction of the incidence-adjusted mortality of CRC, a significant number of CRC detections are made at either the intermediate or later stages of the disease progression despite the roll out of a population based screening program for individuals aged 50 and over. Data shows that ‘one size fits all’ nature of the program despite recommendations from the NHMRC to screen according to the familial risk of an individual and inappropriate colonoscopy referrals, may have led to over screening those at average risk while potentially under-screening and missing those at an increased risk. Furthermore this program may have missed individuals under the age of 50 that have a high familial lifetime risk of developing CRC and require earlier CRC screening with a colonoscopy. It was hypothesised that implementing an online familial risk tool that notified both patients (aged 25-74) and their GPs of their familial CRC lifetime risk would increase the uptake of risk-appropriate screening among the study population relative to controls that receive usual care, during the 12 month study period. In doing so, this thesis used a complex intervention aimed at improving the rate of risk-appropriate screening for colorectal cancer (CRC) among an Australian General Practice population. This intervention utilised an online evidenced -based familial history algorithm, that stratified participants into three Australian National Health and Medical Research Council (NHMRC) recommended relative risk groups for screening CRC. These categories are based on a strong body of evidence showing that familial phenotype as measured by family history is a significant and non-modifiable risk factor for an increased lifetime risk of CRC. The algorithm used in the online tool was adapted from the NHMRC guidelines but were also updated by utilising the most recent evidence-base in addition to consulting with a group of experts. This algorithm was then programmed into an online website called “Which test is best?”. This website notified participants of their familial risk in addition to faxing or emailing this information to their consulting General Practitioner (GP). The website was piloted among members of a cancer consumer group (n=26), before being amended to improve clarity and the website interface. It was then implemented in a clustered RCT to evaluate its effect on risk-appropriate CRC screening. The intervention was implemented at both the cluster (GP practice) (Intervention n=27, Control n=28) and participant (eligible patients aged 25-74 with no personal history of CRC and/or inflammatory bowel diseases) level (Intervention, n=836, Control n=726). Those in the intervention arm were given access to the online website with risk tool and their family history information. In addition to their familial risk category with NHMRC recommended screening guidelines were forwarded to their consulting GP, while the control group had usual care. Both groups were followed up 12 months later to obtain their self-reported CRC screening information using the online survey. Thereafter, the control group was immediately given access to the online website with risk tool so that their family history information could be recorded and the level of risk-appropriate screening could be calculated for both groups. The results from this study showed ,that there was no significant difference in risk-appropriate screening rates amongst participants allocated to the intervention group compared to the control group as there was no main effect of allocation when included as a predictor within a binomial logistic regression when modelled to the GEE. However, participants allocated to the intervention group that were designated as belonging to the potentially high-risk category did engage in significantly higher levels of risk-appropriate screening when compared to the control group at 12 month follow-up. This was observed by a significant interaction effect of both family history and allocation in predicting risk-appropriate screening the final GEE model. Specifically, potentially high-risk individuals that were allocated to the intervention group had higher odds (about five times) of engaging in risk-appropriate screening when compared to those at population level risk that were assigned to either control or intervention, when controlling for other variables. This suggests that the online familial risk tool was effective in changing the behaviour of participants from the intervention group that were categorised as having a family history consistent with a potentially high risk (defined as having lifetime relative risk three times or greater of the general population) of developing CRC in their lifetimes. GPs from participating clusters were followed up by a survey (n=66) to assess their attitudes, knowledge and perceived barriers on utilising family history to risk-appropriately screen their average risk patients. Three important findings emerged from this survey. Firstly it shows that the majority of GPs in this study regard family history as the most important factor in screening their asymptomatic patients for CRC. It also shows that these GPs in principle strongly support the NHMRC guidelines, continuing education and peer-reviewed evidence as the most important knowledge factors in evaluating their CRC screening recommendations for asymptomatic patients, while being somewhat less influenced by government policy and their patients’ personal perceptions about the efficacy of a particular CRC screening test. However GPs appear very sensitive to their patients’ fears and anxiety over CRC screening, assessing this factor as the most important barrier to screening for CRC followed by their subjective lack of experience with CRC screening and time constraints imposed during the consultation. Findings also showed a substantial level of dissonance between what GPs believe to be appropriate CRC screening for their asymptotic patients and what they may be likely to recommend with 77% GPs self-reporting that they still refer up to 10 average risk asymptomatic patients to a colonoscopy during a typical month. Taken together the findings from this thesis show that that an intervention which aims to include both the patient and GP improves the uptake CRC risk-appropriate screening for individuals with potentially high-risk. It shows that a tailored risk tool, that supports GP triage may be sufficient to improve uptake of CRC screening modalities across all risk groups but may not be sufficient to encourage risk-appropriate screening of those from average and moderate risk. This is mainly due to persistent over-screening in the average-risk group within our study sample. Future studies may need to examine and differentiate between under screeners and over-screeners in order to target and tailor interventions to those groups separately.

Background: Based on previous research, conventional mammography screening has been found to be ineffective for women at high risk, mainly because high-risk women have high breast density and a fast progression rate of breast cancer. Recently, MRI screening was proposed as an additional complementary screening for high-risk women in Ottawa. The addition of MRI to mammography to screen the high-risk population is worth exploring as it may well address the limitations of mammography, especially since MRI has higher sensitivity. Purpose: The goal of this study is to assess the cost-effectiveness off adding MRI to mammography screening for early detection among women of the high-risk population in Ottawa by using conventional values for the society’s/government’s willingness to pay for one life year gained (US$ 50,000). Methods: A discrete-event simulation model was developed to evaluate the cost-effectiveness of adding MRI screening to mammography for high risk women breast screening in Ottawa. Three risk groups were considered; BRCA1, BRCA2 and other high risk. Based on breast annual incidence, screening features, breast cancer progression among high-risk women, treatment and breast cancer survival rates, the model simulates a hypothetical cohort consisting of 5000 women progressing from age 30 to 100 (or to natural death) and calculates the accumulated life years and costs in order to predict the cost of one life year gained by each screening strategy. Univariate sensitivity analysis was performed on the key parameters to determine the robustness of the simulation outcomes. Paired t-tests were used to determine whether the parameters’ variations are statistically significant or not. Results: In the base-case scenario, the incremental cost-effectiveness ratio (ICER) of mammography compared to both screening was CAN$30,043.48 /life year gained (95%CI ±2524.40) which means the addition of MRI to mammography is a cost-effective intervention according to the commonly used willingness-to-pay threshold of US$50,000 per life-year gained. The findings of the sensitivity analysis indicate that the cost-effectiveness of adding MRI screening is statistically significant for most of the parameter variations, however, the degree of change in the ICER is not hugely impactful as in all cases the ICER remained well below the commonly used willingness-to-pay threshold per life year gained. Conclusion: Study results suggested that the addition of MRI has an important role in improving high risk women screening in terms of increasing life years gained compared to receiving mammography screening only. The results of this study support the recommendations of Cancer Care Ontario and the Ontario Health Technology Advisory Committee guidelines of expanding the Ontario Screening Program to integrate MRI with mammography screening for high risk women aged 30 to 69 years.

Malignant hyperthermia (MH) is an autosomal dominant, pharmacogenetic disorder. MH susceptible (MHS) patients appear clinically normal, but may present with a hypermetabolic crisis and muscle contracture when exposed to triggering substances which elicit excessive release of calcium ions from the sarcoplasmic reticulum. The underlying cause of MH has emerged as biochemical abnormalities that occur in skeletal muscle. Presymptomatic diagnosis of MH susceptibility is currently made via the in vitro contracture test. The phenotypically similar porcine MH model led to the identification of the chromosomal region bearing the underlying defect. The first human MHS locus, MHS-1, has been mapped to chromosome 19q13. MH is mainly due to mutations in the skeletal muscle ryanodine receptor gene (RYRI). To date the RYRI gene has been associated with an MH phenotype in approximately 50% of MH families. However, the disorder is genetically heterogeneous, as six other loci have to date been associated with MHS. The aim of the molecular investigation presented here was to determine if 24 recently reported causative mutations in the RYRI gene are present in any of the 45 South African MHS probands investigated. Furthermore, eight mutations of the RYRI gene and the Arg1086His mutation of the CACNAIS that have already been analysed in previous phases of the research programme were investigated. One alteration, Thr482611e was detected for the first time in a single South African MH family, contributing to the description of the aetiology of MHS in South Africa. None of the remaining alterations were detected in any South African MH probands analysed. The absence of the majority of reported mutations in all probands included in this study could indicate that the mutations either represent family-specific alterations or could be attributed to the fact that these mutations do not play a role in MHS in the South African population.
Thesis (M.Sc. (Biochemistry))--North-West University, Potchefstroom Campus, 2005

Although the Massachusetts Youth Screening Instrument – Second Version (MAYSI-2) has been widely accepted as a short mental health screener in the juvenile justice system, its utility in predicting juvenile recidivism has not yet been explored. This study comprised of 424 subjects who have been detained at Allen County Juvenile Justice Center (ACJC) for criminal charges. Participant's MAYSI-2 total scores without the Alcohol/Drug Use subscale and Alcohol/Drug Use subscale scores were used to assess their utility in predicting juvenile recidivism. A correlational analysis using urinalysis results and Alcohol/Drug Use subscale scores suggested Alcohol/Drug Use subscale is an efficacious measure for assessing substance use among juvenile offenders. A multiple hierarchical regression and ROC analyses were conducted. Findings indicated that the MAYSI-2 total score and Alcohol/Drug Use subscale scores were not adequate predictors of recidivism. However, in exploratory analysis the Anger-Irritability subscale was found to be a significant predictor of juvenile recidivism.
Department of Psychological Science

Cancer of the colon and rectum is a major cause of ill-health. Options for reducing the burden of the disease include primary prevention, screening for early stage asymptomatic disease and improvements in the treatment of symptomatic disease. If the policy objective is to make a major impact on mortality from the disease then screening appears to be the only technically feasible option. One indication of asymptomatic colorectal cancer is small quantities of blood mixed with faeces. Screening tests capable of detecting bleeding are currently being evaluated in clinical trials. Interim measures of the costs and disease yield of a screening programme using a faecal occult blood test imply that screening may offer good value for money but only if the intended mortality reduction from the disease is realised. There are various ways of 'fine-tuning' the screening programme to improve the balance of costs and benefits; information for making choices regarding important parameters such as the age range of the population to be offered screening are presented. Alternative screening tests are also evaluated and the results presented in terms of the cost-yield trade-off. The policy implications of the evaluation must be qualified at this stage since no proof of mortality reduction will be available until the conclusion of the ongoing trial. Nevertheless, under various assumptions about the impact of screening, the option appears to be an efficient way of reducing the health 'costs' of colorectal cancer.

The purpose of this study was to determine the prevalence and demographic predictors of pulpal and/or periradicular disease in an urban population. A total of 210 subjects were recruited from a population of patients that were screened for acceptance to the dental school clinics. The diagnosis of pulpal and/or periradicular disease was made using the following data: radiographic interpretation, patient's history of previous pain and chief complaint, and objective pulpal testing. Objective pulpal testing included percussion, palpation, electric pulp test, and cold. The unit of observation was the individual, not the tooth. The overall prevalence of endodontic disease among the study sample of the screening patient population was 39.52%. Controlling for gender, patients in the 30-39 age group were 3.05 times more likely to have pulpal disease than patients in the 18-29 age group (OR=3.05, 95%CI 1.04-8.9). Controlling for age, men were 1.82 times more likely to have pulpal disease than women (OR=1.82, 95%CI 1.01-3.26). Non-white patients were 2.69 times more likely to have pulpal disease than white patients (OR=2.69, 95%CI 1.51-4.81). Patients who earned less than $25,000 were 2.06 times more likely to have pulpal disease compared to those who earned more than $25,000 (OR=2.06, 95% CI 1.15-3.69). Overall, this data provides valuable information for identifying vulnerable populations and addressing the policy goals of the U.S. Surgeon General.

The rate of incarcerated individuals in the United States continues to grow. At midyear 2005 the Nation's prisons and jails incarcerated 2,186,230 persons. (Bureau of Justice 1). Prison systems are in need of a brief mental health-screening tool that rapidly and readily identifies mental illness and co-occurring substance abuse in inmates to improve the approach to mental health diagnosis and treatment throughout an offender's incarceration. This study was designed to assess whether the Modified Mini Screen (MMS) is a valid screening measure for identifying mood disorders, anxiety disorders, and psychotic disorders in newly admitted inmates during the intake and reception process in prisons. For this study, 130 individual's MMS scores were compared with results from the Brief Symptom Inventory to determine the proportion in each group with mental illness. Findings show concurrent validity for age, ethnicity, level of education, and history of substance abuse and mental health. Concurrent validity of the MMS with the BSI was better for females than for males for. Results suggest that the sensitivity of the MMS is somewhat weak, as it only has a 55% chance of correctly identifying a mentally ill individual as being mentally ill. For females, the sensitivity of MMS was 87.5%, while the specificity was 100%. Moreover, for males, the sensitivity of MMS was 46.9%, while the specificity was 95.6%. These results suggest that the concurrent validity of the MMS with the BSI was better for females than for males for in this study sample.

Systematic screening for social, emotional, and behavioral concerns (SEBC) identifies at-risk students and provides information to guide interventions that may prevent negative outcomes (Glover & Albers, 2006; Kauffman, 1999; Severson, Walker, Hope-Dolittle, Katochwill, & Gresham, 2007). However, the screening process may be influenced by the gender of the student (Young, Sabbah, Young, Reiser, & Richardson, 2010). This study further examined the influence of student gender on screening by assessing the congruency of gates one and two of a screening process based on student gender. Participants included 59 middle school teachers who nominated at-risk students on the Teacher Nomination Form (TNF; Davis, 2012) and then completed the Behavior Assessment System for Children, Behavioral and Emotional Screening System (BASC-2 BESS; Kamphaus & Reynolds, 2007) on each nominated student. A two-tailed z-score was calculated to see if the TNF predicted BASC-2 BESS T-scores better for one gender over the other. A z score of -0.63 (p > .05) was obtained in the internalizing category and a z score of 0.39 (p > .05) was obtained in the externalizing category; the difference between correlation coefficients for males and females was not statistically significant. While more males were nominated than females in both the internalizing and externalizing categories, the screening instrument does not measure differently for males and females according to the data analysis provided here. Disproportionate identification of males and females in the screening process may be explained by other factors that could be the focus of additional research.

Current literature on sequelae of acquired brain injury reveals that behavioural disturbances such as physical and verbal aggression and disinhibited behaviour present a substantial barrier to community re-integration following severe brain injury. This study applies the concept of 'challenging behaviour', originally applied to people with learning disabilities, to behavioural disturbance following acquired brain injury. Definition of challenging behaviour, assessment, intervention, and impact on carers are discussed. Standardised measures of challenging behaviour are reviewed. The study has two aims. Firstly, to investigate the degree of shared understanding of the concept of challenging behaviour within a group of staff working in a specialist unit for people with behavioural disturbances following acquired brain injury. Twenty-eight members of staff (21 nurses and 7 other professional staff) completed questionnaires, consisting of four brief case vignettes. Each vignette was rated on 5-point scales for important defining aspects of challenging behaviour: overall management difficulty, threat to the physical safety of the patients and others, and impact on the patients' access to community facilities. Results are analysed for agreement between raters, taking consideration of demographic variables. Secondly, the usefulness of screening measures in application to challenging behaviour was evaluated within the same unit. The measures chosen were the Agitated Behaviour Scale (Corrigan 1989) and the Checklist of Challenging Behaviour (Harris et. al. 1994). Three members of staff (2 trained nurses and one other member of therapeutic staff) rated each patient's behaviour during the preceding week. A total of 22 patients were assessed, some on more than one occasion, and results examined for inter-rater reliability and concordance with clinical records. In addition, the behaviour profile of this clinical population is delineated. The application of standardised screening measures in general to challenging behaviour, methodological issues and future research implications are discussed.