Libyan breast cancer: Health services and biology. Diagnosis delay and prognostic value of DNA pploidy, S-phase fraction, and Ki-67 and Bcl-2 immunohistochemistry

The aim of this study was to investigate the diagnosis delay and its impact on the stage of disease. The study also evaluated a nuclear DNA content, immunohistochemical expression of Ki-67 and bcl-2, and the correlation of these biological features with the clinicopathological features and patient outcome. 200 Libyan women, diagnosed during 2008–2009 were interviewed about the period from the first symptoms to the final histological diagnosis of breast cancer. Also retrospective preclinical and clinical data were collected from medical records on a form (questionnaire) in association with the interview. Tumor material of the patients was collected and nuclear DNA content analysed using DNA image cytometry. The expression of Ki-67 and bcl-2 were assessed using immunohistochemistry (IHC). The studies described in this thesis show that the median of diagnosis time for women with breast cancer was 7.5 months and 56% of patients were diagnosed within a period longer than 6 months. Inappropriate reassurance that the lump was benign was an important reason for prolongation of the diagnosis time. Diagnosis delay was also associated with initial breast symptom(s) that did not include a lump, old age, illiteracy, and history of benign fibrocystic disease. The patients who showed diagnosis delay had bigger tumour size (p<0.0001), positive lymph nodes (p<0.0001), and high incidence of late clinical stages (p<0.0001). Biologically, 82.7% of tumors were aneuploid and 17.3% were diploid. The median SPF of tumors was 11% while the median positivity of Ki-67 was 27.5%. High Ki-67 expression was found in 76% of patients, and high SPF values in 56% of patients. Positive bcl-2 expression was found in 62.4% of tumors. 72.2% of the bcl-2 positive samples were ER-positive. Patients who had tumor with DNA aneuploidy, high proliferative activity and negative bcl-2 expression were associated with a high grade of malignancy and short survival. The SPF value is useful cell proliferation marker in assessing prognosis, and the decision cut point of 11% for SPF in the Libyan material was clearly significant (p<0.0001). Bcl-2 is a powerful prognosticator and an independent predictor of breast cancer outcome in the Libyan material (p<0.0001). Libyan breast cancer was investigated in these studies from two different aspects: health services and biology. The results show that diagnosis delay is a very serious problem in Libya and is associated with complex interactions between many factors leading to advanced stages, and potentially to high mortality. Cytometric DNA variables, proliferative markers (Ki-67 and SPF), and oncoprotein bcl-2 negativity reflect the aggressive behavior of Libyan breast cancer and could be used with traditional factors to predict the outcome of individual patients, and to select appropriate therapy.

Predictors and Correlates of Substance Use among Young Men. The Longitudinal “From a Boy to a Man” Birth Cohort Study.

Substance use is one of our most important public health problems. Studying risk factors in a longitudinal study setting helps to identify subgroups of young people at greater risk for substance-use-related problems, and to facilitate targeted prevention efforts. The aim of this thesis was to study childhood predictors and correlates of substance-use-related outcomes among young men in a longitudinal, nationwide birth cohort study. The study population included 10% of all Finnish-speaking boys born in Finland in 1981 (n=2946, 97% of the target population). In 1989, at age eight, valid measures of psychiatric symptoms (Rutter questionnaires and Children’s Depression Inventory) were obtained from parents, teachers and the boys themselves. In 1999, at age 18, boys were reached at their obligatory military call-up (n=2348, 80% of the boys attending the study in 1989). Self-reports of substance use, psychopathology, adaptive functioning (Young Adult Self-Report), and mental health service use were obtained through questionnaires. Information about psychiatric diagnoses from the Military Register (age 18-23 years) and information about offending from the National Police Register (age 16-20 years) were collected in early adulthood (92% of the 1989sample). Boys with childhood conduct, hyperactive, and comorbid conduct-emotional problems had elevated rates of substance use and substance-use-related crime in early adulthood. Depressive symptoms predicted daily smoking, especially among boys of low-educated fathers. Emotional problems predicted lower occurrence of drunkenness-related alcohol use and smoking. Teacher reports on boys’ problem behaviour had the best predictive power for later substance use. At age 18, frequent drunkenness associated with delinquency, smoking and illicit drug use, and having friends. Occasional drunkenness associated with better psychosocial functioning in general compared to boys with frequent drunkenness or without drunkenness-related alcohol use. Illicit drug use without drug offending was not predicted by childhood psychiatric symptoms, but 22% of boys with illicit drug use had a psychiatric diagnosis in early adulthood. Drug offenders, in turn, had psychiatric problems both in childhood and in adulthood. Psychiatric disorders were common among young men with substance-use-related crime. Recidivist crime associated strongly with having a substance use disorder diagnosis according to the Military Register. At age 18, frequent drunkenness was common among boys entering mental health services, but entering substance use treatment was non-existent. According to the findings of this thesis, substance-use-related outcomes accumulate in boys having psychiatric problems both in childhood and in early adulthood. Targeted early interventions in school health care systems, particularly for boys with childhood hyperactive, conduct, and comorbid conduct-emotional problems are recommended. Psychiatric problems and risky behaviours, such as delinquency should always be assessed alongside substance use. Specialized and multidisciplinary care are required for young men who have multiple or complex needs, for instance, for young men with drug offending and recidivist crime. Integrating a substance use treatment perspective with other services where young men are encountered is emphasized.

Configuring Health Care Services - Service Control Improvement

The costs of health care are increasing, and at the same time, population is aging. This leads health care organizations to focus more on home based care services. This thesis focuses on the home care organization of the South Karelian District of Social and Health Services (Eksote), which was established in 2010; how its operation is organized and managed, and which problem types are faced in the daily operation of home care. This thesis examines home care services through an extensive interview study, process mapping and statistical data analysis. To be able to understand the nature of services and special environment theory models, such as service management and performance measurement, service processes and service design are introduced. This study is conducted from an external researcher‟s point of view and should be used as a discussion opener. The outcome of this thesis is an upper level development path for Eksote home care. The organization should evaluate and build a service offering, then productize home care services and modularize the products and identify similarities. Service processes should be mapped to generate efficiency for repeating tasks. Units should be reasonably sized and geographically located to facilitate management and operation. All this can be done by recognizing the different types of service products: runners repeaters and strangers. Furthermore, the organization should not hide behind medical issues and should understand the legislative, medical and operational frameworks in health care.