<p>In this thesis, chitosan, a biocompatible polysaccharide that has been approved as a food additive was selected as a platform for the development of safe, efficient non-viral gene delivery systems to mammalian cells. Previously, chitosan-based gene formulations had been generally associated with high molecular weight chitosans, which were poorly characterised in terms of molecular weight distribution and degree of acetylation. Therefore, in order to improve the properties of chitosan-based gene formulations, the research associated with this thesis focused on establishing the structure-property relationships of well-defined, low molecular weight chitosans (chitosan oligomers) as delivery systems for nucleic acids (pDNA and siRNA)<i> in vitro</i> and after lung administration <i>in vivo</i>. pDNA dissociated more easily from chitosan oligomers than from conventional high molecular weight chitosans, resulting in a faster onset and higher levels of<i> in vivo</i> gene expression, comparable to those mediated by polyethyleneimine (PEI), one of the most efficient non-viral delivery systems. Coupling of a trisaccharide branch to the chitosan oligomers so as to target extracellular lectins resulted in a significant improvement in transfection efficiency because of enhanced cellular uptake and colloidal stability. In contrast to pDNA, longer linear chitosan oligomers were required to form physically-stable nanoparticles with siRNA that mediated efficient, sustained gene silencing <i>in vitro</i>. Finally, the use of an optimised catheter device for the nebulisation of small volumes of pDNA formulations resulted in improved dose precision and lung distribution<i> in vivo</i> compared with conventional intratracheal instillation. In conclusion, chitosan oligomers are interesting and viable alternatives to other non-viral gene delivery systems.</p>

The purpose of this thesis was to study different aspects of nursing content in patient records with special reference to nursing home care. The thesis focused on the content, comprehensiveness, accuracy and auditing of records, as well as the practice and perceptions of nurses in relation to recording. A national sample of nurses was asked to complete a questionnaire. The effects on recording and nurses' practice and perceptions in nursing homes following educational intervention were studied. Accuracy was examined through record reviews and interviews with nurses and patients. A literature review of record auditing methods was performed and findings from this search were applied in the assessment of a set of records. The results indicate that the VIPS model, as a structure for nursing recording, is widespread and shows validity across various areas in Swedish health care. After the educational intervention program, documentation in nursing home care improved significantly in the study group concerning notes on nursing history, nursing status, nursing diagnoses, interventions and discharge notes. Systematic and comprehensive assessment grounded in research-based criteria were not used in the records. Accuracy varied considerably and was significantly better for some areas in the study group. After intervention, the nurses in the study group indicated that they recorded assessments of patients with greater frequency, showed greater satisfaction with their documentation and spent less time on oral reports. Procedures in auditing patient records were found to encompass four approaches: formal structure, process comprehensiveness, knowledge based and accuracy. In conclusion, the evidence suggests that there are serious flaws in the nursing content of nursing home records though improvements can be achieved through educational means. Presently, there are serious limitations in using the patient record as the sole source of data for care delivery, quality assessment and evaluation of care.

The overall aim was to study self-care, foot problems and self-perceived health in 150 consecutively invited Tanzanian diabetic patients and to compare them with gender- and age-matched Swedish diabetic patients (n=150) from a middle Sweden area. The main study was cross-sectional and took place at a diabetes clinic in Dar es Salaam. All patients answered questions about their self-care satisfaction, diabetes knowledge and skills, and educational needs. Foot examination also included questions about foot-care and perceived foot problems. The patients' health was assessed using the SF-36 general health questionnaire. The Swahili version of SF-36 was pre-tested in 518 Tanzanian diabetic patients showing an acceptable validity and reliability. Glycaemic control was measured by HbA1c. The results indicated that 45% of Tanzanians and 43% of the Swedes reported satisfaction with their self-care. The Tanzanian patients reported that following doctor's advice was the most important factor necessary for feeling well, whereas the Swedish patients emphasised diet and exercise. Lack of drugs and education were reasons of dissatisfaction in the Tanzanian group, whilst the Swedes were dissatisfied with their own behaviour. None of the Tanzanians monitored their blood glucose themselves, whilst 50% of the Swedes did it on a daily or weekly basis. Significantly more Swedes than Tanzanians knew the interaction between insulin, food and exercises, and how to manage hyperglycaemia and hypoglycemia. The Tanzanians wanted more education about diabetes, treatment and injection technique, whereas the Swedes wanted education about psychological aspects of diabetes, foot-care and oral anti-diabetic treatment. Foot problems reported in the Tanzanian group were pain, numbness and pricking sensations, whereas the Swedes reported ingrown toenails, pain and fissures. Seven Tanzanians and one Swede had foot ulcers. Twenty Tanzanians and 103 Swedes reported to inspect their own feet. The Tanzanians had significantly poorer self-perceived health and glycaemic control than the Swedish patients. A follow-up study was performed with the Tanzanian group of patients after two years. Many patients did not return for the second investigation and 70 patients were re-assessed. They showed an improved self-perceived health and a significant decrease in HbA1c-value. In conclusion the results indicated that Tanzanian patients needed better access to a continuous and regular supply of diabetes drugs. Furthermore the Tanzanians' burden of diabetes influenced their possibilities to work, whilst Swedish patients were hindered in social activities. In both countries the importance of regular foot inspections of the patients' feet should be emphasised. Glycaemic control and self-perceived health seemed to be poorly related and for that reason diabetes nurse specialists need to use both measures in order to guide the patients towards the goals experiencing a good health despite having diabetes.

The aim of the present thesis is to evaluate the effects of an Intensified Primary Health Care (IPHC) intervention on GPs' and home care nurses' possibilities to monitor and support cancer patients, and on cancer patients utilisation of medical services. A further aim is to identify determinants of cancer patients' utilisation of such services. A total of 485 patients newly diagnosed with breast, colorectal, gastric or prostate cancer were randomised to the intervention or to a control group. The follow-up period was 24 months for all patients. Patients randomised to the IPHC were referred to the home care nurse. The home care nurse and the GP received copies of the medical record each time the patient was discharged from hospital after a period of in-patient care, or had visited a specialist out-patient clinic. In addition to this, recurrent education and supervision in cancer care were arranged. The IPHC resulted in a marked increase of home care nurse follow-up contacts. The majority of control patients (74%) reported no such contacts, while 89% of IPHC patients reported this. High age (=80 yr) was the strongest predictor within the IPHC group for reporting a continuing home care nurse contact. Furthermore, the IPHC increased GPs' knowledge about patients' disease and treatments, and appeared to facilitate their possibilities to support the patients. The IPHC reduced the utilisation of specialist care among elderly cancer patients. The number of days of hospitalisation for older patients (=70 yr) randomised to the IPHC were 393 less than for older control patients during the 3 first months after inclusion. Regression analyses defined diagnosis, extensive treatment, comorbidity, low functional status, pain and socio-economic factors as predictors of a high utilisation of medical services.

The aims of the present thesis were to study: 1. reported eating attitudes, dieting behavior and body image over a 1-year period among preadolescent girls (age 7-8); 2. differences in eating attitudes and coping between groups of teenage girls differing in dieting frequency, and to assess changes with increasing age (age 13-17); and 3. to what extent eating attitudes, self-esteem and coping predict disturbed eating attitudes. A final aim was to explore differences in the reported wish to be thinner, dieting, and eating attitudes between two age-matched cohorts of girls in 1995 and 1999 (7-15 years). The project is designed as a longitudinal prospective study, spanning seven years. 1300 girls in the ages (1995) 7, 9, 11, 13 and 15 years have been assessed annually for three consecutive years (1995-1997) (Main Cohort). An additional group matched for age with the original group was recruited in 1999 (Societal Cohort). The results suggest that dieting and the wish to be thinner starts as early as at 7 years of age, and that repeated dieting attempts correlate with disturbed eating attitudes. A marked increase of the wish to be thinner was evident in the 10- to 14-year age range, and significant increases in dieting attempts occurred mainly between ages 9 and 13. There were no differences between 1995 (Main Cohort) and 1999 (Societal Cohort) (except among 7 and 11-year-olds) with regard to dieting, the wish to be thinner and disturbed eating attitudes. Eating patterns and attitudes were shown to be the strongest predictors of disturbed eating attitudes three years later. Assessment of dieting, the wish to be thinner and eating attitudes is suggested BS a component in school health care.

The aims of the present thesis were to survey the prevalence and incidence ofpressure ulcers in patients with hip fracture and to investigate nursing staffknowledge and documentation regarding pressure ulcer prevention for the samepatient group. Another aim was to test the effect of three preventive interventions:risk assessment and pressure ulcer grading, a pressure-reducing mattress and aneducational programme. Experimental, comparative and descriptive designs wereused and quality improvement philosophy guided the research. In 1997 and 1999, atotal of 124 and 101 patients &gt; 65 years with hip fractures were included andfollowed with risk assessment and skin observation. Audit of patient records, aquestionnaire to nursing staff and a focus group interview were also employed. The findings from the first studies showed that 20% of the patients hadpressure ulcers on arrival to the hospital. During the hospital stay, 55% developednew pressure ulcers. Nursing staff knowledge and documentation regardingpressure ulcer prevention was unsatisfactory. An extensive educational programmewas developed and conducted in 1998. Twenty-five registered nurses participatedfrom the hospital and the community setting. There were no significant differences in the prevalence/incidence ofpressure ulcers between the experimental and control groups in the twoexperimental studies. However, there was a significant reduction of the incidence ofpressure ulcers between 1997 and 1999 (from 55% to 29%). The focus group indicatedthat there had been changes since 1997 in nursing and treatment routines in theAccident and Emergency Department and in the orthopaedic wards.

Left ventricular hypertrophy (LVH) and the insulin resistance syndrome are common conditions associated with a markedly increased cardiovascular risk. In a fairly large prospective longitudinal study of men from the general population, we found that an unfavorable serum fatty acid profile and components of the insulin resistance syndrome such as dyslipidemia, obesity and hypertension at age 50 predicted the prevalence of LVH at age 70. In cross-sectional analyses at age 70, several components of the insulin resistance syndrome were significantly related to left ventricular relative wall thickness and concentric remodeling, but less to LVH. Left ventricular relative wall thickness was inversely related to insulin sensitivity in skeletal muscle and borderline significantly directly related to insulin sensitivity in the myocardium in a healthy, normotensive sample of the cohort investigated with positron emission tomography, whereas left ventricular mass index was not related to myocardial or skeletal muscle insulin sensitivity. At age 70, echocardiographic LVH was related to a variety of common electrocardiographic diagnoses. In a prospective mortality analysis with baseline at age 70 and a median follow-up time of five years, echocardiographic and electrocardiographic LVH predicted mortality independently of each other and of other cardiovascular risk factors, implying that echocardiographic and electrocardiographic LVH in part carry different prognostic information. In summary, components of the insulin resistance syndrome predicted LVH twenty years later, but were cross-sectionally more related to increased left ventricular relative wall thickness and concentric remodeling. Echocardiographic and electrocardiographic LVH predicted mortality independently of each other and of components of the insulin resistance syndrome.

Oral complications and symptoms are common among patients with cancer. The aim of this thesis is to study several aspects of oral status, oral health and its relation to quality of life, and oral care among patients treated with radiotherapy or chemotherapy. Descriptive, comparative and correlational designs were used. A series of consecutive patients admitted to a university hospital or a regional hospital to receive radiotherapy for head and neck cancer or chemotherapy for haematological malignancies, were studied prospectively with regard to oral symptoms and their relation to health-related quality of life using interviews and questionnaires, examination of the oral cavity and saliva tests. All nurses and enrolled nurses who worked with these patients or with patients with lung cancer were interviewed about their education and knowledge in oral care and performed oral care. The medical and nursing records on patients with these cancer diseases at the two hospitals were reviewed. The results indicate that patients receiving radiotherapy experienced increasing oral symptoms, which remained to a large extent one month after treatment. Patients receiving chemotherapy did not experience oral symptoms to the same extent. The oral symptoms were significantly related to patients' health-related quality of life, particularly among those receiving radiotherapy. Data also indicate that there is a lack of adequate education and continuing education in oral care among nursing staff. All patients were not examined orally before or during treatment, nor did they receive sufficient information or instruction related to oral hygiene. Patient compliance with oral hygiene procedures was acceptable, although some patients reported difficulties. Oral status and oral care were insufficiently documented, particularly in nursing records. The attitudes to oral examination and discussion on oral hygiene differed between nursing staff and patients. Nursing staff objected to examining the oral cavity referring to patient integrity. This was not considered as a hindrance among patients. In conclusion, oral health is related to health-related quality of life, which motivates a multi-disciplinary approach to oral care.

Bronchial carcinois are subdivided into typical and atypical. Atypical carcinoids are more malignant, but typical carcinoids may also influence survival. In the present study immunohistochemistry was performed to identify prognostic markets in patients with typical bronchial carcinoids. The diagnostic efficacy of octreoscan was evaluated, in comparison with CT and bone scan, and finally our experience of treating patients with metastatic bronchial carcinoids is reported. In an unselected material of 43 patients with typical bronchial carcinoids, metastatic disease was found in 12 patients (28%). Five patients (12%) developed distant metastases and died from their disease. High Ki-67 index, as well as positive staining for bcl-2 or p53 was associated with de- creased survival time. Positive staining for CD44s, v7-8 and v9, as well as positive nuclear staining for nm23 correlated to decreased mortality. Staining for CD44 and Ki-67 should be performed routinely for prognostic evaluation in these patients. Octreoscan positive tumors were found in altogether 20/28 patients (71%). The primary tumor was detectable in 81% and intrathoracic metastases in 78% of the patients on octreoscan; the corresponding figures for CT were 94% and 89% respectively. Liver metastases, as shown by CT, were demonstable by octreoscan in 64% of patients. Octreoscan showed 70% and bone scan 90% sensitivity for identification of bone metastases. Plasma chromogranin A was elevated in 28/30 patients (94%) with metastatic bronchial carcinoids and was the most sensitive tumor marker. Increased urinary 5'HIAA was found in 68%. Biotherapy with α-interferon and Octreotide relieved carcinoid syndrome in 7/16 patients. However, only 4/27 patients showed stable disease during median 15 months, while 23 patients progressed. Treatment with cisplatinum + etoposide resulted in an objective response or stable disease for 6-8 months in 3/8 patients with widespread tumors. Doxorubicin combined with streptozotocin or paclitaxel was associated with stable disease for 9 months in 2/2 patients each. All 7 patients treated with streptozotocin+5-FU progressed. Among the 43 unselected typical bronchial carcinoid patients, 5-year and 10-year survival was 95% and 91%, respectively. The prognosis in patients with bronchial carcinoids showing distant metastases was poor: 5-year survival was 70% from diagnosis and 22% from treatment start.

Postal work is performed in very different settings, and the works are e.g., drivers, letter carriers, postal sorters, and counter clerks. A finding that a small group of parcel sorters with a good psychosocial work situation had much lower health complaints than comparable workers with a worse psychosocial situation at work, indicated that it might be possible to improve mental and physical health among postal employees by improving work organization. The theoretical framework for this thesis is the demands-control-support (DCS) model by Karasek, Theorell, and Johnson. Two cross-sectional studies were performed with questionnaires. In a study on 144 workers at a postal terminal it was found associations between low support from superiors and high psychological work demands, on one hand and gastrointestinal and sleep problems on the other. In another study on 655 postal workers in 6 different occupations, high psychological work demands and low skill discretion was associated with low-back pain, and low social support at work with neck pain. In this study, the associations differed significantly between men and women. A follow-up study on the postal terminal (136 persons) was performed 8 and 12 months after an organizational change took place. The changes were aimed at improving the shift system, and psychosocial work situation. Authority over decision and skill discretion increased, and sick-leave decreased during the follow up period. Changes in contact with superiors, team-mates, and skill discretion were associated with changes in gastrointestinal and sleep complaints. In another follow up study, 82 individuals were studied before and 1 year after improvement of the psychosocial work environment. Musculoskeletal complaints were significantly reduced in the intervention group but not in the control group. Increased support from superiors was associated with less symptoms. Younger age and higher authority over decisions at baseline was associated with reduced symptoms at follow-up. The main findings of this thesis are that there are significant associations between psychosocial work situation among postal workers and psychosomatic and musculoskeletal symptoms, and that it is possible to reduce symptoms and sick-leave, by changes of organization, and improvement of the psychosocial work situation