Type 2 diabetes is usually caused by a combination of pancreatic β-cell failure and insulin resistance in target tissues like liver, muscle and fat. Insulin resistance is characterised by an impaired effect of insulin to reduce hepatic glucose production and to promote glucose uptake in peripheral tissues. The focus of this study was to further elucidate cellular mechanisms for insulin resistance that may be of relevance for type 2 diabetes in humans. We used rat and human adipocytes as an established model of insulin’s target cells. Glucocorticoids, e.g. cortisol, can induce insulin resistance in vivo. In the present study, pretreatment of rat adipocytes in vitro for 24 h with the cortisol analogue dexamethasone produced a downregulation of glucose uptake capacity as well as a marked depletion of cellular insulin receptor substrate 1 (IRS-1) and protein kinase B (PKB), two proteins suggested to play a critical role in the intracellular signal transduction pathway of insulin. The amount of phosphorylated PKB in response to acute insulin treatment was decreased in parallel to total PKB content. The basal rate of lipolysis was enhanced, but insulin’s antilipolytic effect was not consistently altered following dexamethasone pretreatment. Alterations in blood glucose as well as insulin levels may be of great importance for cellular as well as whole-body insulin resistance. High glucose (≥15 mM) for 24 h induced a decrease in glucose uptake capacity in rat adipocytes and IRS-1 content was reduced whereas IRS-2 was increased. Long-term pretreatment with a high insulin concentration downregulated insulin binding capacity and when combined with high glucose, it produced a pronounced reduction of cellular IRS-1 and 2 content together with insensitivity to insulin’s effect to activate PKB and a decrease in glucose uptake capacity. A common denominator for a decrease in glucose uptake capacity in our rat adipocyte studies seems to be a decrease in IRS-1 content. Adipocytes from type 2 diabetes patients are insulin-resistant, but in our work the insulin resistance could be reversed by incubation of the cells at a physiological glucose level for 24 h. Insulin resistance in fresh adipocytes from type 2 diabetes patients was associated with in vivo insulin resistance and glycemic level and with adipocyte cell size and waist-hip ratio (WHR). As a potential mechanism for postprandial dyslipidemia in type 2 diabetes, we examined the nutritional regulation of subcutaneous adipose tissue lipoprotein lipase (LPL) activity. It was upregulated by ~40-50 % after a standardised lipid-enriched meal and this was very similar in type 2 diabetes patients and control subjects, suggesting that the postprandial hypertriglyceridemia found in type 2 diabetes is not explained by an altered nutritional regulation of LPL in subcutaneous fat. In conclusion, the present work provides evidence for novel interactions between glucocorticoids and insulin in the regulation of glucose metabolism that may potentially contribute to the development of insulin resistance. High levels of glucose and insulin produce perturbations in the insulin signalling pathway that may be of relevance for human type 2 diabetes. Cellular insulin resistance may be secondary to the diabetic state in vivo, e.g. via glucotoxicity. This is supported by our finding that insulin resistance in adipocytes from type 2 diabetes patients can be reversed after incubation at a physiological glucose level. Key words: adipocyte, insulin resistance, type 2 diabetes, insulin signalling, glucose uptake, insulin, glucose, dexamethasone, insulin receptor substrate, protein kinase B, GLUT4, lipoprotein lipase.

The main purpose of this thesis was to examine the relationship of pre-diagnostic circulating levels of sex-steroids (androgens and estrogens), sex hormone binding globuline (SHBG), insulin-like growth factor-I (IGF-I), IGF binding proteins (BP) and C-peptide (as a marker of pancreatic insulin secretion) with risk of ovarian and endometrial cancer. Additionally, the interrelationships of body mass index (BMI), sex-steroids, IGF-I and IGFBP-3 were examined. Two case-control studies were nested within 3 prospective cohort studies centered in New York (USA), Umeå (Sweden) and Milan (Italy). The ovarian study included 132 cancer cases. The endometrial study included 166 cancer cases in the IGF-I and C-peptide component and 124 postmenopausal cases in the sex-steroids component. For each case, two controls matching the case for cohort, age, menopausal status and date at recruitment were selected. In total 286 and 315 controls were included in the ovarian and endometrial cancer studies, respectively. Odds ratios (OR) and their 95% confidence intervals (CI) for cancer risk associated with increasing hormone concentrations were estimated by conditional logistic regression. The cross-sectional analysis was based on anthropometric and hormonal data from 620 controls selected for the two nested case-control studies. There was no association of prediagnostic androstenedione, testosterone, DHEAS, SHBG or estrone with ovarian cancer risk in the whole study population or in women who were pre- or postmenopausal at blood donation. In the premenopausal group, risk appeared to increase with increasing androstenedione (OR (95% CI) for the highest tertile: 2.35 (0.81-6.82), p=0.12). There was no association of IGF-I, IGFBP-1, 2, 3 or C-peptide concentrations with risk of ovarian cancer risk in the study group as a whole. In analyses restricted to subjects who had developed ovarian cancer at an early age (<55), circulating IGF-I was directly and strongly associated with risk (OR (95% CI): 4.74 (1.20-18.7), p<0.05 for the highest IGF-I tertile). In the endometrial study, previous observations were confimed that elevated circulating estrogens and androgens and decreased SHBG increase risk of developing endometrial malignancy after menopause. Multivariate ORs (95% CI) for endometrial cancer for quartiles with the highest hormone levels were: 4.13 (1.76-9.72), p<0.001 for estradiol; 3.67 (1.71-7.88), p=0.001 for estrone; 2.15 (1.05-4.40), p<0.04 for androstenedione; 1.74 (0.88-3.46), p=0.06 for testosterone; 2.90 (1.42-5.90), p<0.01 for DHEAS and 0.46 (0.20-1.05), p<0.01 for SHBG. Prediagnostic IGF-I, IGFBP-1, -2 and –3 were not related to risk of endometrial cancer in the whole study population. In postmenopausal women, levels of IGFBP-1 were inversely related to risk with an OR for the highest quartile of 0.36 (0.13-0.95), p<0.05. Endometrial cancer risk increased with increasing levels of C-peptide (p<0.01), up to an OR of 4.40 (1.65-11.7) for the highest quintile after adjustment for BMI and other confounders. The cross-sectional analyses showed that in both pre- and postmenopausal women SHBG decreased with increasing BMI. In the postmenopausal group, estrogens, testosterone and androstenedione increased with BMI, while the association with IGF-I was non-linear, the highest mean IGF-I concentration being observed in women with BMI between 24 and 25. In postmenopausal women, IGF-I was positively related to androgens, inversely correlated with SHBG, and was not correlated with estrogens. In conclusion, elevated pre-diagnostic sex-steroids, IGF-I or C-peptide increase risk of developing ovarian and endometrial cancer. BMI influences the circulating levels of these hormones, especially after menopause.

Stress has emerged as one of the most important factors to consider in psychiatric diagnoses and has become a common reason for long-term sick leave (LTSL). Roughly 50% of LTSL due to psychiatric diseases are thought to be associated with work-related stress. The demarcation towards major depression is disputed, and no international consensus exists for how to diagnose and rehabilitate these individuals. The Swedish National Board of Health has suggested the term “exhaustion syndrome” to integrate these individuals into stress-related disorders. Prominent features of this syndrome are fatigue, sleeping disorders, and cognitive dysfunction. The cognitive dysfunction may be due to an interaction between personality features, environmental factors, the biological effects of stress hormones, and dysfunction in key brain areas, notably the hippocampus and prefrontal cortex. A consistent feature of chronic stress is activation of the cortisol, or hypothalamic-pituitary-adrenal, axis, which may be linked to cognitive dysfunction. Increased glucocorticoid levels, mainly cortisol in humans, are known to impair memory performance. The aim of this thesis was to investigate whether patients with exhaustion syndrome exhibit specific alterations in an extensive set of biological, psychological and immunological variables. Patients in Study 1 had significant cognitive impairment for specific tasks assumed to tap frontal lobe functioning. In Study 2 anxiety prone, worrying, pessimistic individuals with low executive drive and a persistent personality type were more likely to develop exhaustion syndrome. Decreased reactivity was found on the pituitary level after corticotropin releasing hormone (CRH) in exhaustion syndrome patients. The cortisol/adrenocorticotropic hormone response to CRH was slightly higher in patients compared to controls, indicating increased sensitivity at the adrenal cortex level. No differences were found in hippocampal volume. In Study 3, functional imaging revealed a different pattern of brain activation in working memory tests in patients with exhaustion syndrome compared to healthy individuals and patients with depression. In summary, our data suggests an intimate link between personality and wellbeing, cognitive performance and neuroendocrine dysfunction, in exhaustion syndrome. We thus find similarities with major depression but also distinct differences between the exhaustion syndrome and major depression.

The demand for deep fried chips by public and the number of people entering the fast food industry in the form of fast food outlets has increased tremendously. Frying oils are very expensive and are the most important ingredient used in the preparation of fried foods. Due to high oil costs and lack of knowledge, frying oils are used to their maximum. This has resulted in the abuse of deep fried chip cooking oils. The overall quality of the deep fried chip cooking oil used in the South Central Operational Entity of the eThekwini Municipality is not known but abused cooking oils have been identified by Environmental Health Practitioners (EHP's) during routine inspections of fast food outlets. Considering all of the above, the objectives of the proposed research were: (l) Determine the overall prevalence of the use of abused deep fried chip cooking oils at fast food outlets in the South Central Operational Entity of the eThekwini Municipality. (2) Determine in which supervision areas in the South Central Operational Entity the use of abused cooking oil is most prevalent. (3) Determine current/reported practices in preserving the quality of chip oil. (4) Make appropriate recommendations to owner/managers of the fast food outlets and to Environmental Health Practitioners. The study design was observational utilizing a Rapid Epidemiological Assessment (REA) technique, with both a descriptive and analytical component. All fast food outlets making deep fried chips in the South Central Operational Entity registered with the eThekwini Health Department at the time of the study were included in the study population. The Lot Quality Assurance Sampling (LQAS) method was used to determine the overall prevalence of the use of abused oil and to determine supervision areas reached the predetermined service target. A total of 100 fast food outlets were sampled. An oil sample from each fast food outlet, which was taken and sent to a laboratory where an Oxifrit Test was done on every oil sample taken. The Oxifrit Test was the benchmark in this study. EHP's of eThekwini Municipality collected further data by means of an observational checklist and a closed-ended questionnaire, which aimed to establish cooking oil preservation practices. The study revealed that 60 of the outlets had oil that was acceptable whereas 40 had oil that was unacceptable (abused oil). In the multivariate analysis the only factors significantly associated with abused oil were the condition of the fryer and frequency of oil change. Supervision Areas 6, and 4 had more abused deep fried chip cooking oil than average in the South Central Operational Entity. For further prioritization, Supervision Areas 6 and 4 fell below the decision rule for majority of acceptable oil preservation practices, thus Supervision Areas 6 and 4 will be targeted for intervention. Intervention will include education, monitoring and ultimately enforcing the law by EHP's to ensure safe use of deep fried chip cooking oil in the South Central Operational Entity within eThekwini Municipality. / Thesis (M.P.H.)-University of KwaZulu-Natal, 2006.

Introduction. The Human Immunodeficiency Virus (HIV) is the main contributor to rising child mortality in South Africa. Although prevention of mother-to-child transmission programmes have been implemented in the country, little is known about the clinical and loss to follow-up outcomes of infants born to HIV-infected women attending these programmes. Purpose. The purpose of the study was to describe the clinical and loss to follow-up outcomes of HIV-exposed infants whose mothers had received antiretroviral therapy or prophylaxis during their pregnancy at the Prevention of Mother-to-Child Transmission programme at McCord Hospital. Furthermore, maternal socio-demographic characteristics associated with these outcomes were determined. Methods. An observational retrospective cohort study design was used. The study population consisted of infants whose mothers had received antiretroviral prophylaxis or therapy at McCord Hospital, and were delivered at McCord Hospital, and/or were brought back to McCord Hospital, following delivery from 1 May 2008 to 31 May 2009. Results. Data on 265 infants was analysed. Of the 220 infants who were tested, the HIV transmission risk was 2.7% (n=6; 95% Cl: 1.0% to 5.8%) at 6 weeks of age. Overall, 40.4% of infants in the cohort were lost to follow-up (n=105, 95% Cl: 34.4 to 46.6). In the multivariable model (n=253), late booking for first antenatal visit at or after 28 weeks of gestation (adjusted hazard ratio (AHR) 2.3; 95% Cl: 1.0 to 5.1, p=0.044) was a risk factor for loss to follow-up. Compared to having an emergency caesarean section, having an elective caesarean section (AHR 1.9; 95% Cl: 1.1 to 3.5) or normal vaginal delivery (AHR 2.5; 95% Cl: 1.4 to 4.5) was significantly associated with loss to follow-up of infants. Discussion. The substantial attrition of infants born to HIV-infected mothers in the Prevention of Mother-to-Child Transmission programme at McCord Hospital undermined the goals of the programme, and underestimated the effect of infectious disease morbidity, mortality and HIV transmission risk associated with these infants. Recommendations. Counselling mothers on the health benefits to their HIV-exposed infants of attending the follow-up clinic and tracing of infants who have been lost to follow-up is vital to the operational effectiveness of the Prevention of Mother-to-Child Transmission programme at McCord Hospital. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2011.

Introduction. Stone crushing in Dar-es-Salaam Tanzania is largely an informal occupational activity, with approximately 7000 workers exposed to varying level of respirable dust. A highly marginalized, self employed, informal stonecrusher is prone to multiple work related risks, particularly dust related respiratory diseases. Aim. This study, the first to be done among informal stone crushers in Southern Africa, aimed at determining the prevalence of dust related respiratory outcomes and relationships between these health endpoints and exposure to respirable dust in this sample of stonecrushers. Methods. This was primarly a cross-sectional descriptive study with analytic components. This study analysed a subset of data collected in a health survey of stone crushers in Kigamboni informal stone quarry in Dar-es-Salaam, Tanzania in 2007. All 200 workers working in the quarry were interviewed. A subset of 86 and 59 workers underwent exposure assessment and health assessments (spirometry and chest radiography) respectively. Associations were investigated between exposure measures and respiratory outcomes. Results. The average age of the workers was 36.3 years with 51.5% males participating in the study. Smoking was common with 30.1% male, 8.25% female smokers, with 2% ex-smokers. Personal dust sampling showed varying dust levels ranging from 0.5-2.8mg/m3 with geometric mean of 1.2gm/m3. The exposure duration of workers in the quarry ranged from 1-62 years with mean of 7.8 years. No single worker was found to use personal protective equipment at work. Reported prevalence of doctor diagnosed respiratory diseases was low: pulmonary tuberculosis (2%), chronic bronchitis (2%), asthma (3%), pneumonia (3%). In contrast, there was high prevalence of respiratory symptoms: chronic cough (13.5%), phlegm production (14.5%), productive cough (10%), wheezing (14%), mild breathlessness (9.5% ) and coughing blood (7.5%). Mean forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) adjusted for age, height and sex was 2.6L/min and 3.7 L respectively, among males and 2.1L/min and 3.0L respectively among females. Adjusted exposure odds ratios for symptoms were statistically significant for mild and moderate breathlessness with odds ratios of 3.4 and 3.1 respectively. Linear regression showed statistically significant decline of 2.3mls in FEV1 with years of exposure while controlling for sex, age, height , doctor diagnosed TB and smoking showing that with prolonged exposure in the quarry, workers are at a risk of developing obstructive lung disease. This trend was not evident for FVC. The majority of films were normal (60.9%), with 19.6% read as 1/0 and 19.9% as 0/1. Discussion. This study identified adverse respiratory outcomes among informal stonecrushers, particularly a high prevalence of respiratory symptoms and clinically important lung function deficits. These are in keeping with other environment studies where workers were exposed to respirable dust. Recommendations. Urgent policy initiatives for developing cost effective hazard control, engineering interventions to protect these marginalized self-employed informal sector stonecrushers are needed. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2010.

Introduction: South Africa is currently experiencing one of the most severe AIDS epidemics in the world with South Africa‘s public sector under great stress and under-resourced whilst there exists a vibrant private healthcare sector. Private healthcare sector doctors have a pivotal role to play in the management of HIV and AIDS infection. However not much is known about the extent of private healthcare sector doctor involvement in the management of HIV and AIDS patients. In addition these doctors need to have an accurate knowledge of the management of the infection, and a positive attitude towards the treatment of persons with HIV and AIDS. With the availability of antiretroviral drugs only since around 1996, many of the doctors who were trained prior to 1996 would not have received any formal training in the management of HIV and AIDS patients, further it is very important that these doctors constantly update their knowledge and obtain information in order to practise high-quality medicine. Although private sector doctors are the backbone of treatment service in many countries, caring for patients with HIV brings a whole new set of challenges and difficulties. The few studies done on the quality of care of HIV patients, in the private sector in developing countries, have highlighted some problems with management thus it becomes important to ascertain these doctors‘ training needs together with where these doctors source information on HIV/AIDS to stay updated. In South Africa two thirds of the doctors work in the private sector. To address some of the resource and personnel shortages facing the public sector in South Africa, partnerships between the public and private sectors are slowly being forged. However, little is known about the willingness on the part of private sector doctors in the eThekwini Metro of KwaZulu-Natal, to manage public sector HIV and AIDS patients. Though many studies have been undertaken on HIV/AIDS, fewer have been done in the private sector in terms of the management of this disease which includes doctors‘ adherence monitoring practices, their training needs and sources of information and their willingness to manage public sector patients. A study was therefore undertaken to assess the involvement of private sector doctors in the management of HIV, their training needs and sources of HIV information, the quality of HIV clinical management that they provided, together with their strategies for improving adherence in patients. Further the study assessed factors that affect adherence in patients attending private healthcare, and finally investigated whether private sector doctors are willing to manage public sector HIV infected patients. A literature review of the barriers that prevent doctors from managing HIV/AIDS patients was also undertaken. Method: A descriptive cross sectional study was undertaken using structured self reported questionnaires. All private sector doctors practising in the eThekwini Metro were included in the study. The study was divided into different phases. After exclusions a valid sample of 931 participants was obtained in Phase 1. However only 235 of these doctors indicated that they managed HIV infected patients, of which only 190 consented to be part of Phase 2 of the study. In Phase 2 the questionnaires were administered by trained field workers to the doctors after confirming doctors‘ consent. The questionnaires were thereafter collected, the data captured and analysed using SP55 version 15. Results: Although 235 (71.6%) doctors managed HIV and AIDS patients, 93 (28.4%) doctors did not, and of the latter 48 (51.61%) had not encountered HIV and AIDS patients, twenty five (26.88%) referred such patients to specialists, six (6.45%) cited cost factors as reasons for not treating such patients, whilst twelve (12.90%) doctors, though they indicated that there were other reasons for not managing HIV infected patients, did not specify their reasons. Two doctors (2.15%) indicated that due to inadequate knowledge they did not manage HIV and AIDS patients. Significantly younger (recently qualified) doctors rather than older (qualified for more years) doctors treated HIV/AIDS patients (p<0.001). Most doctors (76.3%) expressed a need for more training/knowledge on the management of HIV patients. Eighty five doctors (54.5%) always measured the CD4 count and viral load levels at diagnosis. Both CD4 counts and viral load were always used by 76 doctors (61.8%) to initiate therapy. Of the doctors 134 (78.5%) initiated therapy at CD4 count < 200cells/mm3. The majority of doctors prescribed triple therapy regimens using the 2 NRTI +1 NNRTI combination. Doctors who used CD4 counts tended to also use viral load (VL) to assess effectiveness and change therapy (p<0.001). At initiation of treatment 68.5% of the doctors saw their patients monthly and 64.3% saw them 3-6 monthly when stable. The majority of the doctors (92.4%) obtained information on HIV and AIDS from journals. Continuing Medical Education (CME), textbooks, pharmaceutical representatives, workshops, colleagues and conferences were identified as other sources of information, while only 35.7% of doctors were found to use the internet for information. GPs and specialists differed significantly with regard to their reliance on colleagues (52.9% versus 72.7%; p < 0.05) and conferences (48.6% versus 78.8%; p < 0.05) as sources of HIV information. Of the respondents, 78.9% indicated that they monitor for adherence. Comparison of GPs and specialists found that 82.6% of the GPs monitor for adherence compared to 63.6% of the specialists. (p=0.016). Doctors used several approaches with 60.6% reporting the use of patient self reports and 18.3% pill counts. Doctors (68.7%) indicated that their adherence monitoring is reliable, whilst 19.7% stated they did not test the reliability of their monitoring tool. The most common strategy used to improve adherence of their patients was by counseling. Other strategies included alarm clocks, SMS, telephoning the patient, encouraging family support and the use of medical aid programmes. One hundred and thirty three (77.8%) doctors were willing to manage public sector HIV and AIDS patients, with 105 (78.9%) reporting adequate knowledge, 99 (74.4%) adequate time, and 83 (62.4%) adequate infrastructure. Of the 38 (22.2%) that were unwilling to manage these patients, more than 80% cited a lack of time, knowledge and infrastructure to manage them. Another reason cited by five doctors (3.8%) who were unwilling was the distance from public sector facilities. Of the 33 specialist doctors, 14 (42.4%) indicated that they would not be willing to manage public sector HIV and AIDS patients, compared with only 24 (17.4%) of the 138 GPs (p < 0.01). There was no statistical difference between adherence to treatment and demographics of the respondent patient such as age, gender and marital status. In this study 89.1% of patients were classified as non-adherent and reasons for non-adherence included difficulty in swallowing medicines (67.3%) (p = 0.01); side effects (61.8%) (p = 0.03); forgetting to take medication (58.2%) (p = 0.003); and not wanting to reveal their HIV status (41.8%) (p = 0.03). Common side effects experienced were nausea, dizziness, insomnia, tiredness or weakness. Reasons for taking their medicines included that tablets would save their lives (83.6%); they understood how to take the medication (81.8%); tablets would help them feel better (80.0%); and that they were educated about their illness (78.2%). All participants that were on a regimen that comprised protease inhibitors and two NRTIs were found to be non-adherent. Conclusion: All doctors in the private healthcare sector were not involved in the management of HIV/AIDS patients. Doctors indicated that they required more training in the management of HIV/AIDS patients. However private sector doctors in the eThekwini Metro do obtain information on HIV from reliable sources in order to have up-to-date knowledge on the management of HIV-infected patients, with the majority of private sector doctors being compliant with the current guidelines, hence maintaining an acceptable quality of clinical health care. These doctors do monitor for adherence and employ strategies to improve adherence in their patients who do have problems adhering to their treatment due to various factors. Many private sector doctors are willing to manage public sector HIV and AIDS patients in the eThekwini Metro, potentially removing some of the current burden on the public health sector. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2010.

Background: Incidence of death and hospitalizations have been observed to depend on short-term changes in weather and to increase with extreme temperatures. This thesis aims to strengthen the scientific knowledge on the relationship between temperature and daily deaths, but also the relationship between temperature and daily hospital admissions. Methods: We constructed time series regression models using daily counts of death and daily weather from the Stockholm area incorporating adjustment for potential confounding factors, season, and long-term time trends. From these models, we established the short-term relationship with daily temperatures and the associated relative risks on daily deaths allowing for a delay between exposure and subsequent deaths. Daily hospital admissions and daily temperatures were analyzed correspondingly using data from Skåne. Results: Hot and cold temperatures significantly impact on mortality rates as well as rates of hospitalization in Sweden. We found an immediate heat effect on daily deaths, while the impacts of cold temperatures were delayed up to a week after exposure. Cold-related deaths are generally cardiovascular in nature, while deaths resulting from warm temperatures are cardiovascular, respiratory as well as non-cardiorespiratory in nature. The impacts following a heat wave appear to increase proportionally with the length of the extreme hot conditions. The results suggest that the population aged 45 years and older is the main group at elevated risk of death when exposed to high and low temperatures. Moreover, the results suggest that there are several factors of susceptibility on an individual basis that correspond to larger relative risk with high and/or low temperatures. Daily hospitalisations increased in particular among individuals with respiratory illnesses during extreme persistent heat, whereas high temperatures in general have little impact. In contrast, hospitalizations increased for up to two weeks following exposure to cold temperatures. Conclusions: The health impacts related to temperature are a serious concern and the attributed impacts are likely to increase to some extent in the future due to an ageing population. Public health preventive strategies should be developed to prevent health consequences related to heat waves and cold temperatures. Future studies should aim at identifying susceptible individuals with elevated death risk at hot and cold ambient temperature conditions.

Background: In 2005, the Västerbotten County Council launched a child health promotion programme, “the Salut Programme”, in response to an alarming prevalence of overweight and obesity, and trends of increased dental caries, among young county citizens. The programme, initially developed in four pilot areas, is built on multidisciplinary and cross-sectoral collaboration and aims to support and strengthen health promotion activities in health care, social services and school settings. It targets children and adolescents (0-18 years of age) and their parents, and starts during pregnancy. This thesis focuses on interventions provided by antenatal care, child health care, dental services, and open pre-schools, directed to expectant parents and families with children aged 0-1 ½ years. Within the programme context, the aim was to explore socio-demographic patterns of overweight and obesity in expectant parents (Paper I), firsttime parents’ experiences of health promotion and lifestyle change during pregnancy and early parenthood (Paper II), professionals’ experiences of factors influencing programme implementation and sustainability (Paper III and IV), and early programme outcomes on professionals’ health promotion practices and collaboration following countywide dissemination and implementation (Paper IV).   Methods and results: A population based cross-sectional study among expectant parents showed overweight and obesity in 29% of women (pre-pregnancy) and in 53% of men (n=4,352♀, 3,949♂). The likelihood for obesity was higher in expectant parents with lower levels of education, among those unemployed or on sick leave, and those living in rural areas. In 62% of couples, at least one of the partners was overweight or obese; a positive partner correlation was also found for BMI (I). An interview study with 24 first-time parents (n=12♀, 12♂) revealed that they primarily undertook lifestyle changes to secure the health of the fetus in pregnancy, and to provide a healthy environment in childhood. Parents described themselves as highly receptive to information about how their lifestyle could influence fetal health, and they frequently discussed pregnancy risks related to tobacco and alcohol, as well as toxins and infectious agents in foods. However, parents did not seem inclined to make lifestyle changes primarily to promote their own health. The antenatal and child health care services were perceived as being mainly directed towards women, and parents described a lack of a holistic view of the family which included experiences of fathers being treated as less important (II). An interview study undertaken with professionals (n=23) in the Salut Programme pilot areas indicated programme sustainability at most sites, two years after implementation, although less adherence was described within child health care. Factors influencing programme sustainability, as described by professionals, were identified at multiple organisational levels (III). A before-and-after survey among professionals (n=144) measured outcomes of the county-wide implementation of the Salut Programme in 13 out of 15 county municipalities. Results showed significant improvements in professionals’ health promotion practices and collaboration across sectors. A number of important implementation facilitators and barriers, acting at different organizational levels, were also identified via a survey comprised of open-ended questions (IV).   Conclusion: The Salut Programme, developed with high involvement of professionals, and strongly integrated in existing organisational structures and practices, shows potential for improving health promotion practices and cross-sectoral collaboration. The findings can inform further development of the Salut Programme.as well as new health promotion initiatives, and inform policy practice and future research. These aspects include approaches in health promotion and prevention, father involvement during pregnancy and early parenthood, and factors influencing implementation and sustainability of cross-sectoral health promotion programmes. / Bakgrund: År 2005 lanserade Västerbottens läns landsting en hälsofrämjande satsning “Salut” som svar på en oroande förekomst av övervikt och fetma samt trender till ökad förekomst av karies hos barn i länet. Satsningen, som initialt utvecklades i fyra pilotområden, bygger på tvärprofessionellt och verksamhetsövergripande samarbete och syftar till att stödja och stärka hälsofrämjande insatser inom landstinget och länets kommuner. Satsningen riktar sig till barn och unga (0-18 år) och deras föräldrar, med start under graviditeten. Denna avhandling fokuserar på insatser som erbjuds via mödrahälsovård, barnhälsovård, tandvård och öppen förskola riktade till blivande föräldrar och familjer med barn i åldern 0-1 ½ år. Med utgångspunkt från Salut-satsningen syftar avhandlingen till att undersöka socio-demografiska mönster av övervikt och fetma hos blivande föräldrar (I), förstagångsföräldrars upplevelser av hälsofrämjande insatser och förändrade levnadsvanor under graviditet och tidigt föräldraskap (II), personalens upplevelser av underlättande och hindrande faktorer för satsningens införande och uthållighet (III, IV), samt förändringar i arbetssätt och samarbete mellan verksamheterna efter den länstäckande spridningen av satsningen (IV).   Metod och resultat: En populationsbaserad tvärsnittsstudie bland blivande föräldrar visade på övervikt och fetma hos 29% av kvinnorna (vikt före graviditet) och hos 53% av männen (n=4352♀, 3949♂). Lägre utbildningsnivå, arbetslöshet och sjukskrivning samt att bo utanför städerna visade sig öka sannolikheten för fetma. Hos en övervägande del av paren (62%) fanns minst en partner med övervikt eller fetma och samband kunde även påvisas mellan kvinnans och mannens BMI (I). En intervjustudie med 24 förstagångsföräldrar (n=12♀, 12♂) visade att föräldrarna främst förändrade sina levnadsvanor för att säkra hälsan hos fostret under graviditeten och för att skapa en hälsosam miljö för barnet under uppväxten. Föräldrarna beskrev sig själva som mycket mottagliga för information om hur deras levnadsvanor kunde påverka fostrets hälsa och de diskuterade ofta graviditetsrisker i relation till tobak och alkohol samt gifter och smittoämnen i livsmedel. Föräldrarna var dock mindre angelägna att förändra sina levnadsvanor med tanke på sin egen hälsa. De upplevde att mödrahälsovårdens och barnhälsovårdens insatser i huvudsak riktades till kvinnor och beskrev en avsaknad av helhetssyn på familjen, vilket även avspeglades i upplevelser av att papporna behandlades som mindre viktiga (II). En intervjustudie med personal (n=23) inom pilotområdena, två år efter utveckling och införandet av Saluts insatser, indikerade god uthållighet av satsningen, även om en lägre följsamhet till insatserna beskrevs inom barnhälsovården. Faktorer som av personalen beskrevs påverka uthålligheten identifierades på flera organisatoriska nivåer (III). En före- och efterstudie bland personal (n=144) mätte effekter av den länstäckande spridningen av satsningen i 13 av länets 15 kommuner. Resultaten visade på flera signifikanta förbättringar av de hälsofrämjande arbetssätten och ett ökat samarbete mellan verksamheterna. En enkät med öppna frågor riktad till personalen belyste också faktorer på flera organisationsnivåer som ansågs underlätta respektive hindra införandeprocessen (IV).   Slutsats: Salut-satsningen, som är utvecklad i nära samarbete med verksamheternas personal och väl integrerad i redan existerande organisatoriska strukturer och arbetssätt, visar på potential att förbättra hälsofrämjande arbetssätt och samarbete mellan verksamheter. Aspekter som beskrivits och diskuterats kan vägleda satsningens fortsatta utveckling såväl som framtida nya initiativ. Resultaten och slutsatserna kan även användas i syfte att påverka policy, praxis och framtida forskning. Detta avser framförallt hälsofrämjande och sjukdomsförebyggande metoder, pappans roll under graviditet och tidigt föräldraskap samt kunskaper om faktorer som kan ha betydelse för genomförande och uthållighet av verksamhetsövergripande hälsofrämjande insatser.