Headache is the most frequently reported pain in children and is associated with missed schooldays, anxiety, depressive symptoms and various physical symptoms. A secular trend of increasing headache prevalence has been suggested. Few studies have focused on tension-type headache among children from the general population. The aims of this thesis were to describe the prevalence, incidence and prognosis of tension-type headache, migraine and overall headache in schoolchildren, to identify medical, psychological and social factors associated with these headache types, and to determine whether the prevalence of headache has increased over the last decades. In 1997, 1850 schoolchildren aged 7-15 years from the city of Uppsala participated in a questionnaire study and 1371 (74.1%) responded. Out of these, a randomly selected, stratified sample of 131 children and their parents were interviewed. Three years later, 122 children from the interview sample replied to an identical headache questionnaire. Compared with a similar study in 1955, a significantly lower proportion of schoolchildren reported no headache. The prevalence of tension-type headache increased with age and was significantly higher in girls than boys after the age of twelve. Similar age and gender differences were obtained for migraine. A higher proportion of girls reported frequent headache than boys. Children with headache, especially those with migraine, as well as their first-degree relatives suffered from other pains and physical symptoms more frequently than headache-free children and their first-degree relatives. Although the likelihood of experiencing the same headache diagnosis and symptoms at follow-up was high, about one fifth of children with migraine developed tension-type headache and vice versa. Female gender was a predictor of migraine and frequent headache a predictor of overall headache at follow-up. The estimated annual incidence for tension-type headache, migraine and overall headache was 81, 65 and 131 per 1000 children, respectively. In conclusion, the results indicate that headache has become increasingly common among schoolchildren over the last decades. Prevention and treatment of headache is particularly important for girls since they have high prevalence of headache, frequent headache episodes and a poor outcome. In children with headache, diagnoses and treatment should be reassessed regularly and other pains should be asked about and treated as well.

Spontaneous reporting systems (SRSs) for adverse drug reactions (ADRs) have been developed as a result of the thalidomide disaster, whereby thousands of children world-wide were born with birth defects. The Swedish Adverse Drug Reactions Advisory Committee was established in 1965. Since 1975, reporting has been compulsory for all suspected serious or new ADRs. International collaboration started in 1968 with countries contributing their ADR reports to an international database set up by the World Health Organization. ADRs represent the negative side of the benefit-to-risk balance that in theory needs to be counteracted by perceived or established positive drug effects. All drugs are subject to preclinical and clinical testing prior to marketing authorization. However, these studies are insufficient to detect rare ADRs, ADRs that occur after long-term administration or with latency, ADRs that occur in special patient groups such as children, the elderly, patients with renal or hepatic insufficiency or patients on concomitant drug treatment, and ADRs that represent a modest increase in the risk of diseases (including mortality) that are prevalent in the study population. Postmarketing surveillance of drugs is therefore essential, and regulatory action may be needed on the basis of new ADR information. SRSs are important sources of ADR information as exemplified here by the evaluation of peripheral sensory disturbances with fluoroquinolones, hyponatremia with antidepressants, blood dyscrasias with dipyrone, glucose intolerance with atypical antipsychotics, pulmonary embolism with combined oral contraceptives and extrapyramidal symptoms with selective serotonin reuptake inhibitors. SRSs can be used to study clinical manifestations of ADRs (that can give insights into potential ADR mechanisms), risk factors for the ADR or for specific outcomes of the ADR, and ADR reporting incidences when combined with sales data. Signals from SRSs may need to be studied further e.g., by use of large-scale epidemiologic studies based on record linkage between drug prescription databases and health databases. Owing to the rapid availability of information, however, SRSs are likely to remain of major importance for the post-marketing surveillance of drugs.

Stroke is one of the leading causes of death and disability in Sweden and in the Western world. Despite this, stroke with focus on elderly is a field where few studies have been conducted from a gender and socioeconomic perspective. The objectives in this thesis were to analyse from a gender, age and socioeconomic perspective how women were affected by stroke compared with men. The focus was on what it meant for elderly women and men to live with stroke and to explore various gender constructions among men and women. The study also included aspects such as incidence, medical treatment and case fatality after stroke. Both quantitative and qualitative methods were used. During a two-year period (15 October 2000–14 October 2002), uniform information was collected for all cases of first-ever and recurrent (>28 days) stroke occurring in people of all ages living the region of Umeå, admitted to the University Hospital. Five different registers were used to achieve maximum coverage; the Riks-Stroke (RS) register, the Hospital Discharge Register (HDR), the Cause of Death Register, the northern Sweden WHO MONICA study, and one case-finding study in nursing homes and homes for elderly performed for this thesis. For the qualitative study a maximum variation sampling procedure was used to retrieve participants for in-depth interviews in a follow-up study. Nine women and seven men were interviewed about their experiences of treatment and care after suffering a stroke, as well as about their perceptions and experiences of help from others (health care personnel, relatives and home help personnel). The first-ever incidence of stroke was higher among low-educated than high educated men and women. Our study showed that there was an education-related age-dependent difference in stroke incidence, where elderly women had the highest incidence of stroke. The 28-day case fatality was shown to be associated with low educational level in patients above 75 years, after controlling for sex, risk factors and acute care variables. The elderly stroke patients experienced subordination in their contacts with health care personnel and the medical context. The participants used different ways to negotiate in the subordinate position, and some of these negotiations were interpreted as being gendered. We have also shown how the elderly stroke patients minimized their own needs of help, strove for independence and accepted help. The men and the women differed in their perceptions and experiences of help from others. Also, the participants expressed multiple types of needs. The elderly stroke patients’ perceptions and experiences of help from others must be studied in relation to their life circumstances and expectations from society. Further analyses of the patients’ perceptions and experiences of help from others were interpreted as being different examples of constructions of masculinities and femininities. Stroke with a focus on the elderly is a field where few studies have been conducted from a gender and socioeconomic perspective. With further community-based stroke incidence studies including elderly men and women and with the development of appropriately targeted interventions, the burden of stroke in the population could be reduced. More research is needed where both qualitative and quantitative methods are used, as this can provide a richer and perhaps more authentic description of the issue under investigation.

Aim: The aim of this project was to study the age and sex specific occurrence of atopic and non-atopic asthma and other atopic manifestations in a nationwide sample of Swedish pre-school children. Methods: All 70 allergen avoidance day-care centres (AADC) with 84 sections and 140 matched ordinary day-care centres with 440 sections in 62 municipalities across Sweden were sampled. In 2000 the staff at each section responded to a questionnaire on indoor and outdoor environment at the section. In 2002 parents of 5,886 children attending the AADCs and ODCs responded to a postal questionnaire regarding symptoms indicating prevalent asthma, allergic rhinitis, eczema, and food, furred pet and pollen allergy and other data in their children. In 2007, parents of 4255 children responded to an almost identical follow-up questionnaire. Results: The AADCs had far more strict rules than ODCs on furred pets and smoking at home and on perfume use, and the indoor environment was better, owing to better cleaning. The age specific asthma prevalence was curvilinear with a peak at age 3 of 11.4% among boys and 9.8% among girls. In addition the prevalence increased by municipality population density, a proxy for degree of urbanisation. There was a highly significant co-occurrence between all asthma-atopic manifestations, but there was no evidence of ordered sequence of manifestation onset. The asthma incidence was highly dependent on presence or absence of co-occurrence variables. Given the variable mix in the present study population, the annual asthma incidence ranged from 0.6% to 1.2%. Conclusions: AADCs had more strict rules and a better indoor environment than ODCs. The asthma prevalence was affected by age, sex and degree of urbanisation. There was close co-occurrence between all asthma and atopic manifestations but no evidence of ordered sequence of onsets. The annual asthma incidence was strongly dependent of co-occurrence conditions.

The prevalence of spasticity after first-ever stroke is approximately 20%, but there are no data on the prevalence of disabling spasticity.The reported prevalence of pain after stroke varies between 19% and 74%, whether pain is associated with spasticity is not known. Until now, there is no health economic analysis of patients with spasticity after stroke. Methods: Two groups of patients were studied. Cohort I was a cross-sectional survey. A representative sample of 140 patients was investigated 1 year after their first-ever stroke. Spasticity was defined as ≥ 1 score on the modified Ashworth scale, disabling spasticity was defined as spasticity having such an impact that intervention, e.g. intensive physiotherapy, orthoses or pharmacological treatment, should be offered. Pain was assesed with the Visual Analogue Scale. All direct costs during one year were identified and converted into Purchasing Power Parities US dollar (PPP$). Cohort II was a prospective cohort study. Forty-nine patients were examined at day 2–10, at one month, and at six months after their first-ever stroke. Assessment and definitions were similar as for cohort I. Results: Spasticity occurs within 1 month and disabling spasticity occur within 6 months. After one year, the prevalence of spasticity was 17% and that of  disabling spasticity 4%. Disabling spasticity was more frequent in the upper extremity. There was an independent effect of severe upper extremity paresis (OR 22, CI 3.9–125) and age below 65 years (OR 9.5, CI 1.5–60). The prevalence of stroke-related pain was 21% after one year. Stroke-related pain was associated with paresis (OR 3.1, 95% CI 1.2–7.7), sensory disturbance (OR 3.1, 95% CI 1.1–8.9) and depression (OR 4.1, 95% CI 1.4–13), but not with spasticity as an independent variable. The majority of the direct costs for one year (78%) were associated with hospitalization, whereas 20% was associated with municipality services. Only 1% of all direct costs were related to primary health care and 1% to medication. The mean (median, inter-quartile range) direct cost for stroke patients with spasticity was PPP$ 84 195 (72 116, 53 707) compared to PPP$ 21 842 (12 385, 17 484) for stroke patients without spasticity (P < 0.001).

Aim: To explore the role of cannabis use for the availability of ecstasy as a potential pathway to subsequent first ecstasy use. Methods: Baseline and 4-year follow-up data from a prospective-longitudinal community study of originally 3021 adolescents and young adults aged 14–24 years at baseline were assessed using the standardized M-CIDI and DSM-IV criteria. Results: Baseline cannabis users reported at follow-up more frequent access to ecstasy than cannabis non-users. Higher cannabis use frequencies were associated with increased ecstasy availability reports. Logistic regression analyses revealed that cannabis use and availability of ecstasy at baseline are predictors for incident ecstasy use during the follow-up period. Testing simultaneously the impact of prior cannabis use and ecstasy availability including potential confounders, the association with cannabis use and later ecstasy use was confirmed (OR = 6.3; 95% CI = 3.6–10.9). However, the association with ecstasy availability was no longer significant (OR = 1.2; 95% CI = 0.3–3.9). Conclusions: Results suggest that cannabis use is a powerful risk factor for subsequent first onset of ecstasy use and this relation cannot be sufficiently explained by availability of ecstasy in the observation period.

The objective of this dissertation is to develop a model to examine the concept of a “worldwide” tax burden. The notion is that due to differential mobility of factors developed nations may be passing on a share of their tax burden to less developed countries while effectively indulging in a form of tax competition. This is important for many reasons especially since it may affect the distribution of income between countries, and influence the flow of capital. As globalization increases, “the race to the bottom” in taxation (which implies tax-cutting) suggests that these spillovers should be reduced over time. The traditional view of taxation implies that taxation imposes an excess burden and increasing most types of taxes will increase this burden. But for whom does this burden increase? Are developed countries passing on a burden to locations that are less able to shift the burden forward? If this phenomenon of tax spillovers can be quantified, we can examine the extent and nature of shifting of the tax burden. Using a version of the famous general equilibrium model first developed by Prof Harberger in 1962, we analyze the extent of tax spillovers in the presence of a public input in an open economy setting. We model two different taxes, the Capital Income Tax and a Consumption Tax and two different types of expenditure patterns, a government input and a transfer payment. The dissertation answers the following research questions: • Can the extent of tax spillovers be quantified using a general equilibrium model that is not dependent on functional forms? • Does the extent of spillovers depend on the type of tax used? • Does the extent of spillovers depend on the use to which the taxes are put? • What are the policy implications? We find that the tax cutting economy can gain from cutting a distorting tax only when the expenditure pattern is neutral, while imposing a cost to the rest of the world in terms of sources and uses of GDP. When revenues are used to provide productive public goods; neither country gains from tax cuts that lower inputs.

The aims of this thesis were to study the incidence, severity and pattern of injury in male and female elite football players; to study time trends in injury risk; to identify risk factors for injury; and to test the effectiveness of an intervention programme aimed at preventing re-injury. All studies followed a prospective design using standardised definitions and data collection forms. Individual training and match exposure was registered for all players participating. Time loss injuries were documented by each team’s medical staff. The amount of training increased by 68% between the 1982 and 2001 Swedish top male division seasons, reflecting the shift from semi-professionalism to full professionalism. No difference in injury incidence or injury severity was found between seasons. The injury incidence was 4.6 vs. 5.2/1000 training hours and 20.6 vs. 25.9/1000 match hours. The incidence of severe injury (absence >4 weeks) was 0.8/1000 hours in both seasons. The Swedish and Danish top male divisions were followed during the spring season of 2001. A higher risk for training injury (11.8 vs. 6.0/1000 hours, p<0.01) and severe injury (1.8 vs. 0.7/1000 hours, p=0.002) was observed among the Danish players. Re-injury accounted for 30% and 24% of injuries in Denmark and Sweden respectively. The Swedish top male division was studied over two consecutive seasons, 2001 and 2002, and comparison of training and match injury incidences between seasons showed similar results. Players who were injured in the 2001 season were at greater risk for injury in the following season compared to non-injured players (relative risk 2.7; 95% CI 1.7-4.3). Players with a previous hamstring injury, groin injury and knee joint trauma were two to three times more likely to suffer an identical injury to the same limb in the following season, but no such relationship was found for ankle sprain. Age was not associated with an increased injury risk. The effectiveness of a coach-controlled rehabilitation programme on the rate of re-injury was studied in a randomised controlled trial at amateur male level. In the control group, 23 of 79 injured players suffered a recurrence during the season compared to 10 of 90 players in the intervention group. There was a 75% lower re-injury risk in the intervention group for lower limb injuries (relative risk 0.25; 95% CI 0.11-0.57). The preventive effect was greatest during the first weeks after return to play. Both the male and female Swedish top divisions were followed during the 2005 season. Male elite players had a higher risk for training injury (4.7 vs. 3.8/1000 hours, p<0.05) and match injury (28.1 vs. 16.1/1000 hours, p<0.001) than women. However, no difference was observed in the rate of severe injury (0.7/1000 hours in both groups). The thigh was the most common site of injury in both men and women, while injury to the hip/groin was more frequent in men and to the knee in women. Knee sprain accounted for 31% and 37% of the time lost from training and match play in men and women respectively. / Serienumret i serien Linköping University medical dissertation är fel. Det korrkta numret är 988. The serial number in the series Linköping University medical dissertation is incorrect. The correct number is 988.

Wegener´s granulomatosis (WG) is an unusual, serious, systemic vasculitis with specific clinical findings. The studies in this thesis aim at broadening our understanding of the aetiology and outcome of WG. Patients with WG were identified in the In-patient Register 1975-2001. During this time the incidence increased three-fold, and neither ANCA-related increased awareness, nor diagnostic drift, seem to fully explain this trend, but it is still unclear if a true rise in incidence exists. Anti- neutrophil cytoplasmic antibodies (ANCA) have been presented as highly specific for vasculitis. In a series of consecutive cANCA/PR3-ANCA positive patients, we investigated the positive predictive value for ANCA, and the outcome of patients with a positive cANCA/PR3-ANCA but not vasculitis. These patients have a low future risk of developing vasculitis, possibly indicating that ANCA, in this setting, reflects neutrophil activating properties not specific to vasculitis. By linkage of the WG-cohort, and randomly selected population controls, to the Multi-generation register, we identified all first-degree relatives and spouses of patients and controls, totally encompassing some 2,000 patients and 70,000 relatives. Familial aggregation of WG was the exception, with absolute risks of < 1 per 1000.However, relative risks in first-grade relatives amounted to 1.56 (95% CI 0.35-6.90) such that a moderate familial aggregation cannot be excluded. In the WG-cohort, cancer occurrence and risk was compared to that of the general population. Patients with WG have an overall doubled risk of cancer, with particularly increased risks of bladder-cancer, haematopoietic cancers including lymphomas and squamous skin-cancer. In a case-control study nested within the WG-cohort, treatment with cyclophosphamide was compared among bladder-cancer patients and matched cancer-free controls. Absolute risk of bladder cancer as high as 10% some years after diagnosis were found, and this risk can partly be attributed to cyclophosphamide-treatment, with a dose-response relationship.

Grazing incidence pumping (GRIP) is a scheme to produce x-ray lasers and extreme ultraviolet lithography is a means of lithographic production which requires soft x-rays with a bandwidth of 2% centred at 13,5 nm. In this work firstly a grazing incidence pumping of Ni-like Mo and Ne-like Ti x-ray laser media were simulated by using EHYBRID and a post-processor code coupled to it. The required atomic data were obtained from the Cowan code. Besides, the timing issue needed for amplification purpose in a Ti:Sapphire laser system has been described theoretically. Afterwards, in order to produce soft x-ray lasers for extreme ultraviolet lithographic applications, emission of soft x-rays in the 2% bandwidth centred at 13.5 nm emitted from Sn XII and Sn XIII ions were simulated by using the EHYBRID code for a laser operating at 1064 nm with 1 J of pulse energy and 6 ns of pulse duration. The intensity range that has been investigated is between 1-5 x 1012 W/cm2. Ion fractions of tin ions and line intensities corresponding to different electron temperatures were calculated by using the collisional radiative code NeF.