Background and purpose - Swedish clinical guidelines for osteoarthritis (OA) prioritize patient education, exercise, and-if necessary-weight reduction before considering adjunct pharmacological intervention. Contrariwise, we investigated the proportion and type of dispensed analgesic prescriptions in Sweden received by patients during 3 years before commencing non-pharmacological primary care interventions for OA (2008-2016) compared with the general population. Furthermore, we analyzed the proportion of analgesic prescriptions dispensed before (2008-2012) compared with after (2012-2016) guideline publication in terms of concordance with clinical guideline recommendations. Patients and methods - Patients with hip or knee OA (n = 72,069) from the Better Management of OA national quality register receiving non-pharmacological interventions in primary care between 2008 and 2016 were included (OA cohort). An age, sex, and residence matched reference cohort (n = 216,207) was formed from the Swedish Total Population Register. Based on a period 3 years prior to inclusion in the OA cohort, Swedish Prescribed Drug Register data was linked to both the OA and reference cohorts. Results - Compared with the reference cohort, a distinctly larger proportion of the OA cohort had dispensed prescriptions for most types of analgesics, increasing exponentially each year prior to commencing non-pharmacological intervention. Since guideline publication, the proportion of the OA cohort having no dispensed prescription analgesics prior to non-pharmacological primary care intervention concordantly increased by 5.0% (95% CI 4.2-5.9). Furthermore, dispensed prescriptions concordantly decreased for non-selective NSAIDs -8.6% (CI -9.6 to -7.6), weak opioids -6.8% (CI -7.7 to -5.9), glucosamine -9.5% (CI -9.8 to -8.8). and hyaluronic acid -1.6% (CI -1.8 to -1.5) but discordantly increased for strong opioids 2.8% (CI 2.1-3.4) and glucocorticoid intra-articular injection for hip OA 2.1% (CI 1.0-3.1). Interpretation - In Sweden, dispensed prescription of analgesics commonly occurred before initiating non-pharmacological primary care interventions for OA but reduced modestly after guideline publication, which prioritizes non-pharmacological before pharmacological interventions. Additional modest improvements occurred in the stepped-care prioritization of analgesic prescription types. However, future strategies are required to curb an increase of strong opioids prescription for OA and glucocorticoid intra-articular injection for hip OA.

Background: The aim of this study was to evaluate possible differences in the functioning of two selected intensive care units in Poland and Finland. The activity of the units was analysed over a period of one year. Methods: The following parameters were compared: demography of treated populations, site of admission, category of illness, severity of illness (APACHE-II scale), mean length of stay, demanded workload (TISS-28 scale), mortality (both ICU and hospital) and standardized mortality ratio (SMR). Results: The results of this study indicated that most of the patients in the Polish ICU, regardless of age, diagnosis and APACHE II score, presented significantly longer lengths of stay (14.65 +/- 13.6 vs 4.1 +/- 4.7 days, P = 0.0001), higher mean TISS-28 score (38.9 +/- 9.1 vs 31.2 +/- 6.1, P = 0.0001) and higher ICU and hospital mortality (41.5% vs 10.2% and 44.7% vs 21.8%, respectively, P = 0.0001). The values of SMR were 0.9 and 0.85 for the Finnish and Polish ICUs, respectively. Conclusion: The collected data indicate huge differences in the utilisation of critical care resources. Treatment in Polish ICU is concentrated on much more severely ill patients which might be sometimes accompanied by futility of care. In order to verify and correctly interpret the presented phenomena, further studies are needed.

Background: The aim of this study was to evaluate possible differences in the functioning of two selected intensive care units in Poland and Finland. The activity of the units was analysed over a period of one year. Methods: The following parameters were compared: demography of treated populations, site of admission, category of illness, severity of illness (APACHE-II scale), mean length of stay, demanded workload (TISS-28 scale), mortality (both ICU and hospital) and standardized mortality ratio (SMR). Results: The results of this study indicated that most of the patients in the Polish ICU, regardless of age, diagnosis and APACHE II score, presented significantly longer lengths of stay (14.65 +/- 13.6 vs 4.1 +/- 4.7 days, P = 0.0001), higher mean TISS-28 score (38.9 +/- 9.1 vs 31.2 +/- 6.1, P = 0.0001) and higher ICU and hospital mortality (41.5% vs 10.2% and 44.7% vs 21.8%, respectively, P = 0.0001). The values of SMR were 0.9 and 0.85 for the Finnish and Polish ICUs, respectively. Conclusion: The collected data indicate huge differences in the utilisation of critical care resources. Treatment in Polish ICU is concentrated on much more severely ill patients which might be sometimes accompanied by futility of care. In order to verify and correctly interpret the presented phenomena, further studies are needed.

Objective This study aimed to explore the attitudes, practices and work-related experiences among Swedish physicians regarding the referral process, integration and transition between oncology care and palliative care (PC). Methods A cross-sectional online survey was performed with a study-specific questionnaire in 2016-2017 in south-eastern Sweden. Physicians working with cancer patients within surgical specialties, medical specialties and paediatric oncology participated. Results The vast majority of the 130 participating physicians (99.2%) stated that PC was beneficial for the patient and were positive about early integration of PC (65.5%). Still, only 27.6% of the participants introduced PC at an early stage of non-curable disease. However, paediatric oncologists had a very early introduction of PC in comparison with medical specialties (p = 0.004). Almost 90% of the study population said they wanted to know that the patient had been taken care of by another care facility. Conclusions Despite the physicians positive attitude towards early integration and referral to PC, they often acted late in the disease trajectory. This late approach can reduce the patients opportunity of improving quality of life during severe circumstances. There is a need for in-depth knowledge of the physicians challenges in order to bridge the gap between intentions and actions.

Hypertension is the most common preventable cause of premature all-cause mortality, primarily from cardiovascular disease (CVD). Individuals with dysglycemia, including prediabetes and diabetes, are at increased risk. Licorice intake raises blood pressure (BP) through the effects of glycyrrhizic acid (GA), but the true limit of safe intake is uncertain. Home BP has several benefits over BP measured at a clinic, including a higher predictive value for CVD. By combining office and home BP, it is possible to diagnose masked hypertension (MH), in which home but not office BP is elevated, and white coat hypertension (WCH), in which office but not home BP is elevated. The aim of this thesis was to advance our knowledge on home BP in relation to dysglycemia, markers of CVD, and licorice intake.  

The first 3 papers used data from the Linköping cohort of the prospective Swedish CArdioPulmonary bioImage Study (SCAPIS). Study IV was a randomized controlled cross-over study. Data was obtained from questionnaires, blood samples and office and home BP measurements. In studies I-III, pulse wave velocity (PWV), coronary artery calcium score (CACS), and carotid artery plaques as markers of CVD were also included.  

In Study I, we examined 5025 men and women aged 50-64 years old for the relation between dysglycemia and home BP. Both the systolic office and home BP measurements were positively as-sociated with dysglycemia. Participants with dysglycemia vs normoglycemia more often had MH. The findings were in line with previous research and strengthened the association between dysglycemia and MH.  

In Study II, we examined the associations between MH and markers of CVD in 4122 individuals without BP-lowering treatment. Of participants, 4.2% had MH, and these were more often men and had higher BMI than those with normotension. Participants with MH also had higher odds for CACS ≥100, an as-sociation which has previously been suggested as a trend.

In Study III, we examined the relation between soluble P-se-lectin (sP-selectin) as a measure of thrombotic activity, plasma high-sensitivity C-reactive protein (hsCRP) as a measure of inflammation, and home BP in 4548 participants. Both markers were higher in each hypertension phenotype compared with sustained normotension. The quartile of participants with the highest sP-se-lectin values had higher odds for CACS ≥100 and carotid artery plaques. The association between sP-selectin and sustained hyper-tension was novel and not affected by adjustments for hsCRP.  

In Study IV, 28 healthy participants aged 18-30 years old were evaluated for the effects of a daily intake of licorice containing 100 mg of GA compared with a control product for 2 weeks. During the licorice intake period, the systolic home BP increased with 3.1 mmHg, and the suppression of serum aldosterone and plasma renin levels indicated that this was due to the licorice intake.  

In conclusion, this thesis further strengthens the idea that both home and office BP measurements have values beyond that of the other, and that home BP may be most valuable in individuals with dysglycemia and obesity, and in men. Finally, licorice may be more potent than previously known, suggesting the need for increased awareness. 

Background: Masked hypertension is more common in individuals with type 2 diabetes than in individuals with normoglycemia. We aimed to explore if there is a discrepancy between office blood pressure (office BP) and home blood pressure monitoring (HBPM) in relation to HbA1c as well as glycemic status in 5,029 middle-aged individuals.

Methods: HBPM was measured in a subsample of 5,029 participants in The Swedish CardioPulmonary BioImage Study (SCAPIS), a population-based cohort of 50–64 years old participants. Both office BP and HBPM were obtained after 5 minutes’ rest using the semiautomatic Omron M10-IT oscillometric device. White coat effect was calculated by subtracting systolic HBPM from systolic office BP. Participants were classified according to glycemic status: Normoglycemia, prediabetes, or diabetes based on fasting glucose, HbA1c value, and self-reported diabetes diagnosis.

Results: Of the included 5,025 participants, 947 (18.8%) had sustained hypertension, 907 (18.0%) reported taking antihypertensive treatment, and 370 (7.4%) had diabetes mellitus. Both systolic office BP and HBPM increased according to worsened glycemic status (P for trend 0.002 and 0.002, respectively). Masked hypertension was more prevalent in participants with dysglycemia compared with normoglycemia (P = 0.036). The systolic white coat effect was reversely associated with HbA1c (P = 0.012).

Conclusions: The systolic white coat effect was reversely associated with HbA1c, and the prevalence of masked hypertension increased with dysglycemia.

Background In previous studies, we investigated the effects of a care manager intervention for patients with depression treated in primary health care. At 6 months, care management improved depressive symptoms, remission, return to work, and adherence to anti-depressive medication more than care as usual. The aim of this study was to compare the long-term effectiveness of care management and usual care for primary care patients with depression on depressive symptoms, remission, quality of life, self-efficacy, confidence in care, and quality of care 12 and 24 months after the start of the intervention. Methods Cluster randomized controlled trial that included 23 primary care centers (11 intervention, 12 control) in the regions of Vastra Gotaland and Dalarna, Sweden. Patients >= 18 years with newly diagnosed mild to moderate depression (n = 376: 192 intervention, 184 control) were included. Patients at intervention centers co-developed a structured depression care plan with a care manager. Via 6 to 8 telephone contacts over 12 weeks, the care manager followed up symptoms and treatment, encouraged behavioral activation, provided education, and communicated with the patient's general practitioner as needed. Patients at control centers received usual care. Adjusted mixed model repeated measure analysis was conducted on data gathered at 12 and 24 months on depressive symptoms and remission (MADRS-S); quality of life (EQ5D); and self-efficacy, confidence in care, and quality of care (study-specific questionnaire). Results The intervention group had less severe depressive symptoms than the control group at 12 (P = 0.02) but not 24 months (P = 0.83). They reported higher quality of life at 12 (P = 0.01) but not 24 months (P = 0.88). Differences in remission and self-efficacy were not significant, but patients in the intervention group were more confident that they could get information (53% vs 38%; P = 0.02) and professional emotional support (51% vs 40%; P = 0.05) from the primary care center. Conclusions Patients with depression who had a care manager maintained their 6-month improvements in symptoms at the 12- and 24-month follow-ups. Without a care manager, recovery could take up to 24 months. Patients with care managers also had significantly more confidence in primary care and belief in future support than controls.

Background: In previous studies, we investigated the effects of a care manager intervention for patients withdepression treated in primary health care. At 6 months, care management improved depressive symptoms, remission,return to work, and adherence to anti-depressive medication more than care as usual. The aim of this study wasto compare the long-term effectiveness of care management and usual care for primary care patients with depressionon depressive symptoms, remission, quality of life, self-efficacy, confidence in care, and quality of care 12 and24 months after the start of the intervention.Methods: Cluster randomized controlled trial that included 23 primary care centers (11 intervention, 12 control)in the regions of Västra Götaland and Dalarna, Sweden. Patients ≥18 years with newly diagnosed mild to moderatedepression (n = 376: 192 intervention, 184 control) were included. Patients at intervention centers co-developed astructured depression care plan with a care manager. Via 6 to 8 telephone contacts over 12 weeks, the care managerfollowed up symptoms and treatment, encouraged behavioral activation, provided education, and communicatedwith the patient’s general practitioner as needed. Patients at control centers received usual care. Adjusted mixedmodel repeated measure analysis was conducted on data gathered at 12 and 24 months on depressive symptomsand remission (MADRS-S); quality of life (EQ5D); and self-efficacy, confidence in care, and quality of care (study-specificquestionnaire).Results: The intervention group had less severe depressive symptoms than the control group at 12 (P = 0.02) butnot 24 months (P = 0.83). They reported higher quality of life at 12 (P = 0.01) but not 24 months (P = 0.88). Differencesin remission and self-efficacy were not significant, but patients in the intervention group were more confident that they could get information (53% vs 38%; P = 0.02) and professional emotional support (51% vs 40%; P = 0.05) from theprimary care center.Conclusions: Patients with depression who had a care manager maintained their 6-month improvements in symptomsat the 12- and 24-month follow-ups. Without a care manager, recovery could take up to 24 months. Patients withcare managers also had significantly more confidence in primary care and belief in future support than controls.

This study aimed to establish Egyptian women's attitudes and beliefs about female genital cutting (FGC) or mutilation by applying a questionnaire module about violence to a subsample of 5249 married women from a total of 19 474 women who participated in the 2005 Egypt Demographic Health Survey. Women were interviewed to determine if they had been exposed to marital violence in the year prior to the survey, their attitudes and beliefs about FGC, and if they physically abused their children. The association of beliefs about FGC with maternal physical abuse was examined, adjusting for exposure to marital violence and other socio-demographic variables. Of the women surveyed 16.4% and 3.4% had been exposed to physical and sexual violence, respectively, during the year prior to the survey. Around 76% of the women surveyed intended to continue the FGC practice, and 69.8% had slapped or hit their children during the year prior to the survey. Holding positive beliefs about the practice of FGC or intending to continue it was associated with maternal physical abuse and this has significant implications for health and welfare workers in Egypt and for society in general.

Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.

Objective: To investigate the factors related to self-perceived work ability in patients with chronic whiplash-associated disorder grades II-III. Design: Cross-sectional analysis. Patients: A total of 166 working age patients with chronic whiplash-associated disorder. Methods: A comprehensive survey collected data on work ability (using the Work Ability Index); demographic, psychosocial, personal, work- and condition-related factors. Forward, stepwise regression modelling was used to assess the factors related to work ability. Results: The proportion of patients in each work ability category were as follows: poor (12.7%); moderate (39.8%); good (38.5%); excellent (9%). Seven factors explained 65% (adjusted R2= 0.65, p < 0.01) of the variance in work ability. In descending order of strength of association, these factors are: greater neck disability due to pain; reduced self-rated health status and health-related quality of life; increased frequency of concentration problems; poor workplace satisfaction; lower self-efficacy for performing daily tasks; and greater work-related stress. Conclusion: Condition-specific and psychosocial factors are associated with self-perceived work ability of individuals with chronic whiplash-associated disorder.

Objective: To investigate the factors related to self-perceived work ability in patients with chronic whiplash-associated disorder grades II-III.

Design: Cross-sectional analysis.

Patients: A total of 166 working age patients with chronic whiplash-associated disorder.

Methods: A comprehensive survey collected data on work ability (using the Work Ability Index); demographic, psychosocial, personal, work- and condition-related factors. Forward, stepwise regression modelling was used to assess the factors related to work ability.

Results: The proportion of patients in each work ability category were as follows: poor (12.7%); moderate (39.8%); good (38.5%); excellent (9%). Seven factors explained 65% (adjusted R-2 = 0.65, p < 0.01) of the variance in work ability. In descending order of strength of association, these factors are: greater neck disability due to pain; reduced self-rated health status and health-related quality of life; increased frequency of concentration problems; poor workplace satisfaction; lower self-efficacy for performing daily tasks; and greater work-related stress.

Conclusion: Condition-specific and psychosocial factors are associated with self-perceived work ability of individuals with chronic whiplash-associated disorder.

Background: Digital rectal examination (DRE) is part of the assessment of trauma patients as recommended by ATLS (R). The theory behind is to aid early diagnosis of potential lower intestinal, urethral and spinal cord injuries. Previous studies suggest that test characteristics of DRE are far from reliable. This study examines the correlation between DRE findings and diagnosis and whether DRE findings affect subsequent management.

Materials and methods: Patients with ICD-10 codes for spinal cord, urethral and lower intestinal injuries were identified from the trauma registry at an urban university hospital between 2007 and 2011. A retrospective review of electronic medical records was carried out to analyse DRE findings and subsequent management.

Results: 253 patients met the inclusion criteria with a mean age of 44 +/- 20 years and mean ISS of 26 +/- 16. 160 patients had detailed DRE documentation with abnormal findings in 48%. Sensitivity rate was 0.47. Correlational analysis between examination findings and diagnosis gave a kappa of 0.12. Subsequent management was not altered in any case due to DRE findings.

Conclusion: DRE in trauma settings has low sensitivity and does not change subsequent management. Excluding or postponing this examination should therefore be considered. (C) 2016 The Author(s). Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background: Non-invasive diagnostic imaging of atherosclerotic coronary artery disease (CAD) is frequently carried out with cardiovascular magnetic resonance imaging (CMR) or myocardial perfusion single photon emission computed tomography (MPS). CMR is the gold standard for the evaluation of scar after myocardial infarction and MPS the clinical gold standard for ischemia. Magnetic Resonance Imaging (MRI) is at times difficult for patients and may induce anxiety while patient experience of MPS is largely unknown.

Aims: To evaluate image quality in CMR with respect to the sequences employed, the influence of atrial fibrillation, myocardial perfusion and the impact of patient information. Further, to study patient experience in relation to MRI with the goal of improving the care of these patients.

Method: Four study designs have been used. In paper I, experimental cross-over, paper (II) experimental controlled clinical trial, paper (III) psychometric crosssectional study and paper (IV) prospective intervention study. A total of 475 patients ≥ 18 years with primarily cardiac problems (I-IV) except for those referred for MRI of the spine (III) were included in the four studies.

Result: In patients (n=20) with atrial fibrillation, a single shot steady state free precession (SS-SSFP) sequence showed significantly better image quality than the standard segmented inversion recovery fast gradient echo (IR-FGRE) sequence (I). In first-pass perfusion imaging the gradient echo-echo planar imaging sequence (GREEPI) (n=30) had lower signal-to-noise and contrast–to-noise ratios than the steady state free precession sequence (SSFP) (n=30) but displayed a higher correlation with the MPS results, evaluated both qualitatively and quantitatively (II). The MRIAnxiety Questionnaire (MRI-AQ) was validated on patients, referred for MRI of either the spine (n=193) or the heart (n=54). The final instrument had 15 items divided in two factors regarding Anxiety and Relaxation. The instrument was found to have satisfactory psychometric properties (III). Patients who prior CMR viewed an information video scored significantly (lower) better in the factor Relaxation, than those who received standard information. Patients who underwent MPS scored lower on both factors, Anxiety and Relaxation. The extra video information had no effect on CMR image quality (IV).

Conclusion: Single shot imaging in atrial fibrillation produced images with less artefact than a segmented sequence. In first-pass perfusion imaging, the sequence GRE-EPI was superior to SSFP. A questionnaire depicting anxiety during MRI showed that video information prior to imaging helped patients relax but did not result in an improvement in image quality.

Background: Non-invasive diagnostic imaging of atherosclerotic coronary artery disease (CAD) is frequently carried out with cardiovascular magnetic resonance imaging (CMR) or myocardial perfusion single photon emission computed tomography (MPS). CMR is the gold standard for the evaluation of scar after myocardial infarction and MPS the clinical gold standard for ischemia. Magnetic Resonance Imaging (MRI) is at times difficult for patients and may induce anxiety while patient experience of MPS is largely unknown.

Aims: To evaluate image quality in CMR with respect to the sequences employed, the influence of atrial fibrillation, myocardial perfusion and the impact of patient information. Further, to study patient experience in relation to MRI with the goal of improving the care of these patients.

Method: Four study designs have been used. In paper I, experimental cross-over, paper (II) experimental controlled clinical trial, paper (III) psychometric crosssectional study and paper (IV) prospective intervention study. A total of 475 patients ≥ 18 years with primarily cardiac problems (I-IV) except for those referred for MRI of the spine (III) were included in the four studies.

Result: In patients (n=20) with atrial fibrillation, a single shot steady state free precession (SS-SSFP) sequence showed significantly better image quality than the standard segmented inversion recovery fast gradient echo (IR-FGRE) sequence (I). In first-pass perfusion imaging the gradient echo-echo planar imaging sequence (GREEPI) (n=30) had lower signal-to-noise and contrast–to-noise ratios than the steady state free precession sequence (SSFP) (n=30) but displayed a higher correlation with the MPS results, evaluated both qualitatively and quantitatively (II). The MRIAnxiety Questionnaire (MRI-AQ) was validated on patients, referred for MRI of either the spine (n=193) or the heart (n=54). The final instrument had 15 items divided in two factors regarding Anxiety and Relaxation. The instrument was found to have satisfactory psychometric properties (III). Patients who prior CMR viewed an information video scored significantly (lower) better in the factor Relaxation, than those who received standard information. Patients who underwent MPS scored lower on both factors, Anxiety and Relaxation. The extra video information had no effect on CMR image quality (IV).

Conclusion: Single shot imaging in atrial fibrillation produced images with less artefact than a segmented sequence. In first-pass perfusion imaging, the sequence GRE-EPI was superior to SSFP. A questionnaire depicting anxiety during MRI showed that video information prior to imaging helped patients relax but did not result in an improvement in image quality.

Objectives: The principle of achieving the most cost-effective level of care in relation to needs is an essential aim for all health care systems. However, it is not certain that the corresponding knowledge and attitudes with respect to the appropriate level of care for different symptoms can be found in the general population. There may be age-related differences in illness behaviour that manifest in ‘overutilisation’ of the system. We studied illness behaviour with regard to attitudes and inclination to seek care for different symptoms at various levels in the health care system.Methods: The study group consisted of a random selection of 296 persons, born in the 1940s, ′50s and ′60s, and living in a defined region in Sweden. In a questionnaire they had to choose between different levels of care for twelve symptom descriptions with varying degrees of severity. The answers were scored according to the level of care, adequacy and overutilisation.Results: The vast majority of participants chose an adequate level of care. However, overutilisation was found, particularly among women born in the 1960s and to some extent among men born in the 1940s. These two groups together constituted about 70% of all the individuals who tended to overutilise the health care in their expressed preferences.Conclusions: These individuals do not receive cost-effective care, or the most adequate care with regard to their needs. The results indicate, however, that the problem was more a question of attitude rather than a lack of knowledge and information.

Purpose: The purpose of this study is to assess and describe the meanings given to "gender" in scientific publications that evaluate multidisciplinary, interdisciplinary or multimodal rehabilitation for patients with chronic musculoskeletal pain.

Method: A systematic literature search for papers evaluating multimodal rehabilitation was conducted. The PubMed and EBSCO databases were searched from 1995 to 2015. Two or three researchers independently read each paper, performed a quality assessment and coded meanings of gender using qualitative content analysis.

Results: Twenty-seven papers were included in the review. Gender was used very differently in the MMR studies investigated but primarily it referred to factual differences between men and women. Only one paper provided a definition of the concept of gender and how it had been used in that study. In the content analysis, the meaning of gender formed three categories: "Gender as a factual difference", "The man is the ideal" and "Gender as a result of social role expectations".

Conclusions: The meaning of the concept of gender in multimodal rehabilitation is undefined and needs to be developed further. The way the concept is used should be defined in the design and evaluation of multimodal rehabilitation in future studies.

Implications for rehabilitation

Healthcare professionals should reflect on gender relations in encounters with patients, selection of patients into rehabilitation programs and design of programs. In rehabilitation for chronic pain the patients' social circumstances and cultural context should be given the same consideration as biological sex and pain symptoms.

Pelvic girdle pain is common during pregnancy, but its multifactorial mechanisms are not completely understood. Generalised joint hypermobility is associated with musculoskeletal pain due to fragile connective tissue. The increased laxity of ligaments during pregnancy may be related to pelvic girdle pain. Women with fragile connective tissue may be more prone to developing pain during pregnancy. The overall aim was to examine whether generalised joint hypermobility increases the likelihood of experiencing pelvic girdle pain and physical disability during and after pregnancy. In Study I, the inter- and intra-rater reliability of joint mobility measurements in 49 adults were investigated, evaluating 12 joints. Study II explored the association between self-reported generalised joint hypermobility and pelvic girdle pain during pregnancy involving 2,217 women. In study III, the association between clinically assessed generalised joint hypermobility and pelvic girdle pain during and after pregnancy were examined, involving 356 women. Study IV focused on the development of physical disability from early pregnancy to nine months postpartum considering pelvic girdle pain, generalised joint hypermobility and overweight, and wheather the onset of pelvic girdle pain and the level of physical disability during pregnancy was associated with physical disability nine months postpartum. The findings in this thesis indicated good-to-excellent inter- and intra-rater reliability in most mobility measurements. Women who self-reported generalised joint hypermobility exhibited higher odds of experiencing pelvic-girdle pain, particularly in early pregnancy. Clinically assessed generalised joint hypermobility was associated with increased pain intensity in early pregnancy and, when combined with overweight, an increased risk of pelvic girdle pain. Physical disability increased during pregnancy irrespective of pelvic girdle pain status, but the overall prognosis was positive. Pelvic girdle pain had the strongest influence on disability, in contrast to generalized joint hypermobility and overweight. Early-onset pelvic girdle pain during pregnancy and a higher disability index during pregnancy were associated with physical disability nine months postpartum. Women experiencing pelvic girdle pain early in pregnancy may benefit from evaluation for generalised joint hypermobility, as they may experience more intense pain. It is crucial to develop methods for preventing and managing pelvic girdle pain, given its strong association with physical disability during and after pregnancy. Early-onset pelvic girdle pain and a higher disability index during pregnancy were predictors of physical disability nine months postpartum.

Introduction: Pelvic girdle pain (PGP) affects approximately 50% of pregnant women. The mechanisms are multifactorial but not fully understood. Women with generalized joint hypermobility (GJH) may be vulnerable to load in the pelvic joints during pregnancy. Our aim was to investigate if women with GJH had an increased risk of PGP and higher pain intensity during and after pregnancy, compared with women with normal joint mobility. We also studied if body mass index (BMI) in early pregnancy influenced that risk.

Material and methods: A prospective cohort study of 356 women, whose data were collected by self-reports and clinical examinations in early and in late pregnancy and 9 months after childbirth. GJH was present with ≥5/9 points on the Beighton score. PGP was defined by a pain drawing and ≥1 positive test. Pain intensity was measured with a visual analogue scale (0-100 mm). We adjusted for age and origin in logistic regression and ordinal logistic regression analysis.

Results: In early pregnancy, 47.1% of the women with GJH had PGP vs 32.6% of women with normal joint mobility (adjusted odds ratio [aOR] 1.76; 95% confidence interval [CI] 0.86-3.62) and had higher odds of reporting higher pain intensity (aOR 2.04; 95% CI 1.02-4.07). The odds of PGP were highest for women with GJH and BMI ≥25 kg/m2 (aOR 6.88; 95% CI 1.34-35.27) compared with women with normal joint mobility and BMI <25 kg/m2 . The estimated associations were weaker and not statistically significant in late pregnancy or after childbirth.

Conclusions: Women with GJH did not have an increased risk of PGP during or after pregnancy but reported higher pain intensity in early pregnancy compared with women with normal joint mobility. Since women with combined GJH and BMI ≥25 kg/m2 had the highest odds of PGP in early pregnancy, our results may suggest that health care needs to pay attention to and develop methods to reduce the risk of PGP and delay the onset of pain during pregnancy in women with this combination.Keywords: Uppsala pelvic pain study; body mass index; generalized joint hypermobility; pelvic girdle pain; pregnancy.

Atrial fibrillation (AF) is a common arrhythmia among patients scheduled for open heart surgery and is associated with increased morbidity and mortality. According to international guidelines, symptomatic and selected asymptomatic patients should be offered concomitant surgical AF ablation in conjunction with valvular or coronary surgery. The gold standard in AF surgery is the Cox Maze III ("cut-and-sew") procedure, with surgical incisions in both atria according to a specified pattern, in order to prevent AF reentry circuits from developing. Over 90% of patients treated with the Cox Maze III procedure are free of AF after 1 year. Recent developments in ablation technology have introduced several energy sources capable of creating nonconducting atrial wall lesions. In addition, simplified lesion patterns have been suggested, but results with these techniques have been unsatisfactory. There is a clear need for standardization in AF surgery. The Swedish Arrhythmia Surgery Group, represented by surgeons from all Swedish units for cardiothoracic surgery, has therefore reached a consensus on surgical treatment of concomitant AF. This consensus emphasizes adherence to the lesion pattern in the Cox Maze III procedure and the use of biatrial lesions in nonparoxysmal AF.

Background: Over the last decades the RA-treatment strategies have changed considerably. Routines for early RA diagnosis and instituted disease modifying anti rheumatic drugs (DMARDs) have been established. In the early 2000s biologic agents also became available for treatment purposes. Despite these altered and improved strategies RA patients continue to report pain and activity limitations; women more so than men.Objectives: To study differences regarding pain and activity limitations during the first three years after diagnosis of RA in today's patients compared with patients diagnosed 10 years earlier from a gender perspective.Methods: This study was based on patients recruited to the project “early interventions in RA” (TIRA). In the first cohort (TIRA-1) 320 patients were included during 1996-1998. In the second cohort (TIRA-2) 463 patients were included during 2006-2008. Disease activity score 28 joint count (DAS-28) and medication were registered. Pain intensity (VAS), bodily pain (BP) in Short Form36 (SF-36) and activity limitation (Health Assessment Questionnaire, HAQ) were reported at inclusion and at follow-ups after one, two and three years.Results: Disease activity did not differ between cohorts at inclusion, but was significant lower at the follow ups in the TIRA-2 cohort compared with the TIRA-1 cohort. Patients in TIRA2 were prescribed traditional DMARD:s and biologic agents more frequent than in TIRA-1. The TIRA-2 patients reported significantly higher pain intensity and activity limitations at inclusion but lower pain intensity and activity limitations at all follow-ups than TIRA-1 patients. There were no significant differences between cohorts regarding bodily pain at inclusion, but thereafter the TIRA-2 patients showed significant lower bodily pain than the TIRA-1 patients. Men reported lower activity limitation than women in TIRA-1; otherwise there were no gender differences in TIRA-1. In TIRA-2, there were no significant gender differences regarding pain at inclusion. However, men reported lower pain than women at all follow-ups. Women, in turn, reported significantly higher activity limitations at all time points in TIRA-2. Pain and activity limitations were significantly reduced from inclusion to the one year follow-up but remained stable thereafter.Conclusions: Both women and men in today's early RA patient cohort report lower pain and less activity limitations at the follow ups after diagnosis of RA compared to 10 years earlier. However, both activity limitations and bodily pain are still pronounced.Disclosure of Interest: None declared

AimsLeft ventricular hypertrophy, obesity, hypertension, and N-terminal B-type natriuretic peptide (Nt-proBNP) predict left ventricular diastolic dysfunction with preserved systolic function (DD-PSF). Self-rated health (SRH) is shown to be associated with chronic diseases, but the association of SRH with DD-PSF is unclear. In light of the clinical implications of DD-PSF, the following goals are of considerable importance: (1) to determine the role of SRH in patients with DD-PSF in the general population and (2) to study the association between Nt-proBNP and DD-PSF.

Methods and resultsThe current study is a cross-sectional study conducted on a random sampling of a rural population. Individuals 30–75 years of age were consecutively subjected to conventional echocardiography and tissue velocity imaging. Data were collected on 500 (48%) men and 538 (52%) women (n = 1038). DD-PSF was the main outcome, and SRH and Nt-proBNP were the primary indicators. Diabetes mellitus, hypertension, and obesity were accounted for as major confounders of the association with SRH. DD-PSF was identified in 137 individuals, namely, 79 men (15.8%) and 58 women (10.8%). In a multivariate regression model, SRH (OR 2.95; 95% CI 1.02–8.57) and Nt-proBNP (quartile 4 vs. quartile 1 OR 4.23; 95% CI 1.74–10.26) were both independently associated with DD-PSF.

ConclusionsSRH, evaluated based on a descriptive question on general health, should be included in the diagnostic process of DD-PSF. In agreement with previous studies, our study confirms that Nt-proBNP is a major indicator of DD-PSF.

BackgroundNeurological manifestations in patients with COVID-19 have been reported previously as outcomes of the infection.The purpose of current study was to investigate the occurrence of neurological signs and symptoms in COVID-19 patients, in the county of ostergotland in southeastern Sweden. MethodsThis is a retrospective, observational cohort study. Data were collected between March 2020 and June 2020. Information was extracted from medical records by a trained research assistant and physician and all data were validated by a senior neurologist. ResultsSeventy-four percent of patients developed at least one neurological symptom during the acute phase of the infection. Headache (43%) was the most common neurological symptom, followed by anosmia and/or ageusia (33%), confusion (28%), hallucinations (17%), dizziness (16%), sleep disorders in terms of insomnia and OSAS (Obstructive Sleep Apnea) (9%), myopathy and neuropathy (8%) and numbness and tingling (5%). Patients treated in the ICU had a higher male presentation (73%). Several risk factors in terms of co-morbidities, were identified. Hypertension (54.5%), depression and anxiety (51%), sleep disorders in terms of insomnia and OSAS (30%), cardiovascular morbidity (28%), autoimmune diseases (25%), chronic lung diseases (24%) and diabetes mellitus type 2 (23%) founded as possible risk factors. ConclusionNeurological symptoms were found in the vast majority (74%) of the patients. Accordingly, attention to neurological, mental and sleep disturbances is warranted with involvement of neurological expertise, in order to avoid further complications and long-term neurological effect of COVID-19. Furthermore, risk factors for more severe COVID-19, in terms of possible co-morbidities that identified in this study should get appropriate attention to optimizing treatment strategies in COVID-19 patients.

Background. Efforts to identify specific variables that impact most on outcomes from interdisciplinary pain rehabilitation are challenged by the complexity of chronic pain. Methods to manage this complexity are needed. The purpose of the study was to determine the network structure entailed in a set of self-reported variables, examine change, and look at potential predictors of outcome, from a network perspective. Methods. In this study we apply network analysis to a large sample of people seeking interdisciplinary pain treatment (N = 2,241). Variables analyzed include pain intensity, pain interference, extent of pain, depression, anxiety, insomnia, and psychological variables from cognitive behavioral models of chronic pain. Results. We found that Acceptance, Pain Interference, and Depression were key, "central," variables in the pretreatment network. Interestingly, there were few changes in the overall network configuration following treatment, specifically with respect to which variables appear most central relative to each other. On the other hand, Catastrophizing, Depression, Anxiety, and Pain Interference each became less central over time. Changes in Life Control, Acceptance, and Anxiety were most strongly related to changes in the remainder of the network as a whole. Finally, no network differences were found between treatment responders and non-responders. Conclusions. This study highlights potential future targets for pain treatment. Further application of a network approach to interdisciplinary pain rehabilitation data is recommended. Going forward, it may be better to next do this in a more comprehensive theoretically guided fashion, and ideographically, to detect unique individual differences in potential treatment processes.

Background: Occupational exposure to cytotoxic drugs is associated with various unfavorable health outcomes. This protocol reports a methodology for a systematic review and meta-analysis that aims to systematically review the published literature and quantify the level of environmental contamination of healthcare settings with cytotoxic drugs.

Methods: This protocol is developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol-2015 (PRISMA-P) guidelines. Six electronic databases (PubMed, Web of Science, Scopus, Cochrane Library, CINAHL, and EMBASE) will be searched with no restrictions on publication period. Eligible studies will be identified and data will be extracted using a predefined data extraction form by at least two independent reviewers following best practice. Eligible studies should report calculated or calculable estimates on the proportion of positive samples tested for cytotoxic drugs and/or estimates on the concentration of the cytotoxic drug(s) in the tested samples. Risk of bias (RoB) will be assessed by using the RoB in Studies estimating Prevalence of Exposure to Occupational risk factors (RoB-SPEO) tool, which developed by the World Health Organization (WHO) and International Labour Organization (ILO) for environmental and occupational health systematic reviews. The random-effects model will be used to perform meta-analyses.

Discussion: Occupational exposure to cytotoxic drugs is associated with short- and long-term adverse health outcomes. Following this protocol, the review to be carried out will be the first to fill an evidence gap on the environmental contamination of healthcare settings with cytotoxic drugs. The findings of this review will help in the understanding of the risk of occupational exposure of healthcare workers to cytotoxic drugs and facilitate the identification of priority areas for specific interventions.

Ethics and dissemination: The systematic review methodology does not require ethics approval due to the nature of the study design. The results of the systematic review will be published in a peer-reviewed journal and will be publicly available.

Systematic review registration: PROSPERO, dated July 14, 2020

Purpose: To present the Uppsala Longitudinal Adolescent Depression Study, initiated in Uppsala, Sweden, in the early 1990s. The initial aim of this epidemiological investigation was to study the prevalence, characteristics and correlates of adolescent depression, and has subsequently expanded to include a broad range of social, economic and health-related long-term outcomes and cost-of-illness analyses.

Participants: The source population was first-year students (aged 16-17) in upper-secondary schools in Uppsala during 1991-1992, of which 2300 (93%) were screened for depression. Adolescents with positive screening and sex/age-matched peers were invited to a comprehensive assessment. A total of 631 adolescents (78% females) completed this assessment, and 409 subsequently completed a 15year follow-up assessment. At both occasions, extensive information was collected on mental disorders, personality and psychosocial situation. Detailed social, economic and health-related data from 1993 onwards have recently been obtained from the Swedish national registries for 576 of the original participants and an age-matched reference population (N=200 000).

Findings to date: The adolescent lifetime prevalence of a major depressive episode was estimated to be 11.4%. Recurrence in young adulthood was reported by the majority, with a particularly poor prognosis for those with a persistent depressive disorder or multiple somatic symptoms. Adolescent depression was also associated with an increased risk of other adversities in adulthood, including additional mental health conditions, low educational attainment and problems related to intimate relationships.

Future plans: Longitudinal studies of adolescent depression are rare and must be responsibly managed and utilised. We therefore intend to follow the cohort continuously by means of registries. Currently, the participants are approaching mid-adulthood. At this stage, we are focusing on the overall long-term burden of adolescent depression. For this purpose, the research group has incorporated expertise in health economics. We would also welcome extended collaboration with researchers managing similar datasets.

OBJECTIVES: Comparison of comorbidity and healthcare consumption in primary healthcare subjects with persistent functional gastrointestinal disorder (FGID) and a strictly gastrointestinal (GI) symptom-free group (SSF). METHODS: A stratified sample (n=1428, 21-86 years) of subjects living in the Osthammar community, Sweden, was limited to half of the community and classified through the Abdominal Symptom Questionnaire (ASQ) into two study groups, one with persistent FGID (n=71), another SSF (n=48). Symptoms were re-evaluated by means of the ASQ at a surgery visit, as was healthcare consumption during 2 years, and the levels of anxiety and depression, as measured with the Hospital Anxiety and Depression Scale. Diagnoses were set according to The International Classification of Diseases (ICD)-9 and the 14 diagnostic groups. RESULTS: Of the FGID patients, 97% had a non-GI diagnosis, compared with 100% of SSF (ns). The mean number of doctors' consultations (OR=3.5), phone calls to doctors (OR=3.4), number of prescriptions (OR=2.4) and number of set diagnoses (OR=3.9), anxiety level (OR=11.5) and depression (OR=5.2) were all statistically significantly higher (p<0.05) for FGID than for SSF, while the number of referrals and sick leave were not. Besides a GI diagnosis, there was no significant difference (p>0.05) in the spectrum of morbidity in terms of ICD-9 subgroup classification, except an increased proportion of older SSF subjects with circulatory disorders and hypertension. CONCLUSIONS: Functional gastrointestinal disorders are related to an increased demand on primary healthcare because of an increased overall comorbidity, which signifies a need for a holistic healthcare approach.

Aims: The objective was to compare anxiety, depression, and quality of life (QoL) in individuals living with type 1 (T1D) and type 2 (T2D) diabetes with matched controls during the second wave of the COVID-19 pandemic. Methods: Via randomization, individuals living with diabetes T1D (n = 203) and T2D (n = 413), were identified during February-July 2021 through health-care registers. Population controls (n = 282) were matched for age, gender, and residential area. Questionnaires included self-assessment of anxiety, depression, QoL, and demographics in relation to SARS-CoV-2 exposure. Blood was collected through home-capillary sampling, and SARS-CoV-2 Nucleocapsid (NCP) and Spike antibodies (SC2_S1) were determined by multiplex Antibody Detection by Agglutination-PCR (ADAP) assays. Results: Younger age and health issues were related to anxiety, depression, and QoL, with no differences between the study groups. Female gender was associated with anxiety, while obesity was associated with lower QoL. The SARS-CoV-2 NCP seroprevalence was higher in T1D (8.9 %) compared to T2D (3.9 %) and controls (4.0 %), while the SARS-CoV-2 SC2_S1 seroprevalence was higher for controls (25.5 %) compared to T1D (16.8 %) and T2D (14.0 %). Conclusions: A higher SARS-CoV-2 infection rate in T1D may be explained by younger age and higher employment rate, and the associated increased risk for viral exposure. (c) 2023 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC

Background: Medical simulation enables the design of learning activities for competency areas (eg, communication and leadership) identified as crucial for future health care professionals. Simulation educators and medical teachers follow different career paths, and their education backgrounds and teaching contexts may be very different in a simulation setting. Although they have a key role in facilitating learning, information on the continuing professional development (pedagogical development) of simulation educators is not available in the literature.

Objectives: To explore changes in experienced simulation educators' perceptions of their own teaching skills, practices, and understanding of teaching over time.

Methods: A qualitative exploratory study. Fourteen experienced simulation educators participated in individual open-ended interviews focusing on their development as simulation educators. Data were analyzed using an inductive thematic analysis.

Results: Marked educator development was discerned over time, expressed mainly in an altered way of thinking and acting. Five themes were identified: shifting focus, from following to utilizing a structure, setting goals, application of technology, and alignment with profession. Being confident in the role as an instructor seemed to constitute a foundation for the instructor's pedagogical development.

Conclusion: Experienced simulation educators' pedagogical development was based on self-confidence in the educator role, and not on a deeper theoretical understanding of teaching and learning. This is the first clue to gain increased understanding regarding educational level and possible education needs among simulation educators, and it might generate several lines of research for further studies.

Objectives: To describe patterns and contextual determinants of antibiotic prescribing for febrile under-five outpatients at primary and secondary healthcare facilities across Bugisu, Eastern Uganda.

Methods: We surveyed 37 public and private-not-for-profit healthcare facilities and conducted a retrospective review of antimicrobial prescribing patterns among febrile under-five outpatients (with a focus on antibiotics) in 2019–20, based on outpatient registers. Multilevel logistic regression analysis was used to identify determinants of antibiotic prescribing at patient- and healthcare facility-levels.

Results: Antibiotics were prescribed for 62.2% of 3471 febrile under-five outpatients. There were a total of 2478 antibiotic prescriptions of 22 antibiotic types: amoxicillin (52.2%), co-trimoxazole (14.7%), metronidazole (6.9%), gentamicin (5.7%), ceftriaxone (5.3%), ampicillin/cloxacillin (3.6%), penicillin (3.1%), and others (8.6%). Acute upper respiratory tract infection (AURTI) was the commonest single indication for antibiotic prescribing, with 76.3% of children having AURTI as their only documented diagnosis receiving antibiotic prescriptions. Only 9.2% of children aged 2–59 months with non-severe pneumonia received antibiotic prescriptions in line with national guidelines. Higher health centre levels, and private-not-for-profit ownership (adjusted OR, 4.30; 95% CI, 1.91–9.72) were significant contextual determinants of antibiotic prescribing.

Conclusions: We demonstrated a high antibiotic prescribing prevalence among febrile under-five outpatients in Bugisu, Eastern Uganda, including prescriptions for co-trimoxazole and ampicillin/cloxacillin (which are not indicated in the management of the common causes of under-five febrile illness in Uganda). Study findings may be linked to limited diagnostic capacity and inadequate antibiotic availability, which require prioritization in interventions aimed at improving rational antibiotic prescribing among febrile under-five outpatients.

Objective:To assess the safety of long-term treatment with flecainide in patients with atrial fibrillation (AF), particularly with regard to sudden cardiac death (SCD) andproarrhythmic events.

Design: Retrospective,observational cohort study.Setting.Single-centre study at Örebro University Hospital, Sweden.

Setting: Single-centre study at Orebro University Hospital, Sweden.

Subjects: A total of 112 patients with paroxysmal (51%) or persistent (49%) AF (mean age 60 ± 11 years) were included after identifying all patients with AF who initiated oral flecainide treatment (mean dose 203 ± 43 mg per day) between 1998 and 2006. Standard exclusion⁄inclusion criteria for flecainide were used,andflecainidetreatmentwasusually combined withanatrioventricular-blocking agent (89%).

Main outcome measure: Death was classified as sudden or nonsudden according to standard definitions. Proarrhythmia was defined as cardiac syncope or lifethreatening arrhythmia.

Results: Eight deaths were reported during a mean follow- up of 3.4 ± .4 years. Compared to the general population, the standardized mortality ratios were 1.57 (95% confidence interval (CI) 0.68–3.09) for allcause mortality and 4.16 (95% CI 1.53–9.06) for death from cardiovascular disease. Three deaths were classified as SCDs. Proarrhythmic events occurred in six patients (two each with wide QRS tachycardia, 1 : 1 conducted atrial flutter and syncope during exercise).

Conclusion: We found an increased incidence of SCD or proarrhythmic events in this real-world study of flecainide used for the treatment of AF. The findings suggest that further investigation into the safety of flecainide for the treatment of patients with AF is warranted.

Background Cancer treatment-related morbidity relevantly compromises health status in cancer survivors, and efforts to optimise health-related outcomes in this population are vital to maximising healthy survivorship. A pre-treatment assessment - and possibly preventive management strategies - of cancer patients at increased risk for cardiovascular disease (CVD) seems a rational approach in this regard. Definitive evidence for such strategies is largely lacking, thereby impeding the formulation of firm recommendations. Results The current scoping review aims to summarise and grade the evidence regarding strategies for prediction and prevention of CVD in adults in relation to oncological treatments. We conducted a scoping literature search for different strategies for primary prevention, such as medical and lifestyle interventions, as well as the use of predictive risk scores. We identified studies with moderate to good strength and up to now limited evidence to recommend primary preventive strategies in unselected patients treated with potentially cardiotoxic oncologic therapies. Conclusion Efforts to minimize the CVD burden in cancer survivors are needed to accomplish healthy survivorship. This can be done by means of robust models predictive for CVD events or application of interventions during or after oncological treatments. Up to now there is insufficient evidence to implement preventive strategies in an unselected group of patients treated with potential cardiotoxic oncological treatments. We conclude that randomised controlled trials are needed that evaluate medical and lifestyle interventions in groups at increased risk for complications, in order to be able to influence chronic illness risks, such as cardiovascular complications, for cancer survivors.

Background: Excess body fat, particularly in the visceral depot, is linked to increased mortality and morbidity, including the development of diseases such as type 2 diabetes, cardiovascular disease, and cancer. Chronic low-grade inflammation in adipose tissue may be a key mediator of obesity-associated diseases. Importantly, specific pro-inflammatory cytokines have been shown to influence adipose tissue function and could therefore be a link to metabolic disorders. Circulating cytokine levels may also be increased in obesity and metabolic diseases. However, although fat distribution and inflammation are clearly linked to metabolic disorders, inflammatory gene expression in the different abdominal adipose depots has not been investigated in detail. The menopausal transition is followed by a centralization of body fat and increased adiposity. Notably, inflammatory changes in fat during the menopausal transition have not been characterized. Finally, there is a lack of studies investigating the long-term effects of weight loss on low-grade inflammation. The aim of this thesis was to characterize differences between fat depots and investigate putative changes in low-grade inflammation in adipose tissue and circulation following menopause or weight loss.

Materials & Methods: The expression of inflammation-related genes was investigated in abdominal adipose tissue depots obtained from women with varying adiposity, before and after menopause or weight loss induced by surgery or dietary intervention. Circulating cytokine levels were analyzed using immunoassays.

Results: Visceral fat displayed a distinct and adverse inflammatory profile compared with subcutaneous adipose tissues, and the higher gene expression in visceral fat was associated with adiposity. Postmenopausal women exhibited a higher expression of pro-inflammatory genes than premenopausal women that associated with central fat accumulation. There was also a menopause-related increase in circulating cytokine levels in postmenopausal women. After surgery-induced weight loss, there was a dramatic reduction in inflammatory gene expression followed by increased insulin sensitivity. We observed no alterations in circulating cytokine levels. Long-term dietary intervention, associated with weight loss, had favorable effects on inflammation in both adipose tissue and serum.

Conclusion: Fat accumulation is linked to low-grade inflammation in abdominal adipose tissue. The unique inflammatory pattern of visceral fat suggests a distinct role in adipose tissue inflammation that is aggravated with increasing adiposity. In postmenopausal women, the adverse adipose inflammatory profile was associated with central fat accumulation, while higher circulating cytokine levels correlated with menopausal state/age. Our data from severely obese women undergoing surgery-induced weight loss clearly supports a link between adipose inflammation and insulin resistance. The long-term beneficial effects of weight loss were also demonstrated by the improved inflammatory profile after dietary intervention. In summary, excess body fat is clearly linked to adipose tissue inflammation. Long-term weight loss is accompanied by improved metabolic profile and reduced low-grade inflammation in fat.

The inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, are relapsing and remitting disorders characterised by chronic inflammation at various sites in the gastrointestinal tract, resulting in diarrhoea and abdominal pain. Neither the aetiology nor the pathophysiology is yet fully understood, and there is currently no cure.

The overall aim of this thesis was to add a piece of the puzzle to understanding the complex pathogenesis of IBD; to determine the role of genetic and environmental factors in the development of antibodies in IBD - which could provide insight to the aetiology of the diseases; and to find sensitive and specific faecal biomarkers to predict future flare in the diseases.

By conducting twin-studies, we found that some serological antibodies associated with Crohn's disease seemed to be genetically predisposed (anti-OmpC and anti-I2). Genetic predisposition do not play a predominant role in the generation of other antibodies, such as ASCA, anti-CBir1 or the autoantibody most commonly found in ulcerative colitis; pANCA. Exposure to environmental factors during childhood are suggested to be of importance in the development of ASCA and anti-CBir1 in CD. Active smoking seemed to have a protective effect against development of pANCA.

Faecal calprotectin is a known marker for intestinal inflammation. In our third study, three faecal calprotectin assays were compared, which revealed overall poor agreement. This implies that standardisation of the method is highly needed.

In our final study, we measured faecal eosinophil derived neurotoxin (EDN) and eosinophil cationic protein (ECP) in patients with IBD every third month over a two-year period. The results revealed that the risk of relapse in UC can be predicted by measuring EDN consecutively.

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterized by impaired attention and hyperactivity/impulsivity. ADHD is associated with several comorbidities and health-related outcomes. However, it is uncertain whether ADHD is more strongly associated with certain disorder domains, and whether ADHD-related comorbidities and health-related outcomes is important to consider during pregnancy. 

Aims: To expand the knowledge regarding the genetic overlap between ADHD and other psychiatric disorder symptoms, and to increase the awareness and understanding related to ADHD in women, with a focus on adverse health behaviors, mental health problems, and pregnancy outcomes. 

Methods: The present thesis includes one systematic review and metaanalysis (Study I), and three studies based on population-based register data from Sweden (Study II, III, and IV), and Norway (Study II).

Results: Individuals with ADHD have an increased liability to meet criteria for externalizing, internalizing and neurodevelopmental disordersymptoms, and these co-occurrences are partly due to shared genetic risks. Further, ADHD is an important risk factor to consider before, during and after pregnancy, as ADHD increases the risk of smoking during pregnancy, mental health problems postpartum, and adverse pregnancy outcomes.

Conclusions: The genetic overlaps between ADHD and other psychiatric disorder symptoms were similar across disorder dimensions. Further, results demonstrated that ADHD is an important risk factor to consider in women surrounding pregnancy. These findings point towards the importance of recognizing that women diagnosed with ADHD need to be prioritized and allowed more attention and support by the healthcare system, specifically during their fertile years. 

Objective: Can renal insufficiency in subjects with acute intermittent porphyria (AIP) be due solely to AIP?

Design: A population-based study.

Subjects: Subjects with AIP ≥ 18 years of age (n = 386) in the four most northerly counties of Sweden.

Interventions: Screening with creatinine clearance at 24 h. Patients below the lower reference level underwent a repeat clearance test and, if still low, also chromEDTA clearance.

Results: 286 (74%) subjects performed the creatinine clearance test and in 57 clearance was low; the second clearance proved normal in 23 who were then excluded. Eighteen subjects with other possible medical reasons for renal insufficiency, ethical reasons or refusing further examinations were also excluded. The 16 remaining subjects with no explanation for their renal insufficiency other than AIP were then studied in detail. All 14 women, mean age 52 years, and two uraemic men, 58 and 67 years, had manifest AIP. Twelve patients had hypertension (HT) and four were normotensive in spite of renal insufficiency. Histological findings of renal biopsies revealed diffuse glomerulosclerotic and interstitial changes with additional ischaemic lesions.

Conclusion: Protracted vasospasm in attacks of AIP may be a cause of renal lesions. This is discussed.

Background

Depressive disorders have been associated with a number of co-morbidities, and we   hypothesized that patients with a depression diagnosis would be heavy users of health   care services, not only when first evaluated for depression, but also for preceding   years. The aim of this study was to investigate whether increased health care utilisation   and co-morbidity could be seen during five years prior to an initial diagnosis of   depression.

Methods

We used a longitudinal register-based study design. The setting comprised the general   population in the county of Östergötland, south-east Sweden. All 2470 patients who   were 20 years or older in 2006 and who received a new diagnosis of depression (F32   according to ICD-10) in 2006, were selected and followed back to the year 2001, five   years before their depression diagnosis. A control group was randomly selected among   those who were aged 20 years or over in 2006 and who had received no depression diagnosis   during the period 2001-2006.

Results

Predictors of a depression diagnosis were a high number of physician visits, female   gender, age below 60, age above 80 and a low socioeconomic status.

Patients who received a diagnosis of depression used twice the amount of health care   (e.g. physician visits and hospital days) during the five year period prior to diagnosis   compared to the control group. A particularly strong increase in health care utilisation   was seen the last year before diagnosis. These findings were supported with a high   level of co-morbidity as for example musculoskeletal disorders during the whole five-year   period for patients with a depression diagnosis.

Conclusions

Predictors of a depression diagnosis were a high number of physician visits, female   gender, age below 60, age above 80 and a low socioeconomic status. To find early signs   of depression in the clinical setting and to use a preventive strategy to handle these   patients is important.

STUDY OBJECTIVE: To explore individual and social factors that could predict health care utilisation and medication among people with chronic pain in an unselected population. DESIGN: A mailed survey with questions about pain and mental symptoms, disability, self care action, visits to health care providers, and medication. SETTING: General populations in two Swedish primary health care (PHC) districts. Medical care was given in a state health system. PARTICIPANTS: A random sample (from the population register) of 15% of the population aged 25-74 (n = 1806). MAIN RESULTS: Among people reporting chronic pain 45.7% (compared with 29.8 of non-chronic pain persons, p < 0.05) consulted a physician and 7.2% (compared with 1.2%, p < 0.05) a physiotherapist during three months. Primary health care was the most frequent care provider. High pain intensity, aging, depression, ethnicity, and socioeconomic level had the greatest impact on physician consultations. Alternative care, used by 5.9%, was associated with high pain intensity and self care. Use of self care was influenced by high pain intensity, regular physical activity, and ethnicity. Alternative care and self care did not imply lower use of conventional health care. Women reporting chronic pain consumed more analgesics and sedatives than corresponding men. Besides female gender, high pain intensity, insomnia, physician consultation, social network, and self care action helped to explain medication with analgesics. Use of herbal remedies and ointments correlated to self care action, visit to an alternative therapist, high pain intensity, and socioeconomic level. CONCLUSIONS: The presence of chronic pain has an impressive impact on primary health care and medication. Various therapeutic actions are common and are partly overlapping. The use of health care among people with chronic pain depends above all on pain perception and intensity of pain but is also affected by ethnicity, age, socioeconomic level, and depressive symptoms. Among people with chronic pain use of analgesics is common in contrast with other types of pain relief (acupuncture, physiotherapy) suitable for treating chronic pain symptoms.

OBJECTIVE: To study the relations between population prevalence of chronic pain and pain-related diagnoses (musculoskeletal and headaches) in primary health care (PHC) and to examine longitudinal variations in these diagnoses. DESIGN: A population-based mailed survey to catch prevalence data and continuous computerised diagnosis registration in PHC. SETTING: General population in a well-defined Swedish PHC district. SUBJECTS: A random sample of 15% of the population aged 25-74, n = 1101. Annual visitors to district physicians at the health centre. MAIN OUTCOME MEASURES: Rates of pain-related diagnoses in PHC in relation to population prevalence of chronic pain. Comparisons of the number of individuals (annual visiting rates) with pain-related diagnoses 1987-1996. RESULTS: Population pain prevalence and pain-related diagnoses in PHC corresponded as regards the magnitude and distribution of chronic pain by age and partly by pain location. Compared to low-back and widespread pain, neck-shoulder pain and headaches were less frequent in PHC in relation to reported prevalence. From 1987 to 1996 we found an increasing number of individuals seeking primary care with pain-related diagnoses. The increase was mainly assigned to the groups of fibrositis/myalgia and headache. CONCLUSION: Pain-related diagnoses in PHC reflect partly the occurrence of self-reported chronic pain symptoms in the population. The observed increase in visits with pain-related diagnoses in the last 10 years is due to an increased number of individuals with soft-tissue rheumatism and headaches. Future studies will have to elucidate whether these findings are due to an increase in morbidity or changes in care-seeking and social conditions.