The association of zonulin-related proteins with prevalent and incident inflammatory bowel disease.

BACKGROUND: Current evidence regarding the association of serum zonulin-related proteins (ZRP) levels with prevalent inflammatory bowel disease (IBD) is contradictory. Moreover, the association with the subsequent risk of incident IBD is still unexplored. This study aimed to investigate the association of serum ZRP levels with both prevalent and incident IBD. METHOD: The study included a total of 130 women (51-61 years) from the Women's Health in Lund Area (WHILA) study, which included 18 prevalent IBD (diagnosed before baseline) and 47 incident IBD diagnosed during the 17 years (median) follow-up and age- and sampling time-matched controls. Serum ZRP was tested in all participants by ELISA. RESULTS: The serum ZRP levels were significantly higher in prevalent IBD compared to their matched controls (63.2 ng/ml vs 57.0 ng/ml, p = 0.02), however, no evidence of a difference in ZRP levels was found between the women who developed IBD during the follow-up period and their matched controls (61.2 ng/ml vs 59.7 ng/ml, p = 0.34). Using linear mixed models, we found that the association between serum ZRP levels and prevalent IBD (ß = 6.2, p = 0.01), remained after adjusting for potential confounders. Conditional logistic regression models showed no evidence of an association between ZRP level and incident IBD (OR 1.03, p = 0.34). CONCLUSION: Higher serum ZRP levels were associated with prevalent IBD, but not with incident IBD in our study samples.

The Association between Blood-Based Global DNA Methylation and Venous Thromboembolism.

Alterations in DNA methylation patterns have been associated with many diseases. However, the role of DNA methylation in venous thromboembolism (VTE) is not well established. The aim of this study was to investigate a possible association between global DNA methylation and VTE. The study participants consisted of 168 individuals including 74 patients with primary VTE from the Malmö Thrombophilia Study (MATS) and 94 healthy controls. Among 74 primary VTE patients, 37 suffered VTE recurrence during the follow-up period; 37 nonrecurrent VTE patients were included for comparison. Blood-based global DNA methylation was assessed by an enzyme-linked immunosorbent assay. Global DNA methylation was significantly higher in primary VTE patients compared with the healthy controls (median: 0.17 vs. 0.08%; p < 0.001). After stratification of data from primary VTE patients according to sex, the association between higher global DNA methylation and shorter recurrence-free survival time was of borderline statistical significance in males (ß = -0.2; p = 0.052) but not in females (ß = 0.02; p = 0.90). Our results show that global DNA methylation is associated with primary VTE and that higher levels of global DNA methylation may be associated with early VTE recurrence in males but not in females. Further investigation on the role of DNA methylation as a diagnostic or preventive biomarker in VTE is warranted.

Inflammatory proteins and miRNA-144-5p in patients with depression, anxiety, or stress- and adjustment disorders after psychological treatment.

Both inflammatory proteins and microRNAs (miRNA) have been reported to be associated with various psychiatric disorders. However, the association between inflammatory proteins and miRNAs remains largely unknown, especially for patients with depression, anxiety, or stress- and adjustment disorders. In this study, we analyzed plasma levels of 92 inflammatory proteins from 178 patients with depression, anxiety, or stress- and adjustment disorders at baseline and after 8-week psychological treatments which resulted in a significant decrease in the Montgomery Åsberg Depression Rating Scale (MADRS-S) score. We investigated the response of the proteins after treatment and the correlation with miR-144-5p. After Benjamini-Hochberg correction for multiple testing, a total of 36 inflammatory proteins changed significantly after 8-week psychological treatments. Among the 36 significantly changed proteins, 21 proteins showed a decrease, and 17/21 proteins were inversely associated with plasma miR-144-5p levels at baseline. In addition, decreases in these proteins were associated with increases in miR-144-5p after treatment. The findings were similar after stratification by use of medications. The associations between the proteins and depression at baseline, measured by MADRS-S, as well as the change in protein levels and treatment response were, however, less clear. These findings need to be examined in future studies.

Diagnostic center for primary care patients with nonspecific symptoms and suspected cancer: compliance to workflow and accuracy of tests and examinations.

OBJECTIVE: To evaluate compliance to workflow and accuracy of tests in Sweden's first fast-track referral pathway for patients with nonspecific symptoms and suspected cancer (SCAN). DESIGN: Prospective cohort study with consecutive inclusion of patients referred to the diagnostic center (DC). SETTING: Patients with nonspecific symptoms were examined in primary care according to a protocol including two test packages and diagnostic imaging. If symptoms were not explained, patients were referred to the DC and a DC-test package was taken. At the DC, further investigations resulted in diagnosis/no diagnosis. SUBJECTS: A total of 290 patients, median age 69 years (interquartile range [IQR] 59-76), 48% men, participated. A total of 64 (22%) were diagnosed with cancer, 186 (64%) with non-malignant disease and 40 (14%) had no new disease. MAIN OUTCOME MEASURE: Compliance was estimated by percentage of compulsory tests taken. Test accuracy was assessed by likelihood ratios (LRs) regarding cancer. RESULTS: A total of 23 (8%) patients had taken both primary care packages, whereas 150 (52%) patients went through entire diagnostic imaging. Abnormal pulmonary X-ray, peak expiratory flow (PEF) and calcium had the highest LRs in primary care (3.5; 3.2; 2.7). A total of 105 (36%) took the complete DC-package, of which bilirubin and cytomegalovirus had the highest LRs (11.5; 10.9). The median number (IQR) of abnormal primary care tests was 5 (3-6) for cancer, 3 (2-6) for other diagnoses and 1 (0-3) for no diagnosis. CONCLUSIONS: Compliance to test packages in primary care was low, which warrants review of the workflow. Few single tests had high accuracy regarding cancer, but the number of abnormal tests can provide guidance in complicated investigations of suspected malignancies.KEY POINTSFast-track referral pathways for patients with nonspecific serious symptoms have been implemented in several countries and are part of the national cancer strategy in all of Scandinavia.Compliance with compulsory tests in primary care was modest in this study; 8% of the patients had taken the entire compulsory test packages.Few single compulsory tests had high accuracy regarding subsequent cancer, which warrants a review of tests and examinations. However, patients diagnosed with cancer had a higher number of abnormal test results compared to the other groups.

Diagnostic spectrum and time intervals in Sweden's first diagnostic center for patients with nonspecific symptoms of cancer.

BACKGROUND: Fast-track referral is an increasingly used method for diagnostic evaluation of patients suspected of having cancer. This approach is challenging and not used as often for patients with only nonspecific symptoms. In order to expedite the diagnostics for these patients, we established Sweden's first Diagnostic Center (DC) focusing on outcomes related to diagnoses and diagnostic time intervals. MATERIAL AND METHODS: The study was designed as a prospective cohort study. Patients aged ≥18 years who presented in primary care with nonspecific symptoms of a serious disease were eligible for referral to the DC after having completed an initial investigation. Acceptable diagnostic time intervals were defined to be a maximum of 15 days in primary care and 22 days at the DC. Diagnostic outcome, length of diagnostic time intervals and patient satisfaction were evaluated. RESULTS: A total of 290 patients were included in the study. Cancer was diagnosed in 22.1%, other diseases in 64.1%, and no diagnosis was identified in 13.8% of these patients. Patients diagnosed with cancer were older, had shorter patient interval (time from first symptom to help-seeking), shorter DC-interval (time from referral decision in primary care to diagnosis) and showed a greater number of symptoms compared to patients with no diagnosis. The median primary care interval was 21 days and the median DC interval was 11 days. Few symptoms, no diagnosis, female sex, longer patient interval, and incomplete investigations were associated with prolonged diagnostic time intervals. Patient satisfaction was high; 86% of patients reported a positive degree of satisfaction with the diagnostic procedures. CONCLUSIONS: We demonstrated that the DC concept is feasible with a diagnosis reached in 86.2% of the patients in addition to favorable diagnostic time intervals at the DC and a high degree of patient satisfaction.

Risk prediction of recurrent venous thromboembolism: a multiple genetic risk model.

A single genetic biomarker is unable to accurately predict the risk for venous thromboembolism (VTE) recurrence. We aimed to: (a) develop a multiple single nucleotide polymorphisms (SNPs) model to predict the risk of VTE recurrence and (b) validate a previously described genetic risk score (GRS) and compare its performance with the model developed in this study. Twenty-two SNPs, including established and putative SNPs associated with VTE risk, were genotyped in the Malmö thrombophilia study cohort (MATS; n = 1465, follow-up ~ 10 years) by using TaqMan PCR. Out of 22-SNPs, 12 had an association with the risk of VTE recurrence and were included for calculating GRSs. The risk of VTE recurrence was calculated by stratifying patients according to number of risk alleles. In 12-SNP GRS, patients with ≥ 7 risk alleles were associated with higher risk of VTE recurrence compared to patients having ≤ 6 risk alleles. In a simplified model (8-SNP GRS), the discriminative power of 8-SNP GRS was similar to that of 12-SNP GRS based on post-test probabilities (PP). Furthermore, 8-SNP GRS further improved the risk prediction of VTE recurrence in unprovoked VTE and male patients (PP% = 15.4 vs 8.3, 17.1 vs 7.2 and 19.0 vs 7.1 for high risk groups vs low risk groups in whole population, males and unprovoked VTE patients respectively). In addition, we also validated previously described 5-SNP GRS in our cohort and found that the 8-SNP GRS performed better than the 5-SNP GRS in terms of higher PP. Our results show that a multiple SNP GRS consisting of 8-SNPs may be an effective model for prediction of VTE recurrence, particularly in unprovoked VTE and male patients.

Macrophage Migration Inhibitory Factor and microRNA-451a in Response to Mindfulness-based Therapy or Treatment as Usual in Patients with Depression, Anxiety, or Stress and Adjustment Disorders.

Background: Macrophage migration inhibitory factor is a proinflammatory cytokine that has been associated with various psychiatric disorders. MicroRNA-451a can directly target macrophage migration inhibitory factor and downregulate its expression in cells. However, the role of macrophage migration inhibitory factor and microRNA-451a in psychiatric patients treated with psychotherapeutic interventions is unknown. In this study, our aim was to investigate levels of macrophage migration inhibitory factor and its regulating microRNA-451a in patients with depression, anxiety, or stress and adjustment disorders who underwent mindfulness-based therapy or treatment as usual. Methods: A total of 168 patients with psychiatric disorders were included from a randomized controlled trial that compared mindfulness-based therapy with treatment as usual. Plasma levels of macrophage migration inhibitory factor and microRNA-451a were measured at baseline and after the 8-week follow-up using Luminex assay and qPCR. Results: Macrophage migration inhibitory factor levels decreased significantly in patients posttreatment, whereas microRNA-451a levels showed a nonsignificant change. Macrophage migration inhibitory factor levels were inversely associated with microRNA-451a expression levels at baseline (ß=-0.04, P=.008). The change in macrophage migration inhibitory factor levels (follow-up levels minus baseline levels) was associated with the change in microRNA-451a (follow-up levels minus baseline levels) (ß=-0.06, P < .0001). The change in either macrophage migration inhibitory factor or microRNA-451a was not associated with improvement in psychiatric symptoms. Conclusion: We demonstrate that the levels of macrophage migration inhibitory factor decreased after psychotherapeutic interventions in patients with psychiatric disorders. However, this reduction was not associated with an improvement in psychiatric symptoms in response to the treatment. We also found an association between macrophage migration inhibitory factor and its regulating microRNA. However, this association needs to be further examined in future studies.

Leukocyte telomere length and depression, anxiety and stress and adjustment disorders in primary health care patients.

BACKGROUND: The primary aim was to examine possible differences in telomere length between primary health care patients, with depression, anxiety or stress and adjustment disorders, and healthy controls. The second aim was to examine the association between telomere length and baseline characteristics in the patients. The third aim was to examine the potential effects of the 8-week treatments (mindfulness-based group therapy or treatment as usual, i.e. mostly cognitive-based therapy) on telomere length, and to examine whether there was a difference in the potential effect on telomere length between the two groups. METHODS: A total of 501 individuals including 181 patients (aged 20-64 years), with depression, anxiety and stress and adjustment disorders, and 320 healthy controls (aged 19-70 years) were recruited in the study. Patient data were collected from a randomized controlled trial comparing mindfulness-based group therapy with treatment as usual. We isolated genomic DNA from blood samples, collected at baseline and after the 8-week follow-up. Telomere length was measured by quantitative real-time (qRT)-PCR. RESULTS: Telomere length was significantly shorter in the patients (mean = 0.77 ± 0.12,), compared to the controls (mean = 0.81 ± 0.14) (p = 0.006). The difference in telomere length remained significant after controlling for age and sex. Old age, male sex and being overweight were associated with shorter telomere length. There was no significant difference in telomere length between baseline and at the 8-week follow-up in any of the treatment groups and no difference between the two groups. CONCLUSION: Our findings confirm that telomere length, as compared with healthy controls, is shortened in patients with depression, anxiety and stress and adjustment disorders. In both groups (mindfulness-based group therapy or treatment as usual), the telomere length remained unchanged after the 8-week treatment/follow-up and there was no difference between the two groups. TRIAL REGISTRATION: (ClinicalTrials.gov ID: NCT01476371 ) Registered November 11, 2011.

Epidemiology of Familial Aggregation of Venous Thromboembolism.

Familial aggregation (clustering) of venous thromboembolism (VTE) is the clustering of VTE within a family. Though several genes, such as antithrombin, protein C, protein S, factor V, and prothrombin are associated with the familial clustering of VTE, these loci only partially explain the familial aggregation of VTE. The epidemiology of the familial aggregation of VTE exhibits typical characteristics of complex traits. The family history of VTE in first-degree relatives is associated with a two to three times increased familial relative risk (FRR). The FRR of VTE is higher in younger individuals, increases with a number of affected relatives, decreases as the familial relationship becomes more distant, increases with severity (unprovoked), and exhibits slightly stronger male transmission (Carter effect). High FRR is observed in individuals with two or more affected siblings (FRR > 50). Because familial aggregation represents the sum of shared family environmental and genetic factors, one should not assume that evidence of familial aggregation implies genetic effects. However, studies in twins, extended families, adoptees, and spouses indicate a weak involvement of shared environmental factors to the familial aggregation of VTE. Moreover, familial aggregation of VTE fulfills the Hill's criteria for causation. In conclusion, familial aggregation of VTE signals a clinically relevant inherent predisposition for VTE.

Mindfulness group therapy in primary care patients with depression, anxiety and stress and adjustment disorders: randomised controlled trial.

BACKGROUND: Individual-based cognitive-behavioural therapy (CBT) is in short supply and expensive. AIMS: The aim of this randomised controlled trial (RCT) was to compare mindfulness-based group therapy with treatment as usual (primarily individual-based CBT) in primary care patients with depressive, anxiety or stress and adjustment disorders. METHOD: This 8-week RCT (ClinicalTrials.gov ID: NCT01476371) was conducted during spring 2012 at 16 general practices in Southern Sweden. Eligible patients (aged 20-64 years) scored ≥10 on the Patient Health Questionnaire-9, ≥7 on the Hospital Anxiety and Depression Scale or 13-34 on the Montgomery-Åsberg Depression Rating Scale (self-rated version). The power calculations were based on non-inferiority. In total, 215 patients were randomised. Ordinal mixed models were used for the analysis. RESULTS: For all scales and in both groups, the scores decreased significantly. There were no significant differences between the mindfulness and control groups. CONCLUSIONS: Mindfulness-based group therapy was non-inferior to treatment as usual for patients with depressive, anxiety or stress and adjustment disorders.

Is acculturation associated with physical activity among female immigrants in Sweden?

BACKGROUND: Immigrant women in Sweden have lower levels of leisure time physical activity (LTPA) than Swedish-born women. The reasons are unclear, although acculturation has been suggested to play a role. METHODS: We used a cross-sectional study design to investigate the association between LTPA and two indicators of acculturation: (i) language proficiency (ability to understand news reports on the radio and television) and (ii) age at the time of migration, and if there existed a modifying effect on these hypothesized associations. The study sample consisted of 1651 women, aged 18-65, living in Sweden and born in Finland, Chile or Iraq. A postal questionnaire (translated into the women's native language) was used to collect the variables. The International Physical Activity Questionnaire was used to assess LTPA. Data were collected in 2002-05 and analyzed in 2009-10. A partial-proportional odds model was used for the analysis. RESULTS: Increased language proficiency was associated with increased LTPA [odds ratio (OR) = 2.31, 95% confidence interval (CI) = 1.57-3.41]. Country of birth modified the association. Furthermore, younger age at migration was associated with increased LTPA (OR = 1.44, 95% CI = 1.01-2.03). CONCLUSIONS: Increased language proficiency has the potential to be an important health-promoting factor among immigrant women.

Preterm birth and unintentional injuries: risks to children, adolescents and young adults show no consistent pattern.

AIM: Preterm birth is associated with a number of physical and mental health issues. The aim of this study was to find out whether there was also any association between individuals born preterm in Sweden between 1984 and 2006 and the risk of unintentional injuries during childhood, adolescence and young adulthood. METHODS: The study followed 2 297 134 individuals, including 5.9% born preterm, from 1985 to 2007 for unintentional injuries leading to hospitalization or death (n = 244 021). The males and females were divided into four age groups: 1-5 years, 6-12 years, 13-18 years and 19-23 years. Hazard ratios were calculated for falls, transport injuries and other injuries. RESULTS: After adjusting for a comprehensive set of covariates, some of the preterm subgroups demonstrated slightly increased risks of unintentional injuries, while others showed slightly decreased risks. However, most of the estimates were borderline or non-significant in both males and females. In addition, the absolute risk differences between individuals born preterm and full term were small. CONCLUSION: Despite the association between preterm birth and a variety of physical and mental health consequences, this study shows that there is no consistent risk pattern between preterm birth and unintentional injuries in childhood, adolescence and young adulthood.

Role of mitochondrial DNA copy number in incident cardiovascular diseases and the association between cardiovascular disease and type 2 diabetes: A follow-up study on middle-aged women.

BACKGROUND AND AIMS: Mitochondrial DNA copy number (mtDNA-CN) is a surrogate biomarker of mitochondrial dysfunction and is associated with type 2 diabetes (T2D) and cardiovascular disease (CVD). However, despite being associated with both CVD and T2D, it is not known what role mtDNA-CN has in the association between T2D and CVD. Our aims were to investigate whether, (1) baseline mtDNA-CN is associated with CVD incidence and (2) mtDNA-CN has a role as a mediator between T2D and CVD. METHOD: We quantified absolute mtDNA-CN by droplet digital PCR method in a population-based follow-up study of middle aged (52-65 years) women (n = 3062). The median follow-up period was 17 years. RESULTS: Our results show that low baseline levels of mtDNA-CN (<111 copies/µL) were associated with an increased risk of CVD (HR = 1.32, 95% CI = 1.08; 1.63) as well as with specific CVDs: coronary heart disease (HR = 1.28, 95% CI = 0.99; 1.66), stroke (HR = 1.26, 95% CI = 0.87; 1.84) and abdominal aortic aneurysm (HR = 2.61, 95% CI = 1.03; 6.62). The associations decreased but persisted even after adjustment for potential confounders. Furthermore, our results show that the total effect of T2D on future risk of CVD was reduced after controlling for mtDNA-CN and the proportion mediated by mtDNA-CN was estimated to be 4.9%. CONCLUSIONS: Lower baseline mtDNA-CN is associated with incident CVD and may have a mediating effect on the association between T2D and CVD; however, this novel observation needs to be confirmed in future studies.

Baseline mitochondrial DNA copy number and heart failure incidence and its role in overall and heart failure mortality in middle-aged women.

Heart failure (HF) is a leading cause of death in both men and women. However, risk factors seem to differ for men and women and significant gaps in sex-specific knowledge exist. Mitochondria are critical for cardiomyocytes and in this study, we investigated the role of baseline mitochondrial DNA copy number (mtDNA-CN) in HF incidence in middle-aged women and its possible role in the association between myocardial infarction (MI) and HF. Finally, we also investigated whether baseline mtDNA-CN was associated with overall and HF mortality. Baseline levels of mtDNA-CN were quantified by droplet digital PCR in a population-based follow-up study of middle-aged (50-59 years) Swedish women (n = 2,508). The median follow-up period was 17 years. Levels of mtDNA-CN were associated with age, BMI, alcohol, smoking, education, physical activity and lipid biomarkers. Multivariable Cox regression analysis adjusted for potential confounders showed that each standard deviation decrease of baseline mtDNA-CN was associated with higher incidence of HF (HR = 1.34; 95% CI=1.11-1.63). Similar results were obtained when mtDNA-CN levels were categorized into quartiles with lowest vs. highest quartile showing the highest risk of HF incidence (HR = 2.04 95% CI=1.14; 3.63). We could not detect any role of mtDNA-CN in the association between MI and HF incidence. Lower baseline mtDNA-CN levels were associated with both overall (HR = 1.27; 95% CI=1.10-1.46) and HF mortality (HR = 1.93; 95% CI=1.04-3.60); however, in multivariable analysis adjusted for potential confounders, the higher risks of HF mortality were no longer significant (HR=1.57; 95% CI=0.85-2.90). In conclusion, low baseline mtDNA-CN is an easily quantifiable molecular risk factor for HF incidence and may be a risk factor for overall and HF-related mortality.

Associations between perceived stress and health outcomes in adolescents.

BACKGROUND: Adolescents are reporting increasing symptoms of anxiety, depression and somatization and an increase in perceived stress is a plausible explanation. The first aim of this study was to examine the occurrence of perceived stress and health outcomes in adolescents, and to evaluate if there are any sex differences. The second aim was to investigate if there is an association between perceived stress and the health outcomes and, if so, possible gender differences in this association. The third aim was to compare samples of adolescent girls and boys from two different European countries to enhance the generalizability of potential findings. METHODS: The sample included 636 students from Sweden and Bulgaria, aged 15-16, 164 (58% males, 41% females, 1% not specified) from Sweden and 472 (71% males, 28% females, 1% not specified) from Bulgaria. Perceived stress and health outcomes were measured by the 14-item "Perceived Stress Scale" (PSS-14), and a shorter version of the questionnaire "Children and Young People in Skåne" (Folkhälsoenkäten, FHE), respectively. T-test and Chi2 and/or Fisher's exact test was used to compare results between boys and girls from the PSS-14 and health outcomes. The association between PSS and the health outcomes was assessed using Spearman's rank correlation and comparisons between boys and girls were calculated using linear regression. RESULTS: There were significant associations between perceived stress and psychiatric symptoms in all groups. Adolescent girls in both Sweden and Bulgaria consistently reported higher levels of perceived stress and more psychiatric and somatic symptoms than the boys. CONCLUSIONS: Evaluating methods for lessening the perception of stress, and their clinical presentation, should be considered in order to reduce the occurrence of psychiatric symptoms in adolescents.

Role of multiple risk factors in mental disorders diagnosed in middle-aged women: A population-based follow-up study.

The aims of the study were 1). to investigate the association between the potential risk factors including socio-demographic, lifestyle and DNA methylation and mental disorders in middle-aged women from a large population-based follow-up study, and 2). to estimate the risk score by combining the potential risk factors to examine the mental disorder's incidence. A total of 6461 women, aged 50-65 years, were included in the study. After a median follow-up of 17 years, 2026 (31%) women were diagnosed with mental disorders. The association between these factors and the risk of mental disorders was analyzed using Cox regression models. Harrell's concordance index (C-index) was used to quantify models' predictive performance for future mental disorders. Blood-based global DNA methylation was assessed by an enzyme-linked immunosorbent assay. We found that smoking (HR = 1.38, 95% CI: 1.24-1.54), less physical activity (HR = 1.33, 95% CI: 1.10-1.60), being single (HR = 1.16, 95% CI: 1.04-1.29) and unemployment (HR = 1.50, 95% CI: 1.33-1.70) were independently associated with an increased risk of overall mental disorders. Risk score models combining all these observed factors showed an increased risk, but the prediction ability was low, except for the risk of alcohol use disorders (AUD) and drug use disorders (DUD) (C-index = 0.8). Finally, women who developed MDD/anxiety during follow-up had significantly higher global DNA methylation at baseline than women who did not develop MDD/anxiety (p = 0.005). In conclusion, our results indicate that the studied risk factors were associated with mental disorders in a type-specific manner. The predictive model showed that smoking, alcohol consumption, education and physical activity may predict future AUD/DUD. Global DNA methylation may be a potential risk factor for MDD/anxiety incidence.

The association of mitochondrial DNA copy number with incident mental disorders in women: A population-based follow-up study.

BACKGROUND: Available evidence suggests that mitochondrial DNA copy number (mtDNA-CN) may differ among patients with mental disorders compared to the general population. However, whether mtDNA-CN is independently associated with the subsequent incidence of mental disorders remains unclear. MATERIAL AND METHODS: We used droplet digital PCR to measure the absolute mtDNA-CN in DNA samples obtained from a population-based follow-up study, which included a total of 2354 middle-aged women (52-63 years) who were free of mental disorders at baseline. After 17 years (median) of follow-up, 727 participants were diagnosed with mental disorders. RESULTS: In the univariate Cox regression, lower baseline mtDNA-CN (mtDNA-CN < 117) was associated with a higher risk of mental disorders (HR = 1.16, p = 0.047). In addition, smoking, marital status and sleeping quality were associated with both mtDNA-CN and mental disorders. After adjusting for these variables, the association between mtDNA-CN and mental disorders decreased and became non-significant (HR = 1.07, p = 0.36). Stratification of data according to the subtype of mental disorders, showed that low mtDNA-CN was associated with a higher risk of alcohol or drug use disorders (HR = 1.82, p = 0.045 after adjusting). CONCLUSION: In the present study, we could not find any independent association between mtDNA-CN blood and the most common mental disorders in a population-based follow-up study of Swedish women, except for alcohol and drug use disorders. The use of blood mtDNA-CN as a biomarker of mental disorders, in addition to other risk factors, needs to be further examined in future studies.

Association of mitochondrial DNA copy number with prevalent and incident type 2 diabetes in women: A population-based follow-up study.

Mitochondrial dysfunction is an important factor of the aging process and may play a key role in various diseases. Mitochondrial DNA copy number (mtDNA-CN) is an indirect measure of mitochondrial dysfunction and is associated with type 2 diabetes mellitus (T2DM); however, whether mtDNA-CN can predict the risk of developing T2DM is not well-known. We quantified absolute mtDNA-CN in both prevalent and incident T2DM by well-optimized droplet digital PCR (ddPCR) method in a population-based follow-up study of middle aged (50-59 years) Swedish women (n = 2387). The median follow-up period was 17 years. Compared to those who were free of T2DM, mtDNA-CN was significantly lower in both prevalent T2DM and in women who developed T2DM during the follow-up period. Mitochondrial DNA-copy number was also associated with glucose intolerance, systolic blood pressure, smoking status and education. In multivariable Cox regression analysis, lower baseline mtDNA-CN was prospectively associated with a higher risk of T2DM, independent of age, BMI, education, smoking status and physical activity. Moreover, interaction term analysis showed that smoking increased the effect of low mtDNA-CN at baseline on the risk of incident T2DM. Mitochondrial DNA-copy number may be a risk factor of T2DM in women. The clinical usefulness of mtDNA-CN to predict the future risk of T2DM warrants further investigation.

Effect of mindfulness on physical activity in primary healthcare patients: a randomised controlled trial pilot study.

Increased physical activity can have health benefits among inactive individuals. In Sweden, the healthcare system uses physical activity on prescription (PAP) to motivate patients to increase their physical activity level. Mindfulness may further heighten the internal motivation to engage in physical activity. However, previous research has not demonstrated clear evidence of such an association. AIM: Examine the feasibility of the study design as a preparation for a full-scale study, and examine the differences, between three interventions, in change over time in physical activity levels and in related variables. METHOD: Comparison between three different interventions in an ordinary primary health care setting: PAP, mindfulness, and a combination of PAP and mindfulness. Physical activity was measured with self-report and ACTi Graph GT1X activity monitor. Statistical analysis was performed with a mixed-effect model to account for repeated observations and estimate differences both within groups and between groups at 3- and 6-months follow-up. RESULTS: Between September 2016 and December 2018, a total of 88 participants were randomised into three groups. The total dropout rate was 20.4%, the attendance rate to the mindfulness courses (52% > 6 times) and the web-based mindfulness training (8% > 800 min) was low according to the stated feasibility criteria. Eleven participants were excluded from analysis due to low activity monitor wear time. Neither the activity monitor data nor self-reported physical activity showed any significant differences between the groups. CONCLUSION: The study design needs adjustment for the mindfulness intervention design before a fully scaled study can be conducted. A combination of PAP and mindfulness may increase physical activity and self-rated health more than PAP or mindfulness alone. TRIAL REGISTRATION: ClinicalTrials.gov, registration number NCT02869854 . Regional Ethical Review Board in Lund registration number 2016/404.

Time Intervals Under the Lens at Sweden's First Diagnostic Center for Primary Care Patients With Nonspecific Symptoms of Cancer. A Comparison With Matched Control Patients.

INTRODUCTION: Fast-track referral pathways for patients with nonspecific, serious symptoms have been implemented in several countries. Our objective was to analyze time intervals in the diagnostic routes of patients diagnosed with cancer at Sweden's first Diagnostic Center (DC) for nonspecific symptoms and compare with time intervals of matched control patients. METHODS: Adult patients with nonspecific symptoms that could not be explained by an initial investigation in primary care were eligible for referral to the DC. Patients diagnosed with cancer were matched with patients at another hospital within the same healthcare organization. We aimed for two control patients per DC-patient and matched on tumor type, age and sex. Five time intervals were compared: 1) patient interval (first symptom-primary care contact), 2) primary care interval (first visit-referral to the DC/secondary care), 3) diagnostic interval (first visit-cancer diagnosis), 4) information interval (cancer diagnosis-patient informed) and 5) treatment interval (cancer diagnosis-treatment start). Comparisons between groups and matched cohort analyses were made. RESULTS: Sixty-four patients (22.1%) were diagnosed with cancer at the DC, of which eight were not matchable. Forty-two patients were matched with two controls and 14 were matched with one control. There were no significant differences in patient-, primary care-, or diagnostic intervals between the groups. The information interval was shorter at the DC compared to the control group (difference between matched pairs 7 days, p = 0.001) and the treatment interval was also shorter at the DC with significant differences in the matched analysis (difference between matched pairs 13 days, p = 0.049). The findings remained the same in four sensitivity analyses, made to compensate for differences between the groups. CONCLUSIONS: Up to diagnosis, we could not detect significant differences in time intervals between the DC and the control group. However, the shorter information and treatment intervals at the DC should be advantageous for these patients who will get timely access to treatment or palliative care. Due to limitations regarding comparability between the groups, the results must be interpreted with caution and further research is warranted. TRIAL REGISTRATION: ClinicalTrials.gov-ID: NCT01709539. Registration-date: October 18, 2012.