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  • 1.
    Ramadona, Aditya Lia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa. Center for Environmental Studies, Universitas Gadjah Mada, Yogyakarta, Indonesia.
    Tozan, Yesim
    Lazuardi, Lutfan
    Rocklöv, Joacim
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    A combination of incidence data and mobility proxies from social media predicts the intra-urban spread of dengue in Yogyakarta, Indonesia2019Ingår i: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 13, nr 4, artikel-id e0007298Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Only a few studies have investigated the potential of using geotagged social media data for predicting the patterns of spatio-temporal spread of vector-borne diseases. We herein demonstrated the role of human mobility in the intra-urban spread of dengue by weighting local incidence data with geo-tagged Twitter data as a proxy for human mobility across 45 neighborhoods in Yogyakarta city, Indonesia. To estimate the dengue virus importation pressure in each study neighborhood monthly, we developed an algorithm to estimate a dynamic mobility-weighted incidence index (MI), which quantifies the level of exposure to virus importation in any given neighborhood. Using a Bayesian spatio-temporal regression model, we estimated the coefficients and predictiveness of the MI index for lags up to 6 months. Specifically, we used a Poisson regression model with an unstructured spatial covariance matrix. We compared the predictability of the MI index to that of the dengue incidence rate over the preceding months in the same neighborhood (autocorrelation) and that of the mobility information alone. We based our estimates on a volume of 1·302·405 geotagged tweets (from 118·114 unique users) and monthly dengue incidence data for the 45 study neighborhoods in Yogyakarta city over the period from August 2016 to June 2018. The MI index, as a standalone variable, had the highest explanatory power for predicting dengue transmission risk in the study neighborhoods, with the greatest predictive ability at a 3-months lead time. The MI index was a better predictor of the dengue risk in a neighborhood than the recent transmission patterns in the same neighborhood, or just the mobility patterns between neighborhoods. Our results suggest that human mobility is an important driver of the spread of dengue within cities when combined with information on local circulation of the dengue virus. The geotagged Twitter data can provide important information on human mobility patterns to improve our understanding of the direction and the risk of spread of diseases, such as dengue. The proposed MI index together with traditional data sources can provide useful information for the development of more accurate and efficient early warning and response systems.

  • 2. Karlsson, Anna
    et al.
    Cirenajwis, Helena
    Ericson-Lindquist, Kajsa
    Brunnström, Hans
    Reuterswärd, Christel
    Jönsson, Mats
    Ortiz-Villalon, Cristian
    Hussein, Aziz
    Bergman, Bengt
    Vikström, Anders
    Monsef, Nastaran
    Branden, Eva
    Koyi, Hirsh
    de Petris, Luigi
    Micke, Patrick
    Patthey, Annika
    Behndig, Annelie F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Johansson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Planck, Maria
    Staaf, Johan
    A combined gene expression tool for parallel histological prediction and gene fusion detection in non-small cell lung cancer2019Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikel-id 5207Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Accurate histological classification and identification of fusion genes represent two cornerstones of clinical diagnostics in non-small cell lung cancer (NSCLC). Here, we present a NanoString gene expression platform and a novel platform-independent, single sample predictor (SSP) of NSCLC histology for combined, simultaneous, histological classification and fusion gene detection in minimal formalin fixed paraffin embedded (FFPE) tissue. The SSP was developed in 68 NSCLC tumors of adenocarcinoma (AC), squamous cell carcinoma (SqCC) and large-cell neuroendocrine carcinoma (LCNEC) histology, based on NanoString expression of 11 (CHGA, SYP, CD56, SFTPG, NAPSA, TTF-1, TP73L, KRT6A, KRT5, KRT40, KRT16) relevant genes for IHC-based NSCLC histology classification. The SSP was combined with a gene fusion detection module (analyzing ALK, RET, ROS1, MET, NRG1, and NTRK1) into a multicomponent NanoString assay. The histological SSP was validated in six cohorts varying in size (n = 11-199), tissue origin (early or advanced disease), histological composition (including undifferentiated cancer), and gene expression platform. Fusion gene detection revealed five EML4-ALK fusions, four KIF5B-RET fusions, two CD74-NRG1 fusion and three MET exon 14 skipping events among 131 tested cases. The histological SSP was successfully trained and tested in the development cohort (mean AUC = 0.96 in iterated test sets). The SSP proved successful in predicting histology of NSCLC tumors of well-defined subgroups and difficult undifferentiated morphology irrespective of gene expression data platform. Discrepancies between gene expression prediction and histologic diagnosis included cases with mixed histologies, true large cell carcinomas, or poorly differentiated adenocarcinomas with mucin expression. In summary, we present a proof-of-concept multicomponent assay for parallel histological classification and multiplexed fusion gene detection in archival tissue, including a novel platform-independent histological SSP classifier. The assay and SSP could serve as a promising complement in the routine evaluation of diagnostic lung cancer biopsies.

  • 3.
    Ott, Michael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Werneke, Ursula
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Sunderby Research Unit.
    A Mixed Presentation of Serotonin Syndrome Versus Neuroleptic Malignant Syndrome in a 12-Year-Old Boy2019Ingår i: Pediatric emergency care, ISSN 0749-5161, E-ISSN 1535-1815, Vol. 35, nr 5, s. E98-E98Artikel i tidskrift (Refereegranskat)
  • 4.
    Olstrup, Henrik
    et al.
    Atmospheric Science Unit, Department of Environmental Science and Analytical Chemistry, Stockholm University, 11418 Stockholm, Sweden. .
    Johansson, Christer
    Atmospheric Science Unit, Department of Environmental Science and Analytical Chemistry, Stockholm University, 11418 Stockholm, Sweden. Environment and Health Administration, SLB, Box 8136, 104 20 Stockholm, Sweden..
    Forsberg, Bertil
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Tornevi, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Ekebom, Agneta
    Swedish Museum of Natural History, 114 18 Stockholm, Sweden..
    Meister, Kadri
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    A Multi-Pollutant Air Quality Health Index (AQHI) Based on Short-Term Respiratory Effects in Stockholm, Sweden2019Ingår i: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 16, nr 1, artikel-id 105Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this study, an Air Quality Health Index (AQHI) for Stockholm is introduced as a tool to capture the combined effects associated with multi-pollutant exposure. Public information regarding the expected health risks associated with current or forecasted concentrations of pollutants and pollen can be very useful for sensitive persons when planning their outdoor activities. For interventions, it can also be important to know the contribution from pollen and the specific air pollutants, judged to cause the risk. The AQHI is based on an epidemiological analysis of asthma emergency department visits (AEDV) and urban background concentrations of NOx, O₃, PM10 and birch pollen in Stockholm during 2001⁻2005. This analysis showed per 10 µg·m⁻3 increase in the mean of same day and yesterday an increase in AEDV of 0.5% (95% CI: -1.2⁻2.2), 0.3% (95% CI: -1.4⁻2.0) and 2.5% (95% CI: 0.3⁻4.8) for NOx, O₃ and PM10, respectively. For birch pollen, the AEDV increased with 0.26% (95% CI: 0.18⁻0.34) for 10 pollen grains·m⁻3. In comparison with the coefficients in a meta-analysis, the mean values of the coefficients obtained in Stockholm are smaller. The mean value of the risk increase associated with PM10 is somewhat smaller than the mean value of the meta-coefficient, while for O₃, it is less than one fifth of the meta-coefficient. We have not found any meta-coefficient using NOx as an indicator of AEDV, but compared to the mean value associated with NO₂, our value of NOx is less than half as large. The AQHI is expressed as the predicted percentage increase in AEDV without any threshold level. When comparing the relative contribution of each pollutant to the total AQHI, based on monthly averages concentrations during the period 2015⁻2017, there is a tangible pattern. The AQHI increase associated with NOx exhibits a relatively even distribution throughout the year, but with a clear decrease during the summer months due to less traffic. O₃ contributes to an increase in AQHI during the spring. For PM10, there is a significant increase during early spring associated with increased suspension of road dust. For birch pollen, there is a remarkable peak during the late spring and early summer during the flowering period. Based on monthly averages, the total AQHI during 2015⁻2017 varies between 4 and 9%, but with a peak value of almost 16% during the birch pollen season in the spring 2016. Based on daily mean values, the most important risk contribution during the study period is from PM10 with 3.1%, followed by O₃ with 2.0%.

  • 5. Farias, Fabiana H. G.
    et al.
    Dahlqvist, Johanna
    Kozyrev, Sergey V.
    Leonard, Dag
    Wilbe, Maria
    Abramov, Sergei N.
    Alexsson, Andrei
    Pielberg, Gerli R.
    Hansson-Hamlin, Helene
    Andersson, Goran
    Tandre, Karolina
    Bengtsson, Anders A.
    Sjöwall, Christopher
    Svenungsson, Elisabet
    Gunnarsson, Iva
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Syvanen, Ann-Christine
    Sandling, Johanna K.
    Eloranta, Maija-Leena
    Rönnblom, Lars
    Lindblad-Toh, Kerstin
    A rare regulatory variant in the MEF2D gene affects gene regulation and splicing and is associated with a SLE sub-phenotype in Swedish cohorts2019Ingår i: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 27, nr 3, s. 432-441Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Systemic lupus erythematosus (SLE) is an autoimmune disorder with heterogeneous clinical presentation and complex etiology involving the interplay between genetic, epigenetic, environmental and hormonal factors. Many common SNPs identified by genome wide-association studies (GWAS) explain only a small part of the disease heritability suggesting the contribution from rare genetic variants, undetectable in GWAS, and complex epistatic interactions. Using targeted resequencing of coding and conserved regulatory regions within and around 215 candidate genes selected on the basis of their known role in autoimmunity and genes associated with canine immune-mediated diseases, we identified a rare regulatory variant rs200395694:G > T located in intron 4 of the MEF2D gene encoding the myocyte-specific enhancer factor 2D transcription factor and associated with SLE in Swedish cohorts (504 SLE patients and 839 healthy controls, p = 0 .014 , CI = 1.1-10). Fisher's exact test revealed an association between the genetic variant and a triad of disease manifestations including Raynaud, anti-Ul-ribonucleoprotein (anti-RNP), and anti-Smith (anti-Sm) antibodies (p = 0.00037) among the patients. The DNA-binding activity of the allele was further studied by EMSA, reporter assays, and minigenes. The region has properties of an active cell-specific enhancer, differentially affected by the alleles of rs200395694:G > T. In addition, the risk allele exerts an inhibitory effect on the splicing of the alternative tissue-specific isoform, and thus may modify the target gene set regulated by this isoform. These findings emphasize the potential of dissecting traits of complex diseases and correlating them with rare risk alleles with strong biological effects.

  • 6.
    Wagenius, Cecilia M.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Norrbotten County Council, Public Health Centre, Sweden.
    San Sebastian, Miguel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Gustafsson, Per E.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Goicolea, Isabel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Access for all?: Assessing vertical and horizontal inequities in healthcare utilization among young people in northern Sweden2019Ingår i: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 47Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Previous studies in Sweden have detected socioeconomic inequities in access to healthcare services. However, there is limited information regarding access in younger populations. The aim of this study was to explore vertical and horizontal inequities in access to healthcare services in young adults in the north of Sweden.

    METHODS: The study used data from the Health on Equal Terms survey (age group 16-24 years, n = 2726) for the health and healthcare variables and from national registers for the sociodemographic characteristics. Self-rated healthcare utilization was measured as visits to general practitioners, youth clinics and nurses. Crude and multivariable binomial regression analysis, stratified by sex, was used to assess vertical equity, adjusting for sociodemographic characteristics, and horizontal equity, adjusting for need variables.

    RESULTS: Vertical inequity was detected for all three healthcare services (youth clinics, general practitioners and nurses), with variations for men and women. Horizontal inequities were also found for both men and women in relation to all three healthcare services.

    CONCLUSIONS: These findings suggest that both vertical and horizontal inequities in access exist for young people in northern Sweden and that the associations between sociodemographic characteristics and healthcare utilization are complex and need further investigation.

  • 7.
    Gaitonde, Rakhal
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Department of Humanities and Social Sciences, Indian Institute of Technology Madras, Chennai, India.
    Muraleedharan, V. R.
    San Sebastian, Miguel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Hurtig, Anna-Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Accountability in the health system of Tamil Nadu, India: exploring its multiple meanings2019Ingår i: Health Research Policy and Systems, ISSN 1478-4505, E-ISSN 1478-4505, Vol. 17, artikel-id 44Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Accountability is increasingly being demanded of public services and is a core aspect of most recent frameworks of health system strengthening. Community-based accountability is an increasingly used strategy, and wasa core aspect of India's flagship National Rural Health Mission (NRHM; 2005-2014). Research on policy implementation has called for policy analysts to go beyond the superficial articulation of a particular policy intervention to study the underlying meaning this has for policy-makers and other actors of the implementation process and to the way in which problems sought to be addressed by the policy have been identified and problematised'.

    Methods: This research, focused on state level officials and health NGO leaders, explores the meanings attached to the concept of accountability among a number of key actors during the implementation of the NRHM in the south Indian state of Tamil Nadu. The overall research was guided by an interpretive approach to policy analysis and the problematisation lens. Through in-depth interviews we draw on the interviewees' perspectives on accountability.

    Results: The research identifies three distinct perspectives on accountability among the key actors involved in the implementation of the NRHM. One perspective views accountability as the achievement of pre-set targets, the other as efficiency in achieving these targets, and the final one as a transformative process that equalises power differentials between communities and the public health system. We also present the ways in which these differences in perspectives are associated with different programme designs.

    Conclusions: This research underlines the importance of going beyond the statements of policy to exploring the underlying beliefs and perspectives in order to more comprehensively understand the dynamics of policy implementation; it further points to the impacts of these perspectives on the design of initiatives in response to the policy.

  • 8. Antoniewicz, Lukasz
    et al.
    Brynedal, Amelie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Hedman, Linnea
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Division of Nursing, Department of Health Science, Luleå University of Technology, Luleå, Sweden..
    Lundbäck, Magnus
    Bosson, Jenny A.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Acute Effects of Electronic Cigarette Inhalation on the Vasculature and the Conducting Airways2019Ingår i: Cardiovascular Toxicology, ISSN 1530-7905, E-ISSN 1559-0259Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The use of electronic cigarettes has increased exponentially since its introduction onto the global market in 2006. However, short- and long-term health effects remain largely unknown due to the novelty of this product. The present study examines the acute effects of e-cigarette aerosol inhalation, with and without nicotine, on vascular and pulmonary function in healthy volunteers. Seventeen healthy subjects inhaled electronic cigarette aerosol with and without nicotine on two separate occasions in a double-blinded crossover fashion. Blood pressure, heart rate, and arterial stiffness measured by pulse wave velocity and pulse wave analysis were assessed at baseline, and then at 0 h, 2 h, and 4 h following exposure. Dynamic spirometry and impulse oscillometry were measured following vascular assessments at these time points, as well as at 6 h following exposure. e-Cigarette aerosol with nicotine caused a significant increase in heart rate and arterial stiffness. Furthermore, e-cigarette aerosol-containing nicotine caused a sudden increase in flow resistance as measured by impulse oscillometry, indicating obstruction of the conducting airways. Both aerosols caused an increase in blood pressure. The present study indicates that inhaled e-cigarette aerosol with nicotine has an acute impact on vascular and pulmonary function. Thus, chronic usage may lead to long-term adverse health effects. Further investigation is warranted.

  • 9. Solans, Marta
    et al.
    Benavente, Yolanda
    Saez, Marc
    Agudo, Antonio
    Naudin, Sabine
    Hosnijeh, Fatemeh Saberi
    Noh, Hwayoung
    Freisling, Heinz
    Ferrari, Pietro
    Besson, Caroline
    Mahamat-Saleh, Yahya
    Boutron-Ruault, Marie-Christine
    Kühn, Tilman
    Kaaks, Rudolf
    Boeing, Heiner
    Lasheras, Cristina
    Rodríguez-Barranco, Miguel
    Amiano, Pilar
    Maria Huerta, Jose
    Barricarte, Aurelio
    Schmidt, Julie A.
    Vineis, Paolo
    Riboli, Elio
    Trichopoulou, Antonia
    Bamia, Christina
    Peppa, Eleni
    Masala, Giovanna
    Agnoli, Claudia
    Tumino, Rosario
    Sacerdote, Carlotta
    Panico, Salvatore
    Skeie, Guri
    Weiderpass, Elisabete
    Jerkeman, Mats
    Ericson, Ulrika
    Späth, Florentin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Nilsson, Lena Maria
    Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum). Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Dahm, Christina C.
    Overvad, Kim
    Bolvig, Anne Katrine
    Tjønneland, Anne
    de Sanjose, Silvia
    Buckland, Genevieve
    Vermeulen, Roel
    Nieters, Alexandra
    Casabonne, Delphine
    Adherence to the mediterranean diet and lymphoma risk in the european prospective investigation into cancer and nutrition2019Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 145, nr 1, s. 122-131Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is a growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, no prospective study has yet investigated its influence on lymphoma. We evaluated the association between adherence to the MD and risk of lymphoma and its subtypes in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The analysis included 476,160 participants, recruited from 10 European countries between 1991 and 2001. Adherence to the MD was estimated through the adapted relative MD (arMED) score excluding alcohol. Cox proportional hazards regression models were used while adjusting for potential confounders. During an average follow-up of 13.9 years, 3,136 lymphomas (135 Hodgkin lymphoma [HL], 2,606 non-HL and 395 lymphoma not otherwise specified) were identified. Overall, a 1-unit increase in the arMED score was associated with a 2% lower risk of lymphoma (95% CI: 0.97; 1.00, p-trend = 0.03) while a statistically nonsignificant inverse association between a high versus low arMED score and risk of lymphoma was observed (hazard ratio [HR]: 0.91 [95% CI 0.80; 1.03], p-trend = 0.12). Analyses by lymphoma subtype did not reveal any statistically significant associations. Albeit with small numbers of cases (N = 135), a suggestive inverse association was found for HL (HR 1-unit increase = 0.93 [95% CI: 0.86; 1.01], p-trend = 0.07). However, the study may have lacked statistical power to detect small effect sizes for lymphoma subtype. Our findings suggest that an increasing arMED score was inversely related to the risk of overall lymphoma in EPIC but not by subtypes. Further large prospective studies are warranted to confirm these findings.

  • 10.
    Larsson, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Johansson, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Wadell, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Avdelningen för fysioterapi.
    Thilen, Ulf
    Sandberg, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Avdelningen för fysioterapi.
    Adults with congenital heart disease overestimate their physical activity level2019Ingår i: IJC Heart & Vasculature, ISSN 2352-9067, Vol. 22, s. 13-17Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Physical activity reduces the risk of acquired cardiovascular disease, which is of great importance in patients with congenital heart disease (CHD). There are diverging data whether physical activity level (PAL) differs between patients with CHD and controls. Furthermore, it is unknown if PAL can be reliably assessed in patients with CHD using self-reported instruments.

    Methods: Seventy-five patients with CHD (mean age 37.5 ± 15.5 years, women n = 29 [38.7%]) and 42 age and sex matched controls completed the International Physical Activity Questionnaire (IPAQ) and carried the activity monitor Actiheart over 4 days. Time spent at ≥3 METS ≥21.4 min/day, i.e. reaching the WHO recommendation for PAL to promote health, was used as the outcome measure. Data on PAL obtained from IPAQ were compared with Actiheart.

    Results: The proportion of individuals reaching target PAL according to IPAQ was similar in patients with CHD and controls (70.7%vs.76.2%, p = 0.52) as well as between patients with simple and complex lesions. There was an overall difference between IPAQ and Actiheart in detecting recommended PAL (72.6%vs.51.3%, p b 0.001). In a subgroup analysis, this difference was also detected in patients but was borderline for controls. The negative predictive value for IPAQ in detecting insufficient PAL was higher in patients than in controls (73%vs.40%).

    Conclusions: The proportion of persons reaching sufficient PAL to promote health was similar in patients and controls. The self-reported instrument overestimated PAL in relation to objective measurements. However, with a high negative predictive value, IPAQ is a potentially useful tool for detecting patients with insufficient PAL.

  • 11.
    Larsson, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Rinnström, Daniel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Sandberg, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Högström, Gabriel
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Thilen, Ulf
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Johansson, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Aerobic capacity in adolescence is associated with time to intervention in adult men with atrial septal defects2019Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 280, s. 57-60Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Atrial septal defect (ASD) is a congenital heart lesion that often remains undiagnosed until adulthood. The reasons for this may be multifactorial. It is, however, known that closure of a hemodynamically significant ASD improves exercise capacity. This study aimed to explore whether the aerobic capacity in late adolescence is associated with time to diagnosis and intervention in adult men with late diagnosis of an atrial shunt.

    Methods: The Swedish Military Conscription Service Register contains data on exercise tests performed in late adolescence. By linking these data with the National Patient Register, 254 men with a later intervention for an ASD were identified.

    Results: Interventions were performed at a mean of 26.5 +/- 7.9 years after the initial exercise tests. The mean absolute workload among those with a later diagnosed ASD was similar to those without a later diagnosed ASD (274 +/- 51W vs. 276 +/- 52 W, p = 0.49). Men with a higher exercise capacity (>= 1 SD) had their intervention earlier (21.9 +/- 8.6 years vs. 27.5 +/- 7.4 years, p < 0.001).

    Conclusions: The aerobic exercise capacity was similar in adolescent men with later interventions for ASD compared to the reference population. Furthermore, those with high exercise capacity appeared to be diagnosed earlier. Thus, low exercise capacity may not be a feature of ASD during adolescence, but rather develop later in life as a natural progression of the disease.

  • 12. Stoner, Marie C. D.
    et al.
    Nguyen, Nadia
    Kilburn, Kelly
    Gómez-Olivé, F. Xavier
    Edwards, Jessie K.
    Selin, Amanda
    Hughes, James P.
    Agyei, Yaw
    Macphail, Catherine
    Kahn, Kathleen
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; eINDEPTH Network, Accra, Ghana.
    Pettifor, Audrey
    Age-disparate partnerships and incident HIV infection in adolescent girls and young women in rural South Africa2019Ingår i: AIDS (London), ISSN 0269-9370, E-ISSN 1473-5571, Vol. 33, nr 1, s. 83-91Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Adolescent girls and young women (AGYW) have a much higher risk of HIV infection than young men of the same age. One hypothesis for this disparity is AGYW are more likely to be in sexual partnerships with older men with HIV; however, evidence has been inconclusive.

    Design: We used longitudinal data from a randomized trial in South Africa (HPTN 068) to determined whether partner age difference is associated with incident HIV infection in AGYW.

    Methods: Age difference was examined continuously and dichotomously (≥5 years). We examined inverse probability of exposure weighted survival curves and calculated time-specific risk differences and risk ratios over 5.5 years of follow-up. We also used a marginal structural Cox model to estimate hazard ratios over the entire study period.

    Results: Risk of HIV was higher in AGYW with an age-disparate partnership versus not and the risk difference was largest at later time points. At 5.5 years, AGYW with an age-disparate partnership had a 12.6% (95% confidence interval 1.9–23.3) higher risk than AGYW with no age-disparate partnerships. The weighted hazard ratio was 1.91 (95% confidence interval 1.33–2.74), an association that remained after weighting for either transactional or condomless sex, and after examining continuous age-differences.

    Conclusion: Age-disparate partnerships increased risk of HIV infection, even after accounting for transactional sex and condomless sex. The relationship between age-disparate partnerships and HIV infection may be explained by increased exposure to infection from men in a higher HIV prevalence pool rather than differences in sexual behaviour within these partnerships.

  • 13. Pape, Kathrine
    et al.
    Svanes, Cecilie
    Malinovschi, Andrei
    Benediktsdottir, Bryndis
    Lodge, Caroline
    Janson, Christer
    Moratalla, Jesus
    Sánchez-Ramos, José Luis
    Bråbäck, Lennart
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Holm, Mathias
    Jögi, Rain
    Jacobsen Bertelsen, Randi
    Sigsgaard, Torben
    Johannessen, Ane
    Schlünssen, Vivi
    Agreement of offspring-reported parental smoking status: the RHINESSA generation study2019Ingår i: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 19, artikel-id 94Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: With increasing interest in exposure effects across generations, it is crucial to assess the validity of information given on behalf of others.

    Aims: To compare adult's report of their parent’s smoking status against parent's own report and examine predictors for discrepant answers.

    Methods: We studied 7185 offspring (18-51 years) and one of their parents, n = 5307 (27-67 years) participating in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study. Information about parent's smoking status during offspring's childhood and mother's smoking status during pregnancy was obtained by questionnaires from parents and their offspring. We calculated sensitivity, specificity and Cohen's Kappa [κ] for agreement using parent's own report as the gold standard. We performed logistic regression to examine if offspring's sex, age, educational level, asthma status, own smoking status or parental status, as well as the parent's sex and amount of smoking during childhood predicted disagreement.

    Results: The sensitivity for offspring's correct report of parent's smoking status during childhood (0-10 years) was 0.82 (95% CI 0.81–0.84), specificity was 0.95 (95% CI 0.95–0.96) and a good agreement was observed, κ = 0.79 (95% CI 0.78–0.80). Offspring's report of mothers' smoking status during pregnancy showed a lower sensitivity, 0.66 (95% CI 0.60–0.71), a slightly lower specificity, 0.92 (95% CI 0.90–0.95) and a good agreement, κ = 0.61 (95% CI 0.55–0.67). In multivariate logistic regression analysis, offspring not having children was a predictor for discrepant answers (odds ratio [OR] 2.11 [95% CI 1.21–3.69]). Low amount of parents' tobacco consumption, < 10 cigarettes/day (OR 2.72 [95% CI 1.71–4.31]) also predicted disagreement compared to ≥10 cigarettes per day, and so did offspring's reports of fathers' smoking status (OR 1.73 [95% CI 1.09–2.74]) compared to mothers' smoking status. Offspring's sex, asthma status, educational level, smoking status or age was not related to discrepant answers.

    Conclusions: Adults report their parent's smoking status during their childhood, as well as their mothers' smoking status when pregnant with them, quite accurately. In the absence of parents' direct report, offspring's reports could be valuable.

  • 14.
    Johansson, Magdalena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Johansson, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Wennberg, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Lind, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Alcohol Consumption and Risk of First-Time Venous Thromboembolism in Men and Women2019Ingår i: Thrombosis and Haemostasis, ISSN 0340-6245Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The relationship between alcohol intake and risk of venous thromboembolism (VTE) is unclear. Men and women differ in their drinking habits, which may affect a possible association.

    OBJECTIVE: This article investigates the association between alcohol consumption, alcohol dependence and VTE in the total population as well as in men and women separately.

    METHODS: We performed a prospective, population-based cohort study in northern Sweden. Study participants were 108,025 (51% women) persons aged 30 to 60 years who underwent a health examination between 1985 and 2014. We assessed alcohol consumption and defined alcohol dependence using a questionnaire. The outcome was a validated first-time VTE.

    RESULTS: The mean follow-up time was 13.9 years, and 2,054 participants had a first-time VTE. The mean alcohol consumption was 3.5 standard drinks weekly in men and 1.5 in women. Alcohol dependence was found in 10% of men and 3% of women. There was an association between alcohol consumption (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.00-1.03 per standard drink weekly) as well as alcohol dependence (HR, 1.27; 95% CI, 1.06-1.52) and VTE after adjustments. In men, the risk of VTE increased over quartiles of weekly alcohol consumption (p for trend 0.02), with a HR of 1.22 (95% CI, 1.01-1.47) for the highest quartile. Alcohol dependence was associated with VTE in men (HR, 1.30; 95% CI, 1.07-1.59). In women, there were no significant associations.

    CONCLUSION: High alcohol consumption and alcohol dependence were associated with increased risk of first-time VTE in men, but not in women.

  • 15.
    Zeng, Yingxu
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Mtintsilana, Asanda
    Goedecke, Julia H.
    Micklesfield, Lisa K.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Alterations in the metabolism of phospholipids, bile acids and branched-chain amino acids predicts development of type 2 diabetes in black South African women: a prospective cohort study2019Ingår i: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 95, s. 57-64Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: South Africa (SA) has the highest global projected increase in diabetes risk. Factors typically associated with insulin resistance and type 2 diabetes risk in Caucasians are not significant correlates in black African populations. Therefore, we aimed to identify circulating metabolite patterns that predict type 2 diabetes development in this high-risk, yet understudied SA population.

    Methods: We conducted a prospective cohort study in black SA women with normal glucose tolerance (NGT). Participants were followed for 13 years and developed (i) type 2 diabetes (n = 20, NGT-T2D), (ii) impaired glucose tolerance (IGT) (n = 27, NGT-IGT), or (iii) remained NGT (n = 28, NGT-NGT). Mass-spectrometry based metabolomics and multivariate analyses were used to elucidate metabolite patterns at baseline and at follow-up that were associated with type 2 diabetes development.

    Results: Metabolites of phospholipid, bile acid and branched-chain amino acid (BCAA) metabolism, differed significantly between the NGT-T2D and NGT-NGT groups. At baseline: the NGT-T2D group had i) a higher lysophosphatidylcholine:lysophosphatidylethanolamine ratio containing linoleic acid (LPC(C18:2):LPE(C18:2)), ii) lower proliferation-related bile acids (ursodeoxycholic- and chenodeoxycholic acid), iii) higher levels of leucine and its catabolic intermediates (ketoleucine and C5-carnitine), compared to the NGT-NGT group. At follow-up: the NGT-T2D group had i) lower LPC(C18:2) levels, ii) higher apoptosis-related bile acids (deoxycholic- and glycodeoxycholic acid), and iii) higher levels of all BCAAs and their catabolic intermediates.

    Conclusions: Changes in lysophospholipid metabolism and the bile acid pool occur during the development of type 2 diabetes in black South African women. Further, impaired leucine catabolism precedes valine and isoleucine catabolism in the development of type 2 diabetes. These metabolite patterns can be useful to identify and monitor type 2 diabetes risk >10 years prior to disease onset and provide insight into the pathophysiology of type 2 diabetes in this high risk, but under-studied population.

  • 16.
    Carlsen, Hanne Krage
    et al.
    Psykiatri Affektiva, Sahlgrenska University Hospital, 416 50 Gothenburg, Sweden. Occupational and Environmental Medicine, Gothenburg University, 40530 Gothenburg, Sweden..
    Oudin, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Occupational and Environmental Medicine, Lund University, 223 63 Lund, Sweden..
    Steingrimsson, Steinn
    Psykiatri Affektiva, Sahlgrenska University Hospital, 416 50 Gothenburg, Sweden. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden..
    Oudin Åström, Daniel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Ambient Temperature and Associations with Daily Visits to a Psychiatric Emergency Unit in Sweden2019Ingår i: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 16, nr 2, artikel-id E286Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    High or low ambient temperatures pose a risk factor for the worsening or onset of psychiatric disorders. The aim of this study was to investigate the association between ambient temperature and psychiatric emergency visits in an urban region in a temperate climate. The daily number of visits to a psychiatric emergency room (PEVs) at Sahlgrenska University Hospital, Gothenburg, Sweden and the daily mean temperature were extracted for the study period 1 July 2012 to 31 December 2017. Case-crossover analysis with distributed lag non-linear models was used to analyse the data by season. The warm season was defined as May to August and the cold season as November to February. Shorter lags periods were used for the warm season than the cold season. In the analysis, temperatures at the 95th percentile was associated with 14% (95% confidence interval (CI): 2%, 28%) increase in PEVs at lag 0⁻3 and 22% (95%CI: 6%, 40%) for lags 0⁻14 during the warm season, relative to the seasonal minimum effect temperature (MET). During the cold season temperatures at the 5th percentile were associated with 25% (95% CI: -8%, 13%) and 18% (95% CI: -30%, 98%) increase in PEVs at lags 0⁻14 and 0⁻21 respectively. We observed an increased number of PEVs at high and low temperatures; however, not to a statistically significant extent for low temperatures. Our findings are similar to what has been found for somatic diseases and in studies of other mental health outcomes in regions with more extreme climates. This merits the inclusion of individuals with psychiatric disorders in awareness planning for climate warning systems.

  • 17.
    Suhr, Ole Bernt
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Wixner, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Anan, Intissar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Lundgren, Hans-Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Wijayatunga, Priyantha
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Westermark, Per
    Ihse, Elisabet
    Amyloid fibril composition within hereditary Val30Met (p. Val50Met) transthyretin amyloidosis families2019Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, nr 2, artikel-id e0211983Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The amyloid fibril in hereditary transthyretin (TTR) Val30Met (pVal50Met) amyloid (ATTR Val30Met) amyloidosis is composed of either a mixture of full-length and TTR fragments (Type A) or of only full-length TTR (Type B). The type of amyloid fibril exerts an impact on the phenotype of the disease, and on the outcome of diagnostic procedures and therapy. The aim of the present study was to investigate if the type of amyloid fibril remains the same within ATTR Val30Met amyloidosis families. Methods: Fifteen families were identified in whom at least two first-degree relatives had their amyloid fibril composition determined. The type of ATTR was determined by Western blot in all but two patients. For these two patients a positive 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy indicated ATTR Type A. Results: In 14 of the 15 families, the same amyloid fibril composition was noted irrespective of differences in age at onset. In the one family, different ATTR fibril types was found in two brothers with similar ages at onset. Conclusions: Family predisposition appears to have an impact on amyloid fibril composition in members of the family irrespective of their age at onset of disease, but if genetically determined, the gene/genes are likely to be situated at another location than the TTR gene in the genome.

  • 18. Mathias, Kaaren
    et al.
    Kermode, Michelle
    San Sebastian, Miguel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Davar, Bhargavi
    Goicolea, Isabel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    An asymmetric burden: experiences of men and women as caregivers of people with psycho-social disabilities in rural North India2019Ingår i: Transcultural Psychiatry, ISSN 1363-4615, E-ISSN 1461-7471, Vol. 56, nr 1, s. 76-102Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Caring for a family member with a psycho-social disability can be both rewarding and burdensome. This study analyses the experiences of caregivers of people with psychosocial disabilities (PPSDs) in rural communities in North India using relational gender theory. In-depth interviews with 18 female and male caregivers of PPSDs probed the social, emotional and health impacts of their caregiving role. Nine themes were identified that were grouped under three meta-themes: intra-personal, inter-personal and institutional impacts. Under the intra-personal meta-theme, all caregivers experienced high tension, with women describing almost overwhelming stress. Women minimised their role as caregivers, and felt negative and hopeless about their futures, while men had a more positive view of the future and themselves. Embodied experiences of psychological and social distress were consistently described by women, but not by men. Within the interpersonal meta-theme, men experienced opportunity for social connection and social support that was seldom available to women. Interpersonal violence with other household members was described by both men and women. Within the institutional meta-theme, both men and women described strength in unity, and gestures leading to the reordering of gender relations. These findings underline the significant and diffuse impacts of a gender order that values males and disadvantages females as caregivers of PPSDs, with the asymmetry of a greater burden for women. The findings point to the urgent need for global mental health policies that support and empower caregivers and that strengthen gender equality.

  • 19. Visuri, I.
    et al.
    Eriksson, C.
    Mardberg, E.
    Grip, O.
    Gustavsson, A.
    Hjortswang, H.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Montgomery, S.
    Myrelid, P.
    Olen, O.
    Ludvigsson, J. F.
    Halfvarson, J.
    Anti-TNF agent drug survival in patients with IBD: real-world comparisons of individual anti-TNF agents based on the Swedish National Quality Registry for IBD (SWIBREG)2019Ingår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 13, s. S443-S444Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Studies comparing drug survival in different anti-tumour necrosis factor (TNF) agents in IBD patients are scarce, especially for second-line anti-TNF agents. We aimed to (A) assess drug survival and predictors of response and adverse drug reactions to first-line anti-TNF treatment and (B) examine drug survival for individual anti-TNF agents when used as second-line anti-TNF. Methods: Well-characterised patients with IBD (n = 955)  starting their first anti-TNF treatment between 2006 and 2016 (Table  1), were identified from the Swedish National Quality Registry for IBD (SWIBREG). Drug survival was examined, stratified by reason for discontinuation, that is, lack/loss of clinical effectiveness or adverse drug reactions. Multi-variable Cox regression models were used to identify predictors of drug survival. Drug survival for the second anti-TNF was assessed by type of first anti-TNF agent. Results: Risk factors at baseline for shorter drug survival, in patients with Crohn’s disease, were use of infliximab as first-line anti-TNF (compared with adalimumab, adjusted HR  =  1.95, 95% CI: 1.19‒3.18) (Figure 1A) and colonic disease (L2) (compared with ileal disease (L1) and ileocolonic disease (L3), adjusted HR = 2.16, 95% CI: 1.25‒3.74). Consistently, Crohn’s disease patients who switched from adalimumab to infliximab had shorter drug survival, compared with those who switched from infliximab to adalimumab (Figure  1B). A  normalisation of CRP level at 3 months was associated with decreased risk of short drug survival in both Crohn’s disease (adjusted HR = 0.40, 95% CI: 0.19‒0.81) and ulcerative colitis (adjusted HR = 0.40, 95% CI: 0.19‒0.86). In Crohn’s disease, but not in ulcerative colitis, immunomodulators were associated with a lower risk of short drug survival due to adverse drug reactions (adjusted HR = 0.50, 95% CI: 0.31‒0.82). Conclusions: Drug survival duration was longer for adalimumab compared with infliximab both when used as first anti-TNF agent and when used as second-line treatment. The consistent pattern indicates that these differences are not only explained by channelling bias (differential prescribing behaviour).

  • 20.
    Al-Alawi, Kamila
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Department of Training and Studies, Royal Hospital, Ministry of Health, Muscat, Oman.
    Johansson, Helene
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Al Mandhari, Ahmed
    Norberg, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Are the resources adoptive for conducting team-based diabetes management clinics? An explorative study at primary health care centers in Muscat, Oman2019Ingår i: Primary Health Care Research and Development, ISSN 1463-4236, E-ISSN 1477-1128, Vol. 20, artikel-id E3Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: The aim of this study is to explore the perceptions among primary health center staff concerning competencies, values, skills and resources related to team-based diabetes management and to describe the availability of needed resources for team-based approaches.

    BACKGROUND: The diabetes epidemic challenges services available at primary health care centers in the Middle East. Therefore, there is a demand for evaluation of the available resources and team-based diabetes management in relation to the National Diabetes Management Guidelines.

    METHOD: A cross-sectional study was conducted with 26 public primary health care centers in Muscat, the capital of Oman. Data were collected from manual and electronic resources as well as a questionnaire that was distributed to the physician-in-charge and diabetes management team members.

    FINDINGS: The study revealed significant differences between professional groups regarding how they perceived their own competencies, values and skills as well as available resources related to team-based diabetes management. The perceived competencies were high among all professions. The perceived team-related values and skills were also generally high but with overall lower recordings among the nurses. This pattern, along with the fact that very few nurses have specialized qualifications, is a barrier to providing team-based diabetes management. Participants indicated that there were sufficient laboratory resources; however, reported that pharmacological, technical and human resources were lacking. Further work should be done at public primary diabetes management clinics in order to fully implement team-based diabetes management.

  • 21.
    Ljungberg, Johan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Johansson, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Engström, Karl Gunnar
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Norberg, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa.
    Bergdahl, Ingvar A
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Arterial hypertension and diastolic blood pressure associate with aortic stenosis2019Ingår i: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 53, nr 2, s. 91-97Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: Due to age-related differences in aortic valve structure, it is likely that the pathophysiology of aortic stenosis (AS) and associated risk factors differ between age groups. Here we prospectively studied the influence of traditional cardiovascular risk factors on AS development requiring surgery among patients without concomitant coronary artery disease (CAD) and stratified for age.

    DESIGN: This study included 322 patients, who had prior to surgery for AS participated in population-based surveys, and 131 of them had no visible CAD upon preoperative coronary angiogram. For each case, we selected four referents matched for age, gender, and geographic area. To identify predictors for surgery, we used multivariable conditional logistic regression with a model including arterial hypertension (or measured blood pressure and antihypertensive medication), cholesterol levels, diabetes, body mass index (BMI), and smoking.

    RESULTS: In patients without CAD, future surgery for AS was associated with arterial hypertension and elevated levels of diastolic blood pressure in patients younger than 60 years at surgery (odds ratio [95% confidence interval]), (3.40 [1.45-7.93] and 1.60 [1.09-2.37], respectively), and with only impaired fasting glucose tolerance in patients 60 years or older at surgery (3.22 [1.19-8.76]).

    CONCLUSION: Arterial hypertension and elevated diastolic blood pressure are associated with a risk for AS requiring surgery in subjects below 60 years of age. Strict blood pressure control in this group is strongly advocated to avoid other cardiovascular diseases correlated to hypertension. If hypertension and elevated diastolic blood pressure are risk factors for developing AS requiring surgery need further investigations. Notably, elevated fasting glucose levels were related to AS requiring surgery in older adults without concomitant CAD.

  • 22. Ramne, Stina
    et al.
    Dias, Joana Alves
    González-Padilla, Esther
    Olsson, Kjell
    Lindahl, Bernt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Engström, Gunnar
    Ericson, Ulrika
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Sonestedt, Emily
    Association between added sugar intake and mortality is nonlinear and dependent on sugar source in 2 Swedish population-based prospective cohorts2019Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 109, nr 2, s. 411-423Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Although sugar consumption has been associated with several risk factors for cardiometabolic diseases, evidence for harmful long-term effects is lacking. In addition, most studies have focused on sugar-sweetened beverages (SSBs), not sugar per se.

    Objective: The aim of this study was to examine the associations between added and free sugar intake, intake of different sugar sources, and mortality risk.

    Methods: Two prospective population-based cohorts were examined: the Malmö Diet and Cancer Study (MDCS; n = 24,272), which collected dietary data by combining a food diary, interview, and food-frequency questionnaire (FFQ), and the Northern Swedish Health and Disease Study (NSHDS; n = 24,475), which assessed diet with an FFQ. Sugar intakes defined as both added and free sugar and different sugar sources were examined. The associations with mortality were examined using a multivariable Cox proportional hazards regression.

    Results: Higher sugar consumption was associated with a less favorable lifestyle in general. The lowest mortality risk was found with added sugar intakes between 7.5% and 10% of energy (E%) intake in both cohorts. Intakes >20E% were associated with a 30% increased mortality risk, but increased risks were also found at intakes <5E% [23% in the MDCS and 9% (nonsignificant) in the NSHDS]. Similar U-shaped associations were found for both cardiovascular and cancer mortality in the MDCS. By separately analyzing the different sugar sources, the intake of SSBs was positively associated with mortality, whereas the intake of treats was inversely associated.

    Conclusions: Our findings indicate that a high sugar intake is associated with an increased mortality risk. However, the risk is also increased among low sugar consumers, although they have a more favorable lifestyle in general. In addition, the associations are dependent on the type of sugar source.

  • 23.
    Olstrup, Henrik
    et al.
    Atmospheric Science Unit, Department of Environmental Science and Analytical Chemistry, Stockholm University, 11418 Stockholm, Sweden..
    Johansson, Christer
    Atmospheric Science Unit, Department of Environmental Science and Analytical Chemistry, Stockholm University, 11418 Stockholm, Sweden. Environment and Health Administration, SLB, Box 8136, 104 20 Stockholm, Sweden..
    Forsberg, Bertil
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Åström, Christofer
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Association between Mortality and Short-Term Exposure to Particles, Ozone and Nitrogen Dioxide in Stockholm, Sweden2019Ingår i: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 16, nr 6, artikel-id E1028Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this study, the effects on daily mortality in Stockholm associated with short-term exposure to ultrafine particles (measured as number of particles with a diameter larger than 4 nm, PNC₄), black carbon (BC) and coarse particles (PM2.5⁻10) have been compared with the effects from more common traffic-pollution indicators (PM10, PM2.5 and NO₂) and O₃ during the period 2000⁻2016. Air pollution exposure was estimated from measurements at a 20 m high building in central Stockholm. The associations between daily mortality lagged up to two days (lag 02) and the different air pollutants were modelled by using Poisson regression. The pollutants with the strongest indications of an independent effect on daily mortality were O₃, PM2.5⁻10 and PM10. In the single-pollutant model, an interquartile range (IQR) increase in O₃ was associated with an increase in daily mortality of 2.0% (95% CI: 1.1⁻3.0) for lag 01 and 1.9% (95% CI: 1.0⁻2.9) for lag 02. An IQR increase in PM2.5⁻10 was associated with an increase in daily mortality of 0.8% (95% CI: 0.1⁻1.5) for lag 01 and 1.1% (95% CI: 0.4⁻1.8) for lag 02. PM10 was associated with a significant increase only at lag 02, with 0.8% (95% CI: 0.08⁻1.4) increase in daily mortality associated with an IQR increase in the concentration. NO₂ exhibits negative associations with mortality. The significant excess risk associated with O₃ remained significant in two-pollutant models after adjustments for PM2.5⁻10, BC and NO₂. The significant excess risk associated with PM2.5⁻10 remained significant in a two-pollutant model after adjustment for NO₂. The significantly negative associations for NO₂ remained significant in two-pollutant models after adjustments for PM2.5⁻10, O₃ and BC. A potential reason for these findings, where statistically significant excess risks were found for O₃, PM2.5⁻10 and PM10, but not for NO₂, PM2.5, PNC₄ and BC, is behavioral factors that lead to misclassification in the exposure. The concentrations of O₃ and PM2.5⁻10 are in general highest during sunny and dry days during the spring, when exposure to outdoor air tend to increase, while the opposite applies to NO₂, PNC₄ and BC, with the highest concentrations during the short winter days with cold weather, when people are less exposed to outdoor air.

  • 24. Baumeister, Sebastian E.
    et al.
    Schlesinger, Sabrina
    Aleksandrova, Krasimira
    Jochem, Carmen
    Jenab, Mazda
    Gunter, Marc J.
    Overvad, Kim
    Tjonneland, Anne
    Boutron-Ruault, Marie-Christine
    Carbonnel, Franck
    Fournier, Agnes
    Kuehn, Tilman
    Kaaks, Rudolf
    Pischon, Tobias
    Boeing, Heiner
    Trichopoulou, Antonia
    Bamia, Christina
    La Vecchia, Carlo
    Masala, Giovanna
    Panico, Salvatore
    Fasanelli, Francesca
    Tumino, Rosario
    Grioni, Sara
    de Mesquita, Bas Bueno
    Vermeulen, Roel
    May, Anne M.
    Borch, Kristin B.
    Oyeyemi, Sunday O.
    Ardanaz, Eva
    Rodriguez-Barranco, Miguel
    Chirlaque Lopez, Maria Dolores
    Felez-Nobrega, Mireia
    Sonestedt, Emily
    Ohlsson, Bodil
    Hemmingsson, Oskar
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Werner, Mårten
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Perez-Cornago, Aurora
    Ferrari, Pietro
    Stepien, Magdalena
    Freisling, Heinz
    Tsilidis, Konstantinos K.
    Ward, Heather
    Riboli, Elio
    Weiderpass, Elisabete
    Leitzmann, Michael F.
    Association between physical activity and risk of hepatobiliary cancers: A multinational cohort study2019Ingår i: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 70, nr 5, s. 885-892Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background & Aims: To date, evidence on the association between physical activity and risk of hepatobiliary cancers has been inconclusive. We examined this association in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC).

    Methods: We identified 275 hepatocellular carcinoma (HCC) cases, 93 intrahepatic bile duct cancers (IHBCs), and 164 non-gallbladder extrahepatic bile duct cancers (NGBCs) among 467,336 EPIC participants (median follow-up 14.9 years). We estimated cause-specific hazard ratios (HRs) for total physical activity and vigorous physical activity and performed mediation analysis and secondary analyses to assess robustness to confounding (e.g. due to hepatitis virus infection).

    Results: In the EPIC cohort, the multivariable-adjusted HR of HCC was 0.55 (95% CI 0.38–0.80) comparing active and inactive individuals. Regarding vigorous physical activity, for those reporting >2 hours/week compared to those with no vigorous activity, the HR for HCC was 0.50 (95% CI 0.33–0.76). Estimates were similar in sensitivity analyses for confounding. Total and vigorous physical activity were unrelated to IHBC and NGBC. In mediation analysis, waist circumference explained about 40% and body mass index 30% of the overall association of total physical activity and HCC.

    Conclusions: These findings suggest an inverse association between physical activity and risk of HCC, which is potentially mediated by obesity.

    Lay summary: In a pan-European study of 467,336 men and women, we found that physical activity is associated with a reduced risk of developing liver cancers over the next decade. This risk was independent of other liver cancer risk factors, and did not vary by age, gender, smoking status, body weight, and alcohol consumption.

  • 25. Donat-Vargas, Carolina
    et al.
    Bergdahl, Ingvar A.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Tornevi, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Wennberg, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Sommar, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Koponen, Jani
    Kiviranta, Hannu
    Åkesson, Agneta
    Associations between repeated measure of plasma perfluoroalkyl substances and cardiometabolic risk factors2019Ingår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 124, s. 58-65Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Perfluoroalkyl substances (PFAS) are persistent synthetic chemicals that may affect components of metabolic risk through the peroxisome proliferator-activated receptor but epidemiological data remain scarce and inconsistent.

    Objective: To estimate associations between repeated measurements of the main PFAS in plasma and total cholesterol, triglycerides and hypertension among the control subjects from a population-based nested case-control study on diabetes type 2 in middle-aged women and men.

    Methods: Participants (n = 187) were free of diabetes at both baseline and follow-up visits to the Västerbotten Intervention Programme, 10 years apart: during 1990 to 2003 (baseline) and 2001 to 2013 (follow-up). Participants left blood samples, completed questionnaires on diet and lifestyle factors, and underwent medical examinations, including measurement of blood pressure. PFAS and lipids were later determined in stored plasma samples. Associations for the repeated measurements were assessed using generalized estimating equations.

    Results: Six PFAS exceeded the limit of quantitation. Repeated measures of PFAS in plasma, cardiometabolic risk factors and confounders, showed an average decrease of triglycerides from −0.16 mmol/l (95% confidence interval [CI]: −0.33, 0.02 for PFOA) to −0.26 mmol/l (95% CI: −0.50, −0.08 for PFOS), when comparing the highest tertile of PFAS plasma levels with the lowest. Associations based on average PFAS measurements and follow-up triglycerides revealed similar inverse associations, although attenuated. The estimates for cholesterol and hypertension were inconsistent and with few exception non-significant.

    Conclusions: This study found inverse associations between PFAS and triglycerides, but did not support any clear link with either cholesterol or hypertension.

  • 26. Scott, David
    et al.
    Johansson, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
    McMillan, Lachlan B
    Ebeling, Peter R
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. School of Sport Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
    Associations of Sarcopenia and Its Components with Bone Structure and Incident Falls in Swedish Older Adults2019Ingår i: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 105, nr 1, s. 26-36Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to compare bone structure parameters and likelihood of falls across European Working Group on Sarcopenia in Older People (EWGSOP2) sarcopenia categories. 3334 Swedish 70-year olds had appendicular lean mass (normalized to height; ALMHt), lumbar spine and total hip areal BMD (aBMD) estimated by dual-energy X-ray absorptiometry. Volumetric BMD (vBMD) and structure at the distal and proximal tibia and radius were estimated by peripheral quantitative computed tomography. Hand grip strength and timed up-and-go were assessed, and sarcopenia was defined according to EWGSOP2 criteria. Incident falls were self-reported 6 and 12 months after baseline. Only 0.8% and 1.0% of participants had probable and confirmed sarcopenia, respectively. Almost one-third of participants with confirmed sarcopenia reported incident falls, compared with 20% for probable sarcopenia and 14% without sarcopenia (P = 0.025). Participants with confirmed sarcopenia had poorer bone parameters (all P < 0.05) except endosteal circumference at the proximal radius and tibia, while those with probable sarcopenia had lower cortical area at the proximal radius (B = - 5.9; 95% CI - 11.7, - 0.1 mm2) and periosteal and endosteal circumferences at the proximal tibia (- 3.3; - 6.4, - 0.3 and - 3.8; - 7.5, - 0.1 mm2, respectively), compared with those without sarcopenia. Compared with probable sarcopenia, confirmed sarcopenic participants had significantly lower lumbar spine and total hip aBMD, distal radius and tibia total vBMD, and proximal radius and tibia cortical vBMD, area and thickness (all P < 0.05). Swedish 70-year olds with confirmed sarcopenia demonstrate poorer BMD and bone architecture than those with probable and no sarcopenia, and have increased likelihood of incident falls.

  • 27. Timm, Signe
    et al.
    Frydenberg, Morten
    Abramson, Michael J.
    Bertelsen, Randi J.
    Bråbäck, Lennart
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Benediktsdottir, Bryndis
    Gislason, Thorarinn
    Holm, Mathias
    Janson, Christer
    Jogi, Rain
    Johannessen, Ane
    Kim, Jeong-Lim
    Malinovschi, Andrei
    Mishra, Gita
    Moratalla, Jesús
    Sigsgaard, Torben
    Svanes, Cecilie
    Schlünssen, Vivi
    Asthma and selective migration from farming environments in a three-generation cohort study2019Ingår i: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 34, nr 6, s. 601-609Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Individuals raised on a farm appear to have less asthma than individual raised elsewhere. However, selective migration might contribute to this as may also the suggested protection from farm environment. This study investigated if parents with asthma are less likely to raise their children on a farm. This study involved three generations: 6045 participants in ECRHS/RHINE cohorts (born 1945-1973, denoted G1), their 10,121 parents (denoted G0) and their 8260 offspring participating in RHINESSA (born 1963-1998, denoted G2). G2-offspring provided information on parents not participating in ECRHS/RHINE. Asthma status and place of upbringing for all three generations were reported in questionnaires by G1 in 2010-2012 and by G2 in 2013-2016. Binary regressions with farm upbringing as outcome were performed to explore associations between parental asthma and offspring farm upbringing in G0-G1 and G1-G2. Having at least one parent with asthma was not associated with offspring farm upbringing, either in G1-G2 (RR 1.11, 95% CI 0.81-1.52) or in G0-G1 (RR 0.99, 0.85-1.15). G1 parents with asthma born in a city tended to move and raise their G2 offspring on a farm (RR 2.00, 1.12-3.55), while G1 parents with asthma born on a farm were less likely to raise their G2 offspring on a farm (RR 0.34, 0.11-1.06). This pattern was not observed in analyses of G0-G1. This study suggests that the protective effect from farm upbringing on subsequent asthma development could not be explained by selective migration. Intriguingly, asthmatic parents appeared to change environment when having children.

  • 28.
    Wahlin, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Atherosclerotic cardiovascular disease in rheumatoid arthritis: aspects of pathogenesis and risk2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Patients with rheumatoid arthritis (RA) have an increased prevalence and severity of atherosclerosis, and a corresponding increased risk of cardiovascular disease. The mechanisms causing this are not well elucidated, but both traditional cardiovascular risk factors and RA-associated factors have been associated with atherosclerosis and increased risk of cardiovascular events in patients with RA. Cardiovascular risk estimation based on traditional cardiovascular risk factors, often underestimates the risk in patients with RA. The aims of this thesis were to examine factors and biomarkers associated with atherosclerosis in patients with RA, and to evaluate an algorithm for cardiovascular risk estimation in patients with RA.

    Methods Patients with early RA in the four northernmost counties of Sweden have since 1995 been included in a prospective study of both the progress of RA and comorbidities. Besides clinical data, radiographs, genetic markers and autoantibodies are registered. Paper I includes 665 patients aged 40-80 years from that cohort, in whom the 10-year risk of a first cardiovascular event was estimated with both Expanded Cardiovascular Risk Prediction Score in Rheumatoid Arthritis (ERS-RA), and the general population based ACC/AHA algorithm. The estimations were then compared to the actual outcomes. Paper II examines factors associated with coronary artery calcification (CAC) in 22 patients with long-standing RA. Papers III and IV use data from a cohort of patients <60 years of age at diagnosis of RA (n=79), in whom development of atherosclerosis has been prospectively followed since diagnosis of RA. This is a subset of patients from the larger cohort in paper I. Controls matched for age and sex (n=44) are examined as well. In paper III, phenotypes of T-cells and IgG-antibodies against cytomegalovirus (CMV) are analysed in relation to carotid intima-media thickness (IMT). In paper IV, bone mineral density and markers and regulators of bone metabolism are analysed in relation to IMT.

    Results Cardiovascular risk estimation with the RA-specific algorithm ERS-RA is not superior to estimation with the ACC/AHA algorithm. Both algorithms underestimate the risk in patients with a high grade of inflammation and in patients with an estimated moderate risk. In patients with long-standing RA, presence of CAC is associated with inflammatory activity, both at time of examination and in earlier stages of RA. Presence of anti-CMV IgG antibodies and altered T-cells (both CD4+ and CD8+) lacking the co-stimulatory molecule CD28 (CD28null) are associated with a higher IMT, and patients IgG-positive for CMV have a rapid increase in IMT after onset of RA. Regulators of bone metabolism (sclerostin, osteoprotegerin and osteocalcin) are associated with a higher IMT in patients with RA.

    Conclusion Cardiovascular risk estimation in patients with RA still needs to be improved. The fact that CMV-positivity, altered populations of T-cells and IMT all are associated, and that also regulators of bone metabolism reflect IMT, suggests that the pathogenesis of atherosclerosis in patients with RA is multifactorial.  This thesis provides knowledge of the accelerated development of atherosclerosis in RA and could possibly be relevant also in other chronic inflammatory diseases, where markers of accelerated atherosclerosis and increased cardiovascular risk are lacking.

  • 29. Marklund, Matti
    et al.
    Wu, Jason H Y
    Imamura, Fumiaki
    Del Gobbo, Liana C
    Fretts, Amanda
    de Goede, Janette
    Shi, Peilin
    Tintle, Nathan
    Wennberg, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Aslibekyan, Stella
    Chen, Tzu-An
    de Oliveira Otto, Marcia C
    Hirakawa, Yoichiro
    Eriksen, Helle Højmark
    Kröger, Janine
    Laguzzi, Federica
    Lankinen, Maria
    Murphy, Rachel A
    Prem, Kiesha
    Samieri, Cécilia
    Virtanen, Jyrki
    Wood, Alexis C
    Wong, Kerry
    Yang, Wei-Sin
    Zhou, Xia
    Baylin, Ana
    Boer, Jolanda M A
    Brouwer, Ingeborg A
    Campos, Hannia
    Chaves, Paulo H M
    Chien, Kuo-Liong
    de Faire, Ulf
    Djoussé, Luc
    Eiriksdottir, Gudny
    El-Abbadi, Naglaa
    Forouhi, Nita G
    Gaziano, J Michael
    Geleijnse, Johanna M
    Gigante, Bruna
    Giles, Graham
    Guallar, Eliseo
    Gudnason, Vilmundur
    Harris, Tamara
    Harris, William S
    Helmer, Catherine
    Hellénius, Mai-Lis
    Hodge, Allison
    Hu, Frank B
    Jacques, Paul F
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Kalsbeek, Anya
    Khaw, Kay-Tee
    Koh, Woon-Puay
    Laakso, Markku
    Leander, Karin
    Lin, Hung-Ju
    Lind, Lars
    Luben, Robert
    Luo, Juhua
    McKnight, Barbara
    Mursu, Jaakko
    Ninomiya, Toshiharu
    Overvad, Kim
    Psaty, Bruce M
    Rimm, Eric
    Schulze, Matthias B
    Siscovick, David
    Skjelbo Nielsen, Michael
    Smith, Albert V
    Steffen, Brian T
    Steffen, Lyn
    Sun, Qi
    Sundström, Johan
    Tsai, Michael Y
    Tunstall-Pedoe, Hugh
    Uusitupa, Matti I J
    van Dam, Rob M
    Veenstra, Jenna
    Verschuren, W M Monique
    Wareham, Nicholas
    Willett, Walter
    Woodward, Mark
    Yuan, Jian-Min
    Micha, Renata
    Lemaitre, Rozenn N
    Mozaffarian, Dariush
    Risérus, Ulf
    Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies2019Ingår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, nr 21, s. 2422-2436Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.

    METHODS: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease (CHD), ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytical plan. Levels of LA and AA, measured as % of total fatty acids, were evaluated linearly according to their interquintile range (i.e., the range between the mid-point of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available).

    RESULTS: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15,198 incident cardiovascular events occurred among 68,659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI: 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower CHD risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; comparing extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships.

    CONCLUSIONS: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.

  • 30. Gaudet, Mia M
    et al.
    Deubler, Emily L
    Kelly, Rachel S
    Diver, W Ryan
    Teras, Lauren R
    Hodge, James M
    Levine, Keith E
    Haines, Laura G
    Lundh, Thomas
    Lenner, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Palli, Domenico
    Vineis, Paolo
    Bergdahl, Ingvar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Gapstur, Susan M
    Kyrtopoulos, Soterios A
    Blood Levels of Cadmium and Lead in Relation to Breast Cancer Risk in Three Prospective Cohorts.2019Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, nr 5, s. 1010-1016Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cadmium and lead have been classified as carcinogens by the International Agency for Research on Cancer. However, their associations with breast cancer risk are unknown despite their persistence in the environment and ubiquitous human exposure. We examined associations of circulating levels of cadmium and lead with breast cancer risk in three case-control studies nested within the Cancer Prevention Study-II (CPS-II) LifeLink Cohort, European Prospective Investigation into Cancer and Nutrition - Italy (EPIC-Italy), and the Northern Sweden Health and Disease Study (NSHDS) cohorts. Metal levels were measured in stored erythrocytes from 1,435 cases and 1,433 controls using inductively coupled plasma-mass spectrometry. Summary relative risks (RR) and 95% confidence intervals (CI) were calculated using random-effects models with each study result weighted by the within- and between-study variances. I2 values were calculated to estimate proportion of between study variation. Using common cut-points, cadmium levels were not associated with breast cancer risk in the CPS-II cohort (continuous RR=1.01, 95% CI 0.76 - 1.34), but were inversely associated with risk in the EPIC- Italy (continuous RR=0.80, 95% CI 0.61 - 1.03) and NSHDS cohorts (continuous RR=0.73, 95% CI 0.54 - 0.97). The inverse association was also evident in the meta-analysis (continuous RR=0.84, 95% CI 0.69 - 1.01) with low between-study heterogeneity. Large differences in lead level distributions precluded a meta-analysis of their association with breast cancer risk; no associations were found in the three studies. Adult cadmium and lead levels were not associated with higher risk of breast cancer in our large meta-analysis. 

  • 31. Clendenen, Tess V.
    et al.
    Ge, Wenzhen
    Koenig, Karen L.
    Afanasyeva, Yelena
    Agnoli, Claudia
    Brinton, Louise A.
    Darvishian, Farbod
    Dorgan, Joanne F.
    Eliassen, A. Heather
    Falk, Roni T.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Hankinson, Susan E.
    Hoffman-Bolton, Judith
    Key, Timothy J.
    Krogh, Vittorio
    Nichols, Hazel B.
    Sandler, Dale P.
    Schoemaker, Minouk J.
    Sluss, Patrick M.
    Sund, Malin
    Swerdlow, Anthony J.
    Visvanathan, Kala
    Zeleniuch-Jacquotte, Anne
    Liu, Mengling
    Breast cancer risk prediction in women aged 35-50 years: impact of including sex hormone concentrations in the Gail model2019Ingår i: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 21, artikel-id 42Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Models that accurately predict risk of breast cancer are needed to help younger women make decisions about when to begin screening. Premenopausal concentrations of circulating anti-Mullerian hormone (AMH), a biomarker of ovarian reserve, and testosterone have been positively associated with breast cancer risk in prospective studies. We assessed whether adding AMH and/or testosterone to the Gail model improves its prediction performance for women aged 35-50.

    Methods: In a nested case-control study including ten prospective cohorts (1762 invasive cases/1890 matched controls) with pre-diagnostic serum/plasma samples, we estimated relative risks (RR) for the biomarkers and Gail risk factors using conditional logistic regression and random-effects meta-analysis. Absolute risk models were developed using these RR estimates, attributable risk fractions calculated using the distributions of the risk factors in the cases from the consortium, and population-based incidence and mortality rates. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminatory accuracy of the models with and without biomarkers.

    Results: The AUC for invasive breast cancer including only the Gail risk factor variables was 55.3 (95% CI 53.4, 57.1). The AUC increased moderately with the addition of AMH (AUC 57.6, 95% CI 55.7, 59.5), testosterone (AUC 56.2, 95% CI 54.4, 58.1), or both (AUC 58.1, 95% CI 56.2, 59.9). The largest AUC improvement (4.0) was among women without a family history of breast cancer.

    Conclusions: AMH and testosterone moderately increase the discriminatory accuracy of the Gail model among women aged 35-50. We observed the largest AUC increase for women without a family history of breast cancer, the group that would benefit most from improved risk prediction because early screening is already recommended for women with a family history.

  • 32.
    Henein, Michael Y.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Tossavainen, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Aroch, Roman
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Can Doppler echocardiography estimate raised pulmonary capillary wedge pressure provoked by passive leg lifting in suspected heart failure?2019Ingår i: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 39, nr 2, s. 128-134Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: Non-invasive estimation of left ventricular filling pressure (LVFP) during stress is important for explaining exertional symptoms in patients with heart failure (HF). The aim of this study was to evaluate ability of Doppler echocardiographic measures of elevated LVFP with passive leg lifting (PLL) in patients with suspected HF.

    METHODS: Twenty-nine patients with clinical signs of HF who underwent simultaneous Doppler echocardiography and right heart catheterization (RHC) at rest and during PLL were consecutively investigated. Seventeen patients had normal PCWP (≤15 mmHg) at rest and during PLL and 12 with normal PCWP at rest but >15 mmHg with PLL. Conventional echo and 2D strain were used to assess early diastolic blood flow velocity (E), LV strain rate during early diastole (LVSRe), left atrial SR during atrial contraction (LASRa) and myocardial tissue Doppler velocities to assess lateral e' and further calculate E/e' and E/LVSRe and their relationship with PCWP, at rest and during PLL.

    RESULTS: Resting LAVI (β = 0·45, P = 0·009) and LASRa (β = -0·51, P = 0·004) were independently related to PCWP during PLL. Also, LASRa (β = -0·77, P<0·001), E/e' (β = 0·40, P = 0·04) and E/LVSRe (β = 0·47, P = 0·021) during PLL correlated with PCWP during PLL. Multiple regression analysis identified E/LVSRe (β = 0·46, P = 0·001) and LASRa (β = -0·58, P = 0·002) during PLL as being independently associated with PCWP during PLL.

    CONCLUSION: Left atrial volume and myocardial contraction (LASRa) at rest both predict unstable LV filling pressures measured as raised PCWP when provoked by PLL. Furthermore, LASRa at PLL seems to have the strongest association to PCWP during PLL.

  • 33.
    Malmqvist, Gunnar
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Claesson Lingehall, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Appelblad, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Svenmarker, Staffan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Cardiopulmonary bypass prime composition: beyond crystalloids versus colloids2019Ingår i: Perfusion, ISSN 0267-6591, E-ISSN 1477-111X, Vol. 34, nr 2, s. 130-135Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: In the literature addressing cardiopulmonary bypass (CPB) prime composition, there is a considerable lack of discussion concerning plasma osmolality changes induced by using a hyperosmolar prime. With this study, we try to determine the magnitude and temporal relationship of plasma osmolality changes related to the use of a hyperosmolar CPB prime.

    METHOD: In this prospective observational study performed in a university hospital setting, we enrolled thirty patients scheduled for elective coronary bypass surgery. Plasma osmolality was analysed on eight occasions. A hyperosmolar CPB prime was used.

    RESULTS: Analyses of the perioperative plasma osmolality on eight occasions gave the following results: the preoperative osmolality level was normal (297±4 mOsm/kg); a significant increase to 322±17 mOsm/kg (p<0.001) was observed at the commencement of CPB and remained elevated after 30 minutes (310±4 mOsm/kg) and throughout the procedure (309±4 mOsm/kg); the osmolality level returned to 291±5 mOsm/kg on day 1 postoperatively and remained normal the following day (291±6 mOsm/kg).

    CONCLUSIONS: Use of hyperosmolar CPB prime resulted in a dramatic and instant elevation of the plasma osmolality. Rapid changes in plasma osmolality are associated with organ dysfunction (e.g. osmotic demyelination syndrome), therefore, effects on plasma osmolality related to the CPB prime composition should be recognised. Influence on organ function and clinical outcome warrants further investigations. - Clinical Trials.gov (NCT03060824). Changes in Plasma Osmolality Related to the Use of Cardiopulmonary Bypass With Hyperosmolar Prime. URL: https://clinicaltrials.gov/ct2/show/NCT03060824?term=cpb&cond=osmolality&rank=1.

  • 34.
    Henein, Michael