uu.seUppsala University Publications
Change search
Refine search result
12345 1 - 50 of 215
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1. Almqvist, Catarina
    et al.
    Adami, Hans-Olov
    Franks, Paul W.
    Groop, Leif
    Ingelsson, Erik
    Kere, Juha
    Lissner, Lauren
    Litton, Jan-Eric
    Maeurer, Markus
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Palmgren, Juni
    Pershagen, Göran
    Ploner, Alexander
    Sullivan, Patrick F.
    Tybring, Gunnel
    Pedersen, Nancy L.
    LifeGene - A large prospective population-based study of global relevance2011In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 26, no 1, p. 67-77Article in journal (Refereed)
    Abstract [en]

    Studying gene-environment interactions requires that the amount and quality of the lifestyle data is comparable to what is available for the corresponding genomic data. Sweden has several crucial prerequisites for comprehensive longitudinal biomedical research, such as the personal identity number, the universally available national health care system, continuously updated population and health registries and a scientifically motivated population. LifeGene builds on these strengths to bridge the gap between basic research and clinical applications with particular attention to populations, through a unique design in a research-friendly setting. LifeGene is designed both as a prospective cohort study and an infrastructure with repeated contacts of study participants approximately every 5 years. Index persons aged 18-45 years old will be recruited and invited to include their household members (partner and any children). A comprehensive questionnaire addressing cutting-edge research questions will be administered through the web with short follow-ups annually. Biosamples and physical measurements will also be collected at baseline, and re-administered every 5 years thereafter. Event-based sampling will be a key feature of LifeGene. The household-based design will give the opportunity to involve young couples prior to and during pregnancy, allowing for the first study of children born into cohort with complete pre-and perinatal data from both the mother and father. Questions and sampling schemes will be tailored to the participants' age and life events. The target of LifeGene is to enrol 500,000 Swedes and follow them longitudinally for at least 20 years.

  • 2.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Farahmand, Bahman
    Ahlbom, Anders
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ljunghall, Sverker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Risk of arrhythmias in 52 755 long-distance cross-country skiers: a cohort study2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no 47, p. 3624-3631Article in journal (Refereed)
    Abstract [en]

    AIMS:

    We aimed to investigate the association of number of completed races and finishing time with risk of arrhythmias among participants of Vasaloppet, a 90 km cross-country skiing event.

    METHODS AND RESULTS:

    All the participants without cardiovascular disease who completed Vasaloppet during 1989-98 were followed through national registries until December 2005. Primary outcome was hospitalization for any arrhythmia and secondary outcomes were atrial fibrillation/flutter (AF), bradyarrhythmias, other supraventricular tachycardias (SVT), and ventricular tachycardia/ventricular fibrillation/cardiac arrest (VT/VF/CA). Among 52 755 participants, 919 experienced arrhythmia during follow-up. Adjusting for age, education, and occupational status, those who completed the highest number of races during the period had higher risk of any arrhythmias [hazard ratio (HR)1.30; 95% CI 1.08-1.58; for ≥5 vs. 1 completed race], AF (HR 1.29; 95% CI 1.04-1.61), and bradyarrhythmias (HR 2.10; 95% CI 1.28-3.47). Those who had the fastest relative finishing time also had higher risk of any arrhythmias (HR 1.30; 95% CI 1.04-1.62; for 100-160% vs. >240% of winning time), AF (1.20; 95% CI 0.93-1.55), and bradyarrhythmias (HR 1.85; 95% CI 0.97-3.54). SVT or VT/VF/CA was not associated with finishing time or number of completed races.

    CONCLUSIONS:

    Among male participants of a 90 km cross-country skiing event, a faster finishing time and a high number of completed races were associated with higher risk of arrhythmias. This was mainly driven by a higher incidence of AF and bradyarrhythmias. No association with SVT or VT/VF/CA was found.

  • 3.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Muscle Morphology And Risk Of Cardiovascular Disease2010In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 28, p. E353-E353Article in journal (Other academic)
  • 4.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Skeletal muscle morphology and risk of cardiovascular disease in elderly men2015In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 22, no 2, p. 231-239Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    While it is well known that physical inactivity is a major risk factor for cardiovascular disease, there is still a search for the mechanisms by which exercise exerts its positive effect. Skeletal muscle fibre type can be affected to some extent by exercise, and different fibre types possess different anti-inflammatory and glucometabolic properties that may influence cardiovascular disease risk.

    DESIGN:

    Population-based cohort study.

    METHODS:

    We investigated relations of skeletal muscle morphology to risk of cardiovascular events in a sample of 466 71-year-old men without cardiovascular disease, of which 295 were physically active (strenuous physical activity at least 3 h/week).

    RESULTS:

    During a median of 13.1 years of follow up, 173 major cardiovascular events occurred. Among physically active men, 10% higher proportion of type-I (slow-twitch oxidative) fibres was associated with a hazard ratio (HR) of 0.84 (95% confidence interval 0.74-0.95) for cardiovascular events, and 10% higher proportion of type-IIx (fast-twitch glycolytic) fibres was associated with a HR of 1.24 (1.06-1.45), adjusting for age. Similar results were observed in several sets of multivariable-adjusted models. No association of muscle fibre type with risk of cardiovascular events was observed among physically inactive men.

    CONCLUSIONS:

    Higher skeletal muscle proportion of type-I fibres was associated with lower risk of cardiovascular events and a higher proportion of type-IIx fibres was associated with higher risk of cardiovascular events. These relations were only observed in physically active men. Skeletal muscle fibre composition may be a mediator of the protective effects of exercise against cardiovascular disease.

  • 5.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hambraeus, Kristina
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Discontinuation of Smokeless Tobacco and Mortality Risk After Myocardial Infarction2014In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 130, no 4, p. 325-323Article in journal (Refereed)
    Abstract [en]

    Background-Given the indications of increased risk for fatal myocardial infarction (MI) in people who use snus, a moist smokeless tobacco product, we hypothesized that discontinuation of snus use after an MI would reduce mortality risk. Methods and Results-All patients who were admitted to coronary care units for an MI in Sweden between 2005 and 2009 and were <75 years of age underwent a structured examination 2 months after discharge (the baseline of the present study). We investigated the risk of mortality in post-MI snus quitters (n=675) relative to post-MI continuing snus users (n=1799) using Cox proportional hazards analyses. During follow-up (mean 2.1 years), 83 participants died. The mortality rate was 9.7 (95% confidence interval, 5.7-16.3) per 1000 person-years at risk in post-MI snus quitters and 18.7 (14.8-23.6) per 1000 person-years at risk in post-MI continuing snus users. After adjustment for age and sex, post-MI snus quitters had half the mortality risk of post-MI continuing snus users (hazard ratio, 0.51; 95% confidence interval, 0.29-0.91). In a multivariable-adjusted model, the hazard ratio was 0.57 (95% confidence interval, 0.32-1.02). The corresponding estimate for people who quit smoking after MI versus post-MI continuing smokers was 0.54 (95% confidence interval, 0.42-0.69). Conclusions-In this study, discontinuation of snus use after an MI was associated with a nearly halved mortality risk, similar to the benefit associated with smoking cessation. These observations suggest that the use of snus after MI should be discouraged.

  • 6.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hambraeus, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Response to Letter Regarding Article, "Discontinuation of Smokeless Tobacco and Mortality Risk After Myocardial Infarction"2015In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 131, no 17, p. E423-E423Article in journal (Refereed)
  • 7.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hergens, M. P.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ye, W.
    Nyrén, O.
    Lambe, M.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Smokeless Tobacco (Snus) And Risk Of Heart Failure In Two Swedish Cohorts2010In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 28, p. E48-E49Article in journal (Other academic)
  • 8.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hergens, Maria-Pia
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ye, Weimin
    Nyrén, Olof
    Lambe, Mats
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Smokeless Tobacco (Snus) and Risk of Heart Failure: Results from Two Swedish Cohorts2012In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 19, no 5, p. 1120-1127Article in journal (Refereed)
    Abstract [en]

    Background:

    Oral moist snuff (snus) is discussed as a safer alternative to smoking, and its use is increasing. Based on its documented effect on blood pressure, we hypothesized that use of snus increases the risk of heart failure.

    Design:

    Two independent Swedish prospective cohorts; the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based sample of 1076 elderly men, and the Construction Workers Cohort (CWC), a sample of 118,425 never-smoking male construction workers.

    Methods:

    Cox proportional hazards models were used to investigate possible associations of snus use with risk of a first hospitalization for heart failure.

    Results:

    In ULSAM, 95 men were hospitalized for heart failure, during a median follow up of 8.9 years. In a model adjusted for established risk factors including past and present smoking exposure, current snus use was associated with a higher risk of heart failure [hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.03-4.22] relative to non-use. Snus use was particularly associated with risk of non-ischaemic heart failure (HR 2.55, 95% CI 1.12-5.82). In CWC, 545 men were hospitalized for heart failure, during a median follow up of 18 years. In multivariable-adjusted models, current snus use was moderately associated with a higher risk of heart failure (HR 1.28, 95% CI 1.00-1.64) and non-ischaemic heart failure (HR 1.28, 95% CI 0.97-1.68) relative to never tobacco use.

    Conclusion:

    Data from two independent cohorts suggest that use of snus may be associated with a higher risk of heart failure.

  • 9. Benetou, V
    et al.
    Orfanos, P
    Feskanich, D
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Pettersson-Kymmer, U
    Ahmed, L A
    Peasey, A
    Wolk, A
    Brenner, H
    Bobak, M
    Wilsgaard, T
    Schöttker, B
    Saum, K-U
    Bellavia, A
    Grodstein, F
    Klinaki, E
    Valanou, E
    Papatesta, E-M
    Boffetta, P
    Trichopoulou, A
    Education, marital status, and risk of hip fractures in older men and women: the CHANCES project2015In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 26, no 6, p. 1733-1746Article in journal (Refereed)
    Abstract [en]

    The role of socioeconomic status in hip fracture incidence is unclear. In a diverse population of elderly, higher education was found to be associated with lower, whereas living alone, compared to being married/cohabiting, with higher hip fracture risk. Educational level and marital status may contribute to hip fracture risk.

    INTRODUCTION: The evidence on the association between socioeconomic status and hip fracture incidence is limited and inconsistent. We investigated the potential association of education and marital status with hip fracture incidence in older individuals from Europe and USA.

    METHODS: A total of 155,940 participants (79 % women) aged 60 years and older from seven cohorts were followed up accumulating 6456 incident hip fractures. Information on education and marital status was harmonized across cohorts. Hip fractures were ascertained through telephone interviews/questionnaires or through record linkage with registries. Associations were assessed through Cox proportional hazard regression adjusting for several factors. Summary estimates were derived using random effects models.

    RESULTS: Individuals with higher education, compared to those with low education, had lower hip fracture risk [hazard ratio (HR) = 0.84, 95 % confidence interval (CI) 0.72-0.95]. Respective HRs were 0.97 (95 % CI 0.82-1.13) for men and 0.75 (95 % CI 0.65-0.85) for women. Overall, individuals living alone, especially those aged 60-69 years, compared to those being married/cohabiting, tended to have a higher hip fracture risk (HR = 1.12, 95 % CI 1.02-1.22). There was no suggestion for heterogeneity across cohorts (P heterogeneity > 0.05).

    CONCLUSIONS: The combined data from >150,000 individuals 60 years and older suggest that higher education may contribute to lower hip fracture risk. Furthermore, this risk may be higher among individuals living alone, especially among the age group 60-69 years, when compared to those being married/cohabiting.

  • 10.
    Benetou, Vassiliki
    et al.
    Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, 75 Mikras Asias Str, Athens 11527, Greece.; Hellen Hlth Fdn, Athens, Greece.
    Orfanos, Philippos
    Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, 75 Mikras Asias Str, Athens 11527, Greece.; Hellen Hlth Fdn, Athens, Greece.
    Feskanich, Diane
    Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.; Harvard Med Sch, Boston, MA USA.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Pettersson-Kymmer, Ulrika
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden.; Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Eriksson, Sture
    Umea Univ, Dept Community Med, Umea, Sweden.
    Grodstein, Francine
    Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.; Harvard Med Sch, Boston, MA USA.
    Wolk, Alicja
    Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden.
    Bellavia, Andrea
    Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden.
    Ahmed, Luai A
    UiT, Fac Hlth Sci, Dept Hlth & Care Sci, Tromso, Norway.; United Arab Emirates Univ, Coll Med & Hlth Sci, Inst Publ Hlth, Al Ain, U Arab Emirates.
    Boffeta, Paolo
    Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA.; Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
    Trichopoulou, Antonia
    Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, 75 Mikras Asias Str, Athens 11527, Greece.; Hellen Hlth Fdn, Athens, Greece .
    Fruit and Vegetable Intake and Hip Fracture Incidence in Older Men and Women: The CHANCES Project2016In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 31, no 9, p. 1743-1752Article in journal (Refereed)
    Abstract [en]

    The role of fruit and vegetable intake in relation to fracture prevention during adulthood and beyond is not adequately understood. We investigated the potential association between fruit and vegetable intake and hip fracture incidence in a large sample of older adults from Europe and the United States. A total of 142,018 individuals (116,509 women) aged ≥60 years, from five cohorts, were followed up prospectively for 1,911,482 person-years, accumulating 5552 hip fractures. Fruit and vegetable intake was assessed by validated, cohort-specific, food-frequency questionnaires (FFQ). Ηip fractures were ascertained through national patient registers or telephone interviews/questionnaires. Adjusted hazard ratios (HRs) derived by Cox proportional hazards regression were estimated for each cohort and subsequently pooled using random effects meta-analysis. Intake of ≤1 serving/day of fruit and vegetables combined was associated with 39% higher hip fracture risk (pooled adjusted HR, 1.39; 95% confidence interval [CI], 1.20 to 1.58) in comparison with moderate intake (>3 and ≤5 servings/day) (pfor heterogeneity  = 0.505), whereas higher intakes (>5 servings/day) were not associated with lower risk in comparison with the same reference. Associations were more evident among women. We concluded that a daily intake of 1 or <1 servings of fruits and vegetables was associated with increased hip fracture risk in relation to moderate daily intakes. Older adults with such low fruit and vegetable consumption may benefit from raising their intakes to moderate amounts in order to reduce their hip fracture risk.

  • 11. Bergkvist, Charlotte
    et al.
    Åkesson, Agneta
    Glynn, Anders
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Rantakokko, Panu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Kiviranta, Hannu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wolk, Alicja
    Berglund, Marika
    Validation of questionnaire-based long-term dietary exposure to polychlorinated biphenyls using biomarkers2012In: Molecular Nutrition & Food Research, ISSN 1613-4125, E-ISSN 1613-4133, Vol. 56, no 11, p. 1748-1754Article in journal (Refereed)
    Abstract [en]

    Scope The health consequences of lifelong low-level exposure to polychlorinated biphenyls (PCBs) via food are largely unknown, mainly due to the lack of large population-based prospective studies addressing this issue. We validated long-term food frequency questionnaire (FFQ)-based dietary PCB exposure against concentrations of six PCB congeners in serum. Methods and results Dietary PCB exposure was estimated in the Swedish Mammography Cohort by constructing a recipe-based database of CB-153, an indicator for total PCBs in food. The Spearman rank correlation (adjusted for within-person variability) was assessed between concurrent (20042006), past (1997), and long-term (mean of 1997 and 20042006) FFQ-based dietary PCB exposure, respectively, and the following serum PCB congeners, CB-118, CB-138, CB-153, CB-156, CB-170, and CB-180, in women (5685 years of age, n = 201). The correlation between FFQ-based dietary PCB exposure and serum CB-153 was 0.41 (p < 0.001) for the concurrent (median 1.6 ng/kg body weight) and 0.34 (p < 0.05) for the past (median 2.6 ng/kg body weight) exposure assessment. Long-term validity of FFQ-based PCB estimates and the six serum PCB congeners ranged from 0.30 to 0.58 (p < 0.05). Conclusion FFQ-based PCB exposure estimates show acceptable validity in relation to PCB concentrations in serum, justifying their use in large-scale epidemiological studies.

  • 12.
    Bergström, Monica Frick
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Extent and consequences of misclassified injury diagnoses in a national hospital discharge registry2011In: Injury Prevention, ISSN 1353-8047, E-ISSN 1475-5785, Vol. 17, no 2, p. 108-113Article in journal (Refereed)
    Abstract [en]

    Background Classification of injuries and estimation of injury severity on the basis of ICD-10 injury coding are powerful epidemiological tools. Little is known about the characteristics and consequences of primary coding errors and their consequences for such applications. Materials and methods From the Swedish national hospital discharge register, 15 899 incident injury cases primarily admitted to the two hospitals in Uppsala County between 2000 and 2004 were identified. Of these, 967 randomly selected patient records were reviewed. Errors in injury diagnosis were corrected, and the consequences of these changes were analysed. Results Out of 1370 injury codes, 10% were corrected, but 95% of the injury codes were correct to the third position. In 21% (95% CI 19% to 24%) of 967 hospital admissions, at least one ICD-10 code for injury was changed or added, but only 13% (127) had some change made to their injury mortality diagnosis matrix classification. Among the cases with coding errors, the mean ICD-based injury severity score changed slightly (difference 0.016; 95% CI 0.007 to 0.032). The area under the receiver operating characteristics curve was 0.892 for predicting hospital mortality and remained essentially unchanged after the correction of codes (95% CI for difference -0.022 to 0.013). Conclusion Errors in ICD-10-coded injuries in hospital discharge data were common, but the consequences for injury categorisation were moderate and the consequences for injury severity estimates were in most cases minor. The error rate for detailed levels of cause-of-injury codes was high and may be detrimental for identifying specific targets for prevention.

  • 13. Björnsdottir, Sigridur
    et al.
    Sääf, Maria
    Bensing, Sophie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Michaelsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ludvigsson, Jonas F
    Risk of Hip Fracture in Addison's Disease: A Population-based Cohort Study2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 270, no 2, p. 187-195Article in journal (Refereed)
    Abstract [en]

    Objectives:  The results of studies of bone mineral density (BMD) in Addison's disease (AD) are inconsistent. There are no published data on hip fracture risk in patients with AD. In this study we compare hip fracture risk in adults with and without AD. Design:  A population-based cohort study. Methods:  Through the Swedish National Patient Register and the Total Population Register, we identified 3,219 patients without prior hip fracture who were diagnosed with AD at the age of ≥30 years during the period 1964-2006, and 31,557 age- and sex-matched controls. Time to hip fracture was measured. Results:  We observed 221 hip fractures (6.9%) in patients with AD and 846 (2.7%) in the controls. Patients with AD had a higher risk of hip fracture (hazard ratio (HR) = 1.8; 95% confidence interval (CI), 1.6-2.1; p < 0.001). This risk increase was independent of sex and age at or calendar period of diagnosis. Risk estimates did not change with adjustment for type 1 diabetes, autoimmune thyroid disease, rheumatoid arthritis or coeliac disease. Women diagnosed with AD ≤50 years old had the highest risk of hip fracture (HR = 2.7; 95% CI, 1.6-4.5). We found a positive association between hip fracture and undiagnosed AD (odds ratio (OR) = 2.4; 95% CI, 2.1- 3.0) with the highest risk estimates in the last year before AD diagnosis (OR = 2.8; 95% CI, 1.8-4.2). Conclusion:  Both clinically undiagnosed and diagnosed AD were associated with hip fractures, with the highest relative risk seen in women diagnosed with AD ≤50 years of age.

  • 14.
    Blomberg, Hans
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaelsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Johansson, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Impact of prehospital trauma life support (PHTLS) training of ambulance caregivers on the outcome of traffic injury victims – a nation-wide study.Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Prehospital trauma life support (PHTLS) is a widely implemented educational program for prehospital trauma care. Evidence for improved patient outcome is, however, limited. The primary aim of this nation-wide study was to investigate the association between regional implementation of PHTLS training and mortality after traffic injuries.

    Methods: We extracted from the Swedish National Patient Registry and the Cause of Death Registry information on victims of motor vehicle traffic injuries in Sweden from 2001 to 2004 (n=28 041). During this time period, PHTLS training was implemented at a varying pace in different regions. We used a Bayesian approach with Markov chain Monte Carlo to estimate odds ratios (OR) for prehospital and 30-day mortality. We entered region and hospital into hierarchical models and controlled for the calendar year for each injury. We analyzed the time to death and time to return to work using Cox’s proportional hazards frailty models.

    Results: A total of 1395 individuals died before being admitted to hospital. After multivariable adjustment, the OR for prehospital mortality with PHTLS-trained prehospital staff was 1.11 (95% credibility interval, 0.88 to 1.38). For 30-day mortality (365 deaths), the adjusted OR was 0.80 (95% credibility interval, 0.53 to 1.17). There was no association between PHTLS training and time to death (hazard ratio 0.99; 95% confidence interval, 0.85 to 1.14) or time to return to work (hazard ratio 0.98, 95% confidence interval, 0.92 to 1.05).

    Conclusion: The implementation of PHTLS training did not appear to reduce mortality or disability after motor vehicle traffic injuries. 

  • 15.
    Blomberg, Hans
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Johansson, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Prehospital Trauma Life Support Training of Ambulance Caregivers and the Outcomes of Traffic-Injury Victims in Sweden2013In: Journal of the American College of Surgeons, ISSN 1072-7515, E-ISSN 1879-1190, Vol. 217, no 6, p. 1010-1019Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    There is limited evidence that the widely implemented Prehospital Trauma Life Support (PHTLS) educational program improves patient outcomes. The primary aim of this national study in Sweden was to investigate the association between regional implementation of PHTLS training and mortality after traffic injuries.

    STUDY DESIGN:

    We extracted information from the Swedish National Patient Registry and the Cause of Death Registry on victims of motor-vehicle traffic injuries in Sweden from 2001 to 2004 (N = 28,041). During this time period, PHTLS training was implemented at a varying pace in different regions. To control for other influences on patient outcomes related to regional and hospital-level effects, such as variations in performance of trauma care systems, we used Bayesian hierarchical regression models to estimate odds ratios for prehospital mortality and 30-day mortality after hospital admission. We also controlled for the calendar year for each injury to account for period effects. We analyzed the time to death after hospital admission and time to return to work using Cox's proportional hazards frailty models.

    RESULTS:

    After multivariable adjustment, the odds ratio for prehospital mortality with PHTLS-trained prehospital staff was 1.54 (95% credibility interval, 1.07-2.13). For 30-day mortality among those surviving to hospital admission, the odds ratio was 0.85 (95% credibility interval, 0.45-1.48). There was no association between PHTLS training and time to death (hazard ratio = 0.99; 95% CI, 0.85-1.14) or time to return to work (hazard ratio = 0.98; 95% CI, 0.92-1.05).

    CONCLUSIONS:

    In this observational study, the implementation of PHTLS training did not appear to be associated with reduced mortality or ability to return to work after motor-vehicle traffic injuries.

  • 16. Burgaz, A.
    et al.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Rautiainen, S.
    Orsini, N.
    Håkansson, N.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Wolk, A.
    Confirmed hypertension and plasma 25(OH)D concentrations amongst elderly men2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 269, no 2, p. 211-218Article in journal (Refereed)
    Abstract [en]

    Objectives.

    The results of experimental studies suggest that vitamin D deficiency activates the renin-angiotensin system and predisposes to hypertension. Results of previous epidemiological studies investigating the association between 25-hydroxyvitamin D [25(OH)D] status and hypertension have not been consistent, perhaps because of their sole reliance on office blood pressure (BP) measurements leading to some misclassification of hypertension status. No previous studies have examined the association between 25(OH)D status and confirmed hypertension assessed with both office and 24-h BP measurements.

    Design.

    In this cross-sectional study, we investigated 833 Caucasian men, aged 71 +/- 0.6 years, to determine the association between plasma 25(OH)D concentrations, measured with high-pressure liquid chromatography mass spectrometry, and the prevalence of hypertension. We used both supine office and 24-h BP measurements for classifying participants as normotensive or confirmed hypertensive; participants with inconsistent classifications were excluded.

    Results.

    In a multivariable adjusted logistic regression model, men with 25(OH)D concentrations < 37.5 nmol L-1 had a 3-fold higher prevalence of confirmed hypertension compared to those with >= 37.5 nmol L-1 25(OH)D (odds ratio = 3.3, 95% CI: 1.0-11.0).

    Conclusions.

    Our results show that low plasma 25(OH)D concentration is associated with a higher prevalence of confirmed hypertension.

  • 17. Burgaz, Ann
    et al.
    Åkesson, A.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Wolk, A.
    25-hydroxyvitamin D accumulation during summer in elderly women at latitude 60 degrees N2009In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 266, no 5, p. 476-483Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: During half of the year, cutaneous synthesis of 25-hydroxyvitamin D (25(OH)D) is not detectable at northern latitudes, leaving the population dependent on other sources for optimal vitamin D status. During April to September, 25(OH)D status may be improved by solar exposure. In this study, we measured seasonal differences in serum 25(OH)D concentrations and identified the major predictors of summer 25(OH)D concentrations. DESIGN: We assessed serum 25(OH)D concentrations during both winter and summer amongst 100 women, aged 61-83 years, randomly sampled from the Swedish Mammography Cohort. Participants completed two detailed questionnaires covering diet, use of dietary supplements and sun-related behaviour, the first in January through March and a second time in August through September. RESULTS: The mean seasonal increase in serum 25(OH)D concentrations was 38% from mean 72 +/- 23 nmol L(-1) during winter to 99 +/- 29 nmol L(-1) in summer. High summer 25(OH)D concentrations were associated with higher winter concentrations, preference of staying in sun instead of shade, having a nonsensitive skin type and normal body mass index. Based on multiple linear regression modelling, preferring sun, having nonsensitive skin type and normal weight as compared with preferring shade, having sensitive skin type and being obese, was associated with a 64 nmol L(-1) higher 25(OH)D concentrations during summer. CONCLUSIONS: Women with high winter 25(OH)D serum concentrations, with preference of staying in the sun instead of shade during summer, a skin type allowing for longer sun exposure and a normal weight had the highest summer 25(OH)D concentrations.

  • 18. Burgaz, Ann
    et al.
    Åkesson, Agneta
    Öster, Annette
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wolk, Alicja
    Associations of diet, supplement use, and ultraviolet B radiation exposure with vitamin D status in Swedish women during winter2007In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 86, no 5, p. 1399-1404Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Vitamin D is produced endogenously after sun exposure but can also be obtained from natural food sources, food fortification, and dietary supplements. OBJECTIVE: We aimed to determine the vitamin D status of women (61-86 y old) living in central Sweden (latitude 60 degrees ) during winter and its relation with vitamin D intake and exposure to ultraviolet B radiation. DESIGN: In a cross-sectional study, we assessed the vitamin D status (serum 25-hydroxyvitamin D [25(OH)D]) of 116 women by using an enzyme immunoassay. The women completed questionnaires covering food habits, use of dietary supplements, and sun-related behavior. RESULTS: In a multiple linear regression model, the main determinants of serum 25(OH)D concentrations (x +/- SD: 69 +/- 23 mmol/L) were dietary vitamin D (6.0 +/- 1.8 mug/d), travel to a sunny location during winter within the previous 6 mo (26%), and the use of dietary supplements (16%). There was no association between serum 25(OH)D status during the winter and age, time spent outdoors, the use of sunscreen, or skin type. Serum 25(OH)D concentrations increased by 25.5 nmol/L with 2-3 servings (130 g/wk) fatty fish/wk, by 6.2 nmol/L with the daily intake of 300 g vitamin D-fortified reduced-fat dairy products, by 11.0 nmol/L with regular use of vitamin D supplements, and by 14.5 nmol/L with a sun vacation during winter. Among nonsupplement users without a wintertime sun vacation, 2-3 servings fatty fish/wk increased serum vitamin D concentrations by 45%. CONCLUSION: Fatty fish, vitamin D-fortified reduced-fat dairy products, regular supplement use, and taking a sun vacation are important predictors for serum concentrations of 25(OH)D during winter at a latitude of 60 degrees .

  • 19.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Bellavia, Andrea
    Karolinska Inst, Unit Nutr Epidemiol, Inst Environm Med, Solna, Sweden.
    Orsini, Nicola
    Karolinska Inst, Unit Nutr Epidemiol, Inst Environm Med, Solna, Sweden.
    Wolk, Alicja
    Karolinska Inst, Unit Nutr Epidemiol, Inst Environm Med, Solna, Sweden.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Fruit and vegetable intake and risk of hip fracture: A cohort study of Swedish men and women2015In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 30, no 6, p. 976-984Article in journal (Refereed)
    Abstract [en]

    Dietary guidelines recommend a daily intake of five servings of fruit and vegetables. Whether such intakes are associated with a lower risk of hip fracture is at present unclear. The aim of the present study was to investigate the dose-response association between habitual fruit and vegetable intake and hip fracture in a cohort study based on 40,644 men from the Cohort of Swedish Men (COSM) and 34,947 women from the Swedish Mammography Cohort (SMC) (total n=75,591), free from cardiovascular disease and cancer, who answered lifestyle questionnaires in 1997 (age 45-83 years). Intake of fruit and vegetables (servings/day) was assessed by food frequency questionnaire and incident hip fractures were retrieved from the Swedish Patient Register (1998-2010). The mean follow-up time was 14.2 years. One third of the participants reported an intake of fruit and vegetables of >5 servings/day, one third >3 to ≤5 servings/day, 28% >1 to ≤3 servings/day, and 6% reported ≤1 serving/day. During 1,037,645 person-years we observed 3,644 hip fractures (2,266, 62%, in women). The doseresponse association was found to be strongly non-linear (P<0.001). Men and women with zero consumption had 88% higher rate of hip fracture compared with those consuming 5 servings/day; adjusted hazard ratio (HR), 1.88 (95% CI, 1.53-2.32). The rate was gradually lower with higher intakes; adjusted HR for 1 vs 5 servings/day, 1.35 (95% CI, 1.21-1.58). However, more than 5 servings/day did not confer additionally lower HRs (adjusted HR for 8 vs. 5 servings/day, 0.96 (95% CI, 0.90-1.03). Similar results were observed when men and women were analyzed separately. We conclude that there is a dose-response association between fruit and vegetable intake and hip fracture such that an intake below the recommended 5 servings/day confers higher rates of hip fracture. Intakes above this recommendation do not seem to further lower the risk.

  • 20.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Cars, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Prediction of fracture risk in men: A cohort study2012In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 27, no 4, p. 797-807Article in journal (Refereed)
    Abstract [en]

    FRAX is a tool that identifies individuals with high fracture risk who will benefit from pharmacological treatment of osteoporosis. However, a majority of fractures among elderly occur in people without osteoporosis and most occur after a fall. Our aim was to accurately identify men with a high future risk of fracture, independent of cause. In the population-based Uppsala Longitudinal Study of Adult Men (ULSAM) and using survival analysis we studied different models' prognostic values (R(2) ) for any fracture and hip fracture within 10 years from age 50 (n = 2322), 60 (n = 1852), 71 (n = 1221), and 82 (n = 526). During the total follow-up period from age 50, 897 fractures occurred in 585 individuals. Of these, 281 were hip fractures occurring in 189 individuals. The rates of any fracture were 5.7/1000 person-years at risk from age 50 and 25.9/1000 person-years at risk from age 82. Corresponding hip fractures rates were 2.9 and 11.7/1000 person-years at risk. The FRAX model included all variables in FRAX except bone mineral density. The full model combining FRAX variables, comorbidity, medications, and behavioral factors explained 25-45% of all fractures and 80-92% of hip fractures, depending on age. The corresponding prognostic values of the FRAX model were 7-17% for all fractures and 41-60% for hip fractures. Net reclassification improvement (NRI) comparing the full model with the FRAX model ranged between 40 and 53% for any fracture and between 40 and 87% for hip fracture. Within the highest quintile of predicted fracture risk with the full model, 1/3 of the men will have a fracture within 10 years after age 71 years and 2/3 after age 82 years. We conclude that the addition of comorbidity, medication and behavioral factors to the clinical components of FRAX can substantially improve the ability to identify men at high risk of fracture, especially hip fracture. 

  • 21.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Warensjö Lemming, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cancer death is related to high palmitoleic acid in serum and to polymorphisms in the SCD-1 gene in healthy Swedish men2014In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 99, no 3, p. 551-558Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    A high proportion of monounsaturated fatty acids (MUFAs) or a high ratio of MUFAs to saturated fatty acids in plasma, reflecting a high activity of the lipogenic enzyme stearoyl-CoA desaturase-1 (SCD-1), has been shown to be related to cancer death and incidence in some studies.

    OBJECTIVES:

    The objective was to study whether the serum cholesteryl ester proportion of palmitoleic acid [16:1n-7 (16:1ω-3)] and the ratio of palmitoleic to palmitic acid (16:1n-7/16:0), as an estimation of the activity of SCD-1, are related to cancer death and to investigate whether polymorphisms in the SCD-1 gene are related to cancer mortality.

    DESIGN:

    A community-based cohort of 50-y-old men was followed for a maximum of >40 y. Survival analysis was used to relate fatty acid composition in serum, analyzed at baseline by gas-liquid chromatography (n = 1981), and single nucleotide polymorphisms in the SCD-1 gene (n = 986) to cancer death. A 7-d dietary record was completed at age 70 y (n = 880).

    RESULTS:

    The proportions of 16:1n-7 and the ratio of 16:1n-7 to 16:0 were associated with cancer mortality during follow-up in a comparison of the highest with the lowest quartile of 16:1n-7 (adjusted HR: 1.37; 95% CI: 1.04, 1.82). Inherited variance of the SCD-1 gene seemed to be related to cancer death, especially among men with a low proportion of PUFA in the diet in a comparison of the highest with the lowest weighted genetic risk score (HR: 2.14; 95% CI: 1.13, 4.04).

    CONCLUSION:

    The findings are compatible with the hypothesis that there is an association between endogenously synthesized MUFAs and cancer death.

  • 22.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Ahlbom, Anders
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berglund, Lars G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wolk, Alicja
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Total mortality after changes in leisure time physical activity in 50 year old men: 35 year follow-up of population based cohort2009In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 338, p. b688-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine how change in level of physical activity after middle age influences mortality and to compare it with the effect of smoking cessation. DESIGN: Population based cohort study with follow-up over 35 years. SETTING: Municipality of Uppsala, Sweden. PARTICIPANTS: 2205 men aged 50 in 1970-3 who were re-examined at ages 60, 70, 77, and 82 years. MAIN OUTCOME MEASURE: Total (all cause) mortality. RESULTS: The absolute mortality rate was 27.1, 23.6, and 18.4 per 1000 person years in the groups with low, medium, and high physical activity, respectively. The relative rate reduction attributable to high physical activity was 32% for low and 22% for medium physical activity. Men who increased their physical activity level between the ages of 50 and 60 continued to have a higher mortality rate during the first five years of follow-up (adjusted hazard ratio 2.64, 95% confidence interval 1.32 to 5.27, compared with unchanged high physical activity). After 10 years of follow-up their increased physical activity was associated with reduced mortality to the level of men with unchanged high physical activity (1.10, 0.87 to 1.38). The reduction in mortality associated with increased physical activity (0.51, 0.26 to 0.97, compared with unchanged low physical activity) was similar to that associated with smoking cessation (0.64, 0.53 to 0.78, compared with continued smoking). CONCLUSIONS: Increased physical activity in middle age is eventually followed by a reduction in mortality to the same level as seen among men with constantly high physical activity. This reduction is comparable with that associated with smoking cessation.

  • 23.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ahlbom, Anders
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berglund, Lars G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wolk, Alicja
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Total mortality after changes in leisure time physical activity in 50 year old men: 35 year follow-up of population based cohort (Reprinted from BMJ, vol 338, b688, 2009)2009In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 43, no 7, p. 482-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine how change in level of physical activity after middle age influences mortality and to compare it with the effect of smoking cessation.

    DESIGN: Population based cohort study with follow-up over 35 years.

    SETTING: Municipality of Uppsala, Sweden.

    PARTICIPANTS: 2205 men aged 50 in 1970-3 who were reexamined at ages 60, 70, 77, and 82 years.

    MAIN OUTCOME MEASURE: Total (all cause) mortality.

    RESULTS: The absolute mortality rate was 27.1, 23.6, and 18.4 per 1000 person years in the groups with low, medium, and high physical activity, respectively. The relative rate reduction attributable to high physical activity was 32% for low and 22% for medium physical activity. Men who increased their physical activity level between the ages of 50 and 60 continued to have a higher mortality rate during the first five years of follow-up (adjusted hazard ratio 2.64, 95% confidence interval 1.32 to 5.27, compared with unchanged high physical activity). After 10 years of follow-up their increased physical activity was associated with reduced mortality to the level of men with unchanged high physical activity (1.10, 0.87 to 1.38). The reduction in mortality associated with increased physical activity (0.51, 0.26 to 0.97, compared with unchanged low physical activity) was similar to that associated with smoking cessation (0.64, 0.53 to 0.78, compared with continued smoking).

    CONCLUSIONS: Increased physical activity in middle age is eventually followed by a reduction in mortality to the same level as seen among men with constantly high physical activity. This reduction is comparable with that associated with smoking cessation

  • 24.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Goodman, Anna
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Koupil, Ilona
    Birth Weight is not Associated With Risk of Fracture: Results from Two Swedish Cohort Studies2014In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 29, no 10, p. 2152-2160Article in journal (Refereed)
    Abstract [en]

    Development and growth in utero has been suggested to influence bone health. However, the relationship with risk of fracture in old age is largely unknown. Using Cox proportional hazards regression, we studied the association between birth weight and fractures at ages 50-94 among 10,893 men and women (48% women) from the Uppsala Birth Cohort Study (UBCoS, born 1915-29) and 1334 men from the Uppsala Longitudinal Study of Adult Men (ULSAM, born 1920-24). Measured birth weight was collected from hospital or midwives' records and fractures from the Swedish National Patient Register. We observed 2796 fractures (717 of these were hip fractures) in UBCoS and 335 fractures (102 hip fractures) in ULSAM. In UBCoS, the hazard ratio (HR) per 1 kg increase in birth weight, adjusted for sex and socioeconomic status at birth, was 1.01 [95% confidence interval (CI), 0.94-1.09] for any fracture and 1.06 (95% CI, 0.91-1.23) for hip fracture. Estimates in ULSAM were similar. We did not observe a differential association of birth weight with fractures occurring before age 70 or after age 70 years. Neither birth weight standardized for gestational age nor gestational duration was associated with fracture rate. In linear regression, birth weight was not associated with bone mineral density among 303 men who were 82-years-old in ULSAM but showed positive associations with total body bone mineral content (β per kg increase in birth weight, adjusted for social class and age, 133; 95% CI, 30-227). This association was attenuated after further adjustment for body mass index and height (β, 41; 95% CI, -43-126). We conclude that birth weight is associated with bone mineral content but this association does not translate into an association with risk of fracture in men and women aged 50-94 years.

  • 25.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Koupil, I
    Size at birth is not associated with risk of hip fracture: results from two population-based cohorts2013In: Bone Abstracts, ISSN 2052-1219, Vol. 1, p. OC1.3-Article in journal (Other academic)
    Abstract [en]

    Early life growth has been suggested to influence bone health. However, the relationship with risk of hip fracture in old age has not been thoroughly investigated. We therefore studied the association between birth weight and hip fracture incidence after age 50 among 10 893 men and women (48% women) from the Uppsala Birth Cohort Study (UBCoS, born 1915–1929) and 1334 men from the Uppsala Longitudinal Study of Adult Men (ULSAM, born 1920–1924). Birth weight was collected from hospital or midwives’ records and hip fractures were obtained from the Swedish Hospital Discharge Register.

    We observed 717 hip fractures in UBCoS (458 in women, 259 in men, end of follow-up: 31 December 2008) and 102 hip fractures in ULSAM (end of follow-up: 31 December 2009). There were no indications of non-linear associations. Results are presented as hazard ratios (HR) and 95% CI per 1 kg increase in birth weight.

    The crude HR for 1 kg increase in birth weight on hip fracture rate in UBCoS was 0.99 (95% CI: 0.85–1.14). After controlling for gender and socioeconomic status at birth, the HR was 1.06 (95% CI: 0.91–1.23). Additional adjustment for adult height and comorbidity in a subgroup of UBCoS men (n=1241, 50 hip fractures) gave a HR of 0.97 (95% CI: 0.52–1.80). Parity and gestational age did not largely influence the estimates. Neither birth weight standardized for gestational age nor gestational duration was associated with hip fracture rate.

    The unadjusted HR in ULSAM was 1.06 (95% CI: 0.73–1.53). After adjustment for adult body mass index, height, social class, comorbidity, and smoking status, the HR was 1.03 (95% CI: 0.70–1.51).

    Based on the results from two population-based cohorts with accurate assessment of both birth weight and hip fractures, we conclude that there is no association between birth weight and risk of hip fracture.

  • 26.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Physical activity, obesity and risk of cardiovascular disease in middle-aged men during a median of 30 years of follow-up2016In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, no 4, p. 359-365Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    We aimed to investigate associations between combinations of body mass index (BMI)-categories, levels of physical activity and long-term risk of cardiovascular disease.

    METHOD AND RESULTS:

    At age 50 years, cardiovascular risk factors were assessed in 2196 participating men of the ULSAM-study. This investigation was repeated at age 60, 70, 77 and 82 years. Being physically active (PA) was defined as three hours of recreational or hard physical training per week. The men were categorized according to BMI/PA-status, as PA/normal weight (n = 593 at baseline), non-PA/normal weight (BMI < 25 kg/m(2), n = 580), PA/overweight (n = 418), non-PA/overweight (BMI 25-30 kg/m(2), n = 462), PA/obese (n = 62), non-PA/obese (BMI >30 kg/m(2), n = 81). We used updated data on BMI and physical activity obtained at all examinations. During follow-up (median 30 years) 850 individuals suffered a cardiovascular disease (myocardial infarction, stroke or heart failure). Using updated data on BMI/PA categories, an increased risk for cardiovascular disease was seen with increasing BMI, but a high physical activity was associated with a lower risk of cardiovascular disease within each BMI category: non-PA/normal weight (hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.04-1.66), PA/overweight (HR 1.52, 95% CI 1.20-1.94), non-PA/overweight (HR 1.65, 95% CI 1.31-2.07) PA/obese (HR 2.05, 95% CI 1.44-2.92) and non-PA/obese (HR 2.39, 95% CI 1.74-3.29), using PA/normal weight men as referent.

    CONCLUSIONS:

    Although physical activity was beneficial at all levels of BMI regarding the risk of future cardiovascular disease, there was still a substantial increased risk associated with being overweight or obese during 30 years of follow-up.

  • 27. Carlsson, Sofia
    et al.
    Andersson, Tomas
    de Faire, Ulf
    Lichtenstein, Paul
    Michaelsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ahlbom, Anders
    Using Twin Controls to Study the Effects of BMI on Mortality2011In: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 22, no 1, p. 107-108Article in journal (Refereed)
  • 28. Carlsson, Sofia
    et al.
    Andersson, Tomas
    de Faire, Ulf
    Lichtenstein, Paul
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Ahlbom, Anders
    Body mass index and mortality: is the association explained by genetic factors?2011In: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 22, no 1, p. 98-103Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Numerous studies have shown that higher body mass index (BMI) is associated with higher mortality. We investigated the extent to which this association might be explained by genetic factors. METHODS: We used data from the Swedish Twin Registry on twins born 1886-1958 who answered a questionnaire in 1969/1970 or 1972 (n = 44,258). Information on mortality from all-causes (n = 14,217), cardiovascular disease (CVD; n = 9009), and coronary heart disease (CHD; n = 3564) was obtained by linkage to the national Causes of Death Registry for the years 1972-2004. The association between BMI and mortality was studied without control for genetic factors in cohort analyses and with control for genetic factors in co-twin control analyses. RESULTS: In cohort analyses, there was a clear dose-response relationship between BMI and mortality. Hazard ratios per 1 unit increase in BMI in subjects with BMI ≥18.5 were 1.05 (95% confidence interval = 1.05-1.06) for all-cause mortality, 1.07 (1.07-1.09) for CVD mortality, and 1.09 (1.08-1.10) for CHD mortality. Similar results were seen in co-twin control analyses of dizygotic twins. However, within monozygotic twins, BMI was associated with death from CHD (OR = 1.06; 1.00-1.12), whereas the association with all-cause mortality (1.01, 0.98-1.04) and CVD mortality (1.02, 0.98-1.06) was weak. CONCLUSIONS: Our findings indicate that there is an association between high BMI and mortality from CHD that is not explained by genetic confounding. However, a large part of the association between BMI and other causes of death may be explained by genes rather than by a causal link between these factors.

  • 29. Carlsson, Sofia
    et al.
    Andersson, Tomas
    Lichtenstein, Paul
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ahlbom, Anders
    Genetic effects on physical activity: results from the Swedish Twin Registry2006In: Medicine & Science in Sports & Exercise, ISSN 0195-9131, E-ISSN 1530-0315, Vol. 38, no 8, p. 1396-1401Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim of this study was to investigate the genetic effects on leisure-time physical activity using data from the Swedish Twin Registry. METHODS: We investigated 13,362 twin pairs (5334 monozygotic and 8028 dizygotic pairs) aged 14-46 yr. Information on leisure-time physical activity was obtained by questionnaire. Correlations and odds ratios of physical activity were calculated for males, females, and monozygotic and dizygotic twins, respectively. Structural equation modeling was used to estimate the contribution of genetic effects as well as common and nonshared environmental factors on leisure-time physical activity. RESULTS: About one third of the twins reported that they exercised regularly (26% in females and 39% in males). The correlations of physical activity were twice as high in monozygotic compared with dizygotic twins, suggesting the presence of genetic effects. The variation in physical activity due to heritage was 57% (95% confidence interval (CI) = 0.49-0.63) in males and 50% (95% CI = 0.49-0.55) in females. The common environmental influence on physical activity was very small compared with the influence from environmental factors unique to the individual. CONCLUSIONS: Our study establishes heredity as an important component behind individual differences in physical activity in adult men and women. This may be one reason behind difficulties in convincing people to adopt an active lifestyle. Still, this study shows that there is a substantial influence on physical activity from environmental factors unique to the individual.

  • 30. Carlsson, Sofia
    et al.
    Andersson, Tomas
    Lichtenstein, Paul
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ahlbom, Anders
    Physical activity and mortality: is the association explained by genetic selection?2007In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 166, no 3, p. 255-259Article in journal (Refereed)
    Abstract [en]

    Public health recommendations promote physical activity to improve health and longevity. Recent data suggest that the association between physical activity and mortality may be due to genetic selection. Using data on twins, the authors investigated whether genetic selection explains the association between physical activity and mortality. Data were based on a postal questionnaire answered by 13,109 Swedish twin pairs in 1972. The national Cause of Death Register was used for information about all-cause mortality (n=1,800) and cardiovascular disease mortality (n=638) during 1975-2004. The risk of death was reduced by 34% for men (relative risk=0.64, 95% confidence interval: 0.50, 0.83) and by 25% for women (relative risk=0.75, 95% confidence interval: 0.50, 1.14) reporting high physical activity levels. Within-pair comparisons of monozygotic twins showed that, compared with their less active co-twin, the more active twin had a 20% (odds ratio=0.80, 95% confidence interval: 0.65, 0.99) reduced risk of all-cause mortality and a 32% (odds ratio=0.68, 95% confidence interval: 0.49, 0.95) reduced risk of cardiovascular disease mortality. Results indicate that physical activity is associated with a reduced risk of mortality not due to genetic selection. This finding supports a causal link between physical activity and mortality.

  • 31. Carlsson, Sofia
    et al.
    Andersson, Tomas
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Vågerö, Denny
    Ahlbom, Anders
    Late retirement is not associated with increased mortality, results based on all Swedish retirements 1991-20072012In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 27, no 6, p. 483-486Article in journal (Refereed)
  • 32.
    Collins, Gary S.
    et al.
    Univ Oxford, Ctr Stat Med, Wolfson Coll Annexe, Oxford OX2 6UD, England.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Fracture risk assessment: state of the art, methodologically unsound, or poorly reported?2012In: Current osteoporosis reports, ISSN 1544-2241, Vol. 10, no 3, p. 199-207Article in journal (Refereed)
    Abstract [en]

    Osteoporotic fractures, including hip fractures, are a global health concern associated with significant morbidity and mortality as well as a major economic burden. Identifying individuals who are at an increased risk of osteoporotic fracture is an important challenge to be resolved. Recently, multivariable prediction tools have been developed to assist clinicians in the management of their patients by calculating their 10-year risk of fracture (FRAX, QFracture, Garvan) using a combination of known risk factors. These prediction models have revolutionized the way clinicians assess the risk of fracture. Studies evaluating the performance of prediction models in this and other areas of medicine have, however, been characterized by poor design, methodological conduct, and reporting. We examine recently developed fracture prediction models and critically discuss issues in their design, validation, and transparency.

  • 33. Cornelis, M C
    et al.
    Byrne, E M
    Esko, T
    Nalls, M A
    Ganna, A
    Paynter, N
    Monda, K L
    Amin, N
    Fischer, K
    Renstrom, F
    Ngwa, J S
    Huikari, V
    Cavadino, A
    Nolte, I M
    Teumer, A
    Yu, K
    Marques-Vidal, P
    Rawal, R
    Manichaikul, A
    Wojczynski, M K
    Vink, J M
    Zhao, J H
    Burlutsky, G
    Lahti, J
    Mikkilä, V
    Lemaitre, R N
    Eriksson, J
    Musani, S K
    Tanaka, T
    Geller, F
    Luan, J
    Hui, J
    Mägi, R
    Dimitriou, M
    Garcia, M E
    Ho, W-K
    Wright, M J
    Rose, L M
    Magnusson, P K E
    Pedersen, N L
    Couper, D
    Oostra, B A
    Hofman, A
    Ikram, M A
    Tiemeier, H W
    Uitterlinden, A G
    van Rooij, F J A
    Barroso, I
    Johansson, I
    Xue, L
    Kaakinen, M
    Milani, L
    Power, C
    Snieder, H
    Stolk, R P
    Baumeister, S E
    Biffar, R
    Gu, F
    Bastardot, F
    Kutalik, Z
    Jacobs, D R
    Forouhi, N G
    Mihailov, E
    Lind, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindgren, C
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Morris, A
    Jensen, M
    Khaw, K-T
    Luben, R N
    Wang, J J
    Männistö, S
    Perälä, M-M
    Kähönen, M
    Lehtimäki, T
    Viikari, J
    Mozaffarian, D
    Mukamal, K
    Psaty, B M
    Döring, A
    Heath, A C
    Montgomery, G W
    Dahmen, N
    Carithers, T
    Tucker, K L
    Ferrucci, L
    Boyd, H A
    Melbye, M
    Treur, J L
    Mellström, D
    Hottenga, J J
    Prokopenko, I
    Tönjes, A
    Deloukas, P
    Kanoni, S
    Lorentzon, M
    Houston, D K
    Liu, Y
    Danesh, J
    Rasheed, A
    Mason, M A
    Zonderman, A B
    Franke, L
    Kristal, B S
    Karjalainen, J
    Reed, D R
    Westra, H-J
    Evans, M K
    Saleheen, D
    Harris, T B
    Dedoussis, G
    Curhan, G
    Stumvoll, M
    Beilby, J
    Pasquale, L R
    Feenstra, B
    Bandinelli, S
    Ordovas, J M
    Chan, A T
    Peters, U
    Ohlsson, C
    Gieger, C
    Martin, N G
    Waldenberger, M
    Siscovick, D S
    Raitakari, O
    Eriksson, J G
    Mitchell, P
    Hunter, D J
    Kraft, P
    Rimm, E B
    Boomsma, D I
    Borecki, I B
    Loos, R J F
    Wareham, N J
    Vollenweider, P
    Caporaso, N
    Grabe, H J
    Neuhouser, M L
    Wolffenbuttel, B H R
    Hu, F B
    Hyppönen, E
    Järvelin, M-R
    Cupples, L A
    Franks, P W
    Ridker, P M
    van Duijn, C M
    Heiss, G
    Metspalu, A
    North, K E
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nettleton, J A
    van Dam, R M
    Chasman, D I
    Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption2015In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 20, no 5, p. 647-656Article in journal (Refereed)
    Abstract [en]

    Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91 462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.

  • 34. Cornelis, M C
    et al.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ärnlöv, J
    Elmståhl, S
    Söderberg, S
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    Targeted proteomic analysis of habitual coffee consumption.2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 2, p. 200-211Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Coffee drinking has been implicated in mortality and a variety of diseases but potential mechanisms underlying these associations are unclear. Large-scale systems epidemiological approaches may offer novel insights to mechanisms underlying associations of coffee with health.

    OBJECTIVE: We performed an analysis of known and novel protein markers linked to cardiovascular disease and their association with habitual coffee intake in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 816) and followed up top proteins in the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 635) and EpiHealth (n = 2418).

    METHODS: In PIVUS and ULSAM, coffee intake was measured by 7-day dietary records whilst a computer-based food frequency questionnaire was used in EpiHealth. Levels of up to 80 proteins were assessed in plasma by a proximity extension assay.

    RESULTS: Four protein-coffee associations adjusted for age, sex, smoking and BMI, met statistical significance in PIVUS (FDR < 5%, P < 2.31 × 10(-3) ): leptin (LEP), chitinase-3-like protein 1 (CHI3L), tumour necrosis factor (TNF) receptor 6 and TNF-related apoptosis-inducing ligand. The inverse association between coffee intake and LEP replicated in ULSAM (β, -0.042 SD per cup of coffee, P = 0.028) and EpiHealth (β, -0.025 SD per time of coffee, P = 0.004). The negative coffee-CHI3L association replicated in EpiHealth (β, -0.07, P = 1.15 × 10(-7) ), but not in ULSAM (β, -0.034, P = 0.16).

    CONCLUSIONS: The current study supports an inverse association between coffee intake and plasma LEP and CHI3L1 levels. The coffee-CHI3L1 association is novel and warrants further investigation given links between CHI3L1 and health conditions that are also potentially influenced by coffee.

  • 35.
    Englund, Gunilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Hallberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. klin farm.
    Artursson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Association between the number of coadministered P-glycoprotein inhibitors and serum digoxin levels in patients on therapeutic drug monitoring2004In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 2, p. 8-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The ABC transporter P-glycoprotein (P-gp) is recognized as a site for drug-drug interactions and provides a mechanistic explanation for clinically relevant pharmacokinetic interactions with digoxin. The question of whether several P-gp inhibitors may have additive effects has not yet been addressed. METHODS: We evaluated the effects on serum concentrations of digoxin (S-digoxin) in 618 patients undergoing therapeutic drug monitoring. P-gp inhibitors were classified as Class I, with a known effect on digoxin kinetics, or Class II, showing inhibition in vitro but no documented effect on digoxin kinetics in humans. Mean S-digoxin values were compared between groups of patients with different numbers of coadministered P-gp inhibitors by a univariate and a multivariate model, including the potential covariates age, sex, digoxin dose and total number of prescribed drugs. RESULTS: A large proportion (47%) of the digoxin patients undergoing therapeutic drug monitoring had one or more P-gp inhibitor prescribed. In both univariate and multivariate analysis, S-digoxin increased in a stepwise fashion according to the number of coadministered P-gp inhibitors (all P values < 0.01 compared with no P-gp inhibitor). In multivariate analysis, S-digoxin levels were 1.26 +/- 0.04, 1.51 +/- 0.05, 1.59 +/- 0.08 and 2.00 +/- 0.25 nmol/L for zero, one, two and three P-gp inhibitors, respectively. The results were even more pronounced when we analyzed only Class I P-gp inhibitors (1.65 +/- 0.07 for one and 1.83 +/- 0.07 nmol/L for two). CONCLUSIONS: Polypharmacy may lead to multiple drug-drug interactions at the same site, in this case P-gp. The S-digoxin levels increased in a stepwise fashion with an increasing number of coadministered P-gp inhibitors in patients taking P-gp inhibitors and digoxin concomitantly. As coadministration of digoxin and P-gp inhibitors is common, it is important to increase awareness about P-gp interactions among prescribing clinicians.

  • 36. Engstrom, Annette
    et al.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Vahter, Marie
    Julin, Bettina
    Wolk, Alicja
    Akesson, Agneta
    Associations between dietary cadmium exposure and bone mineral density and risk of osteoporosis and fractures among women2012In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, no 6, p. 1372-1378Article in journal (Refereed)
    Abstract [en]

    Osteoporosis and its main health outcome, fragility fractures, are large and escalating public health problems. Cadmium, a widespread food contaminant, is a proposed risk factor; still the association between estimated dietary cadmium exposure and bone mineral density (BMD) has never been assessed. Within a sub-cohort of the Swedish Mammography Cohort, we assessed dietary cadmium exposure based on a food frequency questionnaire (1997) and urinary cadmium (2004-2008) in relation to total-body BMD and risk of osteoporosis and fractures (1997-2009) among 2676 women (aged 56-69 years). In multivariable-adjusted linear regression, dietary cadmium was inversely associated with BMD at the total body and lumbar spine. After further adjustment for dietary factors important for bone health and cadmium bioavailability-calcium, magnesium, iron and fiber, the associations became more pronounced. A 32% increased risk of osteoporosis (95% Cl: 2-71%) and 31% increased risk for any first incident fracture (95% Cl; 2-69%) were observed comparing high dietary cadmium exposure (>= 13 mu g/day, median) with lower exposures (<13 mu g/day). By combining high dietary with high urinary cadmium (>= 0.50 mu g/g creatinine), odds ratios among never-smokers were 2.65 (95% Cl: 1.43-4.91) for osteoporosis and 3.05 (95% Cl; 1.66-5.59) for fractures. In conclusion, even low-level cadmium exposure from food is associated with low BMD and an increased risk of osteoporosis and fractures. The partial masking of the associations by essential nutrients indicates important interplay between dietary factors and contaminants present in food. In separate analyses, dietary and urinary cadmium underestimated the association with bone effects.

  • 37. Engström, Annette
    et al.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Suwazono, Yasushi
    Wolk, Alicja
    Vahter, Marie
    Åkesson, Agneta
    Long-term cadmium exposure and the association with bone mineral density and fractures in a population-based study among women2011In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 26, no 3, p. 486-495Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:: All people are exposed to cadmium (Cd) via food, smokers are additionally exposed. High Cd exposure is associated with severe bone damage, but the public health impact in relation to osteoporosis and fractures at low environmental exposure remains to be clarified. METHODS:: Within the population-based Swedish Mammography Cohort, we assessed urinary Cd (U-Cd, mug/g creatinine, cr) as a marker of life-time exposure and bone mineral density (BMD) by DXA among 2,688 women. Register-based information on fractures was retrieved from 1997 to 2009. Associations were evaluated by multivariable regression analyses. RESULTS:: In linear regression U-Cd was inversely associated with BMD at the total body (p<0.001), femoral neck (p=0.025), total hip (p=0.004), lumbar spine (p=0.088), and volumetric femoral neck (p=0.013). In comparison to women with U-Cd <0.50 mug/g cr, those with U-Cd >/=0.75 mug/g cr had OR 2.45 (95% CI, 1.51-3.97) and 1.97 (95% CI, 1.24-3.14) for osteoporosis at the femoral neck and lumbar spine, respectively. Among never-smokers, the corresponding ORs were 3.45 (95% CI, 1.46-8.23) and 3.26 (95% CI, 1.44-7.38). For any first fracture (n=395) OR was 1.16 (95% CI, 0.89-1.50) comparing U-Cd >/=0.5 mug/g cr with lower levels. Among never-smokers, the ORs (95% CIs) were 2.03 (1.33-3.09) for any first fracture, 2.06 (1.28-3.32) for first osteoporotic fracture, 2.18 (1.20-3.94) for first distal forearm fracture and 1.89 (1.25-2.85) for multiple incident fractures. CONCLUSIONS:: U-Cd at low environmental exposure from food in a general population of women showed modest but significant association with both BMD and fractures especially in never smokers indicating a larger concern than previously known.

  • 38.
    Fang, Fang
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, S-17177 Stockholm, Sweden.
    Hållmarker, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Mora Hosp, Dept Internal Med, Mora, Sweden.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ingre, Caroline
    Karolinska Univ Hosp, Dept Neurol, Stockholm, Sweden.; Karolinska Inst, Dept Clin Neurosci, S-17177 Stockholm, Sweden.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ahlbom, Anders
    Karolinska Inst, Inst Environm Med, S-17177 Stockholm, Sweden.
    Feychting, Maria
    Karolinska Inst, Inst Environm Med, S-17177 Stockholm, Sweden.
    Amyotrophic lateral sclerosis among cross-country skiers in Sweden.2016In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 31, no 3, p. 247-253Article in journal (Refereed)
    Abstract [en]

    A highly increased risk of amyotrophic lateral sclerosis (ALS) has been suggested among professional athletes. We aimed to examine whether long distance cross-country skiers have also a higher risk of ALS and whether the increased risk was modified by skiing performance. We followed 212,246 cross-country skiers in the Swedish Vasaloppet cohort and a random selection of 508,176 general Swedes not participating in the Vasaloppet during 1989-2010. The associations between cross-country skiing as well as skiing performance (i.e., type of race, finishing time and number of races) and the consequent risk of ALS were estimated through hazard ratios (HRs) derived from Cox model. During the study, 39 cases of ALS were ascertained among the skiers. The fastest skiers (100-150 % of winner time) had more than fourfold risk of ALS (HR 4.31, 95 % confidence interval [CI] 1.78-10.4), as compared to skiers that finished at >180 % of winner time. Skiers who participated >4 races during this period had also a higher risk (HR 3.13, 95 % CI 1.37-7.17) than those participated only one race. When compared to the non-skiers, the fastest skiers still had a higher risk (HR 2.08, 95 % CI 1.12-3.84), as skiers who had >4 races (HR 1.88, 95 % CI 1.05-3.35), but those finishing at >180 % of winner time had a lower risk (HR 0.46, 95 % CI 0.24-0.87). In conclusion, long distance cross-country skiing is associated with a higher risk of ALS, but only among the best skiers; recreational skiers appear to have a largely reduced risk.

  • 39. Farahmand, Bahman Y.
    et al.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ahlbom, Anders
    Ljunghall, Sverker
    Baron, John A.
    Survival after hip fracture2005In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 16, no 12, p. 1583-90Article in journal (Refereed)
    Abstract [en]

    Although it is known that overall mortality is increased after hip fracture, the influence of hip fracture risk factors on the subsequent mortality and cause of death has not been well studied. The objective of this study was to establish the survival after hip fracture in women and to assess the impact of comorbidity on mortality. We identified a complete population-based set of 2,245 incident hip fracture cases and 4,035 randomly selected population-based controls among women 50-81 years old in Sweden and followed these subjects for an average of 5 years through the Swedish National Inpatient and Cause-of-Death Registers. Information on factors related to hip fracture was obtained through linkage to hospital discharge data and through a mailed questionnaire. We studied excess mortality of hip fracture patients compared to controls using survival curves and proportional hazard regression models. During follow-up, 896 hip fracture patients (40%) and 516 (13%) controls died. The relative risk (RR) of death, adjusted for age and previous hospitalization for serious disease, was 2.3 (95% CI 2.0-2.5). Although the highest mortality risks were in the 1st 6 months post-fracture, RRs for fractures versus controls were increased for at least 6 years. Increased mortality was apparent both in those with evidence of comorbidity and those without. Hip fracture patients have a substantially increased risk of death that persists for at least 6 years post-fracture. The relative excess mortality is independent of comorbidity and known hip fracture risk factors.

  • 40. Försth, P
    et al.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sandén, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Does fusion improve the outcome after decompressive surgery for lumbar spinal stenosis?: a two-year follow-up study involving 5390 patients2013In: The Bone & Joint Journal, ISSN 2049-4408, Vol. 95-B, no 7, p. 960-965Article in journal (Refereed)
    Abstract [en]

    Whether to combine spinal decompression with fusion in patients with symptomatic lumbar spinal stenosis remains controversial. We performed a cohort study to determine the effect of the addition of fusion in terms of patient satisfaction after decompressive spinal surgery in patients with and without a degenerative spondylolisthesis.                  

    The National Swedish Register for Spine Surgery (Swespine) was used for the study. Data were obtained for all patients in the register who underwent surgery for stenosis on one or two adjacent lumbar levels. A total of 5390 patients fulfilled the inclusion criteria and completed a two-year follow-up. Using multivariable models the results of 4259 patients who underwent decompression alone were compared with those of 1131 who underwent decompression and fusion. The consequence of having an associated spondylolisthesis in the operated segments pre-operatively was also considered.                

    At two years there was no significant difference in patient satisfaction between the two treatment groups for any of the outcome measures, regardless of the presence of a pre-operative spondylolisthesis. Moreover, the proportion of patients who required subsequent further lumbar surgery was also similar in the two groups.                  

    In this large cohort the addition of fusion to decompression was not associated with an improved outcome.

  • 41.
    Försth, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sandén, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Fusion Surgery for Lumbar Spinal Stenosis REPLY2016In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 375, no 6, p. 599-600Article in journal (Other academic)
  • 42.
    Försth, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sandén, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    More on Fusion Surgery for Lumbar Spinal Stenosis2016In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 375, no 18, p. 1806-1807Article in journal (Refereed)
  • 43.
    Försth, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Karolinska Inst, Stockholm Spine Ctr, S-10401 Stockholm, Sweden..
    Olafsson, Gylfi
    Karolinska Inst, Dept Learning Informat Management & Eth, S-10401 Stockholm, Sweden.;Quantify Res, Stockholm, Sweden..
    Carlsson, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Frost, Anders
    Karolinska Inst, Stockholm Spine Ctr, S-10401 Stockholm, Sweden..
    Borgstrom, Fredrik
    Karolinska Inst, Dept Learning Informat Management & Eth, S-10401 Stockholm, Sweden.;Quantify Res, Stockholm, Sweden..
    Fritzell, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Futurum Acad Hlth & Care, Neuroorthoped Ctr, Ryhov, Sweden..
    Öhagen, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaelsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sanden, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    A Randomized, Controlled Trial of Fusion Surgery for Lumbar Spinal Stenosis2016In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 374, no 15, p. 1413-1423Article in journal (Refereed)
    Abstract [en]

    BACKGROUND The efficacy of fusion surgery in addition to decompression surgery in patients who have lumbar spinal stenosis, with or without degenerative spondylolisthesis, has not been substantiated in controlled trials.

    METHODS We randomly assigned 247 patients between 50 and 80 years of age who had lumbar spinal stenosis at one or two adjacent vertebral levels to undergo either decompression surgery plus fusion surgery (fusion group) or decompression surgery alone (decompression-alone group). Randomization was stratified according to the presence of preoperative degenerative spondylolisthesis (in 135 patients) or its absence. Outcomes were assessed with the use of patient-reported outcome measures, a 6-minute walk test, and a health economic evaluation. The primary outcome was the score on the Oswestry Disability Index (ODI; which ranges from 0 to 100, with higher scores indicating more severe disability) 2 years after surgery. The primary analysis, which was a per-protocol analysis, did not include the 14 patients who did not receive the assigned treatment and the 5 who were lost to follow-up.

    RESULTS There was no significant difference between the groups in the mean score on the ODI at 2 years (27 in the fusion group and 24 in the decompression-alone group, P = 0.24) or in the results of the 6-minute walk test (397 m in the fusion group and 405 m in the decompression- alone group, P = 0.72). Results were similar between patients with and those without spondylolisthesis. Among the patients who had 5 years of follow-up and were eligible for inclusion in the 5-year analysis, there were no significant differences between the groups in clinical outcomes at 5 years. The mean length of hospitalization was 7.4 days in the fusion group and 4.1 days in the decompression-alone group (P< 0.001). Operating time was longer, the amount of bleeding was greater, and surgical costs were higher in the fusion group than in the decompression-alone group. During a mean follow-up of 6.5 years, additional lumbar spine surgery was performed in 22% of the patients in the fusion group and in 21% of those in the decompression-alone group.

    CONCLUSIONS Among patients with lumbar spinal stenosis, with or without degenerative spondylolisthesis, decompression surgery plus fusion surgery did not result in better clinical outcomes at 2 years and 5 years than did decompression surgery alone.

  • 44.
    Gedeborg, Rolf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Chen, Li-Hui
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Thiblin, Ingemar
    Centers for Disease Control and Prevention, Hyattsville, Maryland; Department of Surgical Sciences—Forensic Medicine.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Warner, Margaret
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Prehospital injury deaths-Strengthening the case for prevention: Nationwide cohort study2012In: Journal of Trauma and Acute Care Surgery, ISSN 2163-0755, E-ISSN 2163-0763, Vol. 72, no 3, p. 765-772Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: To determine the frequency and characteristics of prehospital deaths compared with hospital deaths in different subpopulations with severe injuries.

    METHODS: Population-based cohort study using person-based linkage of the Swedish nationwide hospital discharge register with death certificate data. In all, 28,715 injury deaths were identified among 419,137 cases of severe injury during 1998 to 2004. Prehospital deaths were defined as autopsied out-of-hospital deaths with injury as the underlying cause. Their impact on mortality prediction was assessed using the International Classification of Disease Injury Severity Score with the C statistic as a measure of discrimination.

    RESULTS: The majority of all injury deaths occurred either at the scene or before hospitalization. Among persons younger than 65 years, for each hospital death there were nine prehospital deaths. A high proportion of deaths from drowning, suffocation, and firearm injuries were prehospital (85, 82, and 67% of all cases, respectively). More than 90% of hospital deaths resulted from unintentional injuries, while only 43% of prehospital deaths were unintentional. The largest increase in a cause-specific case fatality risk estimate was seen for poisoning, where inclusion of prehospital deaths increased the risk estimate from 1.6% to 22.8%. Injury mortality prediction based on International Classification of Disease Injury Severity Score improved when prehospital deaths were added to hospital data (C statistic increased from 0.86 to 0.93).

    CONCLUSIONS: Prehospital deaths constitute the majority of trauma deaths and differ in major characteristics from hospital deaths. The high proportion of prehospital deaths among young and middle aged people highlights the potential impact of preventive efforts.

  • 45.
    Gedeborg, Rolf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Engquist, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Identification of Incident Injuries in Hospital Discharge Registers2008In: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 19, no 6, p. 860-867Article in journal (Refereed)
    Abstract [en]

    Background: Hospital discharge data on injuries constitute a potentially powerful data source for epidemiologic studies. However, reliable identification of incident injury admissions is necessary. The objective of this study was to develop a prediction model for identifying incident hospital admissions, based on variables derived from a hospital discharge register.

    Methods: There were 743,022 hospital admissions for injury in Sweden 1998–2004. Of these, 23,920 were in the county of Uppsala and 24% of these people had previous injury admissions. To determine if these admissions were new injuries or readmissions for earlier injuries, we reviewed 817 randomly selected hospital records. A prediction model for incident injury admissions was developed on the basis of patient age, type of admission (urgent or elective), time interval from the previous injury admission, main diagnosis, and department type.

    Results: The final prediction model showed good discrimination (c-statistic = 0.969). This model was applied to the validation dataset using the optimal cut-off level, and the resulting sensitivity and specificity were adjusted according to the proportion with a previous injury admission in each injury category. The injury with the highest proportion of possible readmissions was hip contusion (35%). Nevertheless, using the prediction model, incident hip contusions were identified with a sensitivity of 94% (95% confidence interval = 93%–95%) and a specificity of 95% (94%–97%). The accuracy was higher for all other injury categories.

    Conclusions: Incident injury admissions can be accurately separated from readmissions using a prediction model based on information derived from hospital discharge data.

  • 46.
    Gedeborg, Rolf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Diagnosis-dependent misclassification of infections using administrative data variably affected incidence and mortality estimates in ICU patients2007In: Journal of Clinical Epidemiology, ISSN 0895-4356, E-ISSN 1878-5921, Vol. 60, no 2, p. 155-162Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To determine the accuracy of hospital discharge diagnoses in identifying severe infections among intensive care unit (ICU) patients, and estimate the impact of misclassification on incidence and 1-year mortality. STUDY DESIGN AND SETTING: Sepsis, pneumonia, and central nervous system (CNS) infections among 7,615 ICU admissions were identified using ICD-9 and ICD-10 diagnoses from the Swedish hospital discharge register (HDR). Sensitivity, specificity, and likelihood ratios were calculated using ICU database diagnoses as reference standard, with inclusion in sepsis trials (IST) as secondary reference for sepsis. RESULTS: CNS infections were accurately captured (sensitivity 95.4% [confidence interval (CI)=86.8-100] and specificity 99.6% [CI=99.4-99.8]). Community-acquired sepsis (sensitivity 51.1% [CI=41.0-61.2] and specificity 99.4% [CI=99.2-99.6]) and primary pneumonia (sensitivity 38.2% [CI=31.2-45.2] and specificity 98.6% [CI=98.2-99.0]) were more accurately detected than sepsis and pneumonia in general. One-year mortality was accurately estimated for primary pneumonia but underestimated for community-acquired sepsis. However, there were only small differences in sensitivity and specificity between HDR and ICU data in the ability to identify IST. ICD-9 appeared more accurate for sepsis, whereas ICD-10 was more accurate for pneumonia. CONCLUSION: Accuracy of hospital discharge diagnoses varied depending on diagnosis and case definition. The pattern of misclassification makes estimates of relative risk more accurate than estimates of absolute risk.

  • 47.
    Gedeborg, Rolf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Thiblin, Ingemar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Prediction of mortality risk in victims of violent crimes2017In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 281, p. 92-97Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: To predict mortality risk in victims of violent crimes based on individual injury diagnoses and other information available in health care registries.

    METHODS: Data from the Swedish hospital discharge registry and the cause of death registry were combined to identify 15,000 hospitalisations or prehospital deaths related to violent crimes. The ability of patient characteristics, injury type and severity, and cause of injury to predict death was modelled using conventional, Lasso, or Bayesian logistic regression in a development dataset and evaluated in a validation dataset.

    RESULTS: Of 14,470 injury events severe enough to cause death or hospitalization 3.7% (556) died before hospital admission and 0.5% (71) during the hospital stay. The majority (76%) of hospital survivors had minor injury severity and most (67%) were discharged from hospital within 1day. A multivariable model with age, sex, the ICD-10 based injury severity score (ICISS), cause of injury, and major injury region provided predictions with very good discrimination (C-index=0.99) and calibration. Adding information on major injury interactions further improved model performance. Modeling individual injury diagnoses did not improve predictions over the combined ICISS score.

    CONCLUSIONS: Mortality risk after violent crimes can be accurately estimated using administrative data. The use of Bayesian regression models provides meaningful risk assessment with more straightforward interpretation of uncertainty of the prediction, potentially also on the individual level. This can aid estimation of incidence trends over time and comparisons of outcome of violent crimes for injury surveillance and in forensic medicine.

  • 48.
    Gedeborg, Rolf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Thiblin, Ingemar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Population density and mortality among individuals in motor vehicle crashes2010In: Injury Prevention, ISSN 1353-8047, E-ISSN 1475-5785, Vol. 16, no 5, p. 302-308Article in journal (Refereed)
    Abstract [en]

    Objective

    To assess whether higher mortality rates among individuals in motor vehicle crashes in areas with low population density depend on injury type and severity or are related to the performance of emergency medical services (EMS).

    Methods

    Prehospital and hospital deaths were studied in a population-based cohort of 41 243 motor vehicle crashes that occurred in Sweden between 1998 and 2004. The final multivariable analysis was restricted to 6884 individuals in motor vehicle crashes, to minimise the effects of confounding factors.

    Results

    Crude mortality rates following motor vehicle crashes were inversely related to regional population density. In regions with low population density, the unadjusted rate ratio for prehospital death was 2.2 (95% CI 1.9 to 2.5) and for hospital death 1.5 (95% CI 1.1 to 1.9), compared with a high-density population. However, after controlling for regional differences in age, gender and the type/severity of injuries among 6884 individuals in motor vehicle crashes, low population density was no longer associated with increased mortality. At 25 years of age, predicted prehospital mortality was 9% lower (95% CI 5% to 12%) in regions with low population density compared with high population density. This difference decreased with increasing age, but was still 3% lower (95% CI 0.5% to 5%) at 65 years of age.

    Conclusions

    The inverse relationship between population density and mortality among individuals in motor vehicle crashes is related to pre-crash factors that influence the type and severity of injuries and not to differences in EMS.

  • 49.
    Gedeborg, Rolf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Thiblin, Ingemar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    The impact of clinically undiagnosed injuries on survival estimates2009In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 37, no 2, p. 449-55Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:: Missed injury diagnoses may cause potentially preventable deaths. To estimate the effect of clinically undiagnosed injuries on injury-specific survival estimates and the accuracy of an injury severity score. To also estimate the potentially preventable mortality attributable to these injuries. DESIGN, SETTING, AND PATIENTS:: In a nation-wide, population-based study, data were collected from all hospital admissions for injuries in Sweden between 1998 and 2004. We studied 8627 deaths in hospital among 598,137 incident hospital admissions. MEASUREMENTS AND MAIN RESULTS:: New specific-injury categories were added in 7.4% (95% confidence interval [CI] 6.8-8.0) of all deaths with an autopsy rate of 24.2%. It was estimated that this proportion would have increased to 25.1% (95% CI 23.0-27.2), if all deaths had been autopsied. The most pronounced effect of clinically undiagnosed injuries was found for internal organ injury in the abdomen or pelvis, where they reduced the estimated survival from 0.83 to 0.69 (95% CI for the difference: 0.09-0.20). Autopsy diagnoses also revealed substantial bias of survival estimates for vascular injuries in the thorax and crush injuries to the head. The performance of the International Classification of Diseases Injury Severity Score improved when autopsy diagnoses were added to hospital discharge diagnoses. The maximum proportion of injury deaths attributable to missed injuries was estimated to be 6.5%. CONCLUSIONS:: Maintaining a high autopsy rate and merging accurate hospital discharge data and autopsy data are effective ways to improve the accuracy of survival estimates and mortality prediction models, and to estimate mortality attributable to diagnostic failures.

  • 50.
    Hagforsen, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Hedstrand, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Nyberg, F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Michaelsson, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Novel findings of Langerhans cells and IL-17 expression in relation to the acrosyringium and pustule in palmoplantar pustulosis2010In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 163, no 3, p. 572-579Article in journal (Refereed)
    Abstract [en]

    Backgound Palmoplantar pustulosis (PPP) is a chronic and intensely inflammatory skin disease with pustules, erythema and scaling localized to the palms and soles. To date, no specific treatment is known. Earlier findings indicate the acrosyringium as the target for the inflammation.

    Objectives To identify specific features of the PPP inflammatory cell infiltrate and mediators of inflammation, which might provide insight into the pathogenesis and possible future treatment of the disease.

    Methods Skin biopsies were taken from 23 patients with typical PPP (23 from involved skin and seven from noninvolved skin) and from 18 healthy controls (10 nonsmokers, eight smokers). Cell infiltrates and inflammation mediators were studied with immunohistochemistry.

    Results A strong inflammation was observed in lesional skin of PPP. Our main findings of Langerhans cells and interleukin-17 close to or in the acrosyringium differs from findings in psoriasis vulgaris. Other inflammatory cells such as CD4+, CD8+, regulatory T cells and CD11a+ cells were also accumulated close to the sweat duct in epidermis and papillary dermis. More CD4+, CD8+, Langerhans cells, plasmacytoid dendritic cells and a higher proportion of regulatory T cells/CD3+ cells were seen in noninvolved palmar skin from patients with PPP compared with healthy controls.

    Conclusions Our novel findings indicate that the inflammation in PPP is initiated by the 'stand-by' innate immune system at the acrosyringium.

12345 1 - 50 of 215
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf