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  • 351.
    Rönn, Monika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Örberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Söderberg, Stefan
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden; Umea Univ, Ctr Heart, Umea, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Bisphenol A is related to circulating levels of adiponectin, leptin and ghrelin, but not to fat mass or fat distribution in humans2014In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 112, p. 42-48Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Since bisphenol A (BPA) has been shown to induce obesity in experimental studies, we explored the associations between BPA and fat mass, fat distribution and circulating levels of adiponectin, leptin and ghrelin in humans.

    METHODS: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), fat mass and fat distribution were determined in 70-year-old men and women (n=890) by dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) (n=287). Serum levels of BPA were analyzed using isotope liquid chromatography/tandem mass spectrometer (API4000LC-MS/MS). Hormone levels were analyzed with radioimmunoassays (RIA) or enzyme-linked immunosorbent assay (ELISA). Imaging was performed approximately two years following collection of other data.

    RESULTS: Serum concentrations of BPA were not related to adipose tissue measurements by DXA or MRI. BPA associated positively with adiponectin and leptin, but negatively with ghrelin, following adjustments for sex, height, fat mass, lean mass, smoking, alcohol consumption, physical activity, energy intake, and educational levels (p<0.001, p=0.009, p<0.001, respectively). The relationship between BPA and ghrelin was stronger in women than in men.

    CONCLUSION: Although no relationships between BPA levels and measures of fat mass were seen, BPA associated strongly with the adipokines adiponectin and leptin and with the gut-hormone ghrelin suggesting that BPA may interfere with hormonal control of hunger and satiety.

  • 352.
    Salihovic, Samira
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Stubleski, Jordan
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Kärrman, Anna
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Changes in markers of liver function in relation to changes in perfluoroalkyl substances - A longitudinal study2018In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 117, p. 196-203Article in journal (Refereed)
    Abstract [en]

    Background: While it is known that perfluoroalkyl substances (PFASs) induce liver toxicity in experimental studies, the evidence of an association in humans is inconsistent.

    Objective: The main aim of the present study was to examine the association of PFAS concentrations and markers of liver function using panel data.

    Methods: We investigated 1002 individuals from Sweden (50% women) at ages 70, 75 and 80 in 2001-2014. Eight PFASs were measured in plasma using isotope dilution ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). Bilirubin and hepatic enzymes alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT) were determined in serum using an immunoassay methodology. Mixed-effects linear regression models were used to examine the relationship between the changes in markers of liver function and changes in PFAS levels.

    Results: The changes in majority of PFAS concentrations were positively associated with the changes in activity of ALT, ALP, and GGT and inversely associated with the changes in circulating bilirubin after adjustment for gender and the time-updated covariates LDL- and HDL-cholesterol, serum triglycerides, BMI, statin use, smoking, fasting glucose levels and correction for multiple testing. For example, changes in perfluorononanoic acid (PFNA) were associated with the changes liver function markers beta(BILIRUBIN) = -1.56, 95% confidence interval (CI) -1.93 to -1.19, beta(ALT)= 0.04, 95% CI 0.03-0.06, and beta(ALP)= 0.11, 95% CI 0.06-0.15.

    Conclusion: Our longitudinal assessment established associations between changes in markers of liver function and changes in plasma PFAS concentrations. These findings suggest a relationship between low-dose background PFAS exposure and altered liver function in the general population.

  • 353.
    Schultze, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lind, Monica P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Whole blood and serum concentrations of metals in a Swedish population-based sample2014In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 74, no 2, p. 143-148Article in journal (Refereed)
    Abstract [en]

     Objective

    While the potential toxicity of metals in humans is a well-established field of research, there are few studies that examine circulating concentrations of metals in large population-based samples. The aim of this study was to analyze levels of heavy metals and trace elements in both whole blood and serum in an elderly population, and to examine if gender, kidney function, haemoglobin or serum albumin could impact the distribution of metals between whole blood and serum.

    Methods

    Whole blood and serum samples from 1016 70-year-olds living in Uppsala, Sweden, were analyzed for aluminium, cadmium, cobalt, copper, chromium, mercury, manganese, molybdenum, nickel, lead, and zinc using inductively coupled plasma-sector field mass spectrometry (ICP-SFMS). Distribution between whole blood and serum was evaluated by the ratio between whole blood and serum concentration (B/S-ratio).

    Results

    Concentrations differed significantly between whole blood and serum measurements for all 11 metals (p < 0.00001). The highest B/S-ratios were found for lead (27), zinc (9), manganese (6), and nickel (4). Copper (0.86), cobalt (0.84), and molybdenum (0.86) showed B/S-ratios < 1. Especially the B/S-ratios for chromium, mercury and nickel correlated with kidney function (GFR) (r = 0.21, - 0.21 and - 0.36 respectively, p < 0.0001).

    Conclusions

    The distribution between whole blood and serum varied considerably for different metals. This distribution correlated with physiological factors, mainly with kidney function, for several of the metals.

  • 354.
    Simm, Mikael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Söderberg, Ewa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Castegren, Markus
    Department of Anaesthesia, Intensive Care & Surgical Services, Karolinska University Hospital, Huddinge, Stockholm, Sweden..
    Nilsen, Tom
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Performance of plasma calprotectin as a biomarker of early sepsis: a pilot study2016In: Biomarkers in Medicine, ISSN 1752-0363, E-ISSN 1752-0371, Vol. 10, no 8, p. 811-818Article in journal (Refereed)
    Abstract [en]

    AIM: To determine the performance of plasma calprotectin as a marker of sepsis on intensive care unit (ICU) admission and as a marker of mortality day 30 post-ICU admission.

    MATERIALS & METHODS: Consecutive ICU patients were allocated to: sepsis (n = 15), postoperative inflammation (n = 23) and intoxication without inflammation (n = 7) groups.

    RESULTS: Calprotectin was 4.3 (2.6-8.2; mg/l; median [interquartile range]) in the sepsis, 2.8 (1.6-4.4) in the postoperative and 0.7 (0.4-1.6) in the intoxication groups. Area under the receiver operating characteristic curve for sepsis versus intoxication group was: 0.95, for sepsis versus postoperative groups: 0.65 and for survivors versus nonsurvivors: 0.70.

    CONCLUSION: Calprotectin was a sensitive marker of systemic inflammation, is a potential sepsis marker and performed well as mortality predictor in this pilot study.

  • 355. Sjöberg, B
    et al.
    Qureshi, A R
    Heimbürger, O
    Stenvinkel, P
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Bárány, P
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Association between levels of pentraxin 3 and incidence of chronic kidney disease in the elderly2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 279, no 2, p. 173-179Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Higher levels of the novel inflammatory marker pentraxin 3 (PTX3) predict cardiovascular mortality in patients with chronic kidney disease (CKD). Yet, whether PTX3 predicts worsening of kidney function has been less well studied. We therefore investigated the associations between PTX3 levels, kidney disease measures and CKD incidence.

    METHODS: Cross-sectional associations between serum PTX3 levels, urinary albumin/creatinine ratio (ACR) and cystatin C-estimated glomerular filtration rate (GFR) were assessed in two independent community-based cohorts of elderly subjects: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n = 768, 51% women, mean age 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 651, mean age 77 years). The longitudinal association between PTX3 level at baseline and incident CKD (GFR <60 mL( ) min(-1)  1.73 m(-) ²) was also analysed (number of events/number at risk: PIVUS 229/746, ULSAM 206/315).

    RESULTS: PTX3 levels were inversely associated with GFR [PIVUS: B-coefficient per 1 SD increase -0.16, 95% confidence interval (CI) -0.23 to -0.10, P < 0.001; ULSAM: B-coefficient per 1 SD increase -0.09, 95% CI -0.16 to -0.01, P < 0.05], but not ACR, after adjusting for age, gender, C-reactive protein and prevalent cardiovascular disease in cross-sectional analyses. In longitudinal analyses, PTX3 levels predicted incident CKD after 5 years in both cohorts [PIVUS: multivariable odds ratio (OR) 1.21, 95% CI 1.01-1.45, P < 0.05; ULSAM: multivariable OR 1.37, 95% CI 1.07-1.77, P < 0.05].

    CONCLUSIONS: Higher PTX3 levels are associated with lower GFR and independently predict incident CKD in elderly men and women. Our data confirm and extend previous evidence suggesting that inflammatory processes are activated in the early stages of CKD and drive impairment of kidney function. Circulating PTX3 appears to be a promising biomarker of kidney disease.

  • 356.
    Skorup, Paul
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Maudsdotter, Lisa
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Castegren, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Jonsson, Ann-Beth
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Beneficial Antimicrobial Effect of the Addition of an Aminoglycoside to a β-Lactam Antibiotic in an E. coli Porcine Intensive Care Severe Sepsis Model.2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 2, p. e90441-Article in journal (Refereed)
    Abstract [en]

    This study aimed to determine whether the addition of an aminoglycoside to a ß-lactam antibiotic increases the antimicrobial effect during the early phase of Gram-negative severe sepsis/septic shock. A porcine model was selected that considered each animal's individual blood bactericidal capacity. Escherichia coli, susceptible to both antibiotics, was given to healthy pigs intravenously during 3 h. At 2 h, the animals were randomized to a 20-min infusion with either cefuroxime alone (n = 9), a combination of cefuroxime+tobramycin (n = 9), or saline (control, n = 9). Blood samples were collected hourly for cultures and quantitative polymerase chain reaction (PCR). Bacterial growth in the organs after 6 h was chosen as the primary endpoint. A blood sample was obtained at baseline before start of bacterial infusion for ex vivo investigation of the blood bactericidal capacity. At 1 h after the administration of the antibiotics, a second blood sample was taken for ex vivo investigation of the antibiotic-induced blood killing activity. All animals developed severe sepsis/septic shock. Blood cultures and PCR rapidly became negative after completed bacterial infusion. Antibiotic-induced blood killing activity was significantly greater in the combination group than in the cefuroxime group (p<0.001). Growth of bacteria in the spleen was reduced in the two antibiotic groups compared with the controls (p<0.01); no difference was noted between the two antibiotic groups. Bacterial growth in the liver was significantly less in the combination group than in the cefuroxime group (p<0.05). High blood bactericidal capacity at baseline was associated with decreased growth in the blood and spleen (p<0.05). The addition of tobramycin to cefuroxime results in increased antibiotic-induced blood killing activity and less bacteria in the liver than cefuroxime alone. Individual blood bactericidal capacity may have a significant effect on antimicrobial outcome.

  • 357.
    Skorup, Paul
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Maudsdotter, Lisa
    Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University.
    Lipcsey, Miklós
    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, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Mode of Bacterial Killing Affects the Inflammatory Response and Associated Organ Dysfunctions in a Porcine E. coli Intensive Care Sepsis ModelManuscript (preprint) (Other academic)
  • 358.
    Skorup, Paul
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Wilske, Frida
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Hanslin, Katja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lipcsey, Miklós
    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, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Enhanced Bacterial Clearance at a Secondary Sepsis Challenge in an Endotoxin-tolerant Porcine Intensive Care ModelManuscript (preprint) (Other academic)
  • 359.
    Sohrabian, Azita
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Mathsson Alm, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Thermo Fisher Sci, ImmunoDiagnost Div, Uppsala, Sweden..
    Hansson, M.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Lysholm, J.
    Falun Cent Hosp, Clin Rheumatol, Falun, Sweden..
    Cornillet, M.
    Toulouse Univ, INSERM, U1056, Epithelial Differentiat & Rheumatoid Autoimmun, Toulouse, France..
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Skriner, K.
    Charite, Dept Med, Berlin, Germany..
    Serre, G.
    Toulouse Univ, INSERM, U1056, Epithelial Differentiat & Rheumatoid Autoimmun, Toulouse, France..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Weitoft, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Number Of Peptide-Specific Anti-Citrullinated Peptide Antibodies In Synovial Fluid And In Synovial Fluid Immune Complexes Associate With Degree Of Radiological Destruction And Response To Triamcinolone Hexacetonide For Knee Synovitis In Rheumatoid Arthritis2017In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, p. 509-510Article in journal (Other academic)
  • 360.
    Sohrabian, Azita
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Mathsson Alm, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Hansson, Monika
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Lysholm, Jörgen
    Falun Cent Hosp, Clin Rheumatol, Falun, Sweden.
    Cornillet, Martin
    Toulouse Univ, Lab Epithelial Differentiat & Rheumatoid Autoimmu, INSERM, U1056, Toulouse, France.
    Skriner, Karl
    Charite, Dept Med, Berlin, Germany.
    Serre, Guy
    Toulouse Univ, Lab Epithelial Differentiat & Rheumatoid Autoimmu, INSERM, U1056, Toulouse, France.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Weitoft, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Number of individual ACPA reactivities in synovial fluid immune complexes, but not serum anti-CCP2 levels, associate with inflammation and joint destruction in rheumatoid arthritis2018In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, no 9, p. 1345-1353Article in journal (Refereed)
    Abstract [en]

    Introduction: Individual patients with rheumatoid arthritis (RA) show divergent specific anti-citrullinated protein/peptide antibodies (ACPA) patterns, but hitherto no individual ACPA specificity has consistently been linked to RA pathogenesis. ACPA are also implicated in immune complexes (IC)-associated joint pathology, but until now, there has been no method to investigate the role of individual ACPA in RA IC formation and IC-associated pathogenesis.

    Methods: We have developed a new technique based on IC binding to C1q-coated magnetic beads to purify and solubilise circulating IC in sera and synovial fluids (SF) from 77 patients with RA. This was combined with measurement of 19 individual ACPA in serum, SF and in the IC fractions from serum and SF. We investigated whether occurrence of individual ACPA as well as number of ACPA in these compartments was related to clinical and laboratory measures of disease activity and inflammation.

    Results: The majority of individual ACPA reactivities were enriched in SF as compared with in serum, and levels of ACPA in IC were regulated independently of levels in serum and SF. No individual ACPA reactivity in any compartment showed a dominating association to clinical and laboratory measures of disease activity and severity. Instead, the number of individual ACPA reactivities in the IC fraction from SF associated with a number of markers of joint destruction and inflammation.

    Conclusions: Our data highlight the polyclonality of ACPA in joint IC and the possibility that a broad ACPA repertoire in synovial fluid IC might drive the local inflammatory and matrix-degrading processes in joints, in analogy with antibody-induced rodent arthritis models.

  • 361.
    Sohrabian, Azita
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Noraddin, Feria Hikmet
    Flodin, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Fredricsson, Annika
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Particle enhanced turbidimetric immunoassay for the determination of urine cystatin C on Cobas c5012012In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 45, no 4-5, p. 339-344Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Urinary cystatin C has been reported to be a good marker for tubular damage and acute kidney injury. The aim of this study was to develop a high throughput assay for the quantification of urine cystatin C.

    METHODS:

    Antigen-excess, imprecision, interference, linearity, recovery, sample stability and reference values were evaluated on Cobas c501.

    RESULTS:

    The assay was linear over the dynamic range of the study (R(2)=0.9994). The total assay imprecision was below 5%. The assay recovery was estimated at 87-100%. No tendency to antigen-excess (up to 35mg/L), nor interference with haemoglobin (1.25-10g/L) was observed. Cystatin C was stable for 1day at ambient temperature (19-23°C) but for 2days at +4°C. The reference interval for cystatin C in urine was <0.414mg/L.

    CONCLUSIONS:

    The urinary cystatin C assay verified to be a reliable assay with convenient performance characteristics, enabling routine testing on clinical chemistry platforms.

  • 362.
    Sperber, Jesper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Castegren, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Evaluating the effects of protective ventilation on organ-specific cytokine production in porcine experimental postoperative sepsis2015In: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 15, article id 60Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Protective ventilation with lower tidal volume (VT) and higher positive end-expiratory pressure (PEEP) reduces the negative additive effects of mechanical ventilation during systemic inflammatory response syndrome. We hypothesised that protective ventilation during surgery would affect the organ-specific immune response in an experimental animal model of endotoxin-induced sepsis-like syndrome.

    METHODS: 30 pigs were laparotomised for 2 hours (h), after which a continuous endotoxin infusion was started at 0.25 micrograms × kg(-1) × h(-1) for 5 h. Catheters were placed in the carotid artery, hepatic vein, portal vein and jugular bulb. Animals were randomised to two protective ventilation groups (n = 10 each): one group was ventilated with VT 6 mL × kg(-1) during the whole experiment while the other group was ventilated during the surgical phase with VT of 10 mL × kg(-1). In both groups PEEP was 5 cmH2O during surgery and increased to 10 cmH2O at the start of endotoxin infusion. A control group (n = 10) was ventilated with VT of 10 mL × kg(-1) and PEEP 5 cm H20 throughout the experiment. In four sample locations we a) simultaneously compared cytokine levels, b) studied the effect of protective ventilation initiated before and during endotoxemia and c) evaluated protective ventilation on organ-specific cytokine levels.

    RESULTS: TNF-alpha levels were highest in the hepatic vein, IL-6 levels highest in the artery and jugular bulb and IL-10 levels lowest in the artery. Protective ventilation initiated before and during endotoxemia did not differ in organ-specific cytokine levels. Protective ventilation led to lower levels of TNF-alpha in the hepatic vein compared with the control group, whereas no significant differences were seen in the artery, portal vein or jugular bulb.

    CONCLUSIONS: Variation between organs in cytokine output was observed during experimental sepsis. We see no implication from cytokine levels for initiating protective ventilation before endotoxemia. However, during endotoxemia protective ventilation attenuates hepatic inflammatory cytokine output contributing to a reduced total inflammatory burden.

  • 363.
    Sperber, Jesper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Castegren, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lung protective ventilation induces immunotolerance and nitric oxide metabolites in porcine experimental postoperative sepsis2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, p. e83182-Article in journal (Refereed)
    Abstract [en]

    Low tidal volume ventilation is beneficial in patients with severe pulmonary dysfunction and would, in theory, reduce postoperative complications if implemented during routine surgery. The study aimed to investigate whether low tidal volume ventilation and high positive end-expiratory pressure (PEEP) in a large animal model of postoperative sepsis would attenuate the systemic inflammatory response and organ dysfunction. Thirty healthy pigs were randomized to three groups: Group Prot-7h, i.e. protective ventilation for 7 h, was ventilated with a tidal volume of 6 mL x kg-1 for 7 h; group Prot-5h, i.e. protective ventilation for 5 h, was ventilated with a tidal volume of 10 mL x kg-1 for 2 h, after which the group was ventilated with a tidal volume of 6 mL x kg-1; and a control group that was ventilated with a tidal volume of 10 mL x kg-1 for 7 h. In groups Prot-7h and Prot-5h PEEP was 5 cmH2O for 2 h and 10 cmH2O for 5 h. In the control group PEEP was 5 cmH2O for the entire experiment. After surgery for 2 h, postoperative sepsis was simulated with an endotoxin infusion for 5 h. Low tidal volume ventilation combined with higher PEEP led to lower levels of interleukin 6 and 10 in plasma, higher PaO2/FiO2, better preserved functional residual capacity and lower plasma troponin I as compared with animals ventilated with a medium high tidal volume and lower PEEP. The beneficial effects of protective ventilation were seen despite greater reductions in cardiac index and oxygen delivery index. In the immediate postoperative phase low VT ventilation with higher PEEP was associated with reduced ex vivo plasma capacity to produce TNF-α upon endotoxin stimulation and higher nitrite levels in urine. These findings might represent mechanistic explanations for the attenuation of systemic inflammation and inflammatory-induced organ dysfunction.

  • 364.
    Sperber, Jesper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Nyberg, Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Castegren, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Exposure to Mechanical Ventilation and Endotoxin for 24 Hours Before Infection Influences Pseudomonas Aeruginosa Growth During Experimental Porcine Ventilator-Associated PneumoniaManuscript (preprint) (Other academic)
  • 365.
    Sperber, Jesper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Nyberg, Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Castegren, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Protective Ventilation Reduces Pseudomonas Aeruginosa Growth in a Porcine Pneumonia ModelManuscript (preprint) (Other academic)
  • 366.
    Sperber, Jesper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Centre for Clinical Research Sörmland, Department of Anesthesiology & Intensive Care Mälarsjukhuset, SE-631 88 Eskilstuna, Sweden.
    Nyberg, Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Centre for Clinical Research Sörmland, Department of Anesthesiology & Intensive Care Mälarsjukhuset, SE-631 88 Eskilstuna, Sweden.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Castegren, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Perioperative Medicine and Intensive Care, Karolinska University Hospital and CLINTEC, Karolinska Institute, Stockholm, Sweden.
    Protective ventilation reduces Pseudomonas aeruginosa growth in lung tissue in a porcine pneumonia model2017In: Intensive & Critical Care Nursing, ISSN 0964-3397, E-ISSN 1532-4036, Vol. 5, article id 40Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Mechanical ventilation with positive end expiratory pressure and low tidal volume, i.e. protective ventilation, is recommended in patients with acute respiratory distress syndrome. However, the effect of protective ventilation on bacterial growth during early pneumonia in non-injured lungs is not extensively studied. The main objectives were to compare two different ventilator settings on Pseudomonas aeruginosa growth in lung tissue and the development of lung injury.

    METHODS: A porcine model of severe pneumonia was used. The protective group (n = 10) had an end expiratory pressure of 10 cm H2O and a tidal volume of 6 ml x kg-1. The control group (n = 10) had an end expiratory pressure of 5 cm H2O and a tidal volume of 10 ml x kg-1. 1011 colony forming units of Pseudomonas aeruginosa were inoculated intra-tracheally at baseline, after which the experiment continued for 6 h. Two animals from each group received only saline, and served as sham animals. Lung tissue samples from each animal were used for bacterial cultures and wet-to-dry weight ratio measurements.

    RESULTS: The protective group displayed lower numbers of Pseudomonas aeruginosa (p < 0.05) in the lung tissue, and a lower wet-to-dry ratio (p < 0.01) than the control group. The control group deteriorated in arterial oxygen tension/inspired oxygen fraction, whereas the protective group was unchanged (p < 0.01).

    CONCLUSIONS: In early phase pneumonia, protective ventilation with lower tidal volume and higher end expiratory pressure has the potential to reduce the pulmonary bacterial burden and the development of lung injury.

  • 367.
    Steubl, Dominik
    et al.
    Tech Univ Munich, Klinikum Rechts Isar, Nephrol Abt, Munich, Germany.
    Kumar, Santhosh V
    Klinikum Univ Munchen, Div Renal, Med Klin & Poliklin 4, Campus Innenstadt, Munich, Germany.
    Tato, Maia
    Klinikum Univ Munchen, Div Renal, Med Klin & Poliklin 4, Campus Innenstadt, Munich, Germany.
    Mulay, Shrikant R
    Klinikum Univ Munchen, Div Renal, Med Klin & Poliklin 4, Campus Innenstadt, Munich, Germany.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Renders, Lutz
    Tech Univ Munich, Klinikum Rechts Isar, Nephrol Abt, Munich, Germany.
    Heemann, Uwe
    Tech Univ Munich, Klinikum Rechts Isar, Nephrol Abt, Munich, Germany.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med, Huddinge, Sweden.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Anders, Hans-Joachim
    Klinikum Univ Munchen, Div Renal, Med Klin & Poliklin 4, Campus Innenstadt, Munich, Germany.
    Circulating cathepsin-S levels correlate with GFR decline and sTNFR1 and sTNFR2 levels in mice and humans2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 43538Article in journal (Refereed)
    Abstract [en]

    Cardiovascular complications determine morbidity/mortality in chronic kidney disease (CKD). We hypothesized that progressive CKD drives the release of cathepsin-S (Cat-S), a cysteine protease that promotes endothelial dysfunction and cardiovascular complications. Therefore, Cat-S, soluble tumor-necrosis-factor receptor (sTNFR) 1/2 and glomerular filtration rate (GFR) were measured in a CKD mouse model, a German CKD-cohort (MCKD, n = 421) and two Swedish community-based cohorts (ULSAM, n = 764 and PIVUS, n = 804). Association between Cat-S and sTNFR1/2/GFR was assessed using multivariable linear regression. In the mouse model, Cat-S and sTNFR1/2 concentrations were increased following the progressive decline of GFR, showing a strong correlation between Cat-S and GFR (r = -0.746, p < 0.001) and Cat-S and sTNFR1/sTNFR2 (r = 0.837/0.916, p < 0.001, respectively). In the human cohorts, an increase of one standard deviation of estimated GFR was associated with a decrease of 1.008 ng/ml (95%-confidence interval (95%-CI) -1.576-(-0.439), p < 0.001) in Cat-S levels in MCKD; in ULSAM and PIVUS, results were similar. In all three cohorts, Cat-S and sTNFR1/sTNFR2 levels were associated in multivariable linear regression (p < 0.001). In conclusion, as GFR declines Cat-S and markers of inflammation-related endothelial dysfunction increase. The present data indicating that Cat-S activity increases with CKD progression suggest that Cat-S might be a therapeutic target to prevent cardiovascular complications in CKD.

  • 368.
    Strandberg, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Gustafsson, Mats G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Analysis of intraosseous samples using point of care technology: an experimental study in the anaesthetised pig2012In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 83, no 11, p. 1381-1385Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Intraosseous access is an essential method in emergency medicine when other forms of vascular access are unavailable and there is an urgent need for fluid or drug therapy. A number of publications have discussed the suitability of using intraosseous access for laboratory testing. We aimed to further evaluate this issue and to study the accuracy and precision of intraosseous measurements.

    METHODS:

    Five healthy, anaesthetised pigs were instrumented with bilateral tibial intraosseous cannulae and an arterial catheter. Samples were collected hourly for 6h and analysed for blood gases, acid base status, haemoglobin and electrolytes using an I-Stat(®) point of care analyser.

    RESULTS:

    There was no clinically relevant difference between results from left and right intraosseous sites. The variability of the intraosseous sample values, measured as the coefficient of variance (CV), was maximally 11%, and smaller than for the arterial sample values for all variables except SO(2). For most variables, there seems to be some degree of systematic difference between intraosseous and arterial results. However, the direction of this difference seems to be predictable.

    CONCLUSION:

    Based on our findings in this animal model, cartridge based point of care instruments appear suitable for the analysis of intraosseous samples. The agreement between intraosseous and arterial analysis seems to be good enough for the method to be clinically useful. The precision, quantified in terms of CV, is at least as good for intraosseous as for arterial analysis. There is no clinically important difference between samples from left and right tibia, indicating a good reproducibility.

  • 369.
    Strandberg, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Intraosseous Samples Can Be Used for CreatinineMeasurements - An Experimental Study in the Anaesthetised Pig2014In: Clinical Laboratory, ISSN 1433-6510, Vol. 60, no 10, p. 1587-1591Article in journal (Refereed)
    Abstract [en]

    Background: Intraosseous (IO) access is a valuable tool in prehospital locations and in emergency departments when other forms of vascular access are unavailable. Creatinine is often used for dose adjustment of drugs that may be administered through intraosseous cannulae. We aimed to study the possibility of analysing creatinine in intraosseous samples and study the accuracy and precision of such measurements.

    Methods: Eight pigs with endotoxin induced septic shock were sampled hourly for six hours and analysed for plasma creatinine. Samples were collected from arterial, venous, and IO cannulae.

    Results: There was an increase in creatinine values during the later part of the experiment. The coefficients of variation between the three sampling sites were less than 10% at all sampling times.

    Conclusions: Based on our findings intraosseous samples can be used for creatinine determination in emergency settings.

  • 370.
    Strandberg, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lipcsey, Miklos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Analysis of intraosseous samples in endotoxemic shock: an experimental study in the anaesthetised pig2014In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, no 3, p. 337-344Article in journal (Refereed)
    Abstract [en]

    Background

    Intraosseous (IO) access is used in emergency situations to allow rapid initiation of treatment. IO access is also sometimes used for blood sampling, although data on accuracy of such sampling in critical illness are limited. There is also a potential risk that bone marrow fragments in IO samples may damage laboratory equipment. It is ethically questionable to perform a simultaneous comparison between IO and arterial/venous sampling in critically ill humans. We have, thus, studied the analytical performance of IO sampling in a porcine septic shock model using a cartridge-based analyser.

    Methods

    Eight pigs with endotoxin-induced septic shock were sampled hourly for 6 h, and analysed for blood gases, acid base status, haemoglobin, glucose and lactate using point of care instruments. Samples were taken from three IO cannulae (tibia bilaterally, one with infusion, and humerus), one arterial and one venous. An interaction test was used to assess changes in agreement between methods over time. Bland–Altman plots were constructed to study bias between methods.

    Results

    There were, to a varying extent, differences between IO and arterial/venous levels for all studied variables, but agreement did not change significantly during the experiment. A general finding was a large dispersion of differences between methods.

    Conclusions

    IO sample values should be treated with caution in this setting but may add useful information to the clinical picture. The tibia or humerus may be used for sampling. IO infusion decreases agreement, thus sampling during infusion should be avoided.

  • 371.
    Strandberg, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lipcsey, Miklos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Intraosseous blood aspirates analysed by a portable cartridge-based device2011In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 15, no Suppl 1, p. 49-49Article in journal (Refereed)
  • 372.
    Strandberg, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lipcsey, Miklos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Michalek, J
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Intraosseous and intravenous administration of antibiotics yields comparable plasma concentrations during experimental septic shock2015In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 59, no 3, p. 346-353Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We aimed to investigate whether comparable antibiotic concentrations could be reached with intraosseous and intravenous administration during septic shock.

    METHODS: In this randomized, prospective experimental study conducted at an animal research laboratory at the University Hospital of Uppsala, eight anesthetized pigs, weighing 21.2 to 29.1 kg (mean: 25.2 ± 2.3 kg), received endotoxin infusion at 4 μg/kg/h for 6 h. At the onset of clinical shock, alternatively after 3 h of endotoxemia, they received 75 mg/kg of cefotaxime and 7 mg/kg of gentamicin either in a proximal tibial intraosseous catheter or in a peripheral intravenous catheter. Mixed venous samples were taken after 5, 15, 30, 60, 120 and 180 min and analyzed for antibiotic concentrations.

    RESULTS: For both antibiotics, plasma concentrations after intraosseous and intravenous administration followed similar curves throughout the observation period, and peak concentrations were comparable. Mean concentration area under the curve (AUC mg × h/l) for cefotaxime was 108.1 ± 19.5 after intraosseous and 116.5 ± 11.1 after intravenous administration; ratio 0.93, (95% CI 0.71-1.19). Mean AUC for gentamicin was 28.1 ± 6.8 for intraosseous and 32.2 ± 3.5 for intravenous administration; ratio 0.87 (95% CI 0.62-1.19).

    CONCLUSIONS: In this porcine septic shock model, intraosseous and intravenous administration of gentamicin and cefotaxime yielded comparable concentrations. In an emergency, intraosseous administration of these antibiotics may be considered in severe infections when venous access is difficult.

  • 373.
    Strandberg, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lipcsey, Miklós
    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, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Comparison of Intraosseous, Arterial, and Venous Blood Sampling for Laboratory Analysis in Hemorrhagic Shock2019In: Clinical Laboratory, ISSN 1433-6510, Vol. 65, no 7, p. 1169-1177Article in journal (Refereed)
    Abstract [en]

    Background: Intraosseous (IO) access is often indicated for administration of drugs and fluids in emergencies when venous access is challenging. There is no consensus regarding whether and which laboratory analyses may be performed on IO aspirates, and research on hemodynamically unstable subjects is limited.

    Methods: Twelve anesthetized pigs were sampled from IO, venous, and arterial accesses during stable circulation and after hemorrhage corresponding to 20% and 40% of the blood volume. Samples were analyzed for blood gases and acid-base status, electrolytes, hematocrit, creatinine, glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (γ-GT), alkaline phosphatase (ALP), and creatine kinase (CK).

    Results: Average differences of blood gases and acid-base parameters, sodium, creatinine, hematocrit, ALT, and γ-GT and between IO and venous samples were small at baseline and after hemorrhage while differences for lactate and glucose increased with hypovolemia. Both IO-arterial and venoarterial differences in acid-base parameters increased with hypovolemia. Dispersions of differences were often large.

    Conclusions: Average levels of blood gases, acid base parameters, hematocrit, CK, AST, γ-GT, creatinine, and ALT, but not lactate and glucose, were similar in IO and venous samples in hypovolemia. However, precision was limited, indicating that IO test results should be confirmed when other vascular access is established, and that analysis of IO samples should be limited to acute situations and not used for detailed diagnostics in this setting.

  • 374.
    Strandberg, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    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, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Eriksson, Mats B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lubenow, Norbert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Analysis of Thromboelastography, PT, APTT and Fibrinogen in Intraosseous and Venous Samples: An Experimental Study2016In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 24, article id 131Article in journal (Refereed)
    Abstract [en]

    Background:Laboratory analysis of coagulation is often important in emergencies. If vascular access is challenging,intraosseous catheterization may be necessary for treatment. We studied the analysis of coagulation parameters inintraosseous aspirate during stable conditions and after major haemorrhage in a porcine model.Methods:Ten anesthetized pigs received central venous and intraosseous catheters and samples were taken foranalysis of thromboelastography (TEG), prothrombin time (PT), activated partial thromboplastin time (APTT) andfibrinogen concentration. Analyses were repeated after removal of 50 % of the calculated blood volume andresuscitation with crystalloid. Intraosseous and venous values were compared.Results:Bleeding and resuscitation resulted in haemodilution and hypotension. Median TEG reaction time wasshorter in intraosseous than in venous samples before (1.6 vs 4.6 min) and after (1.6 vs 4.7 min) haemodilution.Median maximal amplitude was smaller in intraosseous samples at baseline (68.3 vs 76.4 mm). No major differenceswere demonstrated for the other TEG parameters. The intraosseous samples often coagulated in vitro, makinganalysis of PT, APTT and fibrinogen difficult. After haemodilution, TEG maximal amplitude andα-angle, andfibrinogen concentration, were decreased and PT increased.Discussion:The intraosseous samples were clinically hypercoagulable and the TEG demonstrated a shortenedreaction time. The reason for this may hypothetically be found in the composition of the IO aspirate or in thesampling technique. After 50 % haemorrhage and haemodilution, a clinically relevant decrease in fibrinogenconcentration and a lower TEG maximal amplitude were observed.Conclusions:Although the sample is small, these data indicate that intraosseous samples are hypercoagulable,which may limit their usefulness for coagulation studies. Major haemodilution only moderately affected the studied parameters.

  • 375.
    Sundelöf, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundstrom, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hansson, Oskar
    Eriksdotter-Jönhagen, Maria
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Degerman-Gunnarsson, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Minthon, Lennart
    Blennow, Kaj
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Basun, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Cystatin C Levels are Positively Correlated with both Aβ42 and Tau Levels in Cerebrospinal Fluid in Persons with Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Controls2010In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 21, no 2, p. 471-478Article in journal (Refereed)
    Abstract [en]

    Cystatin C is suggested to be involved in neurodegeneration and the development of Alzheimer's disease (AD) by binding to soluble amyloid-beta (Abeta) peptides. Studies of cystatin C levels in cerebrospinal fluid (CSF) in relation to risk of AD are conflicting and relations between cystatin C, Abeta42, and tau levels in CSF in AD, mild cognitive impairment (MCI), and healthy controls are unknown. The objective of this study was to investigate cystatin C, Abeta42, and tau levels in CSF in AD, MCI, and controls. As a secondary aim, the relationships between cystatin C, Abeta42, and tau levels across disease groups were investigated. Cystatin C, Abeta42, total tau, and phosphorylated tau levels in CSF were analyzed by turbidimetry (cystatin C) and xMAP Luminex technology (Abeta and tau) in persons with AD (n=101), MCI (n=84), and healthy control subjects (n=28). Mean cystatin C levels were similar in cases of AD (5.6 mumol/L +/- 1.7), MCI (5.4 mumol/L +/- 1.48), and controls (5.6 mumol/L +/- 1.6). However, CSF cystatin C levels were strongly and positively correlated with total tau and phosphorylated tau levels (r=0.61-0.81, p< 0.0001) and Abeta42 (r=0.35-0.65, p< 0.001) independent of age, gender, and APOE genotype. Mean CSF cystatin C levels did not differ between patients with AD and MCI and healthy controls. Interestingly, cystatin C levels were positively correlated with both tau and Abeta42 levels in CSF independent of age, gender, and APOE genotype.

  • 376.
    Sundelöf, Johan
    et al.
    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.
    Hansson, Oskar
    Eriksdotter-Jönhagen, Maria
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Degerman-Gunnarsson, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Minthon, Lennart
    Blennow, Kaj
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Basun, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Higher Cathepsin B Levels in Plasma in Alzheimer's Disease Compared to Healthy Controls2010In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 22, no 4, p. 1223-1230Article in journal (Refereed)
    Abstract [en]

    Cathepsin B is suggested to be involved in amyloid-β (Aβ) processing and Alzheimer's disease (AD). Studies of cathepsin B levels in plasma and cerebrospinal fluid (CSF) have not been previously performed. We examined cathepsin B levels in plasma and CSF samples in persons with AD, mild cognitive impairment (MCI), and healthy controls in order to test the hypothesis that cathepsin B levels can discriminate persons with AD or MCI from healthy controls. Cathepsin B, Cystatin C, Aβ1-40 and Aβ1-42, total tau, phosphorylated tau, and albumin levels in plasma and CSF were analyzed by ELISA (Cathepsin B) turbidimetry (cystatin C), xMAP Luminex technology (Aβ1-40 and Aβ1-42 and tau), and Cobas C501 analyzer (albumin) in persons with AD (n=101), MCI (n=84), and healthy control subjects (n=28). Plasma cathepsin B levels were higher in persons with AD compared to healthy controls, both in unadjusted models and in multivariable models adjusting for age, gender, APOE genotype, cystatin C, and albumin levels: Odds ratio (OR) for AD per 1 SD of plasma cathepsin B; 2.04, 95% confidence interval (CI); 1.01-4.14, p= 0.05. There was no difference between diagnostic groups in cathepsin B levels in CSF: OR for AD per 1 SD of CSF cathepsin B; 0.93, 95% CI; 0.37-2.30, p= 0.87. Plasma cathepsin B levels were higher in persons with AD compared to healthy controls whereas there was no difference between diagnostic groups in cathepsin B levels in CSF. Further investigation of cathepsin B as a predictor of AD is warranted.

  • 377.
    Sundelöf, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ärnlöv, J.
    Ingelsson, E.
    Sundström, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Irizarry, M. C.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Rönnemaa, Elina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Degerman-Gunnarsson, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Hyman, B. T.
    Basun, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Serum cystatin C and the risk of Alzheimer disease in elderly men2008In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 71, no 14, p. 1072-1079Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Multiple lines of research suggest that increased cystatin C activity in the brain protects against the development of Alzheimer disease (AD). METHODS: Serum cystatin C levels were analyzed at two examinations of the Uppsala Longitudinal Study of Adult Men, a longitudinal, community-based study of elderly men (age 70 years, n = 1,153 and age 77 years, n = 761, a subset of the age 70 examination). Cox regressions were used to examine associations between serum cystatin C and incident AD. AD cases were identified by cognitive screening and comprehensive medical chart review in all subjects. RESULTS: On follow-up (median 11.3 years), 82 subjects developed AD. At age 70 years, lower cystatin C was associated with higher risk of AD independently of age, APOE4 genotype, glomerular filtration rate, diabetes, hypertension, stroke, cholesterol, body mass index, smoking, education level, and plasma amyloid-beta protein 40 and 42 levels (hazard ratio [HR] for lowest [<1.12 micromol/L] vs highest [>1.30 micromol/L] tertile = 2.67, 95% CI 1.22-5.83, p < 0.02). The results were similar at age 77 years (43 participants developed AD during follow-up). Furthermore, a 0.1-mumol/L decrease of cystatin C between ages 70 and 77 years was associated with a 29% higher risk of incident AD (HR 1.29, 95% CI 1.03-1.63, p < 0.03). CONCLUSIONS: Low levels of serum cystatin C precede clinically manifest Alzheimer disease (AD) in elderly men free of dementia at baseline and may be a marker of future risk of AD. These findings strengthen the evidence for a role for cystatin C in the development of clinical AD.

  • 378.
    Svenungsson, E.
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Rheumatol Unit, Stockholm, Sweden..
    Gustafsson, J.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Rheumatol Unit, Stockholm, Sweden..
    Lindberg, M. Herlitz
    Karolinska Inst, Sodersjukhuset, Dept Clin Physiol, Stockholm, Sweden..
    Gunnarsson, I.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Rheumatol Unit, Stockholm, Sweden..
    Pettersson, S.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Rheumatol Unit, Stockholm, Sweden..
    Elvin, K.
    Karolinska Inst, Dept Clin Immunol & Transfus Med, Unit Clin Immunol, Stockholm, Sweden..
    Öhrvik, J.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Stockholm, Sweden..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jensen-Urstad, K.
    Karolinska Inst, Sodersjukhuset, Dept Clin Physiol, Stockholm, Sweden..
    Accelerated Atherosclerosis In Systemic Lupus Erythematosus, - A Matter Of Renal Involvement2016In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 34, no 4, p. S19-S19Article in journal (Refereed)
  • 379.
    Sylvén, Sara M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Elenis, Evangelia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Michelakos, Theodoros
    Department of Hygiene and Epidemiology, Athens Medical School, Athens, Greece.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Thyroid function tests at delivery and risk for postpartum depressive symptoms2013In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 38, no 7, p. 1007-1013Article in journal (Refereed)
    Abstract [en]

    Postpartum depression (PPD) is a common childbirth complication, which can have negative effects on both the newly delivered woman and her family. This condition is underdiagnosed and inadequately treated, while a biological diagnostic test is not yet available. Furthermore, postpartum thyroid dysfunction is common among new mothers, and some evidence point to an association between PPD and thyroid function disturbances. The aim of this study was to evaluate the possible association between serum levels of thyroid hormones at the time of delivery, and the later development of depressive symptoms, using data from a population based cohort of Swedish women. Blood samples were collected during delivery from 347 participating women, delivering at Uppsala University Hospital. The participating women filled in at least one of three structured questionnaires, containing the Edinburgh Postnatal Depression Scale (EPDS), at five days, six weeks and six months postpartum. A cut-off of 12 or more was applied on the EPDS, to identify cases of self-reported PPD and controls. Using a binary logistic regression model (adjusting for previous psychiatric contact, smoking during pregnancy, pre-pregnancy body mass index (BMI) and sleep), having a thyroid stimulating hormone (TSH) level over the clinical cut-off level of 4.0mU/L was associated with increased risk for depressive symptoms at six months postpartum (OR 11.30, 95% CI 1.93-66.11). A ROC analysis revealed that the predictive variable (PV) had significant predictive ability for PPD at 6 months postpartum, given that the AUC was 0.764, and at a PV cut-off value of 6.33, the sensitivity and specificity were 76.2% and 69.4%, respectively. If these findings are replicated in future studies, they can have important clinical implications, since TSH determination is an inexpensive routine blood test, and its inclusion in a biological screening test for PPD involving other parameters would be tempting.

  • 380.
    Söderberg, Ewa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lipcsey, Miklos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    The impact of hydrocortisone treatment on neutrophil gelatinase-associated lipocalin release in porcine endotoxemic shock2017In: Intensive Care Medicine Experimental, ISSN 1646-2335, E-ISSN 2197-425X, Vol. 5, article id 4Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A key feature of sepsis is systemic inflammatory activation that could be counteracted by steroids. In this experimental model of systemic inflammation, we sought to investigate whether septic neutrophil activation, evaluated by the plasma levels of neutrophil gelatinase-associated protein (NGAL), is modulated by the timing of hydrocortisone treatment.

    METHODS: Sixteen anesthetized pigs were allocated to one of four equally sized groups. Three of these groups received endotoxin at 2 μg × kg(-1) × h(-1) for 6 h so as to induce endotoxemic shock. Hydrocortisone (5 mg × kg(-1)) was administered intravenously before endotoxemic challenge, or at the onset of endotoxemic shock. Endotoxemic pigs not receiving hydrocortisone and non-endotoxemic pigs served as control groups. Physiologic variables, hematology, and biochemistry, including plasma NGAL, were measured repeatedly.

    RESULTS: Hydrocortisone treatment prior to endotoxemia attenuated some inflammatory, hematological, circulatory, and metabolic manifestations of shock (i.e., higher white blood cell count, higher mean arterial pressure, lower heart rate and mean pulmonary arterial pressure, higher left ventricular stroke work index, higher base excess). Endotoxemic shock increased plasma NGAL (p < 0.001). In pigs given hydrocortisone before the endotoxin infusion, plasma NGAL was lower as compared to those given hydrocortisone at endotoxemic shock (p < 0.05). Plasma NGAL levels correlated inversely to neutrophil granulocyte counts (rho = -0.65) but not to urine output (rho = -0.10) at the end of the experiment.

    CONCLUSIONS: The increase in plasma NGAL is counteracted by hydrocortisone administration prior to endotoxemia; concomitantly, this treatment was associated with less expressed circulatory derangement. Urine NGAL did not differ between the groups, suggesting that the NGAL response was not primarily related to kidney injury.

  • 381.
    Söderberg, Ewa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Eriksson, Mats B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Counteraction of early circulatory derangement by administration of low dose steroid treatment at the onset of established endotoxemic shock is not directly mediated by TNF-α and IL-62012In: Steroids, ISSN 0039-128X, E-ISSN 1878-5867, Vol. 77, no 11, p. 1101-1106Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Once a septic condition is progressing, administration of steroids in the pro-inflammatory phase of septic shock ought to yield maximal effect on the subsequent, devastating inflammatory response. Recently, a retrospective study showed that early initiation of corticosteroid therapy improved survival in septic shock. We aimed to prospectively evaluate effects of early administrated hydrocortisone therapy on physiologic variables in a porcine model of septic shock.

    EXPERIMENT:

    Eight anesthetized pigs were given a continuous infusion of endotoxin during this 6h prospective, randomized, parallel-grouped placebo-controlled experimental study. At the onset of endotoxemic shock, defined as the moment when the mean pulmonary arterial pressure reached the double baseline value, the pigs were either given a single intravenous dose of hydrocortisone (5 mg kg−1) or the corresponding volume of saline.

    RESULTS:

    Mean arterial pressure and systemic vascular resistance index were significantly higher (both p<0.05), and heart rate was significantly lower (p<0.05), in the endotoxin+hydrocortisone group as compared to the endotoxin+saline group. Body temperature and blood hemoglobin levels increased significantly in the endotoxin+saline group (both p<0.05). Urinary hydrocortisone increased significantly in both groups (p<0.05). There were no significant differences in the plasma levels of TNF-alpha, IL-6 or nitrite/nitrate between the groups.

    CONCLUSION:

    Early treatment with hydrocortisone ameliorates some endotoxin mediated circulatory derangements, fever response and microvascular outflow. Our results suggest that these effects are not directly mediated by the pro-inflammatory cytokines TNF-alpha or IL-6, nor by NO.

  • 382.
    Taha, Yesuf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Raab, Yngve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lördal, Mikael
    Lööf, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Thörn, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Steroids reduce local inflammatory mediator secretion and mucosal permeability in collagenous colitis patients2006In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 12, no 43, p. 7012-7018Article in journal (Refereed)
    Abstract [en]

    AIM: To study the effect of oral steroids upon clinical response and rectal mucosa secretion of eosinophil cationic protein (ECP), myeloperoxiclase (MPO), basic fibroblast growth factor (bFGF), vascular enclothelial growth factor (VEGF) and albumin in patients with collagenous colitis (CC).

    METHODS: A segmental perfusion technique was used to collect perfusates from rectum of CC patients once before and twice (one and four weeks) after the start of steroid treatment. Clinical data was monitored and ECP, MPO, bFGF, VEGF and albumin concentrations were analyzed by immunochernical methods in perfusates and in serum.

    RESULTS: Steroids reduced the number of bowel movements by more than five times within one week and all patients reported improved subjective wellbeing at wk 1 and 4. At the same time, the median concentrations of ECP, bFGF, VEGF and albumin in rectal perfusates decreased significantly. MPO values were above the detection limit in only 3 patients before treatment and in none during treatment. VEGF, bFGF, ECP and albumin concentrations correlated with each other with the exception of ECP and albumin. A decrease of serum ECP and VEGF concentrations was also seen even if the overtime reduction was not significant.

    CONCLUSION: Oral steroid treatment in CC patients induced a simultaneous reduction of bowel movements and rectal release of ECP, bFGF, VEGF and albumin, suggesting that these polypeptides and increased mucosal permeability are important components of the pathophysiology in collagenous colitis.

  • 383. Taha, Yesuf
    et al.
    Raab, Yngve
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, Anders
    Department of Medical Sciences. Klinisk kemi.
    Carlson, Marie
    Lööf, Lars
    Interfaculty Units, Centre for Clinical Research.
    Gerdin, Bengt
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Plastic Surgery.
    Thörn, Magnus
    Vascular endothelial growth factor (VEGF)--a possible mediator of inflammation and mucosal permeability in patients with collagenous colitis.2004In: Dig Dis Sci, ISSN 0163-2116, Vol. 49, no 1, p. 109-15Article in journal (Refereed)
  • 384. Ticinesi, Andrea
    et al.
    Lauretani, Fulvio
    Ceda, Gian Paolo
    Ruggiero, Carmelinda
    Ferrucci, Luigi
    Aloe, Rosalia
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Meschi, Tiziana
    Maggio, Marcello
    Uric acid and endothelial function in elderly community-dwelling subjects2017In: Experimental Gerontology, ISSN 0531-5565, E-ISSN 1873-6815, Vol. 89, p. 57-63Article in journal (Refereed)
    Abstract [en]

    The role of serum uric acid (SUA), an inflammatory agent and potential mediator of cardiovascular diseases, in endothelial function (EF) has been tested only in middle-aged subjects affected by specific diseases. Our aim was to assess the relationship between SUA and measures of EF in a cohort of elderly community-dwellers. This study involved 424 males and 426 females aged 70years from the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS), having complete data on SUA and EF assessed by flow-mediated vasodilation (FMD) and by intra-arterial infusion of acetylcholine (endothelium-dependent vasodilation, EDV) and sodium nitroprusside (endothelium-independent vasodilation, EIDV). Univariate and multivariate regression models obtained by backward selection from initial fully-adjusted models were built to assess the relationship between SUA and measures of EF in both genders. Cardiovascular risk factors, serum hormonal and metabolic mediators, and body composition were considered as potential confounders. In the univariate model, SUA was inversely associated in both genders with log(EDV) (β±SE males -0.39±0.17, p=0.03; females -0.57±0.19, p=0.003) and log(EIDV) (males -0.23±0.12, p=0.05; females -0.49±0.15, p=0.002), but not with log(FMD). After adjustment for BMI, only the association between SUA and log(EIDV) in females persisted, though attenuated (-0.32±0.16, p=0.049), and was no longer significant in the fully-adjusted multivariate model including waist/hip ratio. In conclusion, in older subjects, especially women, SUA is associated with EF not independently of a list of confounders including BMI and trunk fat mass, suggesting a role as surrogate metabolic marker rather than an active player in EF.

  • 385. Tryding, Nils
    et al.
    Hultdin, Johan
    Larsson, Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. klinisk kemi-.
    Vad är rätt pris för laboratorieanalyser2004In: Läkartidningen, Vol. 101, no 6, p. 495-496Article in journal (Refereed)
  • 386.
    van der Laan, Sander W.
    et al.
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands..
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Soumare, Aicha
    Univ Bordeaux, INSERM, U1219, Team Vintage, Bordeaux, France..
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, Dept SHIP KEF, Greifswald, Germany.;German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany..
    Sedaghat, Sanaz
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Baumert, Jens
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Zabaneh, Delilah
    UCL, Dept Genet Environm & Evolut, London, England.;UCL, Genet Inst, London, England..
    van Setten, Jessica
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands..
    Isgum, Ivana
    Univ Med Ctr Utrecht, Image Sci Inst, Utrecht, Netherlands..
    Galesloot, Tessel E.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands..
    Arpegard, Johannes
    Karolinska Univ Hosp Solna, Dept Emergency Med, Stockholm, Sweden.;Karolinska Inst, Dept Med Solna, Stockholm, Sweden..
    Amouyel, Philippe
    Univ Lille, INSERM, Lille, France.;Inst Pasteur, Lille, France..
    Trompet, Stella
    Leiden Univ, Med Ctr, Dept Cardiol P C5, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands..
    Waldenberger, Melanie
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany..
    Doerr, Marcus
    German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany.;Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany..
    Magnusson, Patrik K.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Felix, Janine F.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Morrison, Alanna C.
    Univ Texas Hlth Sci Ctr Houston, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA..
    Franceschini, Nora
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA..
    Kavousi, Maryam
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    O'Donnell, Christopher
    Boston Vet Adm Healthcare, Dept Cardiol, West Roxbury, MA USA.;NHLBI, Framingham Heart Study, Framingham, MA USA..
    Drenos, Fotios
    UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England.;Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England..
    Tragante, Vinicius
    Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands..
    Munroe, Patricia B.
    Queen Mary Univ London, William Harvey Res Inst, Natl Inst Hlth Res, Cardiovasc Biomed Res Unit, London, England..
    Malik, Rainer
    Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany..
    Dichgans, Martin
    Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany.;Munich Cluster Syst Neurol SyNergy, Munich, Germany..
    Worrall, Bradford B.
    Univ Virginia, Dept Neurol, Charlottesville, VA USA.;Univ Virginia, Dept Hlth Evaluat Sci, Charlottesville, VA USA..
    Erdmann, Jeanette
    Univ Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany..
    Nelson, Christopher P.
    Univ Leicester, Glenfield Hosp, British Heart Fdn Cardiovasc, Res Ctr,Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, Natl Inst Hlth Res Leicester, Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Samani, Nilesh J.
    Univ Leicester, Glenfield Hosp, British Heart Fdn Cardiovasc, Res Ctr,Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, Natl Inst Hlth Res Leicester, Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Schunkert, Heribert
    Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;German Ctr Cardiovasc Res, DZHK, Munich Heart Alliance, Partner Site, Munich, Germany..
    Marchini, Jonathan
    Univ Oxford, Dept Stat, Oxford, England..
    Patel, Riyaz S.
    UCL, Inst Cardiovasc Sci, Genet Epidemiol Res Grp, London, England.;Barts Heart Ctr, London, England.;UCL, Farr Inst Hlth Informat, London, England..
    Hingorani, Aroon D.
    UCL, Inst Cardiovasc Sci, Genet Epidemiol Res Grp, London, England..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    de Graaf, Jacqueline
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands..
    Kiemeney, Lambertus A. L. M.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands..
    Baumeister, Sebastian E.
    Univ Med Greifswald, Inst Community Med, Dept SHIP KEF, Greifswald, Germany.;Univ Regensburg, Inst Epidemiol & Prevent Med, Regensburg, Germany..
    Franco, Oscar H.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Hofman, Albert
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Uitterlinden, Andre G.
    Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands..
    Koenig, Wolfgang
    German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany.;Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany..
    Meisinger, Christa
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Peters, Annette
    German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Thorand, Barbara
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol P C5, Leiden, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands..
    Eriksen, Bjorn Odvar
    UiT Arctic Univ Norway, Metab & Renal Res Grp, Tromso, Norway.;Univ Hosp North Norway, Nephrol Sect, Tromso, Norway..
    Toft, Ingrid
    Univ Hosp North Norway, Nephrol Sect, Tromso, Norway..
    Wilsgaard, Tom
    UiT Arctic Univ Norway, Dept Community Med, Tromso, Norway..
    Onland-Moret, N. Charlotte
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    van der Schouw, Yvonne T.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Debette, Stephanie
    Univ Bordeaux, INSERM, U1219, Team Vintage, Bordeaux, France..
    Kumari, Meena
    Univ Essex, Biol & Social Epidemiol, Inst Social & Econ Res, Colchester CO4 3SQ, Essex, England..
    Svensson, Per
    Karolinska Univ Hosp Solna, Dept Emergency Med, Stockholm, Sweden.;Karolinska Inst, Dept Med Solna, Stockholm, Sweden..
    van der Harst, Pim
    ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands..
    Kivimaki, Mika
    UCL, Dept Epidemiol & Publ Hlth, London, England..
    Keating, Brendan J.
    Univ Penn, Dept Surg, Div Transplantat, Perelman Sch Med, Philadelphia, PA 19104 USA..
    Sattar, Naveed
    Univ Glasgow, Glasgow, Lanark, Scotland..
    Dehghan, Abbas
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Reiner, Alex P.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA..
    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. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    den Ruijter, Hester M.
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands..
    de Bakker, Paul I. W.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, Utrecht, Netherlands..
    Pasterkamp, Gerard
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.;Univ Med Ctr Utrecht, Div Labs & Pharm, Lab Clin Chem & Hematol, Utrecht, Netherlands..
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Holmes, Michael V.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England..
    Asselbergs, Folkert W.
    Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.;UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London, England..
    Cystatin C and Cardiovascular Disease: A Mendelian Randomization Study2016In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 68, no 9, p. 934-945Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. OBJECTIVES The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. RESULTS Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 x 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 x 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence fora causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0,994), which was statistically different from the observational estimate (p = 1.6 x 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD. CONCLUSIONS Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD.

  • 387.
    Viberg, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy.
    Lannergård, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Cars, Otto
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Karlsson, Mats O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy.
    Sandström, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy.
    A population pharmacokinetic model for cefuroxime using cystatin C as a marker of renal function2006In: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 62, no 3, p. 297-303Article in journal (Refereed)
    Abstract [en]

    Aims: Since cefuroxime mainly is excreted by renal filtration, dosing is currently based on serum creatinine (Scr) or creatinine clearance (CLcr). However, it has been suggested that cystatin C (CysC) is superior to Scr as a marker of renal function. The aim of this prospective study was to develop a population model that describes the pharmacokinetics of cefuroxime and to investigate the usefulness of CysC as a covariate of the model parameters.

    Methods: Ninety-seven patients were studied (CLcr range 6.5-115 ml min(-1)). Blood samples (n = 407) for the determination of cefuroxime were withdrawn according to a sparse data sampling schedule and analysed by liquid chromatography mass spectrometry. The population analysis was performed in NONMEM.

    Results: A two-compartment model described the data well. The biomarkers Scr, CLcr and CysC were evaluated as covariates on clearance (CL). The model that included CysC generated the best fit. In the final population model CL was a function of CysC and body weight, whereas V-1 was only a function of body weight. Final parameter estimates (relative standard errors) were 6.00 (3.2%) l h(-1), 11.4 (5.3%) l and 5.11 (11%) l for CL, V-1 and V-2, respectively.

    Conclusion: Based on the results of the present study, and because CysC is practical to use in the clinic, it is suggested that individual dosing of cefuroxime may be based on CysC rather than on Scr or CLcr. Furthermore, our final population model may be useful as a tool when designing new dosing schedules for cefuroxime.

  • 388. Vilhelmsdotter Allander, Susanne
    et al.
    Marké, Lars-Åke
    Wihlen, Björn
    Svensson, Maria
    Elinder, Carl-Gustaf
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Regional variation in use of exogenous and endogenous glomerular filtration rate (GFR) markers in Sweden2012In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, no 3, p. 273-278Article in journal (Refereed)
    Abstract [en]

    Background.

    Markers of renal function (glomerular filtration rate (GFR)) are frequently used in the Swedish health care. GFR is usually estimated based on plasma creatinine concentration, but plasma cystatin C concentration, creatinine clearance, iohexol clearance, and 51Cr-EDTA clearance are also used. These markers are all part of the daily patient care, but there is little specific information on the clinical use of these markers. The aim of this study was to compare the use of these various GFR markers in different parts of Sweden and potential changes over time.

    Methods.

    Retrospective study using questionnaires to collect information for the years 2006-2009 divided per county on the specific use of GFR markers with type of test reports.

    Results.

    Plasma/serum creatinine concentration (96%) is by far the dominating GFR marker in Sweden, while cystatin C concentration (3.5%), creatinine clearance (0.1%), iohexol clearance (0.1%), and 51Cr-EDTA clearance (0.1%) are less frequently used. The use of GFR markers, including creatinine, continues to increase on a national level with the exception of creatinine clearance and 51Cr-EDTA clearance. There were considerable variations between different counties in the use of GFR markers and the type of test reports that the laboratories provided.

    Conclusions.

    The inter-county variations of GFR markers used in Sweden are large and indicate that savings associated with optimized test utilization in this regard could be substantial. Regional habits and traditions are likely to influence the variations in GFR marker use.

  • 389.
    von Seth, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Engström, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Maripuu, Enn
    Department of Medical Physics, University Hospital, Uppsala, Sweden.
    Widström, Charles
    Department of Medical Physics, University Hospital, Uppsala, Sweden.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Rapid Bolus Administration Does Not Increase the Extravasation Rate of Albumin: A Randomized Controlled Trial in the Endotoxemic Pig2017In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 47, no 4, p. 514-519Article in journal (Refereed)
    Abstract [en]

    Some experimental data suggest that rapid bolus administration of albumin causes less plasma-expanding effects than slow, continuous infusion. To determine whether rapid bolus administration, in comparison with slow infusion, results in greater extravasation of albumin in experimental septic shock we performed a randomized controlled trial with 32 endotoxemic pigs. The animals were monitored and ventilated with standard intensive care equipment and given 10 mL x kg 5% albumin labeled with Technetium-99m, either as a rapid 15-minute bolus (Bolus group, n = 16) or as a 2-hour (h) infusion (Infusion group, n = 16). Radioactivity was monitored in plasma, extracellular microdialysate and urine for 6 h. Physiological parameters were monitored hourly. Radioactivity in the liver, spleen, kidney and lung was analyzed post-mortem.The plasma area under the curve (AUC) activity0-6h was 4.4 ± 0.9 x 10 in the Bolus group and 4.4 ± 1.1 x 10 counts x min x mL x h in the Infusion group. Blood hemoglobin levels increased in both groups, suggesting severe capillary leakage. Yet, there were no group differences in albumin radioactivity in plasma, muscle tissue, urine or in the post-mortem analysis of the organs. Following albumin administration, circulatory and respiratory parameters were similar in the two groups.In conclusion, the present results suggest that albumin might be given as a bolus without leading to increased extravasation of albumin, in contrast to previous animal experiments in rodents.

  • 390.
    von Seth, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Effects of Tigecycline and Doxycycline on Inflammation and Hemodynamics in Porcine Endotoxemia: a Prospective, Randomized and Placebo Controlled Trial2015In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 43, no 6, p. 604-611Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Antibiotics might, apart from an antimicrobial effect, also exert anti-inflammatory effects. The novel antibiotic tigecycline, potentially useful in septic shock from Gram-negative multi-resistant bacteria, is structurally related to antibiotics with known anti-inflammatory properties. However, its anti-inflammatory effects have previously not been explored in vivo. Using a sterile integrative porcine sepsis model, we investigated the anti-inflammatory and circulatory effects of tigecycline in comparison to doxycycline and placebo.

    METHODS: Eighteen pigs were randomized to receive tigecycline 100 mg, doxycycline 200 mg or placebo and subjected to 6 h endotoxin infusion at 0.5 μg x kg x h. Markers of inflammation, nitric oxide (NO) production, vascular permeability, hemodynamics, organ dysfunction, tissue metabolism and acid-base parameters were monitored.

    RESULTS: Peak plasma tumor necrosis alpha (TNF-α) was lower in the doxycycline group (P=0.031) but not in the tigecycline group (P=0.86) compared to placebo with geometric mean plasma concentrations of 16, 79 and 63 ng x ml, respectively. Mean arterial pressure was higher 4-6 h in the tigecycline group with values at 6 h of 107± 9 mmHg compared to the placebo and doxycycline groups (85 ± 27 mmHg and 90 ± 32 mmHg, respectively) (P=0.025). The white blood cell and the neutrophil granulocyte counts were less reduced in the doxycycline group, but not in the tigecycline group at 4-6 h (P=0.009 and p=0.019, respectively). Other markers of inflammation, organ dysfunction, tissue metabolism and acid-base parameters were unaffected by tigecycline.

    CONCLUSIONS: Consistent with known anti-inflammatory properties, doxycycline yielded decreased TNF-α levels. Tigecycline did not affect cytokine levels but counteracted hypotension and hypoperfusion.

  • 391. Vos, T
    et al.
    Abajobir, AA
    Abate, KH
    Abbafati, c
    Abbas, KM
    Abd-Allah, F
    Abdulkader, RS
    Abdulle, AM
    Abebo, TA
    Abera, SF
    Aboyans, V
    Abu-Raddad, LJ
    Ackerman, IN,
    Adamu, AA
    Adetokunboh, O
    Afarideh, M
    Afshin, A
    Ärnlöv, Johan
    Karolinska institute; Dalarna University.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Zhang, X
    Zhou, M
    Zipkin, B
    Zodpey, S,
    Zuhlke, LJ,
    Murray, CJL
    Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.2017In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 390, no 10100, p. 1211-1259, article id S0140-6736(17)32154-2Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.

    METHODS: We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between incidence, prevalence, remission, and cause of death rates for each condition. For some causes, we used alternative modelling strategies if incidence or prevalence needed to be derived from other data. YLDs were estimated as the product of prevalence and a disability weight for all mutually exclusive sequelae, corrected for comorbidity and aggregated to cause level. We updated the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. GBD 2016 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).

    FINDINGS: Globally, low back pain, migraine, age-related and other hearing loss, iron-deficiency anaemia, and major depressive disorder were the five leading causes of YLDs in 2016, contributing 57·6 million (95% uncertainty interval [UI] 40·8-75·9 million [7·2%, 6·0-8·3]), 45·1 million (29·0-62·8 million [5·6%, 4·0-7·2]), 36·3 million (25·3-50·9 million [4·5%, 3·8-5·3]), 34·7 million (23·0-49·6 million [4·3%, 3·5-5·2]), and 34·1 million (23·5-46·0 million [4·2%, 3·2-5·3]) of total YLDs, respectively. Age-standardised rates of YLDs for all causes combined decreased between 1990 and 2016 by 2·7% (95% UI 2·3-3·1). Despite mostly stagnant age-standardised rates, the absolute number of YLDs from non-communicable diseases has been growing rapidly across all SDI quintiles, partly because of population growth, but also the ageing of populations. The largest absolute increases in total numbers of YLDs globally were between the ages of 40 and 69 years. Age-standardised YLD rates for all conditions combined were 10·4% (95% UI 9·0-11·8) higher in women than in men. Iron-deficiency anaemia, migraine, Alzheimer's disease and other dementias, major depressive disorder, anxiety, and all musculoskeletal disorders apart from gout were the main conditions contributing to higher YLD rates in women. Men had higher age-standardised rates of substance use disorders, diabetes, cardiovascular diseases, cancers, and all injuries apart from sexual violence. Globally, we noted much less geographical variation in disability than has been documented for premature mortality. In 2016, there was a less than two times difference in age-standardised YLD rates for all causes between the location with the lowest rate (China, 9201 YLDs per 100 000, 95% UI 6862-11943) and highest rate (Yemen, 14 774 YLDs per 100 000, 11 018-19 228).

    INTERPRETATION: The decrease in death rates since 1990 for most causes has not been matched by a similar decline in age-standardised YLD rates. For many large causes, YLD rates have either been stagnant or have increased for some causes, such as diabetes. As populations are ageing, and the prevalence of disabling disease generally increases steeply with age, health systems will face increasing demand for services that are generally costlier than the interventions that have led to declines in mortality in childhood or for the major causes of mortality in adults. Up-to-date information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response.

    FUNDING: Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health.

  • 392. Waikar, Sushrut S
    et al.
    Sabbisetti, Venkata
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Coresh, Josef
    Feldman, Harold I
    Foster, Meredith C
    Fufaa, Gudeta D
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Hsu, Chi-Yuan
    Kimmel, Paul L
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Liu, Yumin
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Liu, Kathleen D
    Mifflin, Theodore E
    Nelson, Robert G
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Vasan, Ramachandran S
    Xie, Dawei
    Zhang, Xiaoming
    Bonventre, Joseph V
    Relationship of proximal tubular injury to chronic kidney disease as assessed by urinary kidney injury molecule-1 in five cohort studies2016In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 31, no 9, p. 1460-1470Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The primary biomarkers used to define CKD are serum creatinine and albuminuria. These biomarkers have directed focus on the filtration and barrier functions of the kidney glomerulus even though albuminuria results from tubule dysfunction as well. Given that proximal tubules make up ∼90% of kidney cortical mass, we evaluated whether a sensitive and specific marker of proximal tubule injury, urinary kidney injury molecule-1 (KIM-1), is elevated in individuals with CKD or with risk factors for CKD.

    METHODS: We measured urinary KIM-1 in participants of five cohort studies from the USA and Sweden. Participants had a wide range of kidney function and were racially and ethnically diverse. Multivariable linear regression models were used to test the association of urinary KIM-1 with demographic, clinical and laboratory values.

    RESULTS: In pooled, multivariable-adjusted analyses, log-transformed, creatinine-normalized urinary KIM-1 levels were higher in those with lower eGFR {β = -0.03 per 10 mL/min/1.73 m(2) [95% confidence interval (CI) -0.05 to -0.02]} and greater albuminuria [β = 0.16 per unit of log albumin:creatinine ratio (95% CI 0.15-0.17)]. Urinary KIM-1 levels were higher in current smokers, lower in blacks than nonblacks and lower in users versus nonusers of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.

    CONCLUSION: Proximal tubule injury appears to be an integral and measurable element of multiple stages of CKD.

  • 393. Wang, H
    et al.
    Abajobir, AA
    Abate, KH
    Abbafati, C
    Abbas ,, KM
    Abd-Allah, F
    Abera, sf
    Abraha, HN
    Abu-Raddad, LJ
    Abu-Rmeileh, NME
    Adedeji, IA
    Adedoyin, RA
    Adetifa, IMO
    Adetokunboh, O
    Afshin, A
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Zeeb, H
    Zenebe, ZM
    Zerfu, TA
    Zhang, AL
    Zhang, X
    Zodpey, S
    Zuhlke, LJ
    Lopez, AD
    Murray, CJL
    Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970-2016: a systematic analysis for the Global Burden of Disease Study 2016.2017In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 390, no 10100, p. 1084-1150Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016.

    METHODS: We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15-60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0·5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Socio-demographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone.

    FINDINGS: Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5-24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates-a measure of relative inequality-increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86·9 years (95% UI 86·7-87·2), and for men in Singapore, at 81·3 years (78·8-83·7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, and the gap between male and female life expectancy increased with progression to higher levels of SDI. Some countries with exceptional health performance in 1990 in terms of the difference in observed to expected life expectancy at birth had slower progress on the same measure in 2016.

    INTERPRETATION: Globally, mortality rates have decreased across all age groups over the past five decades, with the largest improvements occurring among children younger than 5 years. However, at the national level, considerable heterogeneity remains in terms of both level and rate of changes in age-specific mortality; increases in mortality for certain age groups occurred in some locations. We found evidence that the absolute gap between countries in age-specific death rates has declined, although the relative gap for some age-sex groups increased. Countries that now lead in terms of having higher observed life expectancy than that expected on the basis of development alone, or locations that have either increased this advantage or rapidly decreased the deficit from expected levels, could provide insight into the means to accelerate progress in nations where progress has stalled.

    FUNDING: Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health.

  • 394.
    Wang, Haidong
    et al.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Bhutta, Zulfiriar A.
    Aga Khan Univ, Ctr Excellence Women & Child Hlth, Karachi, Pakistan.;Hosp Sick Children, Ctr Global Child Hlth, Toronto, ON, Canada..
    Coates, Matthew M.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Coggeshall, Megan
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Dandona, Lalit
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA.;Publ Hlth Fdn India, New Delhi, India..
    Diallo, Khassoum
    WHO Reg Off Europe, Copenhagen, Denmark..
    Franca, Elisabeth Barboza
    Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil..
    Fraser, Maya
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Fullman, Nancy
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Gething, Peter W.
    Univ Oxford, Dept Zool, Oxford, England..
    Hay, Simon I.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Kinfu, Yohannes
    Univ Canberra, Fac Hlth, Ctr Res & Act Publ Hlth, Canberra, ACT, Australia..
    Kita, Maaya
    Univ Tokyo, Grad Sch Med, Dept Global Hlth Policy, Tokyo, Japan..
    Kulikoff, Xie Rachel
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Larson, Heidi J.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA.;London Sch Hyg & Trop Med, Dept Infect Dis Epidemiol, London, England..
    Liang, Juan
    Sichuan Univ, West China Univ Hosp 2, Natl Off Maternal & Child Hlth Surveillance, Chengdu, Peoples R China..
    Liang, Xiaofeng
    Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China..
    Lind, Margaret
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Lopez, Alan D.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA.;Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia..
    Lozano, Rafael
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Mensah, George A.
    NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bldg 10, Bethesda, MD 20892 USA..
    Mikesell, Joseph B.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Mokdad, Ali H.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Mooney, Meghan D.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Nguyen, Grant
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Rakovac, Ivo
    WHO Reg Off Europe, Copenhagen, Denmark..
    Salomon, Joshua A.
    Harvard Univ, Dept Global Hlth & Populat, Boston, MA 02115 USA..
    Silpakit, Naris
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Sligar, Amber
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Sorensen, Reed J. D.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Vos, Theo
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Zhu, Jun
    Natl Off MCH Surveillance China, Chengdu, Peoples R China..
    Abajobir, Amanuel Alemu
    Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia.;Univ Queensland, Sch Publ Hlth, Herston, Qld, Australia..
    Abate, Kalkidan Hassen
    Jimma Univ, Jimma, Ethiopia..
    Abbas, Kaja M.
    Virginia Tech, Blacksburg, VA USA..
    Abd-Allah, Foad
    Cairo Univ, Dept Neurol, Cairo, Egypt..
    Abdulle, Abdishakur M.
    New York Univ Abu Dhabi, Abu Dhabi, U Arab Emirates..
    Abera, Semaw Ferede
    Mekelle Univ, Coll Hlth Sci, Mekelle, Ethiopia.;Kilte AwlaeloHealth & Demog Surveillance Site, Mekelle, Ethiopia.;Univ Hohenheim, Food Secur, Stuttgart, Germany.;Univ Hohenheim, Inst Biol Chem & Nutr, Stuttgart, Germany..
    Aboyans, Victor
    Dupuytren Univ Hosp, Limoges, France..
    Abraham, Biju
    NMSM Govt Coll Kalpetta, Kalpetta, Kerala, India..
    Abubakar, Ibrahim
    UCL, Inst Global Hlth, London, England..
    Abu-Raddad, Laith J.
    Weill Cornell Med Coll Qatar, Infect Dis Epidemiol Grp, Doha, Qatar..
    Abu-Rmeileh, Niveen M. E.
    Birzeit Univ, Inst Community & Publ Hlth, Ramallah, Israel..
    Abyu, Gebre Yitayih
    Mekelle Univ, Mekelle, Ethiopia..
    Achoki, Tom
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Adebiyi, Akindele Olupelumi
    Univ Ibadan, Coll Med, Ibadan, Nigeria.;Univ Coll Hosp, Ibadan, Nigeria..
    Adedeji, Isaac Akinkunmi
    Olabisi Onabanjo Univ, Ago Iwoye, Nigeria..
    Adelekan, Ademola Lukman
    Univ Ibadan, Ibadan, Nigeria.;Publ Hlth Promot Alliance, Osogbo, Nigeria..
    Adou, Arsene Kouablan
    Assoc Ivoirienne Bien Etre Familial, Abidjan, Cote Ivoire..
    Agarwal, Arnav
    Univ Toronto, Toronto, ON, Canada.;McMaster Univ, Hamilton, ON, Canada..
    Ajala, Oluremi N.
    Harvard Univ, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA.;Univ Pittsburgh, Med Ctr, Mckeesport, PA USA..
    Akinyemiju, Tomi F.
    Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA..
    Akseer, Nadia
    Hosp Sick Children, Ctr Global Child Hlth, Toronto, ON, Canada.;Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada..
    Alam, Khurshid
    Murdoch Childrens Res Inst, Melbourne, Vic, Australia.;Univ Melbourne, Melbourne, Vic, Australia.;Univ Sydney, Sydney, NSW, Australia..
    Alam, Noore K. M.
    Queensland Hlth, Herston, Qld, Australia.;Univ Queensland, Herston, Qld, Australia..
    Alasfoor, Deena
    Minist Hlth, Al Khuwair, Oman..
    Aldridge, Robert William
    UCL, Ctr Publ Hlth Data Sci, Inst Hlth Informat, London, England..
    Alegretti, Miguel Angel
    Univ Republica, Fac Med, Dept Prevent & Social Med, Montevideo, Uruguay..
    Alemu, Zewdie Aderaw
    Debre Markos Univ, Debre Markos, Ethiopia..
    Ali, Raghib
    Univ Oxford, Oxford, England..
    Alkerwi, Ala'a
    Luxembourg Inst Hlth, Strassen, Luxembourg..
    Alla, Francois
    Univ Lorraine, Sch Publ Hlth, Nancy, France..
    Al-Raddadi, Rajaa
    Minist Hlth, Jeddah, Saudi Arabia..
    Alsharif, Ubai
    Charite, Berlin, Germany..
    Altirkawi, Khalid A.
    King Saud Univ, Riyadh, Saudi Arabia..
    Martin, Elena Alvarez
    Minist Hlth Social Policy & Equal, Spanish Observ Drugs, Govt Delegat Natl Plan Drugs, Madrid, Spain..
    Alvis-Guzman, Nelson
    Univ Cartagena, Cartagena De Indias, Colombia..
    Amare, Azmeraw T.
    Univ Adelaide, Sch Med, Adelaide, SA, Australia.;Bahir Dar Univ, Coll Med & Hlth Sci, Bahir Dar, Ethiopia..
    Amberbir, Alemayehu
    Dignitas Int, Zomba, Malawi..
    Amegah, Adeladza Kofi
    Univ Cape Coast, Cape Coast, Ghana..
    Ameh, Emmanuel A.
    Natl Hosp, Abuja, Nigeria..
    Ammar, Walid
    Minist Publ Hlth, Beirut, Lebanon..
    Amrock, Stephen Marc
    Oregon Hlth & Sci Univ, Portland, OR 97201 USA..
    Andersen, Hjalte H.
    Anderson, Gregory M.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA.;Aalborg Univ, Fac Med, Dept Hlth Sci & Technol, Ctr Sensory Motor Interact, Aalborg, Denmark..
    Antonio, Carl Abelardo T.
    Univ Philippines, Coll Publ Hlth, Dept Hlth Policy & Adm, Manila, Philippines..
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Dalarna Univ, Falun, Sweden..
    Artaman, Al
    Asayesh, Hamid
    Qom Univ Med Sci, Sch Paramed, Dept Emergency Med, Qom, Iran..
    Asghar, Rana Jawad
    South Asian Publ Hlth Forum, Islamabad, Pakistan..
    Assadi, Reza
    Atique, Suleman
    Avokpaho, Euripide Frinel G. Arthur
    Awasthi, Ashish
    Quintanilla, Beatriz Paulina Ayala
    Bacha, Umar
    Badawi, Alaa
    Univ Toronto, Dept Nutr Sci, Fac Med, Toronto, ON, Canada..
    Balakrishnan, Kalpana
    Banerjee, Amitava
    UCL, Farr Inst Hlth Informat Res, London, England..
    Banigbe, Bolanle F.
    Barac, Aleksandra
    Barber, Ryan M.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Barker-Collo, Suzanne L.
    Barnighausen, Till
    Harvard Univ, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Barrero, Lope H.
    Bayou, Tigist Assefa
    Mekelle Univ, Mekelle, Ethiopia..
    Bayou, Yibeltal Tebekaw
    Bazargan-Hejazi, Shahrzad
    Beardsley, Justin
    Bedi, Neeraj
    Bekele, Tolesa
    Bell, Michelle L.
    Bello, Aminu K.
    Bennett, Derrick A.
    Univ Oxford, Oxford, England..
    Bensenor, Isabela M.
    Berhane, Adugnaw
    Bernabe, Eduardo
    Betsu, Balem Demtsu
    Mekelle Univ, Mekelle, Ethiopia..
    Bhatt, Samir
    Biadgilign, Sibhatu
    Bikbov, Boris
    Birlik, Sait Mentes
    Bisanzio, Donal
    Univ Oxford, Nuffield Dept Med, Oxford, England..
    Bjertness, Espen
    Blore, Jed D.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Bourne, Rupert R. A.
    Brainin, Michael
    Brazinova, Alexandra
    Breitborde, Nicholas J. K.
    Brown, Alexandria
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Buckle, Geoffrey Colin
    Burch, Michael
    Butt, Zahid A.
    Campos-Nonato, Ismael Ricardo
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico.;Harvard Univ, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Campuzano, Julio Cesar
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Cardenas, Rosario
    Carpenter, David
    Carrero, Juan Jesus
    Carter, Austin
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Casey, Daniel C.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Castaneda-Oquela, Carlos A.
    Rivas, Jacqueline Castillo
    Castro, Ruben Estanislao
    Catala-Lopez, Ferran
    Cercy, Kelly
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Chang, Hsing-Yi
    Chang, Jung-Chen
    Chibueze, Chioma Ezinne
    Chisumpa, Vesper Hichilombwe
    Choi, Jee-Young Jasmine
    Chowdhury, Rajiv
    Christopher, Devasahayam Jesudas
    Ciobanu, Liliana G.
    Univ Adelaide, Adelaide, SA, Australia..
    Colquhoun, Samantha M.
    Murdoch Childrens Res Inst, Melbourne, Vic, Australia.;Univ Melbourne, Melbourne, Vic, Australia..
    Cooper, Cyrus
    Univ Oxford, NIHR Musculoskeletal Biomed Res Ctr, Oxford, England..
    Cornaby, Leslie
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Damtew, Solomon Abrha
    Danawi, Hadi
    Dandona, Rakhi
    Publ Hlth Fdn India, New Delhi, India..
    das Neves, Jose
    Davis, Adrian C.
    de Jager, Pieter
    De Leo, Diego
    Degenhardt, Louisa
    Deribe, Kebede
    Deribew, Amare
    Univ Oxford, Nuffield Dept Med, Oxford, England..
    Jarlais, Don C. Des
    deVeber, Gabrielle A.
    Hosp Sick Children, Toronto, ON, Canada..
    Dharmaratne, Samath D.
    Dhillon, Preet K.
    Ding, Eric L.
    Harvard Univ, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Doshi, Pratik Pinal
    Doyle, Kerrie E.
    Duan, Leilei
    Natl Ctr Chron & Noncommunicable Dis Control & Pr, Beijing, Peoples R China..
    Dubey, Manisha
    Ebrahimi, Hedyeh
    Ellingsen, Christian Lycke
    Elyazar, Iqbal
    Endries, Aman Yesuf
    Ermakov, Sergey Petrovich
    Eshrati, Babak
    Esteghamati, Alireza
    Faraon, Emerito Jose Aquino
    Univ Philippines, Coll Publ Hlth, Manila, Philippines..
    Farid, Talha A.
    Farinha, Carla Sofia e Sa
    Faro, Andre
    Farvid, Maryam S.
    Harvard Univ, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Farzadfar, Farshad
    Fereshtehnejad, Seyed-Mohammad
    Fernandes, Joao C.
    Fischer, Florian
    Fitchett, Joseph R. A.
    Harvard Univ, Boston, MA 02115 USA..
    Foigt, Nataliya
    Franklin, Richard C.
    Friedman, Joseph
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Furst, Thomas
    Gambashidze, Ketevan
    Gamkrelidze, Amiran
    Ganguly, Parthasarathi
    Gebre, Teshome
    Gebrehiwot, Tsegaye Tewelde
    Jimma Univ, Jimma, Ethiopia..
    Gebremedhin, Amanuel Tesfay
    Jimma Univ, Jimma, Ethiopia..
    Gebru, Alemseged Aregay
    Mekelle Univ, Mekelle, Ethiopia..
    Gelefinse, Johanna M.
    Gessner, Bradford D.
    Ginawi, Ibrahim Abdelmageem Mohamed
    Giref, Ababi Zergaw
    Gishu, Melkamu Dedefo
    Gomez-Dantes, Hector
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Gona, Philimon
    Goodridge, Amador
    Gopalani, Sameer Vali
    Goto, Atsushi
    Gouda, Hebe N.
    Univ Queensland, Brisbane, Qld, Australia..
    Gugnani, Harish Chander
    Guo, Yuming
    Univ Queensland, Brisbane, Qld, Australia..
    Gupta, Rahul
    Gupta, Rajeev
    Gupta, Vipin
    Gyawali, Bishal
    Haagsma, Juanita A.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Hafezi-Nejad, Nima
    Haile, Demewoz
    Hailu, Alemayehu Desalegne
    Hailu, Gessessew Bugssa
    Mekelle Univ, Mekelle, Ethiopia..
    Hamadeh, Randah Ribhi
    Hancock, Jamie
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Handal, Alexis J.
    Hankey, Graeme J.
    Harb, Hilda L.
    Minist Publ Hlth, Beirut, Lebanon..
    Harikrishnan, Sivadasanpillai
    Harun, Kimani M.
    Havmoeller, Rasmus
    Hay, Roderick J.
    Heredia-Pi, Ileana Beatriz
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Hoek, Hans W.
    Horino, Masako
    Horita, Nobuyuki
    Hosgood, H. Dean
    Hotez, Peter J.
    Hoy, Damian G.
    Hsairi, Mohamed
    Hu, Guoqing
    Huang, Cheng
    Huang, John J.
    Huang, Hsiang
    Huiart, Laetitia
    Iburg, Kim Moesgaard
    Idrisov, Bulat T.
    Innos, Kaire
    Jacobsen, Kathryn H.
    Jahanmehr, Nader
    Javanbakht, Mehdi
    Jayatilleke, Achala Upendra
    Jee, Sun Ha
    Jeemon, Panniyammakal
    Publ Hlth Fdn India, Ctr Control Chron Condit, New Delhi, India..
    Jha, Vivekanand
    Univ Oxford, Oxford, England..
    Jiang, Guohong
    Jiang, Ying
    Jibat, Tariku
    Jin, Ye
    Natl Ctr Chron & Noncommunicable Dis Control & Pr, Beijing, Peoples R China..
    Jonas, Jost B.
    Kabir, Zubair
    Kalkonde, Yogeshwar
    Karnak, Ritul
    Kan, Haidong
    Kang, Gagandeep
    Karch, Andre
    Karema, Corine Kakizi
    Kasaeian, Amir
    Kaul, Anil
    Kawakami, Norito
    Univ Tokyo, Sch Publ Hlth, Tokyo, Japan..
    Kayibanda, Jeanne Francoise
    Kazanjan, Konstantin
    Keiyoro, Peter Njenga
    Kemp, Andrew Haddon
    Kengne, Andre Pascal
    Keren, Andre
    Kereselidze, Maia
    Kesavachandran, Chandrasekharan Nair
    Khader, Yousef Saleh
    Khalil, Ibrahim A.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Khan, Abdur Rahman
    Khan, Ejaz Ahmad
    Khang, Young -Ho
    Khonelidze, Irma
    Khubchandani, Jagdish
    Kim, Cho-il
    Kim, Daniel
    Kim, Yun Jin
    Kissoon, Niranjan
    Kivipelto, Miia
    Knibbs, Luke D.
    Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia.;Univ Queensland, Sch Publ Hlth, Herston, Qld, Australia..
    Kokubo, Yoshihiro
    Kosen, Soewarta
    Koul, Parvaiz A.
    Koyanagi, Ai
    Defo, Barthelemy Kuate
    Bicer, Burcu Kucuk
    Kudom, Andreas A.
    Univ Cape Coast, Cape Coast, Ghana..
    Kumar, G. Anil
    Publ Hlth Fdn India, New Delhi, India..
    Kyu, Hmwe H.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Lal, Dharmesh Kumar
    Lalloo, Ratilal
    Univ Queensland, Sch Dent, Brisbane, Qld, Australia.;Univ Queensland, Sch Dent, Herston, Qld, Australia..
    Lam, Hilton
    Lam, Jennifer O.
    Lansingh, Van C.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Leigh, James
    Univ Sydney, Sydney, NSW, Australia..
    Leung, Ricky
    Li, Yichong
    Natl Ctr Chron & Noncommunicable Dis Control & Pr, Beijing, Peoples R China..
    Li, Yongmei
    Lindsay, M. Patrice
    Univ Toronto, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada..
    Liu, Patrick Y.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Liu, Shiwei
    Natl Ctr Chron & Noncommunicable Dis Control & Pr, Beijing, Peoples R China..
    Lloyd, Belinda K.
    Lo, Warren D.
    Logroscino, Giancarlo
    Low, Nicola
    Lunevicius, Raimundas
    Lyons, Ronan A.
    Ma, Stefan
    Abd El Razek, Hassan Magdy
    Abd El Razek, Mohammed Magdy
    Mandavi, Mandi
    Majdan, Marek
    Majeed, Azeem
    Malekzadeh, Reza
    Mapoma, Chabila C.
    Marcenes, Wagner
    -Raga, Jose Martinez
    Marzan, Melvin Barrientos
    Masiye, Felix
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    McGrath, John J.
    Univ Queensland, Brisbane, Qld, Australia..
    Meaney, Peter A.
    Mehari, Alem
    Mehndiratta, Man Mohan
    Mekonnen, Alemayehu B.
    Univ Sydney, Sydney, NSW, Australia..
    Melaku, Yohannes Adama
    Mekelle Univ, Sch Publ Hlth, Mekelle, Ethiopia.;Univ Adelaide, Sch Med, Adelaide, SA, Australia..
    Memiah, Peter
    Memish, Ziad A.
    Mendoza, Walter
    Meretoja, Atte
    Univ Melbourne, Dept Med, Melbourne, Vic, Australia..
    Meretoja, Tuomo J.
    Mhimbira, Francis Apolinary
    Miller, Ted R.
    Mills, Edward J.
    Mirarefin, Mojde
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Misganaw, Awoke
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Mock, Charles N.
    Univ Washington, Harborview Injury Prevent & Res Ctr, Seattle, WA 98195 USA..
    Mohammad, Karzan Abdulmuhsin
    Mohammadi, Alireza
    Mohammed, Shafiu
    Monasta, Lorenzo
    Montanez Hernandez, Julio Cesar
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Montico, Marcella
    Moore, Ami R.
    Moradi-Lakeh, Maziar
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Morawska, Lidia
    Mori, Rintaro
    Mueller, Ulrich O.
    Murphy, Georgina A. V.
    Univ Oxford, Oxford, England..
    Murthy, Srinivas
    Nachega, Jean B.
    Naheed, Aliya
    Naidoo, Kovin S.
    Naldi, Luigi
    Nand, Devina
    Nangia, Vinay
    Neupane, Subas
    Newton, Charles R.
    Newton, John N.
    Ng, Marie
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Ngalesoni, Frida Namnyak
    Nguhiu, Peter
    Nguyen, Quyen Le
    Nisar, Muhammad Imran
    Aga Khan Univ, Karachi, Pakistan..
    Pete, Patrick Martial Nkamedjie
    Norheim, Ole F.
    Norman, Rosana E.
    Ogbo, Felix Akpojene
    Oh, In-Hwan
    Ojelabi, Foluke Adetola
    Univ Ibadan, Ibadan, Nigeria..
    Olivares, Pedro R.
    Olusanya, Bolajoko Olubukunola
    Olusanya, Jacob Olusegun
    Oren, Eyal
    Ota, Erika
    Mahesh, P. A.
    Park, Eun-Kee
    Park, Hye-Youn
    Parsaeian, Mahboubeh
    Caicedo, Angel J. Paternina
    Patten, Scott B.
    Pedro, Joao Mario
    Pereira, David M.
    Perico, Norberto
    Pesudovs, Konrad
    Petzold, Max
    Phillips, Michael Robert
    Pillay, Julian David
    Pishgar, Farhad
    Polinder, Suzanne
    Pope, Daniel
    Popova, Svetlana
    Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada..
    Pourmalek, Farshad
    Qorbani, Mostafa
    Rabiee, Rynaz H. S.
    Rafay, Anwar
    Rahimi-Movaghar, Vafa
    Rahman, Mahfuzar
    Ur Rahman, Mohammad Hifz
    Ur Rahman, Sajjad
    Rai, Rajesh Kumar
    Raju, Murugesan
    Ram, Usha
    Rana, Saleem M.
    Ranabhat, Chhabi Lal
    Rao, Puja
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Refaat, Amany H.
    Remuzzi, Giuseppe
    Resnikoff, Serge
    Reynolds, Alex
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Rojas-Rueda, David
    Ronfani, Luca
    Roshandel, Gholamreza
    Roth, Gregory A.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Roy, Ambuj
    Ruhago, George Mugambage
    Sagar, Rajesh
    Saleh, Muhammad Muhammad
    Sanabria, Juan R.
    Sanchez-Nino, Maria Dolores
    Santos, Itamar S.
    Santos, Joao Vasco
    Sarmiento-Suarez, Rodrigo
    Sartorius, Benn
    Satpathy, Maheswar
    Savic, Miloje
    Sawhney, Monika
    Schneider, Ione J. C.
    Schottker, Ben
    Schwebel, David C.
    Univ Alabama Birmingham, Birmingham, AL USA..
    Seedat, Soraya
    Sepanlou, Sadaf G.
    Servan-Mori, Edson E.
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Setegn, Tesfaye
    Bahir Dar Univ, Bahir Dar, Ethiopia..
    Shahraz, Saeid
    Shaikh, Masood Ali
    Shakh-Nazarova, Marina
    Sharma, Rajesh
    She, Jun
    Sheikhbahaei, Sara
    Shen, Jiabin
    Sheth, Kevin N.
    Shibuya, Kenji
    Univ Tokyo, Grad Sch Med, Dept Global Hlth Policy, Tokyo, Japan..
    Shin, Hwashin Hyun
    Shin, Min-Jeong
    Shiri, Rahman
    Shuie, Ivy
    Sigfusdottir, Inga Dora
    Silva, Diego Augusto Santos
    Silverberg, Jonathan
    Simard, Edgar P.
    Sindi, Shireen
    Singh, Abhishek
    Singh, Jasvinder A.
    Univ Alabama Birmingham, Birmingham, AL USA..
    Singh, Om Prakash
    Singh, Prashant Kumar
    Singh, Virendra
    Soriano, Joan B.
    Soshnikov, Sergey
    Sposato, Luciano A.
    Sreeramareddy, Chandrashekhar T.
    Stathopoulou, Vasiliki
    Steel, Nicholas
    Stroumpoulis, Konstantinos
    Sturua, Lela
    Sunguya, Bruno F.
    Swaminathan, Soumya
    Sykes, Bryan L.
    Szoeke, Cassandra E. I.
    Univ Melbourne, Inst Hlth & Ageing, Melbourne, Vic, Australia..
    Tabares-Seisdedos, Rafael
    Tavakkoli, Mohammad
    Taye, Bineyam
    Tedla, Bemnet Amare
    Tefera, Worku Mekonnen
    Tekle, Tesfaye
    Mekelle Univ, Mekelle, Ethiopia..
    Shifa, Girma Temam
    Terkawi, Abdullah Sulieman
    Tesfay, Fisaha Haile
    Mekelle Univ, Coll Hlth Sci, Mekelle, Ethiopia..
    Tessema, Gizachew Assefa
    Univ Adelaide, Adelaide, SA, Australia..
    Thapa, Kiran
    Thomson, Alan J.
    -Lyman, Andrew L. Thorne
    Harvard Univ, Dept Nutr, Boston, MA 02115 USA..
    Tobe-Gai, Ruoyan
    Tonelli, Marcello
    Topor-Madry, Roman
    Topouzis, Fotis
    Tran, Bach Xuan
    Troeger, Christopher
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Truelsen, Thomas
    Dimbuene, Zacharie Tsala
    Tura, Abera Kenay
    Tyrovolas, Stefanos
    Ukwaja, Kingsley N.
    Uneke, Chigozie Jesse
    Uthman, Olalekan A.
    Vaezghasemi, Masoud
    Vasankari, Tommi
    Vasconcelos, Ana Maria Nogales
    Venketasubramanian, Narayanaswamy
    Verma, Raj Kumar
    Violante, Francesco S.
    Vladimirov, Sergey K.
    Vlassov, Vasiliy Victorovich
    Vollset, Stein Emil
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Wang, Linhong
    Natl Ctr Chron & Noncommunicable Dis Control & Pr, Beijing, Peoples R China..
    Wang, Yanping
    Weichenthal, Scott
    Weiderpass, Elisabete
    Weintraub, Robert G.
    Murdoch Childrens Res Inst, Melbourne, Vic, Australia.;Univ Melbourne, Melbourne, Vic, Australia..
    Weiss, Daniel J.
    Univ Oxford, Oxford, England..
    Werdecker, Andrea
    Westerman, Ronny
    Widdowson, Marc -Alain
    Wijeratne, Tissa
    Univ Melbourne, Melbourne, Vic, Australia..
    Williams, Thomas Neil
    Wiysonge, Charles Shey
    Wolfe, Charles D. A.
    Wolfe, Ingrid
    Won, Sungho
    Wubshet, Mamo
    Xiao, Qingyang
    Xu, Gelin
    Yadav, Ajit Kumar
    Yakob, Bereket
    Yano, Yuichiro
    Yaseri, Mehdi
    Ye, Pengpeng
    Natl Ctr Chron & Noncommunicable Dis Control & Pr, Beijing, Peoples R China..
    Yebyo, Henock Gebremedhin
    Mekelle Univ, Mekelle, Ethiopia..
    Yip, Paul
    Yonemoto, Naohiro
    Yoon, Seok-Jun
    Younis, Mustafa Z.
    Yu, Chuanhua
    Zaidi, Zoubida
    Zaki, Maysaa El Sayed
    Zeeb, Hajo
    Zhang, Hao
    Zhao, Yong
    Zheng, Yingfeng
    Zhou, Maigeng
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA.;Natl Ctr Chron & Noncommunicable Dis Control & Pr, Beijing, Peoples R China..
    Zodpey, Sanjay
    Murray, Christopher J. L.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA..
    Global, regional, national, and selected subnational levels of stillbirths, neonatal, infant, and under-5 mortality, 1980-2015: a systematic analysis for the Global Burden of Disease Study 20152016In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 388, no 10053, p. 1725-1774Article in journal (Refereed)
    Abstract [en]

    Background Established in 2000, Millennium Development Goal 4 (MDG4) catalysed extraordinary political, financial, and social commitments to reduce under-5 mortality by two-thirds between 1990 and 2015. At the country level, the pace of progress in improving child survival has varied markedly, highlighting a crucial need to further examine potential drivers of accelerated or slowed decreases in child mortality. The Global Burden of Disease 2015 Study (GBD 2015) provides an analytical framework to comprehensively assess these trends for under-5 mortality, age-specific and cause-specific mortality among children under 5 years, and stillbirths by geography over time. Methods Drawing from analytical approaches developed and refined in previous iterations of the GBD study, we generated updated estimates of child mortality by age group (neonatal, post-neonatal, ages 1-4 years, and under 5) for 195 countries and territories and selected subnational geographies, from 1980-2015. We also estimated numbers and rates of stillbirths for these geographies and years. Gaussian process regression with data source adjustments for sampling and non-sampling bias was applied to synthesise input data for under-5 mortality for each geography. Age-specific mortality estimates were generated through a two-stage age-sex splitting process, and stillbirth estimates were produced with a mixed-effects model, which accounted for variable stillbirth definitions and data source-specific biases. For GBD 2015, we did a series of novel analyses to systematically quantify the drivers of trends in child mortality across geographies. First, we assessed observed and expected levels and annualised rates of decrease for under-5 mortality and stillbirths as they related to the Soci-demographic Index (SDI). Second, we examined the ratio of recorded and expected levels of child mortality, on the basis of SDI, across geographies, as well as differences in recorded and expected annualised rates of change for under-5 mortality. Third, we analysed levels and cause compositions of under-5 mortality, across time and geographies, as they related to rising SDI. Finally, we decomposed the changes in under-5 mortality to changes in SDI at the global level, as well as changes in leading causes of under-5 deaths for countries and territories. We documented each step of the GBD 2015 child mortality estimation process, as well as data sources, in accordance with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, 5.8 million (95% uncertainty interval [UI] 5.7-6.0) children younger than 5 years died in 2015, representing a 52.0% (95% UI 50.7-53.3) decrease in the number of under-5 deaths since 1990. Neonatal deaths and stillbirths fell at a slower pace since 1990, decreasing by 42.4% (41.3-43.6) to 2.6 million (2.6-2.7) neonatal deaths and 47.0% (35.1-57.0) to 2.1 million (1.8-2.5) stillbirths in 2015. Between 1990 and 2015, global under-5 mortality decreased at an annualised rate of decrease of 3.0% (2.6-3.3), falling short of the 4.4% annualised rate of decrease required to achieve MDG4. During this time, 58 countries met or exceeded the pace of progress required to meet MDG4. Between 2000, the year MDG4 was formally enacted, and 2015, 28 additional countries that did not achieve the 4.4% rate of decrease from 1990 met the MDG4 pace of decrease. However, absolute levels of under-5 mortality remained high in many countries, with 11 countries still recording rates exceeding 100 per 1000 livebirths in 2015. Marked decreases in under-5 deaths due to a number of communicable diseases, including lower respiratory infections, diarrhoeal diseases, measles, and malaria, accounted for much of the progress in lowering overall under-5 mortality in low-income countries. Compared with gains achieved for infectious diseases and nutritional deficiencies, the persisting toll of neonatal conditions and congenital anomalies on child survival became evident, especially in low-income and low-middle-income countries. We found sizeable heterogeneities in comparing observed and expected rates of under-5 mortality, as well as differences in observed and expected rates of change for under-5 mortality. At the global level, we recorded a divergence in observed and expected levels of under-5 mortality starting in 2000, with the observed trend falling much faster than what was expected based on SDI through 2015. Between 2000 and 2015, the world recorded 10.3 million fewer under-5 deaths than expected on the basis of improving SDI alone. Interpretation Gains in child survival have been large, widespread, and in many places in the world, faster than what was anticipated based on improving levels of development. Yet some countries, particularly in sub-Saharan Africa, still had high rates of under-5 mortality in 2015. Unless these countries are able to accelerate reductions in child deaths at an extraordinary pace, their achievement of proposed SDG targets is unlikely. Improving the evidence base on drivers that might hasten the pace of progress for child survival, ranging from cost-effective intervention packages to innovative financing mechanisms, is vital to charting the pathways for ultimately ending preventable child deaths by 2030.

  • 395. Wang, Haidong
    et al.
    Liddell, Chelsea A
    Coates, Matthew M
    Mooney, Meghan D
    Levitz, Carly E
    Schumacher, Austin E
    Apfel, Henry
    Iannarone, Marissa
    Phillips, Bryan
    Lofgren, Katherine T
    Sandar, Logan
    Dorrington, Rob E
    Rakovac, Ivo
    Jacobs, Troy A
    Liang, Xiaofeng
    Zhou, Maigeng
    Zhu, Jun
    Yang, Gonghuan
    Wang, Yanping
    Liu, Shiwei
    Li, Yichong
    Ozgoren, Ayse Abbasoglu
    Abera, Semaw Ferede
    Abubakar, Ibrahim
    Achoki, Tom
    Adelekan, Ademola
    Ademi, Zanfina
    Alemu, Zewdie Aderaw
    Allen, Peter J
    Almazroa, Mohammad Abdulaziz
    Alvarez, Elena
    Amankwaa, Adansi A
    Amare, Azmeraw T
    Ammar, Walid
    Anwari, Palwasha
    Cunningham, Solveig Argeseanu
    Asad, Majed Masoud
    Assadi, Reza
    Banerjee, Amitava
    Basu, Sanjay
    Bedi, Neeraj
    Bekele, Tolesa
    Bell, Michelle L
    Bhutta, Zulfiqar
    Blore, Jed
    Basara, Berrak Bora
    Boufous, Soufiane
    Breitborde, Nicholas
    Bruce, Nigel G
    Bui, Linh Ngoc
    Carapetis, Jonathan R
    Cárdenas, Rosario
    Carpenter, David O
    Caso, Valeria
    Castro, Ruben Estanislao
    Catalá-Lopéz, Ferrán
    Cavlin, Alanur
    Che, Xuan
    Chiang, Peggy Pei-Chia
    Chowdhury, Rajiv
    Christophi, Costas A
    Chuang, Ting-Wu
    Cirillo, Massimo
    da Costa Leite, Iuri
    Courville, Karen J
    Dandona, Lalit
    Dandona, Rakhi
    Davis, Adrian
    Dayama, Anand
    Deribe, Kebede
    Dharmaratne, Samath D
    Dherani, Mukesh K
    Dilmen, Uğur
    Ding, Eric L
    Edmond, Karen M
    Ermakov, Sergei Petrovich
    Farzadfar, Farshad
    Fereshtehnejad, Seyed-Mohammad
    Fijabi, Daniel Obadare
    Foigt, Nataliya
    Forouzanfar, Mohammad H
    Garcia, Ana C
    Geleijnse, Johanna M
    Gessner, Bradford D
    Goginashvili, Ketevan
    Gona, Philimon
    Goto, Atsushi
    Gouda, Hebe N
    Green, Mark A
    Greenwell, Karen Fern
    Gugnani, Harish Chander
    Gupta, Rahul
    Hamadeh, Randah Ribhi
    Hammami, Mouhanad
    Harb, Hilda L
    Hay, Simon
    Hedayati, Mohammad T
    Hosgood, H Dean
    Hoy, Damian G
    Idrisov, Bulat T
    Islami, Farhad
    Ismayilova, Samaya
    Jha, Vivekanand
    Jiang, Guohong
    Jonas, Jost B
    Juel, Knud
    Kabagambe, Edmond Kato
    Kazi, Dhruv S
    Kengne, Andre Pascal
    Kereselidze, Maia
    Khader, Yousef Saleh
    Khalifa, Shams Eldin Ali Hassan
    Khang, Young-Ho
    Kim, Daniel
    Kinfu, Yohannes
    Kinge, Jonas M
    Kokubo, Yoshihiro
    Kosen, Soewarta
    Defo, Barthelemy Kuate
    Kumar, G Anil
    Kumar, Kaushalendra
    Kumar, Ravi B
    Lai, Taavi
    Lan, Qing
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lee, Jong-Tae
    Leinsalu, Mall
    Lim, Stephen S
    Lipshultz, Steven E
    Logroscino, Giancarlo
    Lotufo, Paulo A
    Lunevicius, Raimundas
    Lyons, Ronan Anthony
    Ma, Stefan
    Mahdi, Abbas Ali
    Marzan, Melvin Barrientos
    Mashal, Mohammad Taufiq
    Mazorodze, Tasara T
    McGrath, John J
    Memish, Ziad A
    Mendoza, Walter
    Mensah, George A
    Meretoja, Atte
    Miller, Ted R
    Mills, Edward J
    Mohammad, Karzan Abdulmuhsin
    Mokdad, Ali H
    Monasta, Lorenzo
    Montico, Marcella
    Moore, Ami R
    Moschandreas, Joanna
    Msemburi, William T
    Mueller, Ulrich O
    Muszynska, Magdalena M
    Naghavi, Mohsen
    Naidoo, Kovin S
    Narayan, Km Venkat
    Nejjari, Chakib
    Ng, Marie
    de Dieu Ngirabega, Jean
    Nieuwenhuijsen, Mark J
    Nyakarahuka, Luke
    Ohkubo, Takayoshi
    Omer, Saad B
    Caicedo, Angel J Paternina
    Wyk, Victoria Pillay-van
    Pope, Dan
    Prabhakaran, Dorairaj
    Rahman, Sajjad Ur
    Rana, Saleem M
    Reilly, Robert Quentin
    Rojas-Rueda, David
    Ronfani, Luca
    Rushton, Lesley
    Saeedi, Mohammad Yahya
    Salomon, Joshua
    Sampson, Uchechukwu
    Santos, Itamar S
    Sawhney, Monika
    Schmidt, Jürgen C
    Shakh-Nazarova, Marina
    She, Jun
    Sheikhbahaei, Sara
    Shibuya, Kenji
    Shin, Hwashin Hyun
    Shishani, Kawkab
    Shiue, Ivy
    Sigfusdottir, Inga Dora
    Singh, Jasvinder A
    Skirbekk, Vegard
    Sliwa, Karen
    Soshnikov, Sergey S
    Sposato, Luciano A
    Stathopoulou, Vasiliki Kalliopi
    Stroumpoulis, Konstantinos
    Tabb, Karen M
    Talongwa, Roberto Tchio
    Teixeira, Carolina Maria
    Terkawi, Abdullah Sulieman
    Thomson, Alan J
    Thorne-Lyman, Andrew L
    Toyoshima, Hideaki
    Dimbuene, Zacharie Tsala
    Uwaliraye, Parfait
    Uzun, Selen Begüm
    Vasankari, Tommi J
    Vasconcelos, Ana Maria Nogales
    Vlassov, Vasiliy Victorovich
    Vollset, Stein Emil
    Vos, Theo
    Waller, Stephen
    Wan, Xia
    Weichenthal, Scott
    Weiderpass, Elisabete
    Weintraub, Robert G
    Westerman, Ronny
    Wilkinson, James D
    Williams, Hywel C
    Yang, Yang C
    Yentur, Gokalp Kadri
    Yip, Paul
    Yonemoto, Naohiro
    Younis, Mustafa
    Yu, Chuanhua
    Jin, Kim Yun
    El Sayed Zaki, Maysaa
    Zhu, Shankuan
    Lopez, Alan D
    Murray, Christopher J L
    Global, regional, and national levels of neonatal, infant, and under-5 mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 20132014In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 384, no 9947, p. 957-979Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Remarkable financial and political efforts have been focused on the reduction of child mortality during the past few decades. Timely measurements of levels and trends in under-5 mortality are important to assess progress towards the Millennium Development Goal 4 (MDG 4) target of reduction of child mortality by two thirds from 1990 to 2015, and to identify models of success.

    METHODS: We generated updated estimates of child mortality in early neonatal (age 0-6 days), late neonatal (7-28 days), postneonatal (29-364 days), childhood (1-4 years), and under-5 (0-4 years) age groups for 188 countries from 1970 to 2013, with more than 29 000 survey, census, vital registration, and sample registration datapoints. We used Gaussian process regression with adjustments for bias and non-sampling error to synthesise the data for under-5 mortality for each country, and a separate model to estimate mortality for more detailed age groups. We used explanatory mixed effects regression models to assess the association between under-5 mortality and income per person, maternal education, HIV child death rates, secular shifts, and other factors. To quantify the contribution of these different factors and birth numbers to the change in numbers of deaths in under-5 age groups from 1990 to 2013, we used Shapley decomposition. We used estimated rates of change between 2000 and 2013 to construct under-5 mortality rate scenarios out to 2030.

    FINDINGS: We estimated that 6·3 million (95% UI 6·0-6·6) children under-5 died in 2013, a 64% reduction from 17·6 million (17·1-18·1) in 1970. In 2013, child mortality rates ranged from 152·5 per 1000 livebirths (130·6-177·4) in Guinea-Bissau to 2·3 (1·8-2·9) per 1000 in Singapore. The annualised rates of change from 1990 to 2013 ranged from -6·8% to 0·1%. 99 of 188 countries, including 43 of 48 countries in sub-Saharan Africa, had faster decreases in child mortality during 2000-13 than during 1990-2000. In 2013, neonatal deaths accounted for 41·6% of under-5 deaths compared with 37·4% in 1990. Compared with 1990, in 2013, rising numbers of births, especially in sub-Saharan Africa, led to 1·4 million more child deaths, and rising income per person and maternal education led to 0·9 million and 2·2 million fewer deaths, respectively. Changes in secular trends led to 4·2 million fewer deaths. Unexplained factors accounted for only -1% of the change in child deaths. In 30 developing countries, decreases since 2000 have been faster than predicted attributable to income, education, and secular shift alone.

    INTERPRETATION: Only 27 developing countries are expected to achieve MDG 4. Decreases since 2000 in under-5 mortality rates are accelerating in many developing countries, especially in sub-Saharan Africa. The Millennium Declaration and increased development assistance for health might have been a factor in faster decreases in some developing countries. Without further accelerated progress, many countries in west and central Africa will still have high levels of under-5 mortality in 2030.

  • 396.
    Wang, Haidong
    et al.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Naghavi, Mohsen
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Allen, Christine
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Barber, Ryan M.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Bhutta, Zulfiqar A.
    Ctr Excellence Women & Child Hlth, Karachi, Pakistan.;Hosp Sick Children, Ctr Global Child Hlth, Toronto, ON, Canada..
    Carter, Austin
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Casey, Daniel C.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Charlson, Fiona J.
    Inst Hlth Metr & Evaluat, Seattle, WA USA.;Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia.;Queensland Ctr Mental Hlth Res, Brisbane, Qld, Australia..
    Chen, Alan Zian
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Coates, Matthew M.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Coggeshall, Megan
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Dandona, Lalit
    Inst Hlth Metr & Evaluat, Seattle, WA USA.;Publ Hlth Fdn India, New Delhi, India..
    Dicker, Daniel J.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Erskine, Holly E.
    Inst Hlth Metr & Evaluat, Seattle, WA USA.;Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia.;Queensland Ctr Mental Hlth Res, Brisbane, Qld, Australia..
    Ferrari, Alize J.
    Inst Hlth Metr & Evaluat, Seattle, WA USA.;Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia..
    Fitzmaurice, Christina
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Foreman, Kyle
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Forouzanfar, Mohammad H.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Fraser, Maya S.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Pullman, Nancy
    Gething, Peter W.
    Dept Zool, Oxford, England..
    Goldberg, Ellen M.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Graetz, Nicholas
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Haagsma, Juanita A.
    Univ Med Ctr, Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands..
    Hay, Simon I.
    Huynh, Chantal
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Johnson, Catherine
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Kassebaum, Nicholas J.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Kinfu, Yohannes
    Univ Canberra, Fac Hlth, Ctr Res & Action Publ Hlth, Canberra, ACT, Australia..
    Kulikoff, Xie Rachel
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Kutz, Michael
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Kyu, Hmwe H.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Larson, Heidi J.
    Inst Hlth Metr & Evaluat, Seattle, WA USA.;Dept Infect Dis Epidemiol, London, England..
    Leung, Janni
    Inst Hlth Metr & Evaluat, Seattle, WA USA.;Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia.;Queensland Ctr Mental Hlth Res, Brisbane, Qld, Australia..
    Liang, Xiaofeng
    Chinese Ctr Dis Control, Beijing, Peoples R China..
    Lim, Stephen S.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Lind, Margaret
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Lozano, Rafael
    Inst Hlth Metr & Evaluat, Seattle, WA USA.;Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Marquez, Neal
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Mensah, George A.
    NHLBI, NIH, Ctr Translat Res & Implementat Sci, Bethesda, MD USA..
    Mikesell, Joe
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Mokdad, Ali H.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Mooney, Meghan D.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Nguyen, Grant
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Nsoesie, Elaine
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Pigott, David M.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Pinho, Christine
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Roth, Gregory A.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Salomon, Joshua A.
    Dept Global Hlth & Populat, Boston, MA USA..
    Sandar, Logan
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Silpakit, Naris
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Sligar, Amber
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Sorensen, Reed J. D.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Stanaway, Jeffrey
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Steiner, Caitlyn
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Teeple, Stephanie
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Thomas, Bernadette A.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Troeger, Christopher
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    VanderZanden, Amelia
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Vollset, Stein Emil
    Inst Hlth Metr & Evaluat, Seattle, WA USA.;Ctr Dis Burden, Oslo, Norway.;Dept Global Publ Hlth & Primary Care, Jimma, Ethiopia..
    Wanga, Valentine
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Whiteford, Harvey A.
    Inst Hlth Metr & Evaluat, Seattle, WA USA.;Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia.;Queensland Ctr Mental Hlth Res, Brisbane, Qld, Australia..
    Wolock, Timothy
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Zoeckler, Leo
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Abate, Kalkidan Hassen
    Jimma Univ, Jimma, Ethiopia..
    Abbafati, Cristiana
    Univ Roma La Sapienza, Rome, Italy..
    Abbas, Kaja M.
    Virginia Tech, Blacksburg, VA USA..
    Abd-Allah, Foad
    Cairo Univ, Dept Neurol, Cairo, Egypt..
    Abera, Semaw Ferede
    Sch Publ Hlth, Coll Hlth Sci, Mekelle, Ethiopia.;Kilte AwlaeloHealth & Demog Surveillance Site, Mekelle, Ethiopia.;Univ Hohenheim, Food Secur & Inst Biol Chem & Nutr, Stuttgart, Germany.;Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil..
    Abreu, Daisy M. X.
    Abu-Raddad, Laith J.
    Weill Cornell Med Coll Qatar, Infect Dis Epidemiol Grp, Doha, Qatar..
    Abyu, Gebre Yitayih
    Mekelle Univ, Mekelle, Ethiopia..
    Achoki, Tom
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Adelekan, Ademola Lukman
    Publ Hlth Promot Alliance, Osogbo, Nigeria.;Univ Ibadan, Ibadan, Nigeria..
    Ademi, Zanfina
    Univ Basel, Basel, Switzerland.;Univ Melbourne, Melbourne, Vic, Australia..
    Adou, Arsene Kouablan
    Assoc Ivoirienne Bienetre Familial, Abidjan, Cote Ivoire..
    Adsuar, Jose C.
    Univ Extremadura, Caceres, Spain..
    Afanvi, Kossivi Agbelenko
    Direct Dist Sanitaire Haho, Notse, Togo.;Univ Lome, Fac Sci Sante, Lome, Togo..
    Afshin, Ashkan
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Agardh, Emilie Elisabet
    Inst Publ Hlth Sci, Stockholm, Sweden..
    Agarwal, Arnav
    Univ Toronto, Toronto, ON, Canada.;McMaster Univ, Hamilton, ON, Canada.;SIR Inst Genom & Integrat Biol, Delhi, India.;Baylor Coll Med, Dept Internal Med, Houston, TX USA..
    Agrawal, Anurag
    Kiadaliri, Aliasghar Ahmad
    Lund Univ, Orthoped Clin Epidemiol Unit, Dept Clin Sci Lund, Lund, Sweden.;Kerman Univ Med Sci, Inst Futures Studies Hlth, Hlth Serv Management Res Ctr, Kerman, Iran..
    Ajala, Oluremi N.
    Univ Pittsburgh, Med Ctr, McKeesport, PA USA..
    Akanda, All Shafqat
    Univ Rhode Isl, Kingston, RI USA..
    Akinyemi, Rufus Olusola
    Univ Ibadan, Ibadan, Nigeria.;Newcastle Univ, Newcastle Upon Tyne, Tyne & Wear, England..
    Akinyemiju, Tomi F.
    Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA..
    Akseer, Nadia
    Hosp Sick Children, Ctr Global Child Hlth, Toronto, ON, Canada.;Dalla Lana Sch Publ Hlth, Toronto, ON, Canada..
    Al Lami, Faris Hasan
    Baghdad Coll Med, Baghdad, Iraq..
    Alabed, Samer
    Univ Sheffield, Sheffield, S Yorkshire, England..
    Al-Aly, Ziyad
    Washington Univ, St Louis, MO USA..
    Alam, Khurshid
    Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia.;Murdoch Childrens Res Inst, Melbourne, Vic, Australia.;Univ Sydney, Sydney, NSW, Australia..
    Alam, Noore K. M.
    Univ Melbourne, Melbourne, Vic, Australia.;Queensland Hlth, Herston, Qld, Australia..
    Alasfoor, Deena
    Minist Hlth, Al Khuwair, Oman..
    Aldhahri, Saleh Fahed
    King Saud Univ, Riyadh, Saudi Arabia.;King Fahad Med City, Riyadh, Saudi Arabia..
    Aldridge, Robert William
    UCL, Inst Hlth Informat, Ctr Publ Hlth Data Sci, London, England.;UCL, Farr Inst Hlth Informat Res, London, England.;UCL, Inst Global Hlth, London, England..
    Alegretti, Miguel Angel
    Fac Med, Dept Prevent & Social Med, Montevideo, Uruguay..
    Aleman, Alicia V.
    Sch Med, Montevideo, Uruguay..
    Alemu, Zewdie Aderaw
    Debre Markos Univ, Debre, Markos, Ethiopia..
    Alexander, Lily T.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Alhabib, Samia
    King Abdullah Bin Abdulaziz Univ Hosp, Riyadh, Saudi Arabia..
    Ali, Raghib
    Univ Oxford, Oxford, England..
    Alkerwi, Ala'a
    Luxembourg Inst Hlth, Luxembourg, Luxembourg..
    Alla, Francois
    Univ Lorraine, Sch Publ Hlth, Nancy, France..
    Allebeck, Peter
    Dept Publ Hlth Sci, Stockholm, Sweden..
    Al-Raddadi, Rajaa
    Harvard T H Chan Sch Publ Hlth, Boston, MA USA.;Minist Hlth, Jeddah, Saudi Arabia..
    Alsharif, Ubai
    Charite, Berlin, Germany..
    Altirkawi, Khalid A.
    King Saud Univ, Riyadh, Saudi Arabia..
    Martin, Elena Alvarez
    Minist Hlth Social Policy & Equal, Spanish Observ Drugs Govt Delegat Natl Plan Drugs, Madrid, Spain..
    Alvis-Guzman, Nelson
    Univ Cartagena, Cartagena Indias, Colombia..
    Amare, Azmeraw T.
    Sch Med, Adelaide, SA, Australia.;Bahir Dar Univ, Coll Med & Hlth Sci, Bahir Dar, Ethiopia..
    Amegah, Adeladza Kofi
    Univ Cape Coast, Cape Coast, Ghana..
    Ameh, Emmanuel A.
    Natl Hosp, Abuja, Nigeria..
    Amini, Heresh
    Kurdistan Univ Med Sci, Environm Hlth Res Ctr, Sanandaj, Iran.;Dept Epidemiol & Publ Hlth, Basel, Switzerland..
    Ammar, Walid
    Minist Publ Hlth, Beirut, Lebanon..
    Amrock, Stephen Marc
    Oregon Hlth & Sci Univ, Portland, OR USA..
    Andersen, Hjalte H.
    Aalborg Univ, Fac Med, Dept Hlth Sci & Technol, Ctr Sensory Motor Interact, Aalborg, Denmark..
    Anderson, Benjamin
    Univ Washington, Seattle, WA 98195 USA..
    Anderson, Gregory M.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Antonio, Carl Abelardo T.
    Univ Philippines, Coll Publ Hlth, Dept Hlth Policy & Adm, Manila, Philippines. Univ Philippines, Coll Publ Hlth, Manila, Philippines..
    Aregay, Atsede Fantahun
    Mekelle Univ, Mekelle, Ethiopia..
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Dalarna Univ, Falun, Sweden..
    Arsenijevic, Valentina S. Arsic
    Univ Belgrade, Inst Microbiol & Immunol, Sch Med, Belgrade, Serbia.;Univ Children Hosp, Belgrade, Serbia..
    Artaman, Al
    Asayesh, Hamid
    Qom Univ Med Sci, Sch Paramed, Dept Emergency Med, Qom, Iran..
    Asghar, Rana Jawad
    South Asian Publ Hlth Forum, Islamabad, Pakistan..
    Atique, Suleman
    Taipei Med Univ, Grad Inst Biomed Informat, Taipei, Taiwan..
    Arthur Avokpaho, Euripide Frinel G.
    Inst Rech Clin Benin, Cotonou, Benin.;Lab Etud & Rech Act & Sante, Parakou, Benin..
    Awasthi, Ashish
    Sanjay Gandhi Postgrad Inst Med Sci, Lucknow, Uttar Pradesh, India..
    Azzopardi, Peter
    Dept Paediat, Melbourne, Vic, Australia.;Murdoch Childrens Res Inst, Melbourne, Vic, Australia.;South Australian Hlth & Med Res Inst, Wardliparingga Aboriginal Res Unit, Adelaide, SA, Australia..
    Bacha, Umar
    Univ Management & Technol, Sch Hlth Sci, Lahore, Pakistan..
    Badawi, Alaa
    Fac Med, Dept Nutrit Sci, Toronto, ON, Canada.;Publ Hlth Agcy Canada, Toronto, ON, Canada..
    Bahit, Maria C.
    INECO Neurociencias, Rosario, Argentina..
    Balakrishnan, Kalpana
    Sri Ramachandra Univ, Dept Environm Hlth Engn, Chennai, Tamil Nadu, India..
    Banerjee, Amitava
    UCL, Farr Inst Hlth Informat Res, London, England..
    Barac, Aleksandra
    Univ Belgrade, Fac Med, Belgrade, Serbia..
    Barker-Collo, Suzanne L.
    Univ Auckland, Sch Psychol, Auckland, New Zealand..
    Barnighausen, Till
    Harvard T H Chan Sch Publ Hlth, Boston, MA USA.;Africa Hlth Res Inst, Mtubatuba, South Africa.;Heidelberg Univ, Inst Publ Hlth, Heidelberg, Germany..
    Barregard, Lars
    Univ Gothenburg, Dept Occupat & Environm Hlth, Gothenburg, Sweden..
    Barrero, Lope H.
    Pontificia Univ Javeriana, Sch Engn, Dept Ind Engn, Bogota, Colombia..
    Basu, Arindam
    Univ Canterbury, Sch Hlth Sci, Christchurch, New Zealand..
    Basu, Sanjay
    Stanford Univ, Stanford, CA USA..
    Bayou, Yibeltal Tebekaw
    Jhpiego Ethiopia, Addis Ababa, Ethiopia..
    Bazargan-Hejazi, Shahrzad
    Charles R Drew Univ Med & Sci, Coll Med, Los Angeles, CA USA.;Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.;Kermanshah Univ Med Sci, Kermanshah, Iran..
    Beardsley, Justin
    Univ Oxford, Ho Chi Minh City, Vietnam..
    Bedi, Neeraj
    Coll Publ Hlth & Trop Med, Jazan, Saudi Arabia..
    Beghi, Ettore
    IRCCS Ist Ric Farmacol Mario Negri, Milan, Italy..
    Belay, Haileeyesus Adamu
    Univ Addis Ababa, Addis Ababa, Ethiopia..
    Bell, Brent
    Univ N Carolina, Chapel Hill, NC USA..
    Bell, Michelle L.
    Yale Univ, New Haven, CT USA..
    Bello, Aminu K.
    Univ Alberta, Edmonton, AB, Canada..
    Bennett, Derrick A.
    Univ Oxford, Oxford, England..
    Bensenor, Isabela M.
    Univ Sao Paulo, Sao Paulo, Brazil..
    Berhane, Adugnaw
    Debre Berhane Univ, Debre Berhan, Ethiopia..
    Bernabe, Eduardo
    Kings Coll London, London, England..
    Betsu, Balem Demtsu
    Mekelle Univ, Mekelle, Ethiopia..
    Beyene, Addisu Shunu
    Haramaya Univ, Harar, Ethiopia..
    Bhala, Neeraj
    Queen Elizabeth Hosp Birmingham, Birmingham, W Midlands, England.;Univ Otago, Sch Med, Wellington, New Zealand..
    Bhalla, Ashish
    Postgrad Inst Med Educ & Res, Chandigarh, India..
    Biadgilign, Sibhatu
    Independent Publ Hlth Consultants, Addis Ababa, Ethiopia..
    Bikbov, Boris
    Acad V I Shumakov Fed Res, Ctr Transplantol & Artificial Organs, Dept Nephrol Issues Transplanted Kidney, Moscow, Russia..
    Bin Abdulhak, Aref A.
    Univ Iowa, Hosp & Clin, Iowa City, IA USA..
    Biroscak, Brian J.
    Yale Univ, New Haven, CT USA.;Univ S Florida, Tampa, FL USA..
    Biryukov, Stan
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Bjertness, Espen
    Univ Oslo, Dept Community Med, Oslo, Norway..
    Blore, Jed D.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Blosser, Christopher D.
    Univ Washington, Seattle, WA 98195 USA..
    Bohensky, Megan A.
    Univ Melbourne, Melbourne, Vic, Australia..
    Borschmann, Rohan
    Murdoch Childrens Res Inst, Melbourne, Vic, Australia.;Univ Melbourne, Melbourne, Vic, Australia..
    Bose, Dipan
    World Bank, Washington, DC USA..
    Bourne, Rupert R. A.
    Anglia Ruskin Univ, Vision & Eye Res Unit, Cambridge, England..
    Brainin, Michael
    Danube Univ Krems, Krems, Austria..
    Brayne, Carol E. G.
    Cambridge Inst Publ Hlth, Cambridge, England..
    Brazinova, Alexandra
    Trnava Univ, Dept Publ Hlth, Fac Hlth Sci & Social Work, Trnava, Slovakia.;Int Neurotrama Res Org, Vienna, Austria..
    Breitborde, Nicholas J. K.
    Ohio State Univ, Columbus, OH 43210 USA..
    Brenner, Hermann
    German Canc Res Ctr, Heidelberg, Germany..
    Brewer, Jerry D.
    Mayo Clin, Rochester, MN USA..
    Brown, Alexandria
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Brown, Jonathan
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Brugha, Traolach S.
    Univ Leicester, Leicester, Leics, England..
    Buckle, Geoffrey Colin
    Univ Calif San Francisco, San Francisco, CA 94143 USA..
    Butt, Zahid A.
    Shifa Trust Eye Hosp, Rawalpindi, Pakistan..
    Calabria, Bianca
    Australian Natl Univ, Natl Ctr Epidemiol & Populat Hlth, Canberra, ACT, Australia.;Univ New South Wales, Sydney, NSW, Australia..
    Campos-Novato, Ismael Ricardo
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico.;Harvard T H Chan Sch Publ Hlth, Boston, MA USA..
    Campuzano, Julio Cesar
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Carapetis, Jonathan R.
    Univ Western Australia, Princess Margaret Hosp Children, Telethon Kids Inst, Subiaco, WA, Australia..
    Cardenas, Rosario
    Metropolitan Autonomous Univ, Mexico City, DF, Mexico..
    Carpenter, David
    SUNY Albany, Rensselaer, NY 12222 USA..
    Carrero, Juan Jesus
    Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Castaneda-Oquela, Carlos A.
    Colombian Natl Hlth Observ, Inst Nacl Salud, Bogota, Colombia.;Univ Nacl Colombia, Dept Publ Hlth, Epidemiol & Publ Hlth Evaluat Grp, Bogota, Colombia..
    Rivas, Jacqueline Castillo
    Caja Costarricense Seguro Social, San Jose, Costa Rica.;Univ Costa Rica, San Pedro, Montes Oca, Costa Rica..
    Catala-Lopez, Ferran
    Univ Valencia, INCLIVA Hlth Res Inst & CIBERSAM, Dept Med, Valencia, Spain.;Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada..
    Cavalleri, Fiorella
    Fac Med, Montevideo, Uruguay..
    Cercy, Kelly
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Cerda, Jorge
    Albany Med Coll, Albany, NY 12208 USA..
    Chen, Wanqing
    Chinese Acad Med Sci, Inst Canc, Beijing, Peoples R China..
    Chew, Adrienne
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Chiang, Peggy Pei -Chia
    Gold Coast Hlth, Clin Governance Unit, Southport, Qld, Australia..
    Chibalabala, Mirriam
    Crowd Watch Afr, Lusaka, Zambia..
    Chibueze, Chioma Ezinne
    Natl Ctr Child Hlth & Dev, Tokyo, Japan..
    Chimed-Ochir, Odgerel
    Univ Occupat & Environm Hlth, Dept Environm Epidemiol, Kitakyushu, Fukuoka, Japan..
    Chisumpa, Vesper Hichilombwe
    Univ Zambia, Lusaka, Zambia.;Univ Witwatersrand, Johannesburg, South Africa..
    Choi, Jee-Young Jasmine
    Seoul Natl Univ Med Lib, Seoul, South Korea..
    Chowdhury, Rajiv
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Christensen, Hanne
    Bispebjerg Hosp, Copenhagen, Denmark..
    Christopher, Devasahayam Jesudas
    Christian Med Coll & Hosp, Vellore, Tamil Nadu, India..
    Ciobanu, Liliana G.
    Univ Adelaide, Adelaide, SA, Australia..
    Cirillo, Massimo
    Univ Salerno, Baronissi, Italy..
    Cohen, Aaron J.
    Inst Hlth Metr & Evaluat, Seattle, WA USA.;Hlth Effects Inst, Boston, MA USA..
    Colistro, Valentina
    Univ Republ Montevideo, Montevideo, Uruguay.;Minist Salud Publ, Montevideo, Uruguay..
    Colomar, Mercedes
    UNICEM, Montevideo, Uruguay..
    Colquhoun, Samantha M.
    Murdoch Childrens Res Inst, Melbourne, Vic, Australia.;Univ Melbourne, Melbourne, Vic, Australia..
    Cooper, Cyrus
    NIHR Musculoskeletal Biomed Res Ctr, Oxford, England.;Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England.;Univ Southampton, NIHR Biomed Res Ctr, Southampton, Hants, England.;Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England..
    Cooper, Leslie Trumbull
    Mayo Clin, Jacksonville, FL 32224 USA..
    Cortinovis, Monica
    Mario Negri Inst Pharmacol Res, Milan, Italy..
    Cowie, Benjamin C.
    Peter Doherty Inst Infect & Immun, Melbourne, Vic, Australia.;WHO, Collaborating Ctr Viral Hepatitis, Victorian Infect Dis Reference Lab Melbourne, Melbourne, Vic, Australia..
    Crump, John A.
    Dunedin Sch Med, Ctr Int Hlth, Dunedin, New Zealand..
    Damsere-Derry, James
    Bldg & Rd Res Inst, Kumasi, Ghana..
    Danawi, Hadi
    Walden Univ, Minneapolis, MN USA..
    Dandona, Rakhi
    Publ Hlth Fdn India, New Delhi, India..
    Daoud, Farah
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Darby, Sarah C.
    Clin Trial Serv Unit, Oxford, England..
    Dargan, Paul I.
    Guys & St Thomas NHS Fdn Trust, London, England..
    das Neves, Jose
    Univ Porto, Inst Invest & Inovacao Saude I3S, Oporto, Portugal.;Univ Porto, INEB, Oporto, Portugal..
    Davey, Gail
    Wellcome Trust Brighton & Sussex, Ctr Global Hlth Res, Brighton, E Sussex, England..
    Davis, Adrian C.
    Publ Hlth England, London, England..
    Davitoiu, Dragos V.
    Univ Med Pharm Bucharest, Bucharest, Romania..
    de Castro, E. Filipa
    Natl Inst Publ Hlth, Mexico City, DF, Mexico..
    de Jager, Pieter
    Univ Witwatersrand, Sch Publ Hlth, Johannesburg, South Africa.;Natl Inst Occupat Hlth, Natl Hlth Lab Serv, Johannesburg, South Africa..
    De Leo, Diego
    Griffith Univ, Brisbane, Qld, Australia..
    Degenhardt, Louisa
    Natl Drug & Alcohol Res Ctr, Sydney, NSW, Australia..
    Dellavalle, Robert P.
    Univ Colorado, Sch Med, Aurora, CO USA.;Univ Colorado, Colorado Sch Publ Hlth, Aurora, CO USA..
    Deribe, Kebede
    Univ Addis Ababa, Sch Publ Hlth, Addis Ababa, Ethiopia.;Brighton & Sussex Med Sch, Brighton, E Sussex, England..
    Deribew, Amare
    Nuffield Dept Med, Oxford, England.;KEMRI Wellcome Trust Res Programme, Kilifi, Kenya..
    Dharmaratne, Samath D.
    Univ Peradeniya, Fac Med, Dept Community Med, Peradeniya, Sri Lanka..
    Dhillon, Preet K.
    Publ Hlth Fdn India, Gurgaon, India.;Publ Hlth Fdn India, Gurgaon, India..
    Diaz-Torne, Cesar
    Hosp Santa Creu i Sant Pau, Barcelona, Spain..
    Ding, Eric L.
    Harvard T H Chan Sch Publ Hlth, Boston, MA USA..
    dos Santos, Kadine Priscila Bender
    Univ Estado Santa Catarina, Florianopolis, SC, Brazil..
    Dossou, Edem
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Driscoll, Tim R.
    Sydney Sch Publ Hlth, Sydney, NSW, Australia..
    Duan, Leilei
    Natl Ctr Chron & Noncommunicable Dis Control & Pr, Beijing, Peoples R China..
    Dubey, Manisha
    Int Inst Populat Sci, Mumbai, Maharashtra, India..
    Bartholow, Bruce
    Ellenbogen, Richard G.
    Harborview UW Med, Seattle, WA USA..
    Lycke, Christian
    Elyazar, Iqbal
    Eijkman Oxford Clin Res Unit, Jakarta, Indonesia..
    Endries, Aman Yesuf
    Arba Minch Univ, Arba Minch, Ethiopia..
    Ermakov, Sergey Petrovich
    Russian Acad Sci, Inst Social & Econ Studies Populat, Moscow, Russia.;Russian Federat, Fed Res Inst Hlth Org & Informat, Minist Hlth, Moscow, Russia..
    Eshrati, Babak
    Minist Hlth & Med Educ, Tehran, Iran.;Arak Univ Med Sci, Arak, Iran..
    Esteghamati, Alireza
    Univ Tehran Med Sci, Endocrinol & Metab Res Ctr, Tehran, Iran..
    Estep, Kara
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Faghmous, Imad D. A.
    London Sch Hyg & Trop Med, London, England..
    Fahimi, Saman
    Univ Tehran Med Sci, Digest Dis Res Inst, Tehran, Iran..
    Jose, Emerito
    Farid, Talha A.
    Univ Louisville, Louisville, KY 40292 USA..
    Sa Farinha, Carla Sofia e
    DGS Directorate Gen Hlth, Lisbon, Portugal.;Univ Aberta, Lisbon, Portugal..
    Faro, Andre
    Univ Fed Sergipe, Aracaju, Brazil..
    Farvid, Maryam S.
    Harvard T H Chan Sch Publ Hlth, Boston, MA USA.;Massachusetts Gen Hosp, Harvard MGH Ctr Genom, Mongan Inst Hlth Policy, Vulnerable Populat, Boston, MA 02114 USA..
    Farzadfar, Farshad
    Univ Tehran Med Sci, Non Communicable Dis Res Ctr, Endocrinol & Metab Populat Sci Inst, Tehran, Iran..
    Feigin, Valery L.
    Natl Inst Stroke & Appl Neurosci, Auckland, New Zealand..
    Fereshtehnejad, Seyed-Mohammad
    Dept Neurobiol Care Sci & Soc, Stockholm, Sweden..
    Fernandes, Jefferson G.
    German Hosp Oswaldo Cruz, Inst Sci Educ, Sao Paulo, Brazil..
    Fernandes, Joao C.
    Queen Mary Univ London, Ctr Expt Med & Rheumatol, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England..
    Fischer, Florian
    Univ Bielefeld, Bielefeld, Germany..
    Fitchett, Joseph R. A.
    Harvard Univ, Boston, MA 02115 USA..
    Flaxman, Abraham
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Foigt, Nataliya
    Acad Med Sci, Inst Gerontol, Kiev, Ukraine..
    Fowkes, F. Gerry R.
    Univ Edinburgh, Edinburgh, Midlothian, Scotland..
    Franca, Elisabeth Barboza
    Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil..
    Franklin, Richard C.
    James Cook Univ, Townsville, Qld, Australia..
    Friedman, Joseph
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Frostad, Joseph
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Hirst, Thomas
    Futran, Neal D.
    Inst Hlth Metr & Evaluat, Seattle, WA USA.;Univ Washington, Seattle, WA 98195 USA.;Imperial Coll London, Dept Infect Dis Epidemiol, London, England..
    Gall, Seana L.
    Univ Tasmania, Hobart, Tas, Australia..
    Gambashidze, Ketevan
    Natl Ctr Dis Control & Publ Hlth, Tbilisi, Rep of Georgia..
    Gamkrelidze, Amiran
    Natl Ctr Dis Control & Publ Hlth, Tbilisi, Rep of Georgia..
    Ganguly, Parthasarathi
    Publ Hlth Fdn India, Gurgaon, India.;Indian Inst Publ Hlth Gandhinagar, Ahmadabad, Gujarat, India.;Publ Hlth Fdn India, Gurgaon, India..
    Gankpe, Fortune Gbetoho
    Lab Etud & Rech Act & Sante, Parakou, Benin.;CHU Hassan II, Fes, Morocco..
    Gebre, Teshome
    Task Force Global Hlth, Decatur, GA USA..
    Gebrehiwot, Tsegaye Tsewelde
    Jimma Univ, Jimma, Ethiopia..
    Gebremedhin, Amanuel Tesfay
    Jimma Univ, Jimma, Ethiopia.;Ludwig Maximilians Univ Munchen, Munich, Germany..
    Gebru, Alemseged Aregay
    Mekelle Univ, Mekelle, Ethiopia.;Kilte Awlaelo Hlth & Demog Surveillance Syst, Mekelle, Ethiopia..
    Geleijnse, Johanna M.
    Wageningen Univ, Div Human Nutr, Wageningen, Netherlands..
    Gessner, Bradford D.
    Agence Med Prevent, Paris, France..
    Ghoshal, Aloke Gopal
    Natl Allergy Asthma Bronchitis Inst, Kolkata, India..
    Gibney, Katherine B.
    Peter Doherty Inst Infect & Immun, Melbourne, Vic, Australia.;Royal Melbourne Hosp, Melbourne, Vic, Australia..
    Gillum, Richard F.
    Howard Univ, Coll Med, Washington, DC 20059 USA..
    Gilmour, Stuart
    Univ Tokyo, Grad Sch Med, Tokyo, Japan..
    Giref, Ababi Zergaw
    Univ Addis Ababa, Addis Ababa, Ethiopia..
    Giroud, Maurice
    Univ Hosp Dijon, Dijon, France..
    Gishu, Melkamu Dedefo
    Haramaya Univ, Harar, Ethiopia.;Kersa Hlth & Demog Surveillance Syst, Harar, Ethiopia..
    Giussani, Giorgia
    Mario Negri Inst Pharmacol Res, Milan, Italy..
    Glaser, Elizabeth
    Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA USA..
    Godwin, William W.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Gomez-Dantes, Hector
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Gona, Philimon
    Univ Massachusetts, Boston, MA USA..
    Goodridge, Amador
    Inst Invest Cient & Serv Alta Tecnol INDICASAT AI, Ciudad Del Saber, Panama..
    Gopalani, Sameer Vali
    Govt Federated States Micronesia, Dept Hlth & Social Affairs, Palikir, Micronesia..
    Gosselin, Richard A.
    Univ Calif San Francisco, San Francisco, CA 94143 USA..
    Gotay, Carolyn C.
    Univ British Columbia, Vancouver, BC, Canada..
    Goto, Atsushi
    Ctr Publ Hlth Sci, Div Epidemiol, Tokyo, Japan..
    Gouda, Hebe N.
    Univ Queensland, Brisbane, Qld, Australia..
    Greaves, Felix
    Publ Hlth England, London, England.;Imperial Coll London, London, England..
    Gugnani, Harish Chander
    Dept St James Sch Med, Dept Microbiol, The Quarter, Anguilla, England.;Dept St James Sch Med, Dept Epidemiol & Biostat, The Quarter, Anguilla, England..
    Gupta, Rahul
    Gupta, Rajeev
    West Virginia Bur Publ Hlth, Charleston, WV USA.;Eternal Heart Care Ctr & Res Inst, Jaipur, Rajasthan, India..
    Gupta, Vipin
    Univ Delhi, Dept Anthropol, Delhi, India..
    Gutierrez, Reyna A.
    Natl Inst Psychiat Ramon Fuente, Mexico City, DF, Mexico..
    Hafezi-Nejad, Nima
    Univ Tehran Med Sci, Endocrinol & Metab Res Ctr, Tehran, Iran..
    Haile, Demewoz
    Univ Addis Ababa, Addis Ababa, Ethiopia..
    Hailu, Alemayehu Desalegne
    Univ Bergen, Bergen, Norway.;Univ Addis Ababa, Sch Publ Hlth, Addis Ababa, Ethiopia.;Kilte Awlaelo Hlth & Demog Surveillance Syst, Mekelle, Ethiopia..
    Hailu, Gessessew Bugssa
    Mekelle Univ, Mekelle, Ethiopia..
    Halasa, Yara A.
    Brandeis Univ, Waltham, MA USA..
    Hamadeh, Randah Ribhi
    Arabian Gulf Univ, Manama, Bahrain..
    Hamidi, Samer
    Hamdan Bin Mohammed Smart Univ, Dubai, U Arab Emirates..
    Hancock, Jamie
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Handal, Alexis J.
    Univ New Mexico, Albuquerque, NM 87131 USA..
    Hankey, Graeme J.
    Univ Western Australia, Sch Med & Pharmacol, Fremantle, WA, Australia.;Harry Perkins Inst Med Res, Nedlands, WA, Australia.;Western Australian Neurosci Res Inst, Nedlands, WA, Australia..
    Hao, Yuantao
    Sun Yat Sen Univ, Sch Publ Hlth, Guangzhou, Guangdong, Peoples R China..
    Harb, Hilda L.
    Minist Publ Hlth, Beirut, Lebanon..
    Harikrishnan, Sivadasanpillai
    Sree Chitra Tirunal Inst Med Sci & Technol, Trivandrum, Kerala, India..
    Haro, Josep Maria
    Parc Sanitari Sant Joan Deu CIBERSAM, Barcelona, Spain.;Univ Barcelona, Barcelona, Spain..
    Havmoeller, Rasmus
    Karolinska Inst, Stockholm, Sweden..
    Heckbert, Susan R.
    Univ Washington, Seattle, WA 98195 USA..
    Heredia-Pi, Ileana Beatriz
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Heydarpour, Pouria
    Univ Tehran Med Sci, Multiple Sclerosis Res Ctr, Neuroscience Inst, Tehran, Iran..
    Hilderink, Henk B. M.
    Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands..
    Hoek, Hans W.
    Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands.;Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA..
    Hogg, Robert S.
    Simon Fraser Univ, Burnaby, BC, Canada.;BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada..
    Horino, Masako
    Nevada Div Publ & Behav Hlth, Dept Hlth & Human Serv, Carson City, NV USA..
    Horita, Nobuyuki
    Yokohama City Univ Grad Sch Med, Dept Pulmonol, Yokohama, Kanagawa, Japan..
    Hosgood, H. Dean
    Albert Einstein Coll Med, Bronx, NY 10467 USA..
    Hotez, Peter J.
    Baylor Coll Med, Houston, TX USA..
    Hoy, Damian G.
    Pacific Commun, Publ Hlth Div, Noumea, New Caledonia..
    Hsairi, Mohamed
    Salah Azaiz Inst, Dept Epidemiol, Tunis, Tunisia..
    Htet, Aung Soe
    Univ Oslo, Oslo, Norway.;Minist Hlth, Int Relat Div, Nay Pyi Taw, Myanmar..
    Than Htike, Maung Maung
    Minist Hlth, Nay Pyi Taw, Myanmar..
    Hu, Guoqing
    Cent S Univ, Dept Epidemiol & Hlth Stat, Sch Publ Hlth, Changsha, Hunan, Peoples R China..
    Huang, Cheng
    George Washington Univ, Washington, DC USA..
    Huang, Hsiang
    Cambridge Hlth Alliance, Cambridge, MA USA..
    Huiart, Laetitia
    CHU Reunion, St Denis, France..
    Husseini, Abdullatif
    Birzeit Univ, Birzeit, Israel..
    Huybrechts, Inge
    IARC, Lyon, France.;Univ Ghent, Ghent, Belgium..
    Huynh, Grace
    Inst Dis Modeling, Bellevue, WA USA..
    Iburg, Kim Moesgaard
    Aarhus Univ, Aarhus, Denmark..
    Innos, Kaire
    Natl Inst Hlth Dev, Tallinn, Estonia..
    Inoue, Manami
    Univ Tokyo, Grad Sch Med, Tokyo, Japan.;Natl Canc Ctr, Tokyo, Japan..
    Iyer, Veena J.
    Indian Inst Publ Hlth Gandhinagar, Ahmadabad, Gujarat, India..
    Jacobs, Troy A.
    USAID Global Hlth Bur, MCH Div, HIDN, Washington, DC USA..
    Jacobsen, Kathryn H.
    George Mason Univ, Dept Global & Community Hlth, Fairfax, VA USA..
    Jahanmehr, Nader
    Shahid Beheshti Univ Med Sci, Sch Publ Hlth, Tehran, Iran..
    Jakovljevic, Mihajlo B.
    Univ Kragujevac, Fac Med Sci, Kragujevac, Serbia..
    James, Peter
    Channing Div Network Med, Dept Epidemiol, Boston, MA USA.;Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA..
    Javanbakht, Mehdi
    Univ Aberdeen, Aberdeen, Scotland..
    Jayaraman, Sudha P.
    Virginia Commonwealth Univ, Dept Surg, Richmond, VA USA..
    Jayatilleke, Achala Upendra
    Postgrad Inst Med, Colombo, Sri Lanka.;Inst Violence & Injury Prevent, Colombo, Sri Lanka..
    Jeemon, Panniyammakal
    Ctr Control Chron Condit, Gurgaon, Haryana, India.;Ctr Control Chron Condit, Gurgaon, India.;Ctr Chron Dis Control, New Delhi, India..
    Jensen, Paul N.
    Univ Washington, Seattle, WA 98195 USA..
    Jha, Vivekanand
    Univ Oxford, Oxford, England.;George Inst Global Hlth India, New Delhi, India..
    Jiang, Guohong
    Tianjin Ctr Dis Control & Prevent, Tianjin, Tianjin, Peoples R China..
    Jiang, Ying
    Univ Occupat & Environm Hlth, Dept Hlth Dev, Inst Ind Ecol Sci, Kitakyushu, Fukuoka, Japan..
    Jibat, Tariku
    Univ Addis Ababa, Addis Ababa, Ethiopia.;Wageningen Univ, Wageningen, Netherlands..
    Jimenez-Corona, Aida
    Inst Ophthalmol Conde Valencia, Dept Ocular Epidemiol & Visual Hlth, Mexico City, DF, Mexico.;Gen Directorate Epidemiol, Minist Hlth, Mexico City, DF, Mexico..
    Jonas, Jost B.
    Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Mannheim, Germany..
    Joshi, Tushar Kant
    Ctr Occupat & Environm Hlth, New Delhi, India..
    Kabir, Zubair
    Natl Univ Ireland Univ Coll Cork, Cork, Ireland..
    Karnak, Ritul
    CSIR Indian Inst Toxicol Res, Lucknow, Uttar Pradesh, India..
    Kan, Haidong
    Fudan Univ, Shanghai, Peoples R China..
    Kant, Surya
    King Georges Med Univ, Lucknow, Uttar Pradesh, India..
    Karch, Andre
    Epidemiol & Stat Methods Res Grp, Helmholtz Ctr Infect Res, Braunschweig, Germany.;German Ctr Infect Res, Hannover Braunschweig Site, Braunschweig, Germany..
    Karema, Corine Kakizi
    Swiss Trop & Publ Hlth Inst, Basel, Switzerland.;Qual & Equity Hlth Care, Kigali, Rwanda..
    Karimkhani, Chante
    Case Western Univ Hosp, Cleveland, OH USA..
    Karletsos, Dimitris
    Univ Pompeu Fabra, Ctr Res Hlth & Econ, Barcelona, Spain..
    Karthikeyan, Ganesan
    All India Inst Med Sci, New Delhi, India..
    Kasaeian, Amir
    Inst Hlth Metr & Evaluat, Seattle, WA USA.;Univ Tehran Med Sci, Non Communicable Dis Res Ctr, Endocrinol & Metab Populat Sci Inst, Tehran, Iran.;Univ Tehran Med Sci, Hematol Oncol & Stem Cell Transplantat Res Ctr, Tehran, Iran..
    Katibeh, Marzieh
    Shahid Beheshti Univ Med Sci, Ophthalm Epidemiol Res Ctr, Tehran, Iran..
    Kaul, Anil
    Oklahoma State Univ, Tulsa, OK USA..
    Kawakami, Norito
    Univ Tokyo, Sch Publ Hlth, Tokyo, Japan..
    Kayibanda, Jeanne Francoise
    Inst Rech Ihopital Monttfort, Ottawa, ON, Canada..
    Keiyoro, Peter Njenga
    Inst Trop & Infect Dis, Nairobi, Kenya.;Sch Continuing & Distance Educ, Nairobi, Kenya..
    Kemmer, Laura
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Kemp, Andrew Haddon
    Univ Sydney, Sydney, NSW, Australia.;Swansea Univ, Swansea, W Glam, Wales..
    Kengne, Andre Pascal
    South African Med Res Council, Cape Town, South Africa.;Univ Cape Town, Cape Town, South Africa..
    Keren, Andre
    Assuta Hosp, Assuta Hashalom, Tel Aviv, Israel..
    Kereselidze, Maia
    Natl Ctr Dis Control & Publ Hlth, Tbilisi, Rep of Georgia..
    Kesavachandran, Chandrasekharan Nair
    CSIR Indian Inst Toxicol Res, Lucknow, Uttar Pradesh, India..
    Khader, Yousef Saleh
    Jordan Univ Sci & Technol, Irbid, Jordan..
    Khalil, Ibrahim A.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Khan, Abdur Rahman
    Univ Louisville, Louisville, KY 40292 USA..
    Khan, Ejaz Ahmad
    Hlth Serv Acad, Islamabad, Pakistan..
    Khang, Young-Ho
    Seoul Natl Univ, Coll Med, Seoul, South Korea..
    Khera, Sahil
    New York Med Coll, Valhalla, NY USA..
    Muthafer Khoja, Tawfik Ahmed
    Execut Board Hlth Ministers Council Cooperat Coun, Riyadh, Saudi Arabia..
    Kieling, Christian
    Univ Fed Rio Grande do Sul, Porto Alegre, RS, Brazil.;Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil.;Norwegian Inst Publ Hlth, Oslo, Norway..
    Kim, Daniel
    Kim, Yun Jin
    Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA.;Southern Univ Coll, Skudai, Malaysia..
    Kissela, Brett M.
    Univ Cincinnati, Cincinnati, OH USA..
    Kissoon, Niranjan
    Univ British Columbia, Vancouver, BC, Canada..
    Knibbs, Luke D.
    Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia..
    Knudsen, Ann Kristin
    Ctr Dis Burden, Oslo, Norway.;Dept Global Publ Hlth & Primary Care, Jimma, Ethiopia..
    Kokubo, Yoshihiro
    Natl Cerebral Cardiovasc Ctr, Dept Prevent Cardiol, Suita, Osaka, Japan..
    Kolte, Dhaval
    Brown Univ, Div Cardiol, Providence, RI 02912 USA..
    Kopec, Jacek A.
    Univ British Columbia, Vancouver, BC, Canada..
    Kosen, Soewarta
    NIHRD, Ctr Community Empowerment, Hlth Policy & Human, Jakarta, Indonesia..
    Koul, Parvaiz A.
    Sher Kashmir Inst Med Sci, Srinagar, Jammu & Kashmir, India..
    Koyanagi, Ai
    Parc Sanitari Sant Joan Deu CIBERSAM, Res & Dev Unit, Barcelona, Spain..
    Krog, Norun Hjertager
    Norwegian Inst Publ Hlth, Oslo, Norway.;Norwegian Inst Publ Hlth, Oslo, Norway..
    Defo, Barthelemy Kuate
    Univ Montreal, Dept Demog & Publ Hlth, Res Inst, Montreal, PQ, Canada.;Univ Montreal, Dept Social & Prevent Med, Sch Publ Hlth, Montreal, PQ, Canada..
    Bicer, Burcu Kucuk
    Hacettepe Univ, Inst Publ Hlth, Ankara, Turkey..
    Kudom, Andreas A.
    Univ Cape Coast, Cape Coast, Ghana..
    Kuipers, Ernst J.
    Dept Hlth, Manila, Philippines.;Univ Med Ctr Rotterdam, Erasmus MC, Rotterdam, Netherlands..
    Kulkarni, Veena S.
    Arkansas State Univ, State Univ, AR USA..
    Kumar, G. Anil
    Publ Hlth Fdn India, New Delhi, India..
    Kwan, Gene F.
    Boston Univ, Sch Med, Boston, MA USA..
    Lal, Aparna
    Australian Natl Univ, Natl Ctr Epidemiol & Populat Hlth, Canberra, ACT, Australia..
    Lal, Dharmesh Kumar
    Publ Hlth Fdn India, Gurgaon, India..
    Lalloo, Ratilal
    Univ Queensland, Sch Dent, Brisbane, Qld, Australia..
    Lam, Hilton
    Natl Inst Hlth, Inst Hlth Policy & Dev Studies, Manila, Philippines..
    Lam, Jennifer O.
    Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA..
    Langan, Sinead M.
    London Sch Hyg & Trop Med, London, England..
    Lansingh, Van C.
    Help Me See Inc, New York, NY USA.;Inst Mexicano Oftalmol, Queretaro, Mexico..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Laryea, Dennis Odai
    Komfo Anokye Teaching Hosp, Kumasi, Ghana..
    Latif, Asma Abdul
    WomenUniv, Lahore Coll, Dept Zool, Lahore, Pakistan..
    Lawrynowicz, Alicia Elena Beatriz
    Inst Nacl Epidemiol Dr Juan H Jara, Mar Del Plata, Argentina..
    Leigh, James
    Univ Sydney, Sydney, NSW, Australia..
    Levi, Miriam
    Tuscany Reg Ctr Occupat Injuries & Dis, Florence, Italy..
    Li, Yongmei
    Lindsay, M. Patrice
    Inst Hlth Metr & Evaluat, Seattle, WA USA.;Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada.;Heart & Stroke Fdn Canada, Ottawa, ON, Canada..
    Lipshultz, Steven E.
    Wayne State Univ, Sch Med, Detroit, MI USA.;Childrens Hosp Michigan, Detroit, MI USA..
    Liu, Patrick Y.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Liu, Shiwei
    Natl Ctr Chron & Noncommunicable Dis Control & Pr, Beijing, Peoples R China..
    Liu, Yang
    San Francisco VA Med Ctr, San Francisco, CA USA.;Emory Univ, Atlanta, GA 30322 USA..
    Lo, Loon-Tzian
    UnionHlth Associates LLC, St Louis, MO USA.;Alton Mental Hlth Ctr, Alton, IL USA..
    Logroscino, Giancarlo
    Univ Bari, Bari, Italy..
    Lotufo, Paulo A.
    Univ Sao Paulo, Sao Paulo, Brazil..
    Lucas, Robyn M.
    Australian Natl Univ, Natl Ctr Epidemiol & Populat Hlth, Canberra, ACT, Australia..
    Lunevicius, Raimundas
    Aintree Univ Hosp Natl Hlth Serv Fdn Trust, Liverpool, Merseyside, England.;Univ Liverpool, Sch Med, Liverpool, Merseyside, England..
    Lyons, Ronan A.
    Farr Inst, Swansea, W Glam, Wales..
    Ma, Stefan
    Minist Hlth Singapore, Singapore, Singapore.;Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Pedro Machado, Vasco Manuel
    Dept Publ Hlth, No Region Hlth Adm, Oporto, Portugal..
    Mackay, Mark T.
    Royal Childrens Hosp, Melbourne, Vic, Australia..
    MacLachlan, Jennifer H.
    Peter Doherty Inst Infect & Immun, Melbourne, Vic, Australia..
    Abd El Razek, Hassan Magdy
    Mansoura Fac Med, Mansoura, Egypt..
    Abd El Razek, Mohammed Magdy
    Aswan Univ Hosp, Aswan Fac Med, Aswan, Egypt..
    Majdan, Marek
    Trnava Univ, Dept Publ Hlth, Fac Hlth Sci & Social Work, Trnava, Slovakia..
    Majeed, Azeem
    Imperial Coll London, London, England..
    Malekzadeh, Reza
    Univ Tehran Med Sci, Digest Dis Res Inst, Tehran, Iran..
    Ayele Manamo, Wondimu Ayele
    Univ Addis Ababa, Addis Ababa, Ethiopia..
    Mandisarisa, John
    JSI Res & Training, Harare, Zimbabwe..
    Mangalam, Srikanth
    Tech Stand & Safety Author, Toronto, ON, Canada..
    Mapoma, Chabila C.
    Univ Zambia, Lusaka, Zambia..
    Marcenes, Wagner
    Kings Coll London, Div Populat & Patient Hlth, Inst Dent, London, England..
    Margolis, David Joel
    Univ Penn, Philadelphia, PA USA..
    Martin, Gerard Robert
    Childrens Natl Hlth Syst, Washington, DC USA..
    Martinez-Raga, Jose
    Univ Valencia, Univ Hosp Doctor Peset, Valencia, Spain.;CEU Cardenal Herrera Univ, Valencia, Spain..
    Marzan, Melvin Barrientos
    Univ E Ramon Magsaysay Mem Med Ctr, Quezon City, Philippines..
    Masiye, Felix
    Inst Hlth Metr & Evaluat, Seattle, WA USA.;Univ Zambia, Lusaka, Zambia..
    Mason-Jones, Amanda J.
    Univ York, Dept Hlth Sci, York, N Yorkshire, England..
    Massano, Joao
    Univ Porto, Fac Med, Oporto, Portugal.;ULS Matosinhos, Hosp Pedro Hispano, Matosinhos, Portugal..
    Matzopoulos, Richard
    South African Med Res Council, Cape Town, South Africa.;Univ Cape Town, Sch Publ Hlth & Family Med, Cape Town, South Africa..
    Mayosi, Bongani M.
    Univ Cape Town, Cape Town, South Africa..
    McGarvey, Stephen Theodore
    Brown Univ, Providence, RI 02912 USA..
    McGrath, John J.
    Univ Queensland, Brisbane, Qld, Australia..
    Mckee, Martin
    London Sch Hyg & Trop Med, London, England..
    McMahon, Brian J.
    Alaska Native Tribal Hlth Consortium, Anchorage, AK USA..
    Meaney, Peter A.
    Univ Penn, Perelman Sch Med, Philadelphia, PA USA.;Childrens Hosp Philadelphia, Philadelphia, PA USA..
    Mehari, Alem
    Howard Univ, Coll Med, Washington, DC 20059 USA..
    Mehndiratta, Man Mohan
    Janakpuri Superspecialty Hosp, New Delhi, India..
    Mena-Rodriguez, Fabiola
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Mekonnen, Alemayehu B.
    Univ Sydney, Sydney, NSW, Australia.;Univ Gondar, Gondar, Ethiopia..
    Melaku, Yohannes Adama
    Sch Publ Hlth, Mekelle, Ethiopia.;Sch Med, Adelaide, SA, Australia..
    Memiah, Peter
    Univ Florida, Pensacola, FL USA..
    Memish, Ziad A.
    Saudi Minist Hlth, Riyadh, Saudi Arabia.;Alfaisal Univ, Coll Med, Riyadh, Saudi Arabia..
    Mendoza, Walter
    United Nations Populat Fund, Lima, Peru..
    Meretoja, Atte
    Dept Med, Melbourne, Vic, Australia.;Helsinki Univ Hosp, Dept Neurol, Helsinki, Finland..
    Meretoja, Tuomo J.
    Helsinki Univ Hosp, Breast Surg Unit, Ctr Comprehens Canc, Helsinki, Finland.;Univ Helsinki, Helsinki, Finland..
    Mhimbira, Francis Apolinary
    Ifakara Hlth Inst, Bagamoyo, Tanzania..
    Micha, Renata
    Friedman Sch Nutr Sci & Policy, Boston, MA USA..
    Miller, Ted R.
    Pacific Inst Res Evaluat, Calverton, MD USA.;Curtin Univ, Ctr Populat Hlth, Perth, WA, Australia..
    Mirarefin, Mojde
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Misganaw, Awoke
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Mock, Charles N.
    Harborview Injury Prevent & Res Ctr, Seattle, WA USA..
    Abdulmuhsin Mohammad, Karzan
    Univ Salahaddin, Erbil, Iraq..
    Mohammadi, Alireza
    Baqiyatallah Univ Med Sci, Neurosci Res Ctr, Tehran, Iran..
    Mohammed, Shafiu
    Heidelberg Univ, Inst Publ Hlth, Heidelberg, Germany.;Ahmadu Bello Univ, Hlth Syst & Policy Res Unit, Zaria, Nigeria..
    Mohan, Viswanathan
    Madras Diabet Res Fdn, Chennai, Tamil Nadu, India.;Dr Mohans Diabet Special Ctr, Chennai, Tamil Nadu, India..
    Mola, Glen Liddell D.
    Univ Papua New Guinea, Boroko, Papua N Guinea..
    Monasta, Lorenzo
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Montanez Hernandez, Julio Cesar
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Montero, Pablo
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Montico, Marcella
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Montine, Thomas J.
    Univ Washington, Seattle, WA 98195 USA..
    Moradi-Lakeh, Maziar
    Inst Hlth Metr & Evaluat, Seattle, WA USA.;Iran Univ Med Sci, Prevent Med & Publ Hlth Res Ctr, Gastrointestinal & Liver Dis Res Ctr, Dept Community Med, Brisbane, Qld, Australia..
    Morawska, Lidia
    Queensland Univ Technol, Int Lab Air Qual & Hlth, Brisbane, Qld, Australia..
    Morgan, Katherine
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Mori, Rintaro
    Natl Ctr Child Hlth & Dev, Tokyo, Japan..
    Mozaffarian, Dariush
    Friedman Sch Nutr Sci & Policy, Boston, MA USA..
    Mueller, Ulrich
    Fed Inst Populat Res, Wiesbaden, Germany..
    Satyanarayana Murthy, Gudlavalleti Venkata
    London Sch Hyg & Trop Med, London, England.;Indian Inst Publ Hlth, Gurgaon, India..
    Murthy, Srinivas
    Univ British Columbia, Vancouver, BC, Canada..
    Musa, Kamarul Imran
    Univ Sci Malaysia, Sch Med Sci, Kubang Kerian, Malaysia..
    Nachega, Jean B.
    Bloomberg Sch Publ Hlth, Baltimore, MD USA.;Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.;Univ Stellenbosch, Cape Town, South Africa..
    Nagel, Gabriele
    Univ Ulm, Inst Epidemiol & Med Biometry, Ulm, Germany..
    Naidoo, Kovin S.
    Univ KwaZulu Natal, Durban, South Africa..
    Naik, Nitish
    All India Inst Med Sci, New Delhi, India..
    Naldi, Luigi
    Azienda Osped Papa Giovanni XXIII, Bergamo, Italy..
    Nangia, Vinay
    Suraj Eye Inst, Nagpur, Maharashtra, India..
    Nash, Denis
    CUNY, Inst Implementat Sci Populat Hlth, Sch Publ Hlth, New York, NY USA..
    Nejjari, Chakib
    Fac Med, Fes, Morocco..
    Neupane, Subas
    Univ Tampere, Sch Hlth Sci, Tampere, Finland..
    Newton, Charles R.
    KEMRI Wellcome Trust, Kilifi, Kenya..
    Newton, John N.
    Publ Hlth England, London, England..
    Ng, Marie
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Ngalesoni, Frida Namnyak
    Minist Hlth & Social Welf, Dar Es Salaam, Tanzania..
    Ngirabega, Jean de Dieu
    East African Community Hlth Res Commiss, Kigali, Rwanda..
    Nguyen, Quyen Le
    Nisar, Muhammad Imran
    Aga Khan Univ, Karachi, Pakistan..
    Nkamedjie Pete, Patrick Martial
    Inst Res Socioecon Dev & Commun, Yaounde, Cameroon..
    Nomura, Marika
    Natl Inst Publ Hlth, Saitama, Japan..
    Norheim, Ole F.
    Univ Bergen, Bergen, Norway..
    Norman, Paul E.
    Univ Western Australia, Fremantle, WA, Australia..
    Norrving, Bo
    Lund Univ, Dept Clin Sci Lund, Skane Univ Hosp, Lund, Sweden..
    Nyakarahuka, Luke
    Makerere Univ, Kampala, Uganda..
    Ogbo, Felix Akpojene
    Univ Western Sydney, Ctr Hlth Res, Sydney, NSW, Australia..
    Ohkubo, Takayoshi
    Teikyo Univ, Sch Med, Tokyo, Japan..
    Ojelabi, Foluke Adetola
    Univ Ibadan, Ibadan, Nigeria..
    Olivares, Pedro R.
    Univ Autonoma Chile, Talca, Chile..
    Olusanya, Bolajoko Olubukunola
    Ctr Healthy Start Initiat, Lagos, Nigeria..
    Olusanya, Jacob Olusegun
    Ctr Healthy Start Initiat, Lagos, Nigeria..
    Opio, John Nelson
    Lira Municipal Council, Lira Dist Local Govt, Lira, Uganda..
    Oren, Eyal
    Univ Arizona, Tucson, AZ USA..
    Ortiz, Alberto
    IIS Fdn Jimenez Diaz UAM, Madrid, Spain..
    Osman, Majdi
    Harvard Med Sch, Boston, MA USA.;YBank, Cambridge, MA USA..
    Ota, Erika
    St Lukes Int Univ, Tokyo, Japan..
    Ozdemir, Raziye
    St Lukes Int Univ, Tokyo, Japan.;Karabuk Univ, Karabuk, Turkey..
    Pa, Mahesh
    JSS Univ, JSS Med Coll, Mysore, Karnataka, India..
    Pandian, Jeyaraj D.
    Christian Med Coll Ludhiana, Ludhiana, Punjab, India..
    Pant, Puspa Raj
    Univ W England, Bristol, Avon, England..
    Papachristou, Christina
    Charite Univ Med Berlin, Berlin, Germany..
    Park, Eun-Kee
    Kosin Univ, Dept Med Human & Social Med, Coll Med, Busan, South Korea..
    Park, Jae-Hyun
    Sungkyunkwan Univ, Samsung Biomed Res Inst, Sch Med, Dept Social & Prevent Med, Suwon, South Korea..
    Parry, Charles D.
    Alcohol Tobacco & Other Drug Res Unit, Cape Town, South Africa.;Univ Stellenbosch, Dept Psychiat, Cape Town, South Africa.;Alcohol, Tobacco Other Drug Res Unit, Potchefstroom, South Africa..
    Parsaeian, Mahboubeh
    Univ Tehran Med Sci, Non Communicable Dis Res Ctr, Endocrinol & Metab Populat Sci Inst, Tehran, Iran.;Univ Tehran Med Sci, Dept Epidemiol & Biostat, Sch Publ Hlth, Tehran, Iran..
    Caicedo, Angel J. Paternina
    Univ Pittsburgh, Publ Hlth Dynam Lab, Pittsburgh, PA USA.;Univ Cartagena, Cartagena, Colombia..
    Patten, Scott B.
    Univ Calgary, Dept Community Hlth Sci, Calgary, AB, Canada..
    Patton, George C.
    Murdoch Childrens Res Inst, Melbourne, Vic, Australia..
    Paul, Vinod K.
    All India Inst Med Sci, New Delhi, India..
    Pearce, Neil
    London Sch Hyg & Trop Med, London, England..
    Pedro, Joao Mario
    Univ Porto, EPIUnit, Oporto, Portugal.;Hlth Res Ctr Angola, Caxito, Angola..
    Stokic, Ljiljana Pejin
    Inst Econ, Belgrade, Serbia..
    Pereira, David M.
    Univ Porto, Fac Farm, Dept Quim, Lab Farm,REQUIMTE LAQV, Oporto, Portugal..
    Perico, Norberto
    IRCCS Ist Ric Farmacol Mario Negri, Bergamo, Italy..
    Pesudovs, Konrad
    Flinders Univ S Australia, Adelaide, SA, Australia..
    Petzold, Max
    Univ Gothenburg, Hlth Metr Unit, Gothenburg, Sweden.;Univ Witwatersrand, Johannesburg, South Africa..
    Phillips, Michael Robert
    Emory Univ, Atlanta, GA 30322 USA.;Shanghai Jiao Tong Univ, Sch Med, Shanghai, Peoples R China..
    Piel, Frederic B.
    Imperial Coll London, Dept Epidemiol & Biostat, London, England..
    Pillay, Julian David
    Durban Univ Technol, Durban, South Africa..
    Plass, Dietrich
    German Environm Agcy, Exposure Assessment & Environm Hlth Indicators, Berlin, Germany..
    Platts-Mills, James A.
    Univ Virginia, Charlottesville, VA USA..
    Polinder, Suzanne
    Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands..
    Pope, C. Arden
    Brigham Young Univ, Provo, UT USA..
    Popova, Svetlana
    Ctr Addict & Mental Hlth, Toronto, ON, Canada..
    Poulton, Richie G.
    Univ Otago, Dunedin, New Zealand..
    Pourmalek, Farshad
    Univ British Columbia, Vancouver, BC, Canada..
    Prabhakaran, Dorairaj
    Ctr Chron Dis Control, New Delhi, India..
    Qorbani, Mostafa
    Alborz Univ Med Sci, Sch Med, Dept Community Med, Karaj, Iran..
    Quame-Amaglo, Justice
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Quistberg, D. Alex
    Harborview Injury Prevent & Res Ctr, Seattle, WA USA.;Dept Anesthesiol & Pain Med, Seattle, WA USA..
    Rafay, Anwar
    Sch Publ Hlth, Lahore, Pakistan..
    Rahimi, Kazem
    Univ Oxford, Oxford, England..
    Rahimi-Movaghar, Vafa
    Univ Tehran Med Sci, Sina Trauma & Surg Res Ctr, Tehran, Iran..
    Rahman, Mahfuzar
    Res & Evaluat Div, BRAC, Dhaka, Bangladesh.;Hamad Med Corp, Doha, Qatar..
    Rahman, Mohammad Hifz Ur
    Int Inst Populat Sci, Mumbai, Maharashtra, India..
    Rahman, Sajjad Ur
    Rai, Rajesh Kumar
    Soc Hlth & Demog Surveillance, Suri, India..
    Rajavi, Zhale
    Shahid Beheshti Univ Med Sci, Ophthalm Res Ctr, Tehran, Iran..
    Rajsic, Sasa
    UMIT, ERAWEB Program, Hall, Tyrol, Austria..
    Raju, Murugesan
    Univ Missouri, Columbia, MO USA..
    Rakovac, Ivo
    WHO Reg Off Europe, Copenhagen, Denmark..
    Rana, Saleem M.
    Sch Publ Hlth, Lahore, Pakistan.;Contech Int Hlth Consultants, Lahore, Pakistan..
    Ranabhat, Chhabi L.
    Yonsei Univ, Wonju Coll Med, Inst Poverty Alleviat & Int Dev, Wonju, South Korea..
    Rangaswamy, Thara
    Schizophrenia Res Fdn, Chennai, Tamil Nadu, India..
    Rao, Puja
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Rao, Sowmya R.
    Boston Univ, Dept Surg, Sch Med, Boston, MA USA..
    Refaat, Amany H.
    Walden Univ, Minneapolis, MN USA.;Suez Canal Univ, Ismailia, Egypt..
    Rehm, Jurgen
    Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.;Ctr Addict & Mental Hlth, Toronto, ON, Canada..
    Reitsma, Marissa B.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Remuzzi, Giuseppe
    Azienda Osped Papa Giovanni XXIII, Bergamo, Italy.;IRCCS Ist Ric Farmacol Mario Negri, Bergamo, Italy.;Univ Milan, Dept Biomed & Clin Sci L Sacco, Milan, Italy..
    Resnikofff, Serge
    Brien Holden Vis Inst, Sydney, NSW, Australia.;Sch Optometry & Vis Sci, Sydney, NSW, Australia..
    Ribeiro, Antonio L.
    Univ Fed Minas Gerais, Hosp Clin, Belo Horizonte, MG, Brazil..
    Ricci, Stefano
    UO Neurol USL Umbria 1, Castello, Italy..
    Blancas, Maria Jesus Rios
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Roberts, Bayard
    London Sch Hyg & Trop Med, London, England..
    Roca, Anna
    The Gambia, Med Res Council Unit, Fajara, Gambia..
    Rojas-Rueda, David
    I SGlobal, Barcelona, Spain. Golestan Univ Med Sci, Gorgan, Iran..
    Ronfani, Luca
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Roshandel, Gholamreza
    Univ Tehran Med Sci, Digest Dis Res Inst, Tehran, Iran.;Golestan Univ Med Sci, Golestan Res Ctr Gastroenterol & Hepatol, Gorgan, Iran..
    Rothenbacher, Dietrich
    Univ Ulm, Inst Epidemiol & Med Biometry, Ulm, Germany..
    Roy, Ambuj
    All India Inst Med Sci, New Delhi, India..
    Roy, Nawal K.
    Holmusk, Singapore, Singapore.;Duke NUS Med Sch, Singapore, Singapore..
    Ruhago, George Mugambage
    Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania..
    Sagar, Rajesh
    All India Inst Med Sci, New Delhi, India..
    Saha, Sukanta
    Queensland Ctr Mental Hlth Res, Pk Ctr Mental Hlth, Brisbane, Qld, Australia..
    Sahathevan, Ramesh
    Ballarat Hlth Serv, Ballarat, Vic, Australia.;Univ Kebangsaan Malaysia, Med Ctr, Kuala Lumpur, Malaysia..
    Saleh, Muhammad Muhammad
    Dev Res & Projects Ctr, Abuja, Nigeria..
    Sanabria, Juan R.
    Marshall Univ, Edwards Sch Med J, Huntington, WV USA.;Case Western Reserve Univ, Cleveland, OH 44106 USA..
    Sanchez-Nino, Maria Dolores
    IIS Fdn Jimenez Diaz, Madrid, Spain..
    Sanchez-Riera, Lidia
    LHosp, Inst Invest Biomed Bellvitge IDIBELL, Lhospitalet De Llobregat, Spain..
    Santos, Itamar S.
    Univ Sao Paulo, Dept Internal Med, Sao Paulo, Brazil..
    Sarmiento-Suarez, Rodrigo
    Univ Ciencias Aplicadas & Ambient, Bogota, Colombia..
    Sartorius, Benn
    Univ KwaZulu Natal, Durban, South Africa..
    Satpathy, Maheswar
    All India Inst Med Sci, New Delhi, India..
    Savic, Miloje
    Norwegian Inst Publ Hlth, Oslo, Norway.;Norwegian Inst Publ Hlth, Oslo, Norway..
    Sawhney, Monika
    Marshall Univ, Huntington, WV USA..
    Schaub, Michael P.
    Swiss Res Inst Publ Hlth & Addict, Zurich, Switzerland..
    Schmidt, Maria Ines
    Univ Fed Rio Grande do Sul, Porto Alegre, RS, Brazil..
    Schneider, Ione J. C.
    Univ Fed Santa Catarina, Florianopolis, SC, Brazil..
    Schottker, Ben
    German Canc Res Ctr, Heidelberg, Germany.;FOM Univ, Inst Hlth Care & Social Sci, Essen, Germany..
    Schutte, Aletta E.
    Northwest Univ, Hypertens Africa Res Team HART, Potchefstroom, South Africa.;South African Med Res Council, Potchefstroom, South Africa..
    Schwebel, David C.
    Univ Alabama Birmingham, Birmingham, AL USA..
    Seedat, Soraya
    Univ Stellenbosch, Cape Town, South Africa..
    Sepanlou, Sadaf G.
    Univ Tehran Med Sci, Digest Dis Res Inst, Tehran, Iran..
    Servan-Mori, Edson E.
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Shackelford, Katya A.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Shaddick, Gavin
    Univ Bath, Bath, Avon, England..
    Shaheen, Amira
    Najah Univ, Dept Publ Hlth, Nablus, Israel..
    Shahraz, Saeid
    Tufts Med Ctr, Boston, MA USA..
    Shaikh, Masood Ali
    Independent Consultant, Karachi, Pakistan..
    Shakh-Nazarova, Marina
    Natl Ctr Dis Control & Publ Hlth, Tbilisi, Rep of Georgia..
    Sharma, Rajesh
    Indian Inst Technol Ropar, Rupnagar, India..
    She, Jun
    Zhongshan Hosp, Lucknow, Uttar Pradesh, India..
    Sheikhbahaei, Sara
    Univ Tehran Med Sci, Endocrinol & Metab Res Ctr, Tehran, Iran..
    Shen, Jiabin
    Ohio State Univ, Coll Med, Columbus, OH 43210 USA.;Nationwide Childrens Hosp, Res Inst, Columbus, OH USA..
    Shen, Ziyan
    Zhongshan Hosp, Dept Nephrol, Lucknow, Uttar Pradesh, India.;Shanghai Kidney & Dialysis Inst, Shanghai, Peoples R China..
    Shepard, Donald S.
    Brandeis Univ, Waltham, MA USA..
    Sheth, Kevin N.
    Yale Univ, Sch Med, New Haven, CT USA..
    Shetty, Balakrishna P.
    Sri Siddhartha Univ, Tumkur, India.;ISHA Diagnost, Bangalore, Karnataka, India..
    Shi, Peilin
    Tufts Univ, Boston, MA 02111 USA..
    Shibuya, Kenji
    Univ Tokyo, Tokyo, Japan..
    Shin, Min-Jeong
    Korea Univ, Grad Sch, Dept Publ Hlth Sci, Seoul, South Korea..
    Shiri, Rahman
    Finnish Inst Occupat Hlth, Work Org, Work Disabil Prevent, Helsinki, Finland..
    Shiue, Ivy
    Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland.;Northumbria Univ, Fac Hlth & Life Sci, Newcastle Upon Tyne, Tyne & Wear, England..
    Shrime, Mark G.
    Harvard Med Sch, Boston, MA USA..
    Sigfusdottir, Inga Dora
    Reykjavik Univ, Reykjavik, Iceland..
    Silberberg, Donald H.
    Univ Penn, Philadelphia, PA USA..
    Silva, Diego Augusto Santos
    Univ Fed Santa Catarina, Florianopolis, SC, Brazil..
    Silveira, Dayane Gabriele Alves
    Univ Brasilia, Brasilia, DF, Brazil..
    Silverberg, Jonathan I.
    Feinberg Sch Med, Chicago, IL USA..
    Simard, Edgar P.
    Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA..
    Singh, Abhishek
    Int Inst Populat Sci, Mumbai, Maharashtra, India..
    Singh, Gitanjali M.
    Tufts Univ, Boston, MA 02111 USA..
    Singh, Jasvinder A.
    Univ Alabama Birmingham, Birmingham, AL USA..
    Singh, Om Prakash
    Banaras Hindu Univ, Inst Med Sci, Dept Med, Varanasi, Uttar Pradesh, India..
    Singh, Prashant Kumar
    Inst Human Dev, New Delhi, India..
    Singh, Virendra
    Asthma Bhawan, Jaipur, Rajasthan, India..
    Soneji, Samir
    Dartmouth Coll, Hanover, NH USA..
    Soreide, Kjetil
    Stavanger Univ Hosp, Stavanger, Norway..
    Soriano, Joan B.
    Univ Autonoma Madrid, Inst Invest Hosp Univ Princesa, Madrid, Spain..
    Sposato, Luciano A.
    Western Univ, Dept Clin Neurol Sci, London, ON, Canada..
    Sreeramareddy, Chandrashekhar T.
    Int Med Univ, Dept Community Med, Kuala Lumpur, Malaysia..
    Stathopoulou, Vasiliki
    Attikon Univ Hosp, Athens, Greece..
    Stein, Dan J.
    Univ Cape Town, Dept Psychiat, Cape Town, South Africa.;South African Med Res Council, Unit Anxiety & Stress Disorders, Cape Town, South Africa..
    Stein, Murray B.
    Univ Calif San Diego, San Diego, CA 92103 USA..
    Stranges, Saverio
    Luxembourg Inst Hlth, Luxembourg, Luxembourg..
    Stroumpoulis, Konstantinos
    Alexandra Gen Hosp Athens, Athens, Greece.;Ctr Hosp Publ Cotentin, Cherbourg, France..
    Sunguya, Bruno F.
    Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania..
    Sur, Patrick
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Swaminathan, Soumya
    Indian Council Med Res, New Delhi, India..
    Sykes, Bryan L.
    Univ Calif Irvine, Dept Criminol, Irvine, CA USA.;Univ Calif Irvine, Law & Soc Sociol & Publ Hlth, Irvine, CA USA.;Univ Calif Irvine, Irvine, CA USA..
    Szoeke, Cassandra E. I.
    Inst Hlth & Ageing, Melbourne, Vic, Australia..
    Tabares-Seisdedos, Rafael
    Univ Valencia, Dept Med, INCLIVA Hlth Res Inst & CIBERSAM, Valencia, Spain..
    Tabb, Karen M.
    Univ Illinois, Sch Social Work, Urbana, IL USA..
    Takahashi, Ken
    Univ Occupat & Environm Hlth, Inst Ind Ecol Sci, Dept Environm Epidemiol, Kitakyushu, Fukuoka, Japan..
    Takala, Jukka S.
    WSH Inst, Minist Manpower, Singapore, Singapore.;Tampere Univ Technol, Tampere, Finland..
    Talongwa, Roberto Tchio
    Minist Hlth, MINSANTE, Yaounde, Cameroon..
    Tandon, Nikhil
    All India Inst Med Sci, New Delhi, India..
    Tavakkoli, Mohammad
    New York Med Coll, Valhalla, NY USA..
    Taye, Bineyam
    Colgate Univ, Dept Biol, Hamilton, NY USA..
    Taylor, Hugh R.
    Univ Melbourne, Melbourne, Vic, Australia..
    Ao, Braden J. Te
    Auckland Univ Technol, Auckland, New Zealand..
    Tedla, Bemnet Amare
    Univ Gondar, Gondar, Ethiopia.;James Cook Univ, Cairns, Qld, Australia..
    Tefera, Worku Mekonnen
    Univ Addis Ababa, Addis Ababa, Ethiopia.;Addis Ababa City Govt, Addis Ababa, Ethiopia..
    Ten Have, Margreet
    Netherlands Inst Mental Hlth & Addict, Utrecht, Netherlands..
    Terkawi, Abdullah Sulieman
    King Fahad Med City, Dept Anesthesiol, Riyadh, Saudi Arabia.;Univ Virginia, Dept Anesthesiol, Charlottesville, VA USA.;Outcomes Res Consortium, Cleveland, OH USA..
    Tesfay, Fisaha Haile
    Coll Hlth Sci, Mekelle, Ethiopia.;Flinders Univ S Australia, Adelaide, SA, Australia..
    Tessema, Gizachew Assefa
    Univ Adelaide, Adelaide, SA, Australia.;Univ Gondar, Gondar, Ethiopia..
    Thomson, Alan J.
    Adapt Knowledge Management, Victoria, BC, Canada..
    Thorne-Lyman, Andrew L.
    WorldFish, George Town, Malaysia..
    Thrift, Amanda G.
    Monash Univ, Sch Clin Sci Monash Hlth, Dept Med, Melbourne, Vic, Australia..
    Thurston, George D.
    New York Univ, Nelson Inst Environm Med, Sch Med, Tuxedo Pk, NY USA..
    Tillmann, Taavi
    UCL, Dept Epidemiol & Publ Hlth, London, England..
    Tirschwell, David L.
    Univ Washington, Seattle, WA 98195 USA..
    Tonelli, Marcello
    Univ Calgary, Calgary, AB, Canada..
    Topor-Madry, Roman
    Jagiellonian Univ Med Coll, Inst Publ Hlth, Fac Hlth Sci, Krakow, Poland.;Wroclaw Med Univ, Fac Hlth Sci, Wroclaw, Poland..
    Topouzis, Fotis
    Aristotle Univ Thessaloniki, Thessaloniki, Greece..
    Nx, Jeffrey Allen Towb
    Bonheur Childrens Hosp Memphis, Memphis, TN USA.;Univ Tennessee Hlth Sci Ctr, Memphis, TN USA.;St Jude Childrens Res Hosp, Memphis, TN USA..
    Traebert, Jefferson
    Univ Southern Santa Catarina, Palhoca, Brazil..
    Tran, Bach Xuan
    Johns Hopkins Univ, Baltimore, MD USA.;Hanoi Med Univ, Hanoi, Vietnam..
    Truelsen, Thomas
    Univ Copenhagen, Dept Neurol, Rigshosp, Copenhagen, Denmark..
    Trujillo, Ulises
    Serv Canario Salud, Santa Cruz de La Palma, CA, Spain..
    Tura, Abera Kenay
    Univ Med Ctr Groningen, Groningen, Netherlands.;Haramaya Univ, Dire Dawa, Ethiopia..
    Tuzcu, Emin Murat
    Cleveland Clin, Cleveland, OH USA..
    Uchendu, Uche S.
    Dept Vet Affairs, Washington, DC USA..
    Ukwaja, Kingsley N.
    Fed Teaching Hosp, Dept Internal Med, Abakaliki, Nigeria..
    Undurraga, Eduardo A.
    Brandeis Univ, Waltham, MA USA..
    Uthman, Olalekan A.
    Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England..
    Van Dingenen, Rita
    Joint Res Ctr, European Commiss, Ispra, Italy..
    Van Donkelaar, Aaron
    Univ Oxford, Oxford, England.;Dalhousie Univ, Dept Phys & Atsmopher Sci, Halifax, NS, Canada..
    Vasankari, Tommi
    Vasconcelos, Ana Maria Nogales
    UKK Inst Hlth Promot Res, Tampere, Finland.;Univ Brasilia, Brasilia, DF, Brazil..
    Venketasubramanian, Narayanaswamy
    Raffles Hosp, Raffles Neurosci Ctr, Singapore, Singapore..
    Vidavalur, Ramesh
    Weill Cornell Med Coll, New York, NY USA..
    Vijayakumar, Lakshmi
    Ctr Youth Mental Hlth, Melbourne, Vic, Australia.;VHS SNEHA, Chennai, Tamil Nadu, India..
    Villalpando, Salvador
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Violante, Francesco S.
    Univ Bologna, Bologna, Italy..
    Vlassov, Vasiliy Victorovich
    Natl Res Univ, Higher Sch Econ, Moscow, Russia..
    Wagner, Joseph A.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Wagner, Gregory R.
    Harvard T H Chan Sch Publ Hlth, Boston, MA USA.;Natl Inst Occupat Safety & Hlth, Washington, DC USA..
    Wallin, Mitchell T.
    VA Med Ctr, Washington, DC USA.;Georgetown Univ, Dept Neurol, Washington, DC USA..
    Wang, Linhong
    Natl Ctr Chron & Noncommunicable Dis Control & Pr, Beijing, Peoples R China..
    Watkins, David A.
    Univ Washington, Seattle, WA 98195 USA.;Univ Cape Town, Cape Town, South Africa..
    Weichenthal, Scott
    McGill Univ, Montreal, PQ, Canada..
    Weiderpass, Elisabete
    Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Canc Registry Norway, Inst Populat Based Canc Res, Dept Res, Oslo, Norway.;Univ Tromso, Arctic Univ Norway, Dept Community Med, Fac Hlth Sci, Tromso, Norway.;Genet Epidemiol Grp, Folkhalsan Res Ctr, Helsinki, Finland..
    Weintraub, Robert G.
    Murdoch Childrens Res Inst, Melbourne, Vic, Australia.;Univ Melbourne, Melbourne, Vic, Australia.;Royal Childrens Hosp, Melbourne, Vic, Australia..
    Werdecker, Andrea
    Competence Ctr Mortal Follow Up German Natl Cohor, Wiesbaden, Germany..
    Westerman, Ronny
    Fed Inst Populat Res, Wiesbaden, Germany.;German Natl Cohort Consortium, Heidelberg, Germany..
    White, Richard A.
    Norwegian Inst Publ Hlth, Dept Infect Dis Epidemiol & Modelling, Oslo, Norway..
    Wijeratne, Tissa
    Univ Melbourne, Melbourne, Vic, Australia.;Western Hlth, Footscray, Vic, Australia..
    Wilkinson, James D.
    Wayne State Univ, Sch Med, Detroit, MI USA.;Childrens Hosp Michigan, Detroit, MI 48201 USA..
    Williams, Hywel C.
    Wiysonge, Charles Shey
    South African Med Res Council, Cape Town, South Africa.;Univ Stellenbosch, Cape Town, South Africa..
    Woldeyohannes, Solomon Meseret
    Univ Gondar, Dept Epidemiol & Biostat, Inst Publ Hlth, Gondar, Ethiopia..
    Wolfe, Charles D. A.
    Div Hlth & Social Care Res, London, England.;Guys & St Thomas NHS Fdn Trust & Kings Coll, Natl Inst Hlth Res Comprehens Biomed Res Ctr, London, England..
    Won, Sungho
    Seoul Natl Univ, Grad Sch Publ Hlth, Seoul, South Korea..
    Wong, John Q.
    Manila Univ, Ateneo Sch Med & Publ Hlth, Pasig, Philippines..
    Woolf, Anthony D.
    Royal Cornwall Hosp, Truro, England..
    Xavier, Denis
    St Johns Med Coll & Res Inst, Bangalore, Karnataka, India..
    Xiao, Qingyang
    Emory Univ, Atlanta, GA 30322 USA..
    Xu, Gelin
    Nanjing Univ, Sch Med, Dept Neurol, Jinling Hosp, Nanjing, Jiangsu, Peoples R China..
    Yakob, Bereket
    Univ KwaZulu Natal, Sch Nursing & Publ Hlth, Discipline Publ Hlth Med, Durban, South Africa..
    Yalew, Ayalnesh Zemene
    Mekelle Univ, Mekelle, Ethiopia..
    Yan, Lijing L.
    Duke Kunshan Univ, Global Hlth Res Ctr, Kunshan, Peoples R China..
    Yano, Yuichiro
    Northwestern Univ, Dept Prevent Med, Chicago, IL USA..
    Yaseri, Mehdi
    Shahid Beheshti Univ Med Sci, Ophthalm Res Ctr, Tehran, Iran..
    Ye, Pengpeng
    Yebyo, Henock Gebremedhin
    Mekelle Univ, Mekelle, Ethiopia.;Univ Zurich, Zurich, Switzerland..
    Yip, Paul
    Social Work & Social Adm Dept, Hong Kong, Hong Kong, Peoples R China.;Univ Hong Kong, Hong Kong Jockey Club Ctr Suicide Res & Prevent, Hong Kong, Hong Kong, Peoples R China..
    Yirsaw, Biruck Desalegn
    Univ Addis Ababa, Addis Ababa, Ethiopia.;Univ South Australia, Mawson Lakes, SA, Australia..
    Yonemoto, Naohiro
    Kyoto Univ, Sch Publ Hlth, Dept Biostatist, Kyoto, Japan..
    Yonga, Gerald
    Aga Khan Univ, Nairobi, Kenya..
    Younis, Mustafa Z.
    Jackson State Univ, Jackson, MS USA..
    Yu, Shicheng
    Chinese Ctr Dis Control, Beijing, Peoples R China..
    Zaidi, Zoubida
    Univ Hosp, Setif, Algeria..
    Zaki, Maysaa El Sayed
    Mansoura Univ, Fac Med, Mansoura, Egypt..
    Zannad, Faiez
    Univ Lorraine, Clin Invest Ctr, INSERM, Natl Inst Hlth & Med Res, Vandoeuvre Ies Nancy, France.;CHU Nancy, Vandoeuvre Les Nancy, France..
    Zavala, Diego E.
    Ponce Hlth Sci Univ, Ponce, PR USA..
    Zeeb, Hajo
    Leibniz Inst Prevent Res & Epidemiol, Bremen, Germany..
    Zeleke, Berihun M.
    Univ Gondar, Gondar, Ethiopia.;Monash Univ, Melbourne, Vic, Australia..
    Zhang, Hao
    Zhongshan Hosp, Dept Nephrol, Lucknow, Uttar Pradesh, India.;Shanghai Inst Kidney Dis & Dialysis, Shanghai, Peoples R China..
    Zodpey, Sanjay
    Publ Hlth Fdn India, Gurgaon, India.;Publ Hlth Fdn India, Gurgaon, India..
    Zonies, David
    Oregon Hlth & Sci Univ, Portland, OR 97201 USA..
    Zuhlke, Liesl Joanna
    Red Cross War Mem Childrens Hosp, Cape Town, South Africa..
    Vos, Theo
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Lopez, Alan D.
    Inst Hlth Metr & Evaluat, Seattle, WA USA.;Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia..
    Murray, Christopher J. L.
    Inst Hlth Metr & Evaluat, Seattle, WA USA..
    Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 20152016In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 388, no 10053, p. 1459-1544Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.

    METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).

    FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.

    INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.

  • 397. Wang, Haidong
    et al.
    Wolock, Tim M
    Carter, Austin
    Nguyen, Grant
    Kyu, Hmwe Hmwe
    Gakidou, Emmanuela
    Hay, Simon I
    Mills, Edward J
    Trickey, Adam
    Msemburi, William
    Coates, Matthew M
    Mooney, Meghan D
    Fraser, Maya S
    Sligar, Amber
    Salomon, Joshua
    Larson, Heidi J
    Friedman, Joseph
    Abajobir, Amanuel Alemu
    Abate, Kalkidan Hassen
    Abbas, Kaja M
    Razek, Mohamed Magdy Abd El
    Abd-Allah, Foad
    Abdulle, Abdishakur M
    Abera, Semaw Ferede
    Abubakar, Ibrahim
    Abu-Raddad, Laith J
    Abu-Rmeileh, Niveen M E
    Abyu, Gebre Yitayih
    Adebiyi, Akindele Olupelumi
    Adedeji, Isaac Akinkunmi
    Adelekan, Ademola Lukman
    Adofo, Koranteng
    Adou, Arsène Kouablan
    Ajala, Oluremi N
    Akinyemiju, Tomi F
    Akseer, Nadia
    Lami, Faris Hasan Al
    Al-Aly, Ziyad
    Alam, Khurshid
    Alam, Noore K M
    Alasfoor, Deena
    Aldhahri, Saleh Fahed S
    Aldridge, Robert William
    Alegretti, Miguel Angel
    Aleman, Alicia V
    Alemu, Zewdie Aderaw
    Alfonso-Cristancho, Rafael
    Ali, Raghib
    Alkerwi, Ala'a
    Alla, François
    Mohammad, Rajaa
    Al-Raddadi, Salem
    Alsharif, Ubai
    Alvarez, Elena
    Alvis-Guzman, Nelson
    Amare, Azmeraw T
    Amberbir, Alemayehu
    Amegah, Adeladza Kofi
    Ammar, Walid
    Amrock, Stephen Marc
    Antonio, Carl Abelardo T
    Anwari, Palwasha
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Artaman, Al
    Asayesh, Hamid
    Asghar, Rana Jawad
    Assadi, Reza
    Atique, Suleman
    Atkins, Lydia S
    Avokpaho, Euripide Frinel G Arthur
    Awasthi, Ashish
    Quintanilla, Beatriz Paulina Ayala
    Bacha, Umar
    Badawi, Alaa
    Barac, Aleksandra
    Bärnighausen, Till
    Basu, Arindam
    Bayou, Tigist Assefa
    Bayou, Yibeltal Tebekaw
    Bazargan-Hejazi, Shahrzad
    Beardsley, Justin
    Bedi, Neeraj
    Bennett, Derrick A
    Bensenor, Isabela M
    Betsu, Balem Demtsu
    Beyene, Addisu Shunu
    Bhatia, Eesh
    Bhutta, Zulfiqar A
    Biadgilign, Sibhatu
    Bikbov, Boris
    Birlik, Sait Mentes
    Bisanzio, Donal
    Brainin, Michael
    Brazinova, Alexandra
    Breitborde, Nicholas J K
    Brown, Alexandria
    Burch, Michael
    Butt, Zahid A
    Campuzano, Julio Cesar
    Cárdenas, Rosario
    Carrero, Juan Jesus
    Castañeda-Orjuela, Carlos A
    Rivas, Jacqueline Castillo
    Catalá-López, Ferrán
    Chang, Hsing-Yi
    Chang, Jung-Chen
    Chavan, Laxmikant
    Chen, Wanqing
    Chiang, Peggy Pei-Chia
    Chibalabala, Mirriam
    Chisumpa, Vesper Hichilombwe
    Choi, Jee-Young Jasmine
    Christopher, Devasahayam Jesudas
    Ciobanu, Liliana G
    Cooper, Cyrus
    Dahiru, Tukur
    Damtew, Solomon Abreha
    Dandona, Lalit
    Dandona, Rakhi
    das Neves, José
    de Jager, Pieter
    De Leo, Diego
    Degenhardt, Louisa
    Dellavalle, Robert P
    Deribe, Kebede
    Deribew, Amare
    Des Jarlais, Don C
    Dharmaratne, Samath D
    Ding, Eric L
    Doshi, Pratik Pinal
    Driscoll, Tim R
    Dubey, Manisha
    Elshrek, Yousef Mohamed
    Elyazar, Iqbal
    Endries, Aman Yesuf
    Ermakov, Sergey Petrovich
    Eshrati, Babak
    Esteghamati, Alireza
    Faghmous, Imad D A
    Farinha, Carla Sofia E Sa
    Faro, Andre
    Farvid, Maryam S
    Farzadfar, Farshad
    Fereshtehnejad, Seyed-Mohammad
    Fernandes, Joao C
    Fischer, Florian
    Fitchett, Joseph Robert Ander
    Foigt, Nataliya
    Fullman, Nancy
    Fürst, Thomas
    Gankpé, Fortuné Gbètoho
    Gebre, Teshome
    Gebremedhin, Amanuel Tesfay
    Gebru, Alemseged Aregay
    Geleijnse, Johanna M
    Gessner, Bradford D
    Gething, Peter W
    Ghiwot, Tsegaye Tewelde
    Giroud, Maurice
    Gishu, Melkamu Dedefo
    Glaser, Elizabeth
    Goenka, Shifalika
    Goodridge, Amador
    Gopalani, Sameer Vali
    Goto, Atsushi
    Gugnani, Harish Chander
    Guimaraes, Mark D C
    Gupta, Rahul
    Gupta, Rajeev
    Gupta, Vipin
    Haagsma, Juanita
    Hafezi-Nejad, Nima
    Hagan, Holly
    Hailu, Gessessew Bugssa
    Hamadeh, Randah Ribhi
    Hamidi, Samer
    Hammami, Mouhanad
    Hankey, Graeme J
    Hao, Yuantao
    Harb, Hilda L
    Harikrishnan, Sivadasanpillai
    Haro, Josep Maria
    Harun, Kimani M
    Havmoeller, Rasmus
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    Heredia-Pi, Ileana Beatriz
    Hoek, Hans W
    Horino, Masako
    Horita, Nobuyuki
    Hosgood, H Dean
    Hoy, Damian G
    Hsairi, Mohamed
    Hu, Guoqing
    Huang, Hsiang
    Huang, John J
    Iburg, Kim Moesgaard
    Idrisov, Bulat T
    Innos, Kaire
    Iyer, Veena J
    Jacobsen, Kathryn H
    Jahanmehr, Nader
    Jakovljevic, Mihajlo B
    Javanbakht, Mehdi
    Jayatilleke, Achala Upendra
    Jeemon, Panniyammakal
    Jha, Vivekanand
    Jiang, Guohong
    Jiang, Ying
    Jibat, Tariku
    Jonas, Jost B
    Kabir, Zubair
    Kamal, Ritul
    Kan, Haidong
    Karch, André
    Karema, Corine Kakizi
    Karletsos, Dimitris
    Kasaeian, Amir
    Kaul, Anil
    Kawakami, Norito
    Kayibanda, Jeanne Françoise
    Keiyoro, Peter Njenga
    Kemp, Andrew Haddon
    Kengne, Andre Pascal
    Kesavachandran, Chandrasekharan Nair
    Khader, Yousef Saleh
    Khalil, Ibrahim
    Khan, Abdur Rahman
    Khan, Ejaz Ahmad
    Khang, Young-Ho
    Khubchandani, Jagdish
    Kim, Yun Jin
    Kinfu, Yohannes
    Kivipelto, Miia
    Kokubo, Yoshihiro
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    Kumar, G Anil
    Lal, Dharmesh Kumar
    Lam, Hilton
    Lam, Jennifer O
    Langan, Sinead M
    Lansingh, Van C
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Leigh, James
    Leung, Ricky
    Li, Yongmei
    Lim, Stephen S
    Lipshultz, Steven E
    Liu, Shiwei
    Lloyd, Belinda K
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    Murimira, Brighton
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    de Dieu Ngirabega, Jean
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    Norheim, Ole F
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    Park, Jae-Hyun
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    Rahman, Sajjad Ur
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    Rajsic, Sasa
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    Saleh, Muhammad Muhammad
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    Shen, Jiabin
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    Shin, Hwashin Hyun
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    Silva, Diego Augusto Santos
    Silveira, Dayane Gabriele Alves
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    Singh, Jasvinder A
    Singh, Om Prakash
    Singh, Prashant Kumar
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    Swaminathan, Soumya
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    Talongwa, Roberto Tchio
    Tavakkoli, Mohammad
    Taye, Bineyam
    Tedla, Bemnet Amare
    Tekle, Tesfaye
    Shifa, Girma Temam
    Temesgen, Awoke Misganaw
    Terkawi, Abdullah Sulieman
    Tesfay, Fisaha Haile
    Tessema, Gizachew Assefa
    Thapa, Kiran
    Thomson, Alan J
    Thorne-Lyman, Andrew L
    Tobe-Gai, Ruoyan
    Topor-Madry, Roman
    Towbin, Jeffrey Allen
    Tran, Bach Xuan
    Dimbuene, Zacharie Tsala
    Tsilimparis, Nikolaos
    Tura, Abera Kenay
    Ukwaja, Kingsley Nnanna
    Uneke, Chigozie Jesse
    Uthman, Olalekan A
    Venketasubramanian, N
    Vladimirov, Sergey K
    Vlassov, Vasiliy Victorovich
    Vollset, Stein Emil
    Wang, Linhong
    Weiderpass, Elisabete
    Weintraub, Robert G
    Werdecker, Andrea
    Westerman, Ronny
    Wijeratne, Tissa
    Wilkinson, James D
    Wiysonge, Charles Shey
    Wolfe, Charles D A
    Won, Sungho
    Wong, John Q
    Xu, Gelin
    Yadav, Ajit Kumar
    Yakob, Bereket
    Yalew, Ayalnesh Zemene
    Yano, Yuichiro
    Yaseri, Mehdi
    Yebyo, Henock Gebremedhin
    Yip, Paul
    Yonemoto, Naohiro
    Yoon, Seok-Jun
    Younis, Mustafa Z
    Yu, Chuanhua
    Yu, Shicheng
    Zaidi, Zoubida
    Zaki, Maysaa El Sayed
    Zeeb, Hajo
    Zhang, Hao
    Zhao, Yong
    Zodpey, Sanjay
    Zoeckler, Leo
    Zuhlke, Liesl Joanna
    Lopez, Alan D
    Murray, Christopher J L
    Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015: the Global Burden of Disease Study 2015.2016In: The lancet. HIV, ISSN 2352-3018, Vol. 3, no 8, p. e361-e387Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.

    METHODS: For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification.

    FINDINGS: Global HIV incidence reached its peak in 1997, at 3·3 million new infections (95% uncertainty interval [UI] 3·1-3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5-2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6-40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7-1·9 million) in 2005, to 1·2 million deaths (1·1-1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections.

    INTERPRETATION: Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030.

  • 398. Wang, Lu
    et al.
    Bauer, Maria
    Curry, Regina
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sessler, Daniel I
    Eisenach, James C
    Intrathecal ketorolac does not improve acute or chronic pain after hip arthroplasty: a randomized controlled trial2014In: Journal of Anesthesia, ISSN 0913-8668, E-ISSN 1438-8359, Vol. 28, no 5, p. 790-793Article in journal (Refereed)
    Abstract [en]

    Hypersensitivity to mechanical stimuli following surgery has been reported in patients who subsequently develop chronic pain after surgery. In animals, peripheral injury increases prostaglandin production in the spinal cord, and spinal cyclooxygenase inhibitors reduce hypersensitivity after injury. We therefore tested the hypothesis that spinal ketorolac reduces hypersensitivity and acute and chronic pain after hip arthroplasty ( www.clinicaltrials.gov NCT 00621530). Sixty-two patients undergoing total hip arthroplasty with spinal anesthesia were randomized to receive 13.5 mg hyperbaric bupivacaine with spinal saline or 13.5 mg hyperbaric bupivacaine with 2 mg preservative-free ketorolac. The primary outcome was area of hypersensitivity surrounding the wound 48 h after surgery, but this only occurred in 4 patients, precluding assessment of this outcome. The groups did not differ in acute pain, acute opioid use, or pain incidence or severity at 2 and 6 months after surgery. There were no serious adverse events. Our results suggest that a single spinal dose of ketorolac does not substantially reduce acute surgical pain and is thus unlikely to reduce the risk of persistent incisional pain.

  • 399.
    Weitoft, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Manivel, Vivek A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Lysholm, Jörgen
    Clinic of Rheumatology, Falun Hospital, Falun.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Cathepsin S and cathepsin L in serum and synovial fluid in rheumatoid arthritis with and without autoantibodies2015In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 54, no 10, p. 1923-1928Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Cathepsin S and cathepsin L are endosomal proteolytic enzymes involved in the degradation of extracellular matrixes, angiogenesis and antigen presentation. Cathepsins could thus play several roles in the disease process of RA. The aim of this study was to examine differences in cathepsin S and cathepsin L levels in serum and SF of RA patients with and without ACPA and RF.

    METHODS: In this study 121 patients with RA and clinical signs of knee synovitis were recruited. Patient characteristics were collected and matched samples of serum and SF were analysed for cathepsin S, cathepsin L, ACPA, IgA and IgM RF, CRP and MMP3.

    RESULTS: SF levels of cathepsin L, cathepsin S and MMP3 were significantly higher than in serum. Serum levels of both cathepsins were significantly higher in patients with ACPA, IgM-RF and IgA-RF compared with patients without these antibodies. SF levels of both cathepsins correlated with DAS28 and CRP in ACPA- and RF-positive but not in seronegative patients.

    CONCLUSION: The differences in cathepsin S and cathepsin L between RA patients with and without autoantibodies indicate that these cathepsins have a specific role in the disease process of seropositive RA. In this phenotype, cathepsin serum levels may reflect the autoimmune activity, whereas the levels in SF may reflect the local inflammatory and matrix degrading process in the joint.

  • 400.
    Weitoft, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Manivel, Vivek
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Lysholm, J.
    Knight, A.
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Cathepsin S and cathepsin L in serum and synovial fluid in rheumatoid arthritis with and without autoantibodies2014In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, no S127, p. 53-53Article in journal (Other academic)
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