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  • 201.
    Rönn, Monika
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Örberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Söderberg, Stefan
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden; Umea Univ, Ctr Heart, Umea, Sweden.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Bisphenol A is related to circulating levels of adiponectin, leptin and ghrelin, but not to fat mass or fat distribution in humans2014Inngår i: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 112, s. 42-48Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 202. Salazar, Vivian A.
    et al.
    Rubin, Jenny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Moussaoui, Mohammed
    Pulido, David
    Victoria Nogues, Maria
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Boix, Ester
    Protein post-translational modification in host defense: the antimicrobial mechanism of action of human eosinophil cationic protein native forms2014Inngår i: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 281, nr 24, s. 5432-5446Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Knowledge on the contribution of protein glycosylation in host defense antimicrobial peptides is still scarce. We have studied here how the post-translational modification pattern modulates the antimicrobial activity of one of the best characterized leukocyte granule proteins. The human eosinophil cationic protein (ECP), an eosinophil specific granule protein secreted during inflammation and infection, can target a wide variety of pathogens. Previous work in human eosinophil extracts identified several ECP native forms and glycosylation heterogeneity was found to contribute to the protein biological properties. In this study we analyze for the first time the antimicrobial activity of the distinct native proteins purified from healthy donor blood. Low and heavy molecular weight forms were tested on Escherichiacoli cell cultures and compared with the recombinant non-glycosylated protein. Further analysis on model membranes provided an insight towards an understanding of the protein behavior at the cytoplasmic membrane level. The results highlight the significant reduction in protein toxicity and bacteria agglutination activity for heavy glycosylated fractions. Notwithstanding, the lower glycosylated fraction mostly retains the lipopolysaccharide binding affinity together with the cytoplasmic membrane depolarization and membrane leakage activities. From structural analysis we propose that heavy glycosylation interferes with the protein self-aggregation, hindering the cell agglutination and membrane disruption processes. The results suggest the contribution of post-translational modifications to the antimicrobial role of ECP in host defense.

  • 203. Savukoski, Tanja
    et al.
    Engstrom, Emilia
    Engblom, Janne
    Ristiniemi, Noora
    Wittfooth, Saara
    Lindahl, Bertil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Eggers, Kai M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Pettersson, Kim
    Troponin-Specific Autoantibody Interference in Different Cardiac Troponin I Assay Configurations2012Inngår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 58, nr 6, s. 1040-1048Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Autoantibodies to cardiac troponins (cTnAAb) can interfere with the measurement of cardiac troponin I (cTnI) by immunoassays. The aim of this study was to explore the degree of cTnAAb interference in different cTnI assay configurations. METHODS: Ternary troponin complex was added into samples (serum or plasma, n = 132, 68% cTnAAb positive) from individuals without known cardiac conditions. The recovery of cTnI was then measured with 6 investigational cTnI assays (2, 3, or 4 antibodies per assay). Three of these assays were then selected for further comparison by use of samples (plasma, n = 210, 33% cTnAAb positive) from non-ST-elevation acute coronary syndrome patients in the FRISC-II (FRagmin/Fast Revascularisation during InStability in Coronary artery disease) cohort. Finally, these results were compared to those obtained with 3 commercial cTnI assays. RESULTS: Analytical recoveries varied widely among the 6 investigational assays. Notably the low recoveries (median 9%) of the midfragment-targeting reference assay were normalized (median 103%) with the use of the 4-antibody assay construct (3 capture, 1 tracer antibody) with only 1 antibody against a midfragment epitope. Reduced analytical recoveries correlated closely with measured autoantibody amounts. cTnI concentrations from cTnAAb-positive patient samples determined with 3 investigational assays confirmed the reduced concentrations expected from the low analytical recoveries. The results from the commercial cTnI assays with antibody selections representative for contemporary assay constructs revealed a similar underestimation (up to 20-fold) of cTnI in cTnAAb-positive samples. CONCLUSIONS: A novel cTnI assay deviating from the conventional IFCC-recommended midfragment approach substantially improves cTnI detection in samples containing cTnAAbs.

  • 204. Savukoski, Tanja
    et al.
    Jacobino, Jenna
    Laitinen, Paivi
    Lindahl, Bertil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Ristiniemi, Noora
    Wittfooth, Saara
    Pettersson, Kim
    Novel sensitive cardiac troponin I immunoassay free from troponin I-specific autoantibody interference2014Inngår i: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 52, nr 7, s. 1041-1048Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Cardiac troponins (cTnI and cTnT) are the recommended biomarkers of myocardial infarction. As cTn-specific autoantibodies (cTnAAb) can interfere with the cTn detection by state-of-the-art cTnI assays, our objective was to develop a sensitive cTnI immunoassay free from this analytical interference. Methods: The assay used antibody-coated spots containing three capture Mabs/Fabs directed against the N-terminus, midfragment and C-terminus of cTnI and a europium chelate-labeled tracer Mab against the C-terminus. Following a 3-h sample incubation and washing, cTnI was quantified by time-resolved fluorometry. Results: The limit of detection (LoD) was 2.9 ng/L and the assay was linear up to 50,000 ng/L. The total precision of 10% CV was not reached, but 20% CV was reached at 10 ng/L. Mean cTnI (10-50,000 ng/L) recoveries were 100% and 119% in three cTnAAb-positive and two cTnAAb-negative individuals, respectively, verifying the interference resistance of the antibody design used. On average, Architect hs-cTnI assay gave seven-fold higher cTnI concentrations than the new assay but the correlation between the assays was good (r=0.958). Of apparently healthy individuals (n=159), 18% had measurable cTnI values (>LoD) and 10% were cTnAAb-positive. The proportion of measurable cTnI values, however, was significantly higher in cTnAAb-positive individuals (13/16, median cTnI 8.5 ng/L) than in cTnAAb-negative individuals (15/143, median cTnI <LoD) (p<0.001). Conclusions: Although the developed sensitive cTnI assay without cTnAAb interference takes too long for diagnostic purposes, it could serve as an important analytical tool for exploring the impact of cTnAAbs for cTn testing and for unraveling the etiology behind cTn-related autoimmune responses.

  • 205. Savukoski, Tanja
    et al.
    Mehtala, Laura
    Lindahl, Bertil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Pettersson, Kim
    Elevation of cardiac troponins measured after recreational resistance training2015Inngår i: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 48, nr 12, s. 803-806Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Whereas elevated cardiac troponin (cTn) concentrations i.e. above the 99th percentile of healthy reference population (recommended cutoff for the diagnosis of myocardial infarction) are well-documented in healthy individuals after prolonged and/or intensive exercises such as marathons, data on less-strenuous sports are scarce. Therefore, our aim was to investigate cTnI and cTnT release in response to recreational resistance training, here a single-bout of 1-h kettlebell workout. Methods: Serum samples were collected from 11 apparently healthy volunteers the previous day (pre-exercise), three hours after the kettlebell class (post-exercise), the next day and three days later. The aliquoted samples were analyzed with Abbott Laboratories' Architect high-sensitivity (hs)-cTnI assay (limit of detection, LoD = 2 ng/L), our 3 + 1-type cTnI assay free from cTn-specific autoantibody interference (LoD = 3 ng/L) and Roche Diagnostics' hs-cTnT assay CLOD = 5 ng/L). Results: The post-exercise cTn concentrations were significantly higher than the pre-exercise values (median 5.5-9.6 ng/L vs. <LoD, P < 0.05 for all) and they correlated strongly between the three assays (Spearman r = 0.881-0.960, P < 0.001 for all). Furthermore, a few post-exercise concentrations even exceeded the 99th percentile of Architect hs-cTnI (>26 ng/L, n = 2) and/or hs-cTnT (>14 ng/L, n = 4). The cTn concentrations returned to baseline during the three days of follow-up. Conclusions: Our study demonstrates abnormally elevated cTns with well-validated sensitive cTn assays after resistance training. This confirms that different kinds of recreational physical activity are yet another confounder that may affect the determination and use of 99th percentile reference values. Therefore, exercise-associated changes should be carefully addressed as part of the evaluation what is "normal cTn".

  • 206. Schmekel, Birgitta
    et al.
    Blomstrand, Peter
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Serum lysozyme a surrogate marker of pulmonary microvascular injury in smokers?2013Inngår i: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 33, nr 4, s. 307-312Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Progression rate of disease processes in smoke-induced lung injuries varies greatly. Diverse pathophysiological mechanisms may trigger these divergences. The aim of this study was to evaluate whether circulating markers of monocytes/macrophages and/or neutrophil [i.e. lysozyme (LZM) or myeloperoxidase (MPO)] were associated with reduced values of diffusion capacity (DL,CO), which is considered to serve as a mirror of pulmonary microvascular derangement and an early sign of tissue remodelling in smokers. Data obtained from 134 smokers (GOLD stage 1) and 24 matched healthy non-smoking volunteers were evaluated in a cross-sectional study design. Lung function tests as well as single breath test of DL,CO were assessed according to ATS/ERS guidelines. Biomarkers were measured in serum by means of sensitive immunoassays. A subgroup of smokers with normal lung function was created to minimize confounding, by excluding datasets showing significant airflow limitation and abnormally high values of carboxy haemoglobin (COHb), the latter indicating recent smoking. The capacity of serum lysozyme to correctly identify abnormally low values of DL,CO (i.e. <1 center dot 9SD units), tended to be higher than that of Myeloperoxidase as assessed by analyses of receiver operated curves (ROC; AUC 0 center dot 81, 95%CI: 0 center dot 690 center dot 89 versus AUC 0 center dot 67, 95%CI: 0 center dot 600 center dot 81). It is concluded that serum levels of lysozyme, reflecting mainly activated monocytes/macrophages but also neutrophils, were significantly associated with isolated decrements of DL,CO in smokers with normal lung function tests. This suggests monocytes/macrophages to have a significant mechanistic role in early phases of the disease process and/or pulmonary microvascular damage.

  • 207.
    Schultze, Björn
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Lind, Monica P
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Whole blood and serum concentrations of metals in a Swedish population-based sample2014Inngår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 74, nr 2, s. 143-148Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 208.
    Shahana, Shahida
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Björnsson, Eythor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lungmedicin och allergologi.
    Ludviksdottir, Dora
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lungmedicin och allergologi.
    Janson, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lungmedicin och allergologi.
    Nettelbladt, Otto
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lungmedicin och allergologi.
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Roomans, Godfried M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Ultrastructure of bronchial biopsies from patients with allergic and non-allergic asthma2005Inngår i: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 99, nr 4, s. 429-443Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Epithelial damage is commonly found in airways of asthma patients. The aim of this study was to investigate epithelial damage in allergic and non-allergic asthma at the ultrastructural level.

    Bronchial biopsies obtained from patients with allergic asthma (n=11n=11), non-allergic asthma (n=7n=7), and healthy controls (n=5n=5) were studied by transmission electron microscopy.

    Epithelial damage was found to be extensive in both asthma groups. Both in basal and in columnar cells, relative desmosome length was reduced by 30–40%. In columnar cells, half-desmosomes (i.e., desmosomes of which only one side was present) were frequently noticed. Eosinophils showing piece-meal degranulation were commonly observed in allergic asthma. Degranulating mast cells were more often observed in allergic asthma. Goblet cell hyperplasia was only found in allergic asthma. Lymphocytes were increased in both groups. In both groups, the lamina densa of the basal lamina was thicker than the control by about 40–50%. In allergic asthma the lamina densa was irregular with focal thickening.

    While there was always a tendency for changes (epithelial damage, desmosomes, degranulating mast cells, basal lamina) to be more extensive in allergic asthma compared to non-allergic asthma, there was no significant difference between the two groups in this respect. Reduced desmosomal contact may be an important factor in the epithelial shedding observed in patients with asthma.

  • 209.
    Simm, Mikael
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Söderberg, Ewa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Castegren, Markus
    Department of Anaesthesia, Intensive Care & Surgical Services, Karolinska University Hospital, Huddinge, Stockholm, Sweden..
    Nilsen, Tom
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Performance of plasma calprotectin as a biomarker of early sepsis: a pilot study2016Inngår i: Biomarkers in Medicine, ISSN 1752-0363, E-ISSN 1752-0371, Vol. 10, nr 8, s. 811-818Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 210. Sjöberg, B
    et al.
    Qureshi, A R
    Heimbürger, O
    Stenvinkel, P
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Bárány, P
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Association between levels of pentraxin 3 and incidence of chronic kidney disease in the elderly2016Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 279, nr 2, s. 173-179Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 211.
    Skorup, Paul
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Maudsdotter, Lisa
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Jonsson, Ann-Beth
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Beneficial Antimicrobial Effect of the Addition of an Aminoglycoside to a β-Lactam Antibiotic in an E. coli Porcine Intensive Care Severe Sepsis Model.2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 2, s. e90441-Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 212. Smith, Margaretha E.
    et al.
    Bozinovski, Steven
    Malmhall, Carina
    Sjostrand, Margareta
    Glader, Pernilla
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Hiemstra, Pieter S.
    Anderson, Gary P.
    Linden, Anders
    Qvarfordt, Ingemar
    Increase in Net Activity of Serine Proteinases but Not Gelatinases after Local Endotoxin Exposure in the Peripheral Airways of Healthy Subjects2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 9, s. e75032-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We tested the hypothesis that activation of the innate immune response induces an imbalance in the proteolytic homeostasis in the peripheral airways of healthy subjects, towards excess serine or gelatinase proteinase activity. During bronchoscopy, 18 healthy human subjects underwent intra-bronchial exposure to endotoxin and contra-lateral exposure to vehicle. Bronchoalveolar lavage (BAL) samples were harvested 24 or 48 hours (h) later. We quantified archetype proteinases, anti-proteinases, inflammatory BAL cells, and, importantly, total plus net proteinase activities using functional substrate assays. As expected, endotoxin exposure increased the concentrations of polymorphonuclear leukocytes (PMN's) and macrophages, of proteinases and the anti-proteinases tissue inhibitor of metalloproteinase-1, alpha-1-antitrypsin and, to a lesser extent, secretory leukoproteinase inhibitor, at both time points. Notably, at these time points, endotoxin exposure substantially increased the quantitative NE/SLPI ratio and the net serine proteinase activity corresponding to neutrophil elastase (NE). Endotoxin exposure also increased the total gelatinase activity corresponding to matrix metalloproteinase (MMP)-9; an activity dominating over that of MMP-2. However, endotoxin exposure had no impact on net gelatinolytic activity at 24 or 48 h after exposure. Thus, local activation of the innate immune response induces an imbalance towards increased net serine proteinase activity in the proteolytic homeostasis of the peripheral airways in healthy subjects. Hypothetically, this serine proteinase activity can contribute to tissue remodelling and hypersecretion via NE from PMN's, if it is triggered repeatedly, as might be the case in chronic inflammatory airway disorders.

  • 213.
    Sperber, Jesper
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, 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 sepsis2015Inngår i: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 15, artikkel-id 60Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 214.
    Sperber, Jesper
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, 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 sepsis2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 12, s. e83182-Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 215.
    Sperber, Jesper
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Nyberg, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, 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 PneumoniaManuskript (preprint) (Annet vitenskapelig)
  • 216.
    Sperber, Jesper
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Nyberg, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Melhus, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi och infektionsmedicin.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Protective Ventilation Reduces Pseudomonas Aeruginosa Growth in a Porcine Pneumonia ModelManuskript (preprint) (Annet vitenskapelig)
  • 217.
    Sperber, Jesper
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Melhus, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. 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 model2017Inngår i: Intensive & Critical Care Nursing, ISSN 0964-3397, E-ISSN 1532-4036, Vol. 5, artikkel-id 40Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 218.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med, Huddinge, Sweden.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. 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 humans2017Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikkel-id 43538Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 219.
    Strandberg, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Gustafsson, Mats G
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Analysis of intraosseous samples using point of care technology: an experimental study in the anaesthetised pig2012Inngår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 83, nr 11, s. 1381-1385Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 220.
    Strandberg, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklos
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Intraosseous Samples Can Be Used for CreatinineMeasurements - An Experimental Study in the Anaesthetised Pig2014Inngår i: Clinical Laboratory, ISSN 1433-6510, Vol. 60, nr 10, s. 1587-1591Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 221.
    Strandberg, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lipcsey, Miklos
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Analysis of intraosseous samples in endotoxemic shock: an experimental study in the anaesthetised pig2014Inngår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, nr 3, s. 337-344Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 222.
    Strandberg, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lipcsey, Miklos
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Intraosseous blood aspirates analysed by a portable cartridge-based device2011Inngår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 15, nr Suppl 1, s. 49-49Artikkel i tidsskrift (Fagfellevurdert)
  • 223.
    Strandberg, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lipcsey, Miklos
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Michalek, J
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Intraosseous and intravenous administration of antibiotics yields comparable plasma concentrations during experimental septic shock2015Inngår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 59, nr 3, s. 346-353Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 224.
    Strandberg, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Eriksson, Mats B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lubenow, Norbert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Analysis of Thromboelastography, PT, APTT and Fibrinogen in Intraosseous and Venous Samples: An Experimental Study2016Inngår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 24, artikkel-id 131Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 225.
    Stålhammar, Maria E.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Douhan Håkansson, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sindelar, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Bacterial N-formyl Peptides Reduce PMA and Escherichia coli-Induced Neutrophil Respiratory Burst in Term Neonates and Adults2017Inngår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 85, nr 5, s. 365-371Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neutrophil migration and respiratory burst is the prerequisite for efficient first line defense against invading microorganisms. However, migration and respiratory burst can be compromised in adults and especially in newborn infants, where sustained neutrophil accumulation, uncontrolled burst and reduced scavenging of ROS might cause inadvertent tissue damage due to uncontrolled inflammation. The aim of this study was to investigate the modulatory effect of the chemoattractants formyl-methionyl-leucyl-phenylalanine (fMLP) and IL-8 on respiratory burst in neutrophils from term newborn infants and adults. Whole blood from the umbilical cord of 17 healthy term newborn infants delivered by caesarean section and from 17 healthy adults as reference was preincubated with fMLP or IL-8 and stimulated with PMA or E.coli bacteria. Respiratory burst was quantified by flow cytometry analysis of dihydrorhodamine 123 fluorescence. fMLP reduced the PMA-induced respiratory burst of neutrophils from newborn infants and adults by 12% and 21% respectively (p<0.05). E.coli-induced burst was also reduced by fMLP in neutrophils from newborn infants (10%; p<0.01) and adults (6%; p<0.05). No such changes were observed with IL-8. Similar respiratory burst in response to single stimulus with PMA or E.coli were observed in both newborn infants and adults. fMLP reduced PMA- and E.coli-induced respiratory burst of neutrophils in whole blood from term newborn infants as well as in adults. The reduced respiratory burst by fMLP might be a mechanism to reduce the detrimental effects of uncontrolled inflammation during neutrophil migration

  • 226.
    Svennberg, Emma
    et al.
    Danderyds Univ Hosp, Karolinska Inst, Dept Clin Sci, Cardiol Unit, Stockholm, Sweden.
    Lindahl, Bertil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Eggers, Kai M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Med Prod Agcy, Sci Support, Uppsala, Sweden.
    Rosenqvist, Mårten
    Danderyds Univ Hosp, Karolinska Inst, Dept Clin Sci, Cardiol Unit, Stockholm, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Hijazi, Ziad
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    NT-proBNP is a powerful predictor for incident atrial fibrillation: Validation of a multimarker approach2016Inngår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 223, s. 74-81Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Biomarkers may be of value to identify individuals at risk of developing atrial fibrillation (AF). Using a multimarker approach, this study investigated if the biomarkers; NT-proBNP, high-sensitivity cardiac troponin (hs-cTn), growth differentiation factor-15 (GDF-15), cystatin C and high-sensitivity C-reactive protein (CRP) are independent predictors for incident AF.

    METHODS: Blood samples were collected from 883 individuals in the Uppsala Longitudinal Study of Adult Men (ULSAM) and 978 individuals in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Participants were followed for 10-13years with n=113 incident AF cases in ULSAM and n=148 in PIVUS. The associations between biomarkers and incident AF were analysed in Cox proportional hazards regression models.

    RESULTS: The hazard ratio (HR) for incident AF was significant for all five biomarkers in unadjusted analyses in both cohorts. Only NT-proBNP remained significant when adjusting for cardiovascular risk factors and the other biomarkers (HR (1SD) 2.05 (1.62-2.59) (ULSAM) and 1.56 (1.30-1.86) (PIVUS), both p<0.001). The C-index improved from 0.64 to 0.69 in ULSAM and from 0.62 to 0.68 in PIVUS, by adding NT-proBNP to cardiovascular risk factors (both p<0.001). The C-index of the CHARGE-AF risk score increased from 0.62 to 0.68 (ULSAM) and 0.60 to 0.66 (PIVUS) by addition of NT-proBNP (p<0.001).

    CONCLUSIONS: Using a multimarker approach NT-proBNP was the strongest predictor of incident AF in two cohorts, and improved risk prediction when added to traditional risk factors. NT-proBNP significantly improved the predictive ability of the novel CHARGE-AF risk score, although the predictive value remained modest.

  • 227.
    Svennerholm, Kristina
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Anesthesiol & Intens Care Med, Gothenburg, Sweden..
    Rodsand, Pouria
    Umea Univ, Inst Surg & Perioperat Sci, Anesthesiol & Intens Care Med, Umea, Sweden..
    Hellman, Urban
    Umea Univ, Cardiol, Inst Heart Ctr, Umea, Sweden.;Umea Univ, Dept Publ Hlth & Clin Med, Med, Umea, Sweden..
    Waldenstrom, Anders
    Umea Univ, Cardiol, Inst Heart Ctr, Umea, Sweden.;Umea Univ, Dept Publ Hlth & Clin Med, Med, Umea, Sweden..
    Lundholm, Marie
    Umea Univ, Inst Med Biosci, Pathol, Umea, Sweden..
    Ahren, Dag
    Lund Univ, Inst Biol, Natl Bioinformat Infrastruct Sweden, Lund, Sweden..
    Biber, Bjorn
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Anesthesiol & Intens Care Med, Gothenburg, Sweden..
    Ronquist, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Haney, Michael
    Umea Univ, Inst Surg & Perioperat Sci, Anesthesiol & Intens Care Med, Umea, Sweden..
    DNA Content in Extracellular Vesicles Isolated from Porcine Coronary Venous Blood Directly after Myocardial Ischemic Preconditioning2016Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 7, artikkel-id e0159105Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Extracellular vesicles (EV) are nano-sized membranous structures released from most cells. They have the capacity to carry bioactive molecules and gene expression signals between cells, thus mediating intercellular communication. It is believed that EV confer protection after ischemic preconditioning (IPC). We hypothesize that myocardial ischemic preconditioning will lead to rapid alteration of EV DNA content in EV collected from coronary venous effluent. Materials and Methods In a porcine myocardial ischemic preconditioning model, EV were isolated from coronary venous blood before and after IPC by differential centrifugation steps culminating in preparative ultracentrifugation combined with density gradient ultracentrifugation. The EV preparation was validated, the DNA was extracted and further characterized by DNA sequencing followed by bioinformatics analysis. Results Porcine genomic DNA fragments representing each chromosome, including mitochondrial DNA sequences, were detected in EV isolated before and after IPC. There was no difference detected in the number of sequenced gene fragments (reads) or in the genomic coverage of the sequenced DNA fragments in EV isolated before and after IPC. Gene ontology analysis showed an enrichment of genes coding for ion channels, enzymes and proteins for basal metabolism and vesicle biogenesis and specific cardiac proteins. Conclusions This study demonstrates that porcine EV isolated from coronary venous blood plasma contain fragments of DNA from the entire genome, including the mitochondria. In this model we did not find specific qualitative or quantitative changes of the DNA content in EV collected immediately after an in vivo myocardial IPC provocation. This does not rule out the possibility that EV DNA content changes in response to myocardial IPC which could occur in a later time frame.

  • 228.
    Sylvén, Sara M
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Elenis, Evangelia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Michelakos, Theodoros
    Department of Hygiene and Epidemiology, Athens Medical School, Athens, Greece.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Sundström Poromaa, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Skalkidou, Alkistis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Thyroid function tests at delivery and risk for postpartum depressive symptoms2013Inngår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 38, nr 7, s. 1007-1013Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 229.
    Söderberg, Ewa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Eriksson, Mats B
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    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-62012Inngår i: Steroids, ISSN 0039-128X, E-ISSN 1878-5867, Vol. 77, nr 11, s. 1101-1106Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 230.
    Thorsteinsdottir, Ingunn
    et al.
    Iceland Heart Assoc, Res Inst, Kopavogur, Iceland.;Landspitali Univ Hosp, Dept Clin Biochem, Reykjavik, Iceland..
    Aspelund, Thor
    Iceland Heart Assoc, Res Inst, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Gudmundsson, Elias
    Iceland Heart Assoc, Res Inst, Kopavogur, Iceland..
    Eiriksdottir, Gudny
    Iceland Heart Assoc, Res Inst, Kopavogur, Iceland..
    Harris, Tamara B.
    NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA..
    Launer, Lenore J.
    NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA..
    Gudnason, Vilmundur
    Iceland Heart Assoc, Res Inst, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    High-Sensitivity Cardiac Troponin I Is a Strong Predictor of Cardiovascular Events and Mortality in the AGES-Reykjavik Community-Based Cohort of Older Individuals2016Inngår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 62, nr 4, s. 623-630Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The objective of this study was to investigate the predictive power of a high-sensitivity cardiac troponin I (hs-cTnI) assay for cardiovascular events and mortality in a large population of older community dwellers.

    METHODS: Blood was collected from 5764 individuals (age 66-98 years) during the period of 2002-2006 and the outcome as to all-cause death and incidence of cardiovascular disease (CVD) and coronary heart disease (CHD) followed up to 10 years. hs-cTnI (Abbott) was measured in serum to assess the association of this marker with CVD, CHD and death, and finally, to compare the results with conventional risk factors by multivariable statistical analysis.

    RESULTS: The median (interquartile range) concentrations of hs-cTnI were 8.4 ng/L (5.6-14.2 ng/L) and 5.3 ng/L (3.8-8.1 ng/L) in men (2416) and women (3275), respectively, and the concentrations increased linearly with age. Outcomes as to all-cause death and incidence of CVD and CHD were significantly associated with increasing concentrations of hs-cTnI beginning well below the 99th percentile concentrations. The associations with outcome remained after adjustments for conventional risk factors and were similar in men and women.

    CONCLUSIONS: Our findings suggest that hs-cTnI reflects the status of the myocardium even in seemingly healthy individuals and that the measurements of hs-cTnI may be useful for primary prediction of heart disease; this should form the basis for future prospective clinical trials for determining whether measuring hs-cTnI can be used in the prevention of CVD/CHD.

  • 231. Ticinesi, Andrea
    et al.
    Lauretani, Fulvio
    Ceda, Gian Paolo
    Ruggiero, Carmelinda
    Ferrucci, Luigi
    Aloe, Rosalia
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Meschi, Tiziana
    Maggio, Marcello
    Uric acid and endothelial function in elderly community-dwelling subjects2017Inngår i: Experimental Gerontology, ISSN 0531-5565, E-ISSN 1873-6815, Vol. 89, s. 57-63Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 232.
    Tonkonogi, Aleksandra
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Carlsson, Axel C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med, Huddinge, Sweden.
    Helmersson-Karlqvist, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Associations between urinary kidney injury biomarkers and cardiovascular mortality risk in elderly men with diabetes2016Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, nr 3, s. 174-178Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM: Three urinary biomarkers, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin C, have been suggested as clinically relevant highly specific biomarkers of acute kidney tubular damage. Yet, the utility of these biomarkers in the prognostication of diabetic nephropathy has been less studied. Therefore, we aimed to investigate the longitudinal association between these urinary biomarkers and cardiovascular mortality in patients with diabetes.

    METHODS: The study sample consisted of participants with diabetes in the community-based Uppsala Longitudinal Study of Adult Men (n = 91; mean age 77.8 years). During follow-up (median 8.3 years, interval 0.7-13.4 years), 33 participants died of cardiovascular causes.

    RESULTS: In a multivariable Cox regression model adjusting for age, glomerular filtration rate, and urinary albumin/creatinine ratio, higher urinary KIM-1/creatinine was associated with an increased risk for cardiovascular mortality (HR per SD increase 1.51, 95% confidence intervals 1.03-2.24, P = 0.03). Neither urinary NGAL/creatinine nor urinary cystatin C/creatinine were independently associated with an increased cardiovascular mortality risk.

    CONCLUSION: In elderly men with diabetes, higher urinary KIM-1/creatinine was associated with an increased long-term risk of cardiovascular mortality independently of established markers of diabetic nephropathy. Our data provide support for kidney tubular damage as an important aspect of diabetic nephropathy that merits further investigation.

  • 233.
    Vahlquist, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Dermatologi och venereologi.
    Håkansson, Lena Douhan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Karawajczyk, Malgorzata
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Fasth, Anders
    van Gijn, Marielle E.
    Roos, Dirk
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Recurrent Pyoderma Gangrenosum and Cystic Acne Associated with Leucocyte Adhesion Deficiency due to Novel Mutations in ITGB2: Successful Treatment with Infliximab and Adalimumab2015Inngår i: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 95, nr 3, s. 349-351Artikkel i tidsskrift (Fagfellevurdert)
  • 234.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    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 Study2016Inngår i: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 68, nr 9, s. 934-945Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 235.
    Venge, Per
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Douhan Håkansson, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Garwicz, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Peterson, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Xu, Shengyuan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Pauksen, Karlis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Human Neutrophil Lipocalin as a Superior Diagnostic Means To Distinguish between Acute Bacterial and Viral Infections2015Inngår i: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 22, nr 9, s. 1025-1032Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The distinction between causes of acute infections is a major clinical challenge. Current biomarkers, however, are not sufficiently accurate. Human neutrophil lipocalin (HNL) concentrations in serum or whole blood activated by formyl-methionine-leucine-phenylalanine (fMLP) were shown to distinguish acute infections of bacterial or viral cause with high accuracy. The aim was therefore to compare the clinical performance of HNL with currently used biomarkers. Seven hundred twenty-five subjects (144 healthy controls and 581 patients with signs and symptoms of acute infections) were included in the study. C-reactive protein (CRP), the expression of CD64 on neutrophils, procalcitonin (PCT), and blood neutrophil counts were measured by established techniques, and HNL concentrations were measured in whole-blood samples after activation with fMLP. All tested biomarkers were elevated in bacterial as opposed to viral infections (P<0.001). CRP, PCT, and CD64 expression in neutrophils was elevated in viral infections compared to healthy controls (P<0.001). In the distinction between healthy controls and patients with bacterial infections, the areas under the receiver operating characteristic (ROC) curves were >0.85 for all biomarkers, whereas for the distinction between bacterial and viral infections, only HNL concentration in fMLP-activated whole blood showed an area under the ROC curve (AUROC) of >0.90 and superior clinical performance. The clinical performance of HNL in fMLP-activated whole blood was superior to current biomarkers and similar to previous results of HNL in serum. The procedure can be adopted for point-of-care testing with response times of <15 min.

  • 236.
    Venge, Per
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Douhan, Lena Håkansson
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Garwicz, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Peterson, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Xu, Shengyuan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Pauksen, Karlis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Human neutrophil lipocalin in fMLP-activated whole blood as a diagnostic means to distinguish between acute bacterial and viral infections2015Inngår i: JIM - Journal of Immunological Methods, ISSN 0022-1759, E-ISSN 1872-7905, Vol. 424, s. 85-90Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The distinction between causes of acute infections is a major clinical challenge. Current biomarkers, however, are not sufficiently accurate. Human neutrophil lipocalin (HNL) in serum distinguishes acute infections with high accuracy, but in the emergency setting the assay time should be <15-20 min, which excludes the use of serum samples. The aim was therefore to develop a novel rapid assay principle and test its clinical performance. Methods: Serum and neutrophils obtained from 84 infected and 20 healthy subjects were used in the experimental study. 725 subjects (144 healthy controls and 581 patients with signs and symptoms of acute infections) were included in the clinical study. HNL was measured in EDTA-plasma by ELISA or in heparinized whole blood after fMLP activation by a prototype point-of-care assay. Results: Increased release of HNL from neutrophils after activation with fMLP was seen already after 5 min incubation. The release of HNL from purified neutrophils after 15 min incubation with fMLP was significantly correlated to the HNL concentrations in serum obtained from the same patient (r = 0.74, p < 0.001). In the distinction between healthy controls and patients with bacterial infections, the areas under the ROC-curves were 0.95 (95% CI 0.91-0.97) and 0.88 (95% CI 0.84-0.91) for HNL in fMLP-activated whole blood and EDTA-plasma, respectively, (p <0.001) and in the distinction between bacterial and viral infections 0.91 (95% CI 0.86-0.95) and 0.76 (95% CI 0.70-0.81), respectively (p <0.001). Conclusion: The clinical performance of HNL in fMLP-activated whole blood was superior to HNL in EDTA-plasma and similar to HNL in serum. The procedure can be adopted for point-of-care testing with response times of <15 min.

  • 237.
    Venge, Per
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lindahl, Bertil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Cardiac Troponin Assay Classification by Both Clinical and Analytical Performance Characteristics: A Study on Outcome Prediction2013Inngår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 59, nr 6, s. 976-981Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Cardiac troponin assays have been classified according to whether they measure the 99th percentile concentration of a healthy reference population with imprecision (expressed as CV) of <= 10%, between 10% and 20%, or >20%. Assays in these categories have been deemed "guideline acceptable," "clinically usable," or not acceptable," respectively. We compared four widely used "clinically usable" cardiac troponin I (cTnI) assays with an assay designated "not acceptable" for accuracy in predicting the clinical outcome of death. METHODS: Blood was collected from 259 men and 249 women, mean (SD) age 68.8 (17.8) and 70.2 (17.8) years, respectively, admitted to the emergency department for suspected myocardial infarction. We measured cTnI by the Access, Architect, i-Stat, Stratus CS, and VIDAS assays. Deaths in this population were recorded over a 31-month period. RESULTS: We found VIDAS cTnI assay measurement CVs of 10% and 20% at concentrations of 0.04 and 0.02 mu g/L, respectively. Comparing at the 10% CV cutoff concentration, VIDAS cTnI was less sensitive than the Access and Architect assays (P < 0.001) but more sensitive than i-Stat (P < 0.001) and Stratus CS (P < 0.001) in identifying patients with poor outcomes. At the 20% CV cutoff, the VIDAS assay was equivalent to the other assays in identifying patients with poor outcomes. CONCLUSIONS: For outcome prediction, the VIDAS cTnI assay was clinically equivalent or superior to other cTnI assays judged to be acceptable from a pure analytical standpoint. Thus, comparison of cardiac troponin assays should consider not only ana-lytical performance, but also clinical performance characteristics.

  • 238. Vilhelmsdotter Allander, Susanne
    et al.
    Marké, Lars-Åke
    Wihlen, Björn
    Svensson, Maria
    Elinder, Carl-Gustaf
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Regional variation in use of exogenous and endogenous glomerular filtration rate (GFR) markers in Sweden2012Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, nr 3, s. 273-278Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 239.
    von Seth, Magnus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Engström, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Maripuu, Enn
    Department of Medical Physics, University Hospital, Uppsala, Sweden.
    Widström, Charles
    Department of Medical Physics, University Hospital, Uppsala, Sweden.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Rapid Bolus Administration Does Not Increase the Extravasation Rate of Albumin: A Randomized Controlled Trial in the Endotoxemic Pig2017Inngår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 47, nr 4, s. 514-519Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 240.
    von Seth, Magnus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Effects of Tigecycline and Doxycycline on Inflammation and Hemodynamics in Porcine Endotoxemia: a Prospective, Randomized and Placebo Controlled Trial2015Inngår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 43, nr 6, s. 604-611Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 241.
    Wadelius, Mia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Marshall, S. E.
    Islander, G.
    Nordang, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Karawajczyk, Malgorzata
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Yue, Q-Y
    Terreehorst, I.
    Baranova, E. V.
    Hugosson, S.
    Skoldefors, K.
    Pirmohamed, M.
    Maitland-van der Zee, A-H
    Alfirevic, A.
    Hallberg, Pär
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Palmer, C. N. A.
    Phenotype Standardization of Angioedema in the Head and Neck Region Caused by Agents Acting on the Angiotensin System2014Inngår i: Clinical Pharmacology and Therapeutics, ISSN 0009-9236, E-ISSN 1532-6535, Vol. 96, nr 4, s. 477-481Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Angioedema is a potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. To study the genetic etiology of this rare adverse event, international consortia and multicenter recruitment of patients are needed. To reduce patient heterogeneity, we have standardized the phenotype. In brief, it comprises swelling in the head and neck region that first occurs during treatment. It should not coincide with urticaria or have another likely cause such as hereditary angioedema.

  • 242. Waikar, Sushrut S
    et al.
    Sabbisetti, Venkata
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Carlsson, Axel C
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Coresh, Josef
    Feldman, Harold I
    Foster, Meredith C
    Fufaa, Gudeta D
    Helmersson-Karlqvist, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Hsu, Chi-Yuan
    Kimmel, Paul L
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Liu, Yumin
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Liu, Kathleen D
    Mifflin, Theodore E
    Nelson, Robert G
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och 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 studies2016Inngår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 31, nr 9, s. 1460-1470Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 243.
    Wallentin, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Lindhagen, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Ärnström, Elisabet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Husted, Steen
    Hosp Unit West, Dept Med, Herning Holstebro, Denmark..
    Janzon, Magnus
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.;Linkoping Univ, Div Hlth Care Anal, Dept Med & Hlth Sci, Ctr Med Technol Assessment, Linkoping, Sweden..
    Johnsen, Sören Paaske
    Aarhus Univ Hosp, Dept Clin Epidemiol, Aarhus, Denmark..
    Kontny, Frederic
    Stavanger Univ Hosp, Dept Cardiol, Stavanger, Norway.;Drammen Heart Ctr, Drammen, Norway..
    Kempf, Tibor
    Hannover Med Sch, Dept Cardiol & Angiol, Hannover, Germany..
    Levin, Lars-Åke
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.;Linkoping Univ, Div Hlth Care Anal, Dept Med & Hlth Sci, Ctr Med Technol Assessment, Linkoping, Sweden..
    Lindahl, Bertil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Stridsberg, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk endokrinologi.
    Ståhle, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Thoraxkirurgi.
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Wollert, Kai C.
    Hannover Med Sch, Dept Cardiol & Angiol, Hannover, Germany..
    Swahn, Eva
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Lagerqvist, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Early invasive versus non-invasive treatment in patients with non-ST-elevation acute coronary syndrome (FRISC-II): 15 year follow-up of a prospective, randomised, multicentre study2016Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 388, nr 10054, s. 1903-1911Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background The FRISC-II trial was the first randomised trial to show a reduction in death or myocardial infarction with an early invasive versus a non-invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome. Here we provide a remaining lifetime perspective on the effects on all cardiovascular events during 15 years' follow-up. Methods The FRISC-II prospective, randomised, multicentre trial was done at 58 Scandinavian centres in Sweden, Denmark, and Norway. Between June 17, 1996, and Aug 28, 1998, we randomly assigned (1:1) 2457 patients with non-ST-elevation acute coronary syndrome to an early invasive treatment strategy, aiming for revascularisation within 7 days, or a non-invasive strategy, with invasive procedures at recurrent symptoms or severe exercise-induced ischaemia. Plasma for biomarker analyses was obtained at randomisation. For long-term outcomes, we linked data with national health-care registers. The primary endpoint was a composite of death or myocardial infarction. Outcomes were compared as the average postponement of the next event, including recurrent events, calculated as the area between mean cumulative count-of-events curves. Analyses were done by intention to treat. Findings At a minimum of 15 years' follow-up on Dec 31, 2014, data for survival status and death were available for 2421 (99%) of the initially recruited 2457 patients, and for other events after 2 years for 2182 (89%) patients. During follow-up, the invasive strategy postponed death or next myocardial infarction by a mean of 549 days (95% CI 204-888; p= 0.0020) compared with the non-invasive strategy. This effect was larger in non-smokers (mean gain 809 days, 95% CI 402-1175; p(interaction) = 0.0182), patients with elevated troponin T (778 days, 357-1165; p (interaction) = 0.0241), and patients with high concentrations of growth differentiation factor-15 (1356 days, 507-1650; p (interaction) = 0.0210). The difference was mainly driven by postponement of new myocardial infarction, whereas the early difference in mortality alone was not sustained over time. The invasive strategy led to a mean of 1128 days (95% CI 830-1366) postponement of death or next readmission to hospital for ischaemic heart disease, which was consistent in all subgroups (p< 0.0001). Interpretation During 15 years of follow-up, an early invasive treatment strategy postponed the occurrence of death or next myocardial infarction by an average of 18 months, and the next readmission to hospital for ischaemic heart disease by 37 months, compared with a non-invasive strategy in patients with non-ST-elevation acute coronary syndrome. This remaining lifetime perspective supports that an early invasive treatment strategy should be the preferred option in most patients with non-ST-elevation acute coronary syndrome.

  • 244. Wallin, S.
    et al.
    Hardie, L. J.
    Kotova, N.
    Warensjö-Lemming, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Nalsen, C.
    Ridefelt, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Turner, P. C.
    White, K. L. M.
    Olsen, M.
    Biomonitoring study of deoxynivalenol exposure and association with typical cereal consumption in Swedish adults2013Inngår i: World Mycotoxin Journal, ISSN 1875-0710, E-ISSN 1875-0796, Vol. 6, nr 4, s. 439-448Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Deoxynivalenol (DON) is a mycotoxin of the trichothecene family commonly found in cereals infested with different Fusarium species. DON acts primarily on the gastrointestinal and immune system and is suspected to be an underlying agent causing several outbreaks of gastrointestinal disorder among humans, which prompts studies of human exposure and estimations of intake among populations. However, assessing human exposure to mycotoxins is associated with several difficulties. Therefore, a study was undertaken among adults (18-80 years) in a subgroup of Riksmaten, the Swedish national survey investigating dietary habits, examining both the association between urinary DON concentration and dietary intake of cereals, and estimations of daily DON intake. The results indicate that exposure to DON is common among Swedish adults, as this mycotoxin was detected in 292 out of 326 urine samples (90%) at levels ranging from non-detectable to 65.8 ng DON/mI urine with a median level of 2.9 ng/ml. Furthermore, urinary DON (ng/mg creatinine) was associated with intake (g/day) of total cereal grain as well as whole grain. Urinary DON was also significantly associated with breakfast cereals and porridge consumption (P<0.05). Estimated DON intake in this study ranged between 2.5 and 5,443 ng/kg body weight (bw). 1% of the individuals had estimated intakes above the group provisional maximum tolerable daily intake (PMTDI; 1 mu g/kg), whereas the mean and median intakes of 159 and 84 ng DON/kg bw, respectively, were considerably below the PMTDI. Along with the toxicological profile of DON, no serious health implications are to be expected for the majority of Swedish adults, although a potential health concern remains for some high cereal consumers. In conclusion, biomonitoring could prove to be a valuable tool for observing DON exposure among populations.

  • 245.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    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 20152016Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 388, nr 10053, s. 1725-1774Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 246. 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    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 20132014Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 384, nr 9947, s. 957-979Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 247.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    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..
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    Finnish Inst Occupat Hlth, Work Org, Work Disabil Prevent, Helsinki, Finland..
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    Feinberg Sch Med, Chicago, IL USA..
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    Int Inst Populat Sci, Mumbai, Maharashtra, India..
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    Tufts Univ, Boston, MA 02111 USA..
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    Univ Alabama Birmingham, Birmingham, AL USA..
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    Banaras Hindu Univ, Inst Med Sci, Dept Med, Varanasi, Uttar Pradesh, India..
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    Inst Human Dev, New Delhi, India..
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    Asthma Bhawan, Jaipur, Rajasthan, India..
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    Dartmouth Coll, Hanover, NH USA..
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    Stavanger Univ Hosp, Stavanger, Norway..
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    Univ Calif San Diego, San Diego, CA 92103 USA..
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    Luxembourg Inst Hlth, Luxembourg, Luxembourg..
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    Alexandra Gen Hosp Athens, Athens, Greece.;Ctr Hosp Publ Cotentin, Cherbourg, France..
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    Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania..
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    Inst Hlth Metr & Evaluat, Seattle, WA USA..
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    Indian Council Med Res, New Delhi, India..
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    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..
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    Inst Hlth & Ageing, Melbourne, Vic, Australia..
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    Univ Valencia, Dept Med, INCLIVA Hlth Res Inst & CIBERSAM, Valencia, Spain..
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    WSH Inst, Minist Manpower, Singapore, Singapore.;Tampere Univ Technol, Tampere, Finland..
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    Minist Hlth, MINSANTE, Yaounde, Cameroon..
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    All India Inst Med Sci, New Delhi, India..
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    New York Med Coll, Valhalla, NY USA..
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    Colgate Univ, Dept Biol, Hamilton, NY USA..
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    Univ Melbourne, Melbourne, Vic, Australia..
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    Auckland Univ Technol, Auckland, New Zealand..
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    Univ Gondar, Gondar, Ethiopia.;James Cook Univ, Cairns, Qld, Australia..
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    Univ Addis Ababa, Addis Ababa, Ethiopia.;Addis Ababa City Govt, Addis Ababa, Ethiopia..
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    Netherlands Inst Mental Hlth & Addict, Utrecht, Netherlands..
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    King Fahad Med City, Dept Anesthesiol, Riyadh, Saudi Arabia.;Univ Virginia, Dept Anesthesiol, Charlottesville, VA USA.;Outcomes Res Consortium, Cleveland, OH USA..
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    Coll Hlth Sci, Mekelle, Ethiopia.;Flinders Univ S Australia, Adelaide, SA, Australia..
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    Univ Adelaide, Adelaide, SA, Australia.;Univ Gondar, Gondar, Ethiopia..
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    Adapt Knowledge Management, Victoria, BC, Canada..
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    WorldFish, George Town, Malaysia..
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    Monash Univ, Sch Clin Sci Monash Hlth, Dept Med, Melbourne, Vic, Australia..
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    New York Univ, Nelson Inst Environm Med, Sch Med, Tuxedo Pk, NY USA..
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    UCL, Dept Epidemiol & Publ Hlth, London, England..
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    Univ Washington, Seattle, WA 98195 USA..
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    Univ Calgary, Calgary, AB, Canada..
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    Jagiellonian Univ Med Coll, Inst Publ Hlth, Fac Hlth Sci, Krakow, Poland.;Wroclaw Med Univ, Fac Hlth Sci, Wroclaw, Poland..
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    Aristotle Univ Thessaloniki, Thessaloniki, Greece..
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    Bonheur Childrens Hosp Memphis, Memphis, TN USA.;Univ Tennessee Hlth Sci Ctr, Memphis, TN USA.;St Jude Childrens Res Hosp, Memphis, TN USA..
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    Univ Southern Santa Catarina, Palhoca, Brazil..
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    Johns Hopkins Univ, Baltimore, MD USA.;Hanoi Med Univ, Hanoi, Vietnam..
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    Univ Copenhagen, Dept Neurol, Rigshosp, Copenhagen, Denmark..
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    Serv Canario Salud, Santa Cruz de La Palma, CA, Spain..
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    Cleveland Clin, Cleveland, OH USA..
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    Dept Vet Affairs, Washington, DC USA..
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    Ctr Youth Mental Hlth, Melbourne, Vic, Australia.;VHS SNEHA, Chennai, Tamil Nadu, India..
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    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
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    Univ Bologna, Bologna, Italy..
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    Natl Res Univ, Higher Sch Econ, Moscow, Russia..
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    Natl Ctr Chron & Noncommunicable Dis Control & Pr, Beijing, Peoples R China..
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    Univ Washington, Seattle, WA 98195 USA.;Univ Cape Town, Cape Town, South Africa..
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    McGill Univ, Montreal, PQ, Canada..
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    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..
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    Murdoch Childrens Res Inst, Melbourne, Vic, Australia.;Univ Melbourne, Melbourne, Vic, Australia.;Royal Childrens Hosp, Melbourne, Vic, Australia..
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    Wayne State Univ, Sch Med, Detroit, MI USA.;Childrens Hosp Michigan, Detroit, MI 48201 USA..
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    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..
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    Jackson State Univ, Jackson, MS USA..
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    Univ Lorraine, Clin Invest Ctr, INSERM, Natl Inst Hlth & Med Res, Vandoeuvre Ies Nancy, France.;CHU Nancy, Vandoeuvre Les Nancy, France..
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    Ponce Hlth Sci Univ, Ponce, PR USA..
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    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 20152016Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 388, nr 10053, s. 1459-1544Artikkel i tidsskrift (Fagfellevurdert)
    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.

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    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
    Hedayati, Mohammad T
    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
    Kosen, Soewarta
    Koul, Parvaiz A
    Koyanagi, Ai
    Defo, Barthelemy Kuate
    Bicer, Burcu Kucuk
    Kulkarni, Veena S
    Kumar, G Anil
    Lal, Dharmesh Kumar
    Lam, Hilton
    Lam, Jennifer O
    Langan, Sinead M
    Lansingh, Van C
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Leigh, James
    Leung, Ricky
    Li, Yongmei
    Lim, Stephen S
    Lipshultz, Steven E
    Liu, Shiwei
    Lloyd, Belinda K
    Logroscino, Giancarlo
    Lotufo, Paulo A
    Lunevicius, Raimundas
    Razek, Hassan Magdy Abd El
    Mahdavi, Mahdi
    Majdan, Marek
    Majeed, Azeem
    Makhlouf, Carla
    Malekzadeh, Reza
    Mapoma, Chabila C
    Marcenes, Wagner
    Martinez-Raga, Jose
    Marzan, Melvin Barrientos
    Masiye, Felix
    Mason-Jones, Amanda J
    Mayosi, Bongani M
    McKee, Martin
    Meaney, Peter A
    Mehndiratta, Man Mohan
    Mekonnen, Alemayehu B
    Melaku, Yohannes Adama
    Memiah, Peter
    Memish, Ziad A
    Mendoza, Walter
    Meretoja, Atte
    Meretoja, Tuomo J
    Mhimbira, Francis Apolinary
    Miller, Ted R
    Mikesell, Joseph
    Mirarefin, Mojde
    Mohammad, Karzan Abdulmuhsin
    Mohammed, Shafiu
    Mokdad, Ali H
    Monasta, Lorenzo
    Moradi-Lakeh, Maziar
    Mori, Rintaro
    Mueller, Ulrich O
    Murimira, Brighton
    Murthy, Gudlavalleti Venkata Satyanarayana
    Naheed, Aliya
    Naldi, Luigi
    Nangia, Vinay
    Nash, Denis
    Nawaz, Haseeb
    Nejjari, Chakib
    Ngalesoni, Frida Namnyak
    de Dieu Ngirabega, Jean
    Nguyen, Quyen Le
    Nisar, Muhammad Imran
    Norheim, Ole F
    Norman, Rosana E
    Nyakarahuka, Luke
    Ogbo, Felix Akpojene
    Oh, In-Hwan
    Ojelabi, Foluke Adetola
    Olusanya, Bolajoko Olubukunola
    Olusanya, Jacob Olusegun
    Opio, John Nelson
    Oren, Eyal
    Ota, Erika
    Padukudru, Mahesh Anand
    Park, Hye-Youn
    Park, Jae-Hyun
    Patil, Snehal T
    Patten, Scott B
    Paul, Vinod K
    Pearson, Katherine
    Peprah, Emmanuel Kwame
    Pereira, Claudia C
    Perico, Norberto
    Pesudovs, Konrad
    Petzold, Max
    Phillips, Michael Robert
    Pillay, Julian David
    Plass, Dietrich
    Polinder, Suzanne
    Pourmalek, Farshad
    Prokop, David M
    Qorbani, Mostafa
    Rafay, Anwar
    Rahimi, Kazem
    Rahimi-Movaghar, Vafa
    Rahman, Mahfuzar
    Rahman, Mohammad Hifz Ur
    Rahman, Sajjad Ur
    Rai, Rajesh Kumar
    Rajsic, Sasa
    Ram, Usha
    Rana, Saleem M
    Rao, Paturi Vishnupriya
    Remuzzi, Giuseppe
    Rojas-Rueda, David
    Ronfani, Luca
    Roshandel, Gholamreza
    Roy, Ambuj
    Ruhago, George Mugambage
    Saeedi, Mohammad Yahya
    Sagar, Rajesh
    Saleh, Muhammad Muhammad
    Sanabria, Juan R
    Santos, Itamar S
    Sarmiento-Suarez, Rodrigo
    Sartorius, Benn
    Sawhney, Monika
    Schutte, Aletta E
    Schwebel, David C
    Seedat, Soraya
    Sepanlou, Sadaf G
    Servan-Mori, Edson E
    Shaikh, Masood Ali
    Sharma, Rajesh
    She, Jun
    Sheikhbahaei, Sara
    Shen, Jiabin
    Shibuya, Kenji
    Shin, Hwashin Hyun
    Sigfusdottir, Inga Dora
    Silpakit, Naris
    Silva, Diego Augusto Santos
    Silveira, Dayane Gabriele Alves
    Simard, Edgar P
    Sindi, Shireen
    Singh, Jasvinder A
    Singh, Om Prakash
    Singh, Prashant Kumar
    Skirbekk, Vegard
    Sliwa, Karen
    Soneji, Samir
    Sorensen, Reed J D
    Soriano, Joan B
    Soti, David O
    Sreeramareddy, Chandrashekhar T
    Stathopoulou, Vasiliki
    Steel, Nicholas
    Sunguya, Bruno F
    Swaminathan, Soumya
    Sykes, Bryan L
    Tabarés-Seisdedos, Rafael
    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 2015.2016Inngår i: The lancet. HIV, ISSN 2352-3018, Vol. 3, nr 8, s. e361-e387Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 249. Wang, Lu
    et al.
    Bauer, Maria
    Curry, Regina
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sessler, Daniel I
    Eisenach, James C
    Intrathecal ketorolac does not improve acute or chronic pain after hip arthroplasty: a randomized controlled trial2014Inngår i: Journal of Anesthesia, ISSN 0913-8668, E-ISSN 1438-8359, Vol. 28, nr 5, s. 790-793Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 250.
    Warensjö Lemming, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Nälsén, Cecilia
    Becker, Wulf
    Ridefelt, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Mattisson, Iréne
    Lindroos, Anna Karin
    Relative validation of the dietary intake of fatty acids among adults in the Swedish National Dietary Survey using plasma phospholipid fatty acid composition.2015Inngår i: Journal of Nutritional Science, ISSN 2048-6790, E-ISSN 2048-6790, Vol. 4Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aims of a national dietary study are several-fold. One purpose is to monitor the intake of foods and nutrients in the population and to compare intakes with dietary recommendations. It is, however, difficult to measure dietary fat intake and plasma biomarker fatty acid (FA) composition may be used as an objective measure of dietary fat intake. Thus, the relative ability of a diet record to capture habitual fat intake was validated against biomarker FA. Dietary fat intake was measured in a novel self-assisted web-based 4-d food record - the 'Riksmaten' method. Spearman rank correlations between dietary FA, certain food groups (fish-shellfish, dairy products, meat and sausages, and spreads) and the fat content of these food groups and biomarker FA were explored. Participants were 150 women and 129 men, aged 18-80 years, who took part in the Swedish National Dietary Survey, Riksmaten adults 2010-11. Blood samples were collected on average 20 d after the diet record and FA composition was measured in plasma phospholipids by GLC. Total n-3 FA (r 0·31), EPA (r 0·34) and DHA (r 0·42) were correlated between plasma and diet (all P ≤ 0·001). Adjustment for covariates attenuated the relationships. Linoleic acid was only marginally correlated (r 0·15; P = 0·06) in women. Plasma pentadecaenoic acid and heptadecaenoic acid were correlated with dairy product intake as previously reported. In conclusion, the Riksmaten method appears valid for the purpose of collecting data on dietary fat composition, at least in a healthy adult population.

23456 201 - 250 of 272
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