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  • 251.
    Löf, Liza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Arngården, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Olsson-Strömberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Siart, Benjamin
    Jansson, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Dahlin, Joakim S
    Thörn, Ingrid
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Christiansson, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hermansson, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ahlstrand, Erik
    Wålinder, Göran
    Söderberg, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Rosenquist, Richard
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Landegren, Ulf
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Flow Cytometric Measurement of Blood Cells with BCR-ABL1 Fusion Protein in Chronic Myeloid Leukemia2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, p. 1-9, article id 623Article in journal (Refereed)
    Abstract [en]

    Chronic myeloid leukemia (CML) is characterized in the majority of cases by a t(9;22)(q34;q11) translocation, also called the Philadelphia chromosome, giving rise to the BCR-ABL1 fusion protein. Current treatment with tyrosine kinase inhibitors is directed against the constitutively active ABL1 domain of the fusion protein, and minimal residual disease (MRD) after therapy is monitored by real-time quantitative PCR (RQ-PCR) of the fusion transcript. Here, we describe a novel approach to detect and enumerate cells positive for the BCR-ABL1 fusion protein by combining the in situ proximity ligation assay with flow cytometry as readout (PLA-flow). By targeting of the BCR and ABL1 parts of the fusion protein with one antibody each, and creating strong fluorescent signals through rolling circle amplification, PLA-flow allowed sensitive detection of cells positive for the BCR-ABL1 fusion at frequencies as low as one in 10,000. Importantly, the flow cytometric results correlated strongly to those of RQ-PCR, both in diagnostic testing and for MRD measurements over time. In summary, we believe this flow cytometry-based method can serve as an attractive approach for routine measurement of cells harboring BCR-ABL1 fusions, also allowing simultaneously assessment of other cell surface markers as well as sensitive longitudinal follow-up.

  • 252. Mahmoodi, Bakhtawar K
    et al.
    Matsushita, Kunihiro
    Woodward, Mark
    Blankestijn, Peter J
    Cirillo, Massimo
    Ohkubo, Takayoshi
    Rossing, Peter
    Sarnak, Mark J
    Stengel, Bénédicte
    Yamagishi, Kazumasa
    Yamashita, Kentaro
    Zhang, Luxia
    Coresh, Josef
    de Jong, Paul E
    Astor, Brad C
    Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis.2012In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 380, no 9854, p. 1649-61Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Hypertension is the most prevalent comorbidity in individuals with chronic kidney disease. However, whether the association of the kidney disease measures, estimated glomerular filtration rate (eGFR) and albuminuria, with mortality or end-stage renal disease (ESRD) differs by hypertensive status is unknown.

    METHODS: We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and ESRD associated with eGFR and albuminuria in individuals with and without hypertension.

    FINDINGS: We analysed data for 45 cohorts (25 general population, seven high-risk, and 13 chronic kidney disease) with 1,127,656 participants, 364,344 of whom had hypertension. Low eGFR and high albuminuria were associated with mortality irrespective of hypertensive status in the general population and high-risk cohorts. All-cause mortality risk was 1·1-1·2 times higher in individuals with hypertension than in those without hypertension at preserved eGFR. A steeper relative risk gradient in individuals without hypertension than in those with hypertension at eGFR range 45-75 mL/min per 1·73 m(2) led to much the same mortality risk at lower eGFR. With a reference eGFR of 95 mL/min per 1·73 m(2) in each group to explicitly assess interaction, adjusted HR for all-cause mortality at eGFR 45 mL/min per 1·73 m(2) was 1·77 (95% CI 1·57-1·99) in individuals without hypertension versus 1·24 (1·11-1·39) in those with hypertension (p for overall interaction=0·0003). Similarly, for albumin-creatinine ratio of 300 mg/g (vs 5 mg/g), HR was 2·30 (1·98-2·68) in individuals without hypertension versus 2·08 (1·84-2·35) in those with hypertension (p for overall interaction=0·019). We recorded much the same results for cardiovascular mortality. The associations of eGFR and albuminuria with ESRD, however, did not differ by hypertensive status. Results for chronic kidney disease cohorts were similar to those for general and high-risk population cohorts.

    INTERPRETATION: Chronic kidney disease should be regarded as at least an equally relevant risk factor for mortality and ESRD in individuals without hypertension as it is in those with hypertension.

    FUNDING: US National Kidney Foundation.

  • 253. Mandic-Havelka, Aleksandra
    et al.
    Nilsen, Tom
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sunde, Kathrin
    Norell, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Hansson, Lars O
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Turbidimetric Determination of Fecal Calprotectin Using Two Table Top Chemistry Analyzers: Mindray BS-200E and Cobas® c1112017In: Clinical Laboratory, ISSN 1433-6510, Vol. 63, no 5, p. 907-913Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Fecal calprotectin assays are widely used in diagnosis and monitoring of inflammatory bowel disease (IBD) in patients with suspected IBD. The most frequently used technique is ELISA and microtiter plates. Turbidimetric assays for analysis of fecal calprotectin can significantly reduce turnaround time. Many laboratories may be reluctant to run fecal samples on their large chemistry analyzers. The aim of this study was to evaluate fecal calprotectin particle enhanced turbidimetric immunoassay (PETIA) on smaller chemistry analyzers that could be dedicated for fecal samples.

    METHODS: The BÜHLMANN fCAL® turbo assay was validated on two table top chemistry analyzers, Mindray BS-200E and cobas® c111.

    RESULTS: The assay was linear in the range between 20 and 1,900 µg/g with a limit of quantification around 20 µg/g on both instruments. The total coefficient of variation was < 7% in the range between 50 and 1,300 µg/g on both instruments. No antigen excess hook effect was observed up to 18,000 µg/g on the Mindray BS-200E and up to 20,000 µg/g on cobas® c111. The BÜHLMANN fCAL® turbo assay showed a high correlation with the BÜHLMANN fCAL® ELISA.

    CONCLUSIONS: Running the BÜHLMANN fCAL® turbo on Mindray BS-200E or cobas® c111 chemistry analyzers can provide rapid test results without exposing large routine chemistry analyzers to stool samples.

  • 254. Mascialino, B.
    et al.
    Hermansson, L. L.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ruling Out IBD In The United Kingdom And Brazil: Is The Usage Of F-Calprotectin In Primary Care Cost-Effective?2013In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 16, no 7, p. A692-A692Article in journal (Other academic)
  • 255. Mascialino, B.
    et al.
    Hermansson, L. L.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ruling Out IBD In The United Kingdom And Spain: Is The Usage Of F-Calprotectin In Primary Care Cost-Effective?2013In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 16, no 7, p. A493-A493Article in journal (Other academic)
  • 256. Matsushita, Kunihiro
    et al.
    Mahmoodi, Bakhtawar K
    Woodward, Mark
    Emberson, Jonathan R
    Jafar, Tazeen H
    Jee, Sun Ha
    Polkinghorne, Kevan R
    Shankar, Anoop
    Smith, David H
    Tonelli, Marcello
    Warnock, David G
    Wen, Chi-Pang
    Coresh, Josef
    Gansevoort, Ron T
    Hemmelgarn, Brenda R
    Levey, Andrew S
    Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate2012In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 307, no 18, p. 1941-1951Article in journal (Refereed)
    Abstract [en]

    CONTEXT:

    The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation more accurately estimates glomerular filtration rate (GFR) than the Modification of Diet in Renal Disease (MDRD) Study equation using the same variables, especially at higher GFR, but definitive evidence of its risk implications in diverse settings is lacking.

    OBJECTIVE:

    To evaluate risk implications of estimated GFR using the CKD-EPI equation compared with the MDRD Study equation in populations with a broad range of demographic and clinical characteristics.

    DESIGN, SETTING, AND PARTICIPANTS:

    A meta-analysis of data from 1.1 million adults (aged ≥ 18 years) from 25 general population cohorts, 7 high-risk cohorts (of vascular disease), and 13 CKD cohorts. Data transfer and analyses were conducted between March 2011 and March 2012.

    MAIN OUTCOME MEASURES:

    All-cause mortality (84,482 deaths from 40 cohorts), cardiovascular mortality (22,176 events from 28 cohorts), and end-stage renal disease (ESRD) (7644 events from 21 cohorts) during 9.4 million person-years of follow-up; the median of mean follow-up time across cohorts was 7.4 years (interquartile range, 4.2-10.5 years).

    RESULTS:

    Estimated GFR was classified into 6 categories (≥90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73 m2) by both equations. Compared with the MDRD Study equation, 24.4% and 0.6% of participants from general population cohorts were reclassified to a higher and lower estimated GFR category, respectively, by the CKD-EPI equation, and the prevalence of CKD stages 3 to 5 (estimated GFR <60 mL/min/1.73 m2) was reduced from 8.7% to 6.3%. In estimated GFR of 45 to 59 mL/min/1.73 m2 by the MDRD Study equation, 34.7% of participants were reclassified to estimated GFR of 60 to 89 mL/min/1.73 m2 by the CKD-EPI equation and had lower incidence rates (per 1000 person-years) for the outcomes of interest (9.9 vs 34.5 for all-cause mortality, 2.7 vs 13.0 for cardiovascular mortality, and 0.5 vs 0.8 for ESRD) compared with those not reclassified. The corresponding adjusted hazard ratios were 0.80 (95% CI, 0.74-0.86) for all-cause mortality, 0.73 (95% CI, 0.65-0.82) for cardiovascular mortality, and 0.49 (95% CI, 0.27-0.88) for ESRD. Similar findings were observed in other estimated GFR categories by the MDRD Study equation. Net reclassification improvement based on estimated GFR categories was significantly positive for all outcomes (range, 0.06-0.13; all P < .001). Net reclassification improvement was similarly positive in most subgroups defined by age (<65 years and ≥65 years), sex, race/ethnicity (white, Asian, and black), and presence or absence of diabetes and hypertension. The results in the high-risk and CKD cohorts were largely consistent with the general population cohorts.

    CONCLUSION:

    The CKD-EPI equation classified fewer individuals as having CKD and more accurately categorized the risk for mortality and ESRD than did the MDRD Study equation across a broad range of populations.

  • 257.
    Mindemark, Mirja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Ruling out IBD: Estimation of the possible economic effects of pre-endoscopic screening with F-calprotectin2012In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 45, no 7-8, p. 552-555Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To estimate the possible economic effects of a sequential testing strategy with F-calprotectin to minimize colonoscopies.

    DESIGN AND METHODS: Retrospective study in a third party payer perspective. The costs were calculated from initial F-calprotectin test results of 3639 patients. Two cut-off levels were used: 50μg/g feces and 100μg/g feces, respectively. The cost-effectiveness of the testing strategy was estimated through the short-term cost avoidance and reduction in demand for colonoscopies.

    RESULTS: The estimated demand for colonoscopies was reduced by 50% with the 50μg/g cut-off and 67% with the 100μg/g cut-off. This corresponded to a cost avoidance of approximately €1.57million and €2.13million, respectively.

    CONCLUSIONS: The use of F-calprotectin as a screening test substantially could reduce the number of invasive measurements necessary in the diagnostic work-up of patients with suspected IBD, as well as the associated costs.

  • 258. Minelli, Alba
    et al.
    Ronquist, Gunnar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. klinisk kemi.
    Carlsson, Lena
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. klinisk kemi.
    Mearini, Ettore
    Nilsson, Ove
    Larsson, Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. klinisk kemi.
    Antiprostasome antibody titres in benign and malignant prostate disease.2005In: Anticancer Res, ISSN 0250-7005, Vol. 25, no 6C, p. 4399-402Article in journal (Refereed)
  • 259.
    Mobarrez, F.
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Vikerfors, A.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Gustafsson, J.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Gunnarsson, I.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Zickert, A.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Larsson, Anders
    Akad Hosp, Dept Clin Chem & Pharmacol, Uppsala, Sweden..
    Pisetsky, D.
    Duke Univ, Med Ctr, Dept Med, Med Res Serv, Durham, NC 27710 USA..
    Wallen, H.
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Div Cardiovasc Med, Stockholm, Sweden..
    Svenungsson, E.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    The Expression Of Microparticles In The Blood Of Patients With Systemic Lupus Erythematosus (SLE): Phenotypic Characterization And Clinical Associations2016In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 34, no 4, p. S70-S70Article in journal (Refereed)
  • 260.
    Mokdad, Ali H.
    et al.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Azzopardi, Peter
    SAHMRI, Wardliparingga Aboriginal Res Unit, Adelaide, SA, Australia.
    Cini, Karly
    Ctr Adolescent Hlth, Murdoch Childrens Res Inst, Melbourne, Vic, Australia.
    Kennedy, Elissa
    Burnet Inst, Melbourne, Vic, Australia. Murdoch Childrens Res Inst, Melbourne, Vic, Australia.
    Sawyer, Susan
    Univ Melbourne, Murdoch Childrens Res Inst, Parkville, Vic, Australia.
    El Bcheraoui, Charbel
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Charara, Raghid
    Amer Univ Beirut, Beirut, Lebanon.
    Khalil, Ibrahim
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Moradi-Lakeh, Maziar
    Iran Univ Med Sci, Dept Community Med, Prevent Med & Publ Hlth Res Ctr, Gastrointestinal & Liver Dis Res Ctr GILDRC, Tehran, Iran.
    Collison, Michael
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Afifi, Rima A.
    Amer Univ Beirut, Beirut, Lebanon.
    Al-Raiby, Jamela
    WHO, Cairo, Egypt.
    Krohn, Kristopher J.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Daoud, Farah
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Chew, Adrienne
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Afshin, Ashkan
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Foreman, Kyle J.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA;Imperial Coll London, London, England.
    Kassebaum, Nicholas J.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA;Seattle Childrens Hosp, Dept Anesthesiol & Pain Med, Seattle, WA USA.
    Kutz, Michael
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Kyu, Hmwe H.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Liu, Patrick
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Olsen, Helen E.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Smith, Alison
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Stanaway, Jeffrey D.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Wang, Haidong
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Arnlov, Johan
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden;Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Kiadaliri, Aliasghar Ahmad
    Lund Univ, Dept Clin Sci Lund, Clin Epidemiol Unit, Orthoped, Lund, Sweden.
    Alam, Khurshid
    Univ Melbourne, Murdoch Childrens Res Inst, Parkville, Vic, Australia;Univ Melbourne, Melbourne, Vic, Australia;Univ Sydney, Sydney, NSW, Australia.
    Alasfoor, Deena
    Minist Hlth, Muscat, Oman.
    Ali, Raghib
    Univ Oxford, Oxford, England.
    Alizadeh-Navaei, Reza
    Mazandaran Univ Med Sci, Gastrointestinal Canc Res Ctr, Sari, Mazandaran, Iran.
    Al-Raddadi, Rajaa
    Joint Program Family & Community Med, Jeddah, Makkah, Saudi Arabia.
    Altirkawi, Khalid A.
    King Saud Univ, Riyadh, Saudi Arabia.
    Alvis-Guzman, Nelson
    Univ Cartagena, Cartagena De Indias, Colombia.
    Anber, Nahla
    Mansoura Univ, Mansoura, Egypt.
    Antonio, Carl Abelardo T.
    Univ Philippines Manila, Dept Hlth Policy & Adm, Coll Publ Hlth, Manila, Philippines.
    Anwari, Palwasha
    Artaman, Al
    Univ Manitoba, Winnipeg, MB, Canada.
    Asayesh, Hamid
    Qom Univ Med Sci, Sch Paramed, Dept Med Emergency, Qom, Iran.
    Barker-Collo, Suzanne L.
    Univ Auckland, Sch Psychol, Auckland, New Zealand.
    Bedi, Neeraj
    Coll Publ Hlth & Trop Med, Jazan, Saudi Arabia.
    Beghi, Ettore
    IRCCS, Ist Ric Farmacol Mario Negri, Milan, Italy.
    Bennett, Derrick A.
    Univ Oxford, Nuffield Dept Populat Hlth, Oxford, England.
    Bensenor, Isabela M.
    Univ Sao Paulo, Sao Paulo, Brazil.
    Bhutta, Zulfiqar A.
    Aga Khan Univ, Ctr Excellence Women & Child Hlth, Karachi, Pakistan;Hosp Sick Children, Ctr Global Child Hlth, Toronto, ON, Canada.
    Butt, Zahid A.
    Al Shifa Trust Eye Hosp, Rawalpindi, Pakistan.
    Castaneda-Orjuela, Carlos A.
    Colombian Natl Hlth Observ, Inst Nacl Salud, Bogota, DC, Colombia;Univ Nacl Colombia, Publ Hlth Dept, Epidemiol & Publ Hlth Evaluat Grp, Bogota, Colombia.
    Catala-Lopez, Ferran
    Univ Valencia, Dept Med, INCLIVA Hlth Res Inst, Valencia, Spain;CIBERSAM, Valencia, Spain;Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada.
    Charlson, Fiona J.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA;Queensland Ctr Mental Hlth Res, Brisbane, Qld, Australia.
    Danawi, Hadi
    Walden Univ, Minneapolis, MN USA.
    De Leo, Diego
    Griffith Univ, Brisbane, Qld, Australia.
    Degenhardt, Louisa
    Univ New South Wales, Natl Drug & Alcohol Res Ctr, Sydney, NSW, Australia.
    Denno, Donna
    Univ Washington, Dept Pediat, Seattle, WA 98195 USA;Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
    Deribe, Kebede
    Brighton & Sussex Med Sch, Brighton, E Sussex, England.
    Jarlais, Don C. Des
    Mt Sinai Beth Israel, New York, NY USA;Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
    Dey, Subhojit
    Indian Inst Publ Hlth Delhi, Publ Hlth Fdn India, Gurgaon, India.
    Dharmaratne, Samath D.
    Univ Peradeniya, Dept Community Med, Fac Med, Peradeniya, Sri Lanka.
    Djalalinia, Shirin
    Minist Hlth & Med Educ, Undersecretary Res & Technol, Tehran, Iran.
    Erskine, Holly E.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA;Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia;Queensland Ctr Mental Hlth Res, Brisbane, Qld, Australia.
    Fereshtehnejad, Seyed-Mohammad
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Stockholm, Sweden.
    Ferrari, Alize J.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA;Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia;Queensland Ctr Mental Hlth Res, Brisbane, Qld, Australia.
    Fischer, Florian
    Bielefeld Univ, Sch Publ Hlth, Bielefeld, Germany.
    Gebrehiwot, Tsegaye Tewelde
    Jimma Univ, Jimma, Ethiopia.
    Geleijnse, Johanna M.
    Wageningen Univ, Div Human Nutr, Wageningen, Netherlands.
    Gona, Philimon N.
    Univ Massachusetts, Boston, MA 02125 USA.
    Gugnani, Harish Chander
    St James Sch Med, Dept Microbiol, Melbourne, Vic, Australia;St James Sch Med, Dept Epidemiol & Biostat, Melbourne, Vic, Australia.
    Gupta, Rajeev
    Eternal Heart Care Ctr & Res Inst, Jaipur, Rajasthan, India.
    Hamadeh, Randah Ribhi
    Arabian Gulf Univ, Manama, Bahrain.
    Hamidi, Samer
    Hamdan Bin Mohammed Smart Univ, Dubai, U Arab Emirates.
    Maria Haro, Josep
    Parc Sanitari St Joan de Deu GIBERSAM, Sant Boi De Llobregat, Spain.
    Hay, Roderick J.
    Int Fdn Dermatol London, London, England;Kings Coll London, London, England.
    Hearps, Stephen J. C.
    Murdoch Childrens Res Hosp, Child Neuropsychol, Parkville, Vic, Australia.
    Hendrie, Delia
    Curtin Univ, Ctr Populat Hlth Res, Bentley, WA, Australia.
    Hotez, Peter J.
    Baylor Univ, Coll Med, Houston, TX 77030 USA.
    Hu, Guoqing
    Cent S Univ, Sch Publ Hlth, Dept Epidemiol & Hlth Stat, Changsha, Hunan, Peoples R China.
    Jonas, Jost B.
    Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Mannheim, Germany.
    Karch, Andre
    Helmholtz Ctr Infect Res, Epidemiol & Stat Methods Res Grp, Braunschweig, Germany;German Ctr Infect Res, Hannover Braunschweig Site, Braunschweig, Germany.
    Karimi, Seyed M.
    Univ Washington Tacoma, Tacoma, WA USA.
    Kasaeian, Amir
    Univ Tehran Med Sci, Hematol Oncol & Stem Cell Transplantat Res Ctr, Tehran, Iran;Univ Tehran Med Sci, Endocrinol & Metab Populat Sci Inst, Tehran, Iran.
    Kebede, Seifu
    Univ Addis Ababa, Sch Publ Hlth, Addis Ababa, Ethiopia;Mekelle Univ, Mekele, Ethiopia.
    Kengne, Andre Pascal
    South African Med Res Council, Cape Town, South Africa;Univ Cape Town, Cape Town, South Africa.
    Khan, Ejaz Ahmad
    Hlth Serv Acad, Islamabad, Pakistan.
    Khosravi, Ardeshir
    Iranian Minist Hlth & Med Educ, Tehran, Iran;Univ Tehran Med Sci, Noncommunicable Dis Res Ctr, Tehran, Iran.
    Khubchandani, Jagdish
    Ball State Univ, Dept Nutr & Hlth Sci, Muncie, IN 47306 USA.
    Kokubo, Yoshihiro
    Natl Cerebral & Cardiovasc Ctr, Dept Prevent Cardiol, Suita, Osaka, Japan.
    Kopec, Jacek A.
    Univ British Columbia, Vancouver, BC, Canada.
    Kosen, Soewarta
    Natl Inst Hlth Res & Dev, Ctr Community Empowerment Hlth Policy & Humanitie, Jakarta, Indonesia.
    Larson, Heidi J.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA;London Sch Hyg & Trop Med, Dept Infect Dis Epidemiol, London, England.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Leasher, Janet L.
    Nova Southeastern Univ, Coll Optometry, Ft Lauderdale, FL USA.
    Leung, Janni
    Univ Washington, Seattle, WA 98195 USA.
    Li, Yongmei
    San Francisco VA Med Ctr, San Francisco, CA USA.
    Lotufo, Paulo A.
    Univ Sao Paulo, Sao Paulo, Brazil.
    Lunevicius, Raimundas
    Aintree Univ Hosp Natl Hlth Serv Fdn Trust, Liverpool, Merseyside, England;Univ Liverpool, Sch Med, Liverpool, Merseyside, England.
    Abd El Razek, Hassan Magdy
    Mansoura Fac Med, Mansoura, Egypt.
    Majdzadeh, Reza
    Univ Tehran Med Sci, Knowledge Utilizat Res Ctr & Community Based Part, Tehran, Iran.
    Majeed, Azeem
    Imperial Coll London, Dept Primary Care & Publ Hlth, London, England.
    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.
    Mhimbira, Francis Apolinary
    Ifakara Hlth Inst, Bagamoyo, Tanzania.
    Miller, Ted R.
    Pacific Inst Res Evaluat, Calverton, MD USA;Curtin Univ, Ctr Populat Hlth, Perth, WA, Australia.
    Mitchell, Philip B.
    Univ New South Wales, Kensington, NSW, Australia.
    Monasta, Lorenzo
    Inst Maternal & Child Hlth Burlo Garofolo, Trieste, Italy.
    Obermeyer, Carla Makhlouf
    Amer Univ Beirut, Ctr Res Populat & Hlth, Fac Hlth Sci, Beirut, Lebanon.
    Oh, In-Hwan
    Kyung Hee Univ, Sch Med, Dept Prevent Med, Seoul, South Korea.
    Olusanya, Bolajoko Olubukunola
    Ctr Hlth Start Initiat, Lagos, Nigeria.
    Ortiz, Alberto
    IIS Fdn Jimenez Diaz UAM, Madrid, Spain.
    Park, Eun-Kee
    Kosin Univ, Dept Med Humanities & Social Med, Coll Med, Busan, South Korea.
    Parry, Matti
    WHO, Reprod Hlth & Res Adolescents & Rsk Populat RHR A, Geneva, Switzerland.
    Pereira, David M.
    Univ Porto, Dept Quim, Lab Farmacognosia, REQUIMTE LAQV,Fac Farm, Porto, Portugal.
    Phillips, Michael Robert
    Shanghai Jiao Tong Univ, Sch Med, Shanghai, Peoples R China;Emory Univ, Atlanta, GA 30322 USA.
    Pourmalek, Farshad
    Univ British Columbia, Vancouver, BC, Canada.
    Qorbani, Mostafa
    Alborz Univ Med Sci, Noncommunicable Dis Res Ctr, Karaj, Iran.
    Radfar, Amir
    AT Still Univ, Kirksville, MO USA.
    Rafay, Anwar
    Contech Int Hlth Consultants, Lahore, Pakistan;Contech Sch Publ Hlth, Lahore, Pakistan.
    Rahimi-Movaghar, Vafa
    Univ Tehran Med Sci, Sina Trauma & Surg Res Ctr, Tehran, Iran.
    Rai, Rajesh Kumar
    Soc Hlth & Demog Surveillance, Suri, India.
    Rana, Saleem M.
    Contech Sch Publ Hlth, Lahore, Pakistan.
    Rawaf, David Laith
    Imperial Coll London, WHO Collaborating Ctr, London, England;North Hampshire Hosp, Basingstroke, England;Univ Coll London Hosp, London, England.
    Rawaf, Salman
    Imperial Coll London, London, England.
    Reavley, Nicola
    Univ Melbourne, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia.
    Renzaho, Andre M. N.
    Western Sydney Univ, Penrith, NSW, Australia.
    Rezaei, Satar
    Kermanshah Univ Med Sci, Sch Publ Hlth, Kermanshah, Iran.
    Sadegh-Rezai, Mohammad
    Mazandaran Univ Med Sci ences, Infect Dis Res Ctr Focus Nosocomial Infect, Sari, Iran.
    Rios-Zertuche, Diego
    Salud Mesoamer 2015 Initiat, Panama City, Panama.
    Roshandel, Gholamreza
    Golestan Univ Med Sci, Golestan Res Ctr Gastroenterol & Hepatol, Gorgan, Iran;Univ Tehran Med Sci, Digest Dis Res Inst, Tehran, Iran.
    Rothenbacher, Dietrich
    Univ Ulm, Inst Epidemiol & Med Biometry, Ulm, Germany.
    Safdarian, Mahdi
    Univ Tehran Med Sci, Sina Trauma & Surg Res Ctr, Tehran, Iran.
    Safi, Sare
    Safiri, Saeid
    Shahid Beheshti Univ Med Sci, Ophthalm Epidemiol Res Ctr, Tehran, Iran;Maragheh Univ Med Sci, Sch Nursing & Midwifery, Dept Publ Hlth, Managerial Epidemiol Res Ctr, Maragheh, Iran.
    Sahraian, Mohammad Ali
    Univ Tehran Med Sci, Neurosci Inst, Res Ctr, Tehran, Iran.
    Salamati, Payman
    Univ Tehran Med Sci, Sina Trauma & Surg Res Ctr, Tehran, Iran.
    Samy, Abdallah M.
    Ain Shams Univ, Cairo, Egypt.
    Sanabria, Juan Ramon
    Marshall Univ, J Edwards Sch Med, Huntington, WV USA;Case Western Reserve Univ, Cleveland, OH 44106 USA.
    Santomauro, Damian
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA;Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia;Queensland Ctr Mental Hlth Res, Brisbane, Qld, Australia.
    Sartorius, Benn
    SAMRC, UKZN Gastrointestinal Canc Res Ctr, Durban, South Africa.
    Schwebel, David C.
    Univ Alabama Birmingham, Birmingham, AL USA.
    Seedat, Soraya
    Stellenbosch Univ, Cape Town, South Africa.
    Sepanlou, Sadaf G.
    Univ Tehran Med Sci, Digest Dis Res Inst, Tehran, Iran.
    Setegn, Tesfaye
    Bahir Dar Univ, Bahir Dar, Ethiopia.
    Shaheen, Amira
    An Najah Univ, Dept Publ Hlth, Nablus, Palestine.
    Shaikh, Masood Ali
    Shiri, Rahman
    Univ Helsinki, Finnish Inst Occupat Hlth, Fac Med, Dept Publ Hlth,Work Org,Work Diabil Program, Helsinki, Finland.
    Sigfusdottir, Inga Dora
    Reykjavik Univ, Reykjavik, Iceland.
    Singh, Jasvinder A.
    Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
    Sobaih, Badr H. A.
    King Saud Univ, Riyadh, Saudi Arabia.
    Sreeramareddy, Chandrashekhar T.
    Int Med Univ, Dept Community Med, Kuala Lumpur, Malaysia.
    Abdulkader, Rizwan Suliankatchi
    Minist Hlth, Riyadh, Saudi Arabia.
    Tehrani-Banihashemi, Arash
    Iran Univ Med Sci, Prevent Med & Publ Hlth Res Ctr, Tehran, Iran.
    Temsah, Mohamad-Hani
    King Saud Univ, Riyadh, Saudi Arabia.
    Terkawi, Abdullah Sulieman
    Univ Virginia, Dept Anesthesiol, Charlottesville, VA USA;King Fahad Med City, Dept Anesthesiol, Riyadh, Saudi Arabia;Cleveland Clin, Outcomes Res Consortium, Cleveland, OH USA.
    Thomson, Alan J.
    Adapt Knowledge Management, Victoria, BC, Canada.
    Tonelli, Marcello
    Univ Calgary, Calgary, AB, Canada.
    Topor-Madry, Roman
    Jagiellonian Univ Med Coll, Inst Publ Hlth, Fac Hlth Sci, Krakow, Poland;Wroclaw Med Univ, Fac Hlth Sci, Wroclaw, Poland.
    Tran, Bach Xuan
    Johns Hopkins Univ, Baltimore, MD USA;Hanoi Med Univ, Hanoi, Vietnam.
    Ukwaja, Kingsley Nnanna
    Fed Teaching Hosp, Dept Internal Med, Abakaliki, Nigeria.
    Uthman, Olalekan A.
    Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England.
    Vasankari, Tommi
    UKK Inst Hlth Promot Res, Tampere, Finland.
    Venketasubramanian, Narayanaswamy
    Raffles Hosp, Raffles Neurosci Ctr, Singapore, Singapore.
    Vlassov, Vasiliy Victorovich
    Natl Res Univ Higher Sch Econ, Moscow, Russia.
    Vollset, Stein Emil
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA;Norwegian Inst Publ Hlth, Ctr Dis Burden, Bergen, Norway;Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.
    Weiderpass, Elisabete
    Karolinska Inst, 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;Folkhalsan Res Ctr, Genet Epidemiol Grp, Helsinki, Finland.
    Weintraub, Robert G.
    Univ Melbourne, Melbourne, Vic, Australia;Royal Childrens Hosp, Melbourne, Vic, Australia;Murdoch Childrens Res Inst, Melbourne, Vic, Australia.
    Werdecker, Andrea
    Fed Inst Populat Res, Competence Ctr Mortal Follow Up German Natl Cohor, Wiesbaden, Germany.
    Whiteford, Harvey A.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA;Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia;Queensland Ctr Mental Hlth Res, Brisbane, Qld, Australia.
    Yano, Yuichiro
    Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA.
    Yaseri, Mehdi
    Shahid Beheshti Univ Med Sci, Ophthalm Epidemiol Res Ctr, Tehran, Iran;Univ Tehran Med Sci, Tehran, Iran.
    Yonemoto, Naohiro
    Kyoto Univ, Sch Publ Hlth, Dept Biostat, Kyoto, Japan.
    Younis, Mustafa Z.
    Jackson State Univ, Jackson, MS USA.
    Yu, Chuanhua
    Wuhan Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Wuhan, Hubei, Peoples R China;Wuhan Univ, Global Hlth Inst, Wuhan, Hubei, Peoples R China.
    Jumaan, Aisha O.
    Vos, Theo
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Hay, Simon I.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA;Univ Oxford, Oxford Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England.
    Naghavi, Mohsen
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Patton, George C.
    Univ Melbourne, Murdoch Childrens Res Inst, Dept Paediat, Melbourne, Vic, Australia.
    Murray, Christopher J. L.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Adolescent health in the Eastern Mediterranean Region: findings from the global burden of disease 2015 study2018In: International Journal of Public Health, ISSN 1661-8556, E-ISSN 1661-8564, Vol. 63, p. 79-96Article in journal (Refereed)
    Abstract [en]

    The 22 countries of the East Mediterranean Region (EMR) have large populations of adolescents aged 10-24 years. These adolescents are central to assuring the health, development, and peace of this region. We described their health needs. Using data from the Global Burden of Disease Study 2015 (GBD 2015), we report the leading causes of mortality and morbidity for adolescents in the EMR from 1990 to 2015. We also report the prevalence of key health risk behaviors and determinants. Communicable diseases and the health consequences of natural disasters reduced substantially between 1990 and 2015. However, these gains have largely been offset by the health impacts of war and the emergence of non-communicable diseases (including mental health disorders), unintentional injury, and self-harm. Tobacco smoking and high body mass were common health risks amongst adolescents. Additionally, many EMR countries had high rates of adolescent pregnancy and unmet need for contraception. Even with the return of peace and security, adolescents will have a persisting poor health profile that will pose a barrier to socioeconomic growth and development of the EMR.

  • 261.
    Mokdad, Ali H.
    et al.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Moradi-Lakeh, Maziar
    Iran Univ Med Sci, Dept Community Med, Gastrointestinal & Liver Dis Res Ctr GILDRC, Preventat Med & Publ Hlth Res Ctr, Tehran, Iran.
    El Bcheraoui, Charbel
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Khalil, Ibrahim
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Charara, Raghid
    Amer Univ Beirut, Beirut, Lebanon.
    Afshin, Ashkan
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Wang, Haidong
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Collison, Michael
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Krohn, Kristopher J.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Chew, Adrienne
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Daoud, Farah
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Blosser, Christopher D.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Cornaby, Leslie
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Foreman, Kyle J.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Kassebaum, Nicholas J.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA;Seattle Childrens Hosp, Dept Anesthesiol & Pain Med, Seattle, WA USA.
    Kemmer, Laura
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Kutz, Michael
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Liu, Patrick
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Zipkin, Ben
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Arnlov, Johan
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden;Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Abate, Kalkidan Hassen
    Jimma Univ, Jimma, Oromia, Ethiopia.
    Ahmadi, Alireza
    Kermanshah Univ Med Sci, Kermanshah, Iran.
    Ahmadieh, Hamid
    Shahid Beheshti Univ Med Sci, Ophthalm Res Ctr, Tehran, Iran;Labbafinejad Med Ctr, Dept Ophthalmol, Tehran, Iran.
    Ahmed, Muktar Beshir
    Jimma Univ, Coll Hlth Sci, Dept Epidemiol, Oromiya, Ethiopia.
    Al-Aly, Ziyad
    Washington Univ, St Louis, MO USA.
    Alam, Khurshid
    Univ Melbourne, Murdoch Childrens Res Inst, Parkville, Vic, Australia;Univ Melbourne, Melbourne, Vic, Australia;Univ Sydney, Sydney, NSW, Australia.
    Alasfoor, Deena
    Minist Hlth, Muscat, Oman.
    Ali, Raghib
    Univ Oxford, Oxford, England.
    Alizadeh-Navaei, Reza
    Mazandaran Univ Med Sci ences, Gastrointestinal Canc Res Ctr, Sari, Mazandaran, Iran.
    Alkaabi, Juma M.
    Coll Med & Hlth Sci UAEU, ALAIN UAE, Abu Zaby, U Arab Emirates.
    Alkerwi, Ala'a
    LIH, Luxembourg, Luxembourg.
    Al-Raddadi, Rajaa
    Joint Program Family & Community Med, Jeddah, Saudi Arabia.
    Altirkawi, Khalid A.
    King Saud Univ, Riyadh, Saudi Arabia.
    Alvis-Guzman, Nelson
    Univ Cartagena, Cartagena De Indias, Colombia.
    Amini, Erfan
    Univ Tehran Med Sci, Urooncol Res Ctr, Tehran, Iran;Univ Tehran Med Sci, Endocrinol & Metab Res Inst, Noncommunicable Dis Res Ctr, Tehran, Iran.
    Anber, Nahla
    Mansoura Univ, Mansoura, Egypt.
    Anwari, Palwasha
    Asgedom, Solomon Weldegebreal
    Mekelle Univ, Mekelle, Tigray, Ethiopia.
    Atey, Tesfay Mehari
    Mekelle Univ, Mekelle, Tigray, Ethiopia.
    Avila-Burgos, Leticia
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico.
    Awasthi, Ashish
    Sanjay Gandhi Postgrad Inst Med Sci, Lucknow, Uttar Pradesh, India.
    Azzopardi, Peter
    Univ Melbourne, 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;Burnet Inst, Ctr Int Hlth, Melbourne, Vic, Australia.
    Baernighausen, Till
    Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA;Africa Hlth Res Inst, Mtubatuba, Kwazulu Natal, South Africa;Heidelberg Univ, Inst Publ Hlth, Heidelberg, Germany.
    Bacha, Umar
    Univ Management & Technol, Sch Hlth Sci, Lahore, Punjab, Pakistan.
    Barac, Aleksandra
    Univ Belgrade, Fac Med, Belgrade, Serbia.
    Bazargan-Hejazi, Shahrzad
    Charles R Drew Univ Med & Sci, Coll Med, 1621 E 120th St, Los Angeles, CA 90059 USA;Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
    Drew, Charles R.
    Geffen, David
    Bedi, Neeraj
    Coll Publ Hlth & Trop Med, Jazan, Saudi Arabia.
    Berhe, Derbew Fikadu
    Mekelle Univ, Sch Pharm, Mekelle, Tigray, Ethiopia.
    Beyene, Addisu Shunu
    Haramaya Univ, Coll Hlth & Med Sci, Harar, Oromia, Ethiopia.
    Bhutta, Zulfiqar A.
    Aga Khan Univ, Ctr Excellence Women & Child Hlth, Karachi, Pakistan;Hosp Sick Children, Ctr Global Child Hlth, Toronto, ON, Canada.
    Bikbov, Boris
    Haramaya Univ, Ctr Excellence Women & Child Hlth, Harar, Oromia, Ethiopia.
    Birhanu, Mulugeta M.
    Univ Groningen, UMCG, Groningen, Netherlands;Mekelle Univ, Mekelle 03, Ayder, Ethiopia.
    Butt, Zahid A.
    Al Shifa Trust Eye Hosp, Rawalpindi, Punjab, Pakistan.
    Cahuana-Hurtado, Lucero
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico.
    Carpenter, David O.
    SUNY Albany, Albany, NY USA.
    Carrero, Juan Jesus
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Choi, Jee-Young Jasmine J.
    Seoul Natl Univ Hosp, Seoul, South Korea;Seoul Natl Univ, Med Lib, Seoul, South Korea.
    Danawi, Hadi
    Walden Univ, Minneapolis, MN USA.
    Dharmaratne, Samath D.
    Univ Peradeniya, Dept Community Med, Fac Med, Peradeniya, Sri Lanka.
    Ding, Eric L.
    Harvard Univ, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA.
    Djalalinia, Shirin
    Minist Hlth & Med Educ Tehran, Undersecretary Res & Technol, Tehran, Iran.
    Doyle, Kerrie E.
    RMIT Univ, Bundoora, Vic, Australia;Australian Natl Univ, Canberra, ACT, Australia.
    Ebrahimi, Hedyeh
    Univ Tehran Med Sci, Noncommunicable Dis Res Ctr, Tehran, Iran;Univ Tehran Med Sci, Digest Dis Res Inst, Shariati Hosp, Liver & Pancreaticobiliary Dis Res Ctr, Tehran, Iran.
    Endries, Aman Yesuf
    Arba Minch Univ, Arba Minch, Arba Minch, Snnpr, Ethiopia.
    Esteghamati, Alireza
    Univ Tehran Med Sci, Endocrinol & Metab Res Ctr, Tehran, Iran.
    Farvid, Maryam S.
    Harvard Univ, Dept Nutr, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA;Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Harvard MGH Ctr Genom Vulnerable Populat & Hlth D, Boston, MA 02114 USA.
    Fereshtehnejad, Seyed-Mohammad
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Stockholm, Sweden.
    Feyissa, Tesfaye Regassa
    Wollega Univ, Nekemte, Oromia, Ethiopia.
    Fischer, Florian
    Univ Bielefeld, Bielefeld, North Rhine Wes, Germany.
    Gebrehiwot, Tsegaye Tewelde
    Jimma Univ, Jimma, Oromia, Ethiopia.
    Gona, Philimon N.
    Univ Massachusetts, Boston, MA 02125 USA.
    Gopalani, Sameer Vali
    Govern Federated States Micronesia, Dept Hlth & Social Affairs, Palikir, Pohnpei, Micronesia.
    Gyawali, Bishal
    Aarhus Univ, Aarhus, Denmark.
    Hafezi-Nejad, Nima
    Univ Tehran Med Sci, Endocrinol & Metab Res Ctr, Tehran, Iran.
    Hamadeh, Randah Ribhi
    Arabian Gulf Univ, Manama, Bahrain.
    Hamidi, Samer
    Hamdan Bin Mohammed Smart Univ, Dubai, U Arab Emirates.
    Horino, Masako
    Bur Child Family Community Wellness, Nevada Div Publ & Behav Hlth, Carson City, NV USA.
    Hsairi, Mohamed
    Salah Azaiz Inst, Dept Epidemiol, Tunis, Tunisia.
    Jakovljevic, Mihajlo B.
    Univ Kragujevac Kragujevac, Cent Serbia Sumadija, Fac Med Sci, Kragujevac, Serbia;Univ Washington, IHME, Ctr Hlth Trends & Forecasts, Seattle, WA 98195 USA.
    Jimenez-Corona, Aida
    Inst Ophthalmol Condede Valencia, Dept Ocular Epidemiol & Visual Hlth, Mexico City, DF, Mexico;Minist Hlth, Gen Directorate Epidemiol, Mexico City, DF, Mexico.
    John, Denny
    Int Ctr Res Women, Delhi, India.
    Jonas, Jost B.
    Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Mannheim, Germany.
    Kasaeian, Amir
    Univ Tehran Med Sci, Hematol Oncol & Stem Cell Transplantat Res Ctr, Tehran, Iran;Univ Tehran Med Sci, Endocrinol & Metab Populat Sci Inst, Tehran, Iran.
    Kengne, Andre Pascal
    South African Med Res Council, Cape Town, Western Cape, South Africa;Univ Cape Town, Cape Town, Western Cape, South Africa.
    Ketema, Ezra Belay
    Mekelle Univ, Mekelle, Tigray, Ethiopia.
    Khader, Yousef Saleh
    Jordan Univ Sci & Technol, Dept Community Med Publ Hlth & Family Med, Irbid, Jordan.
    Khan, Ejaz Ahmad
    Hlth Serv Acad, Islamabad, Punjab, Pakistan.
    Kim, Daniel
    Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA.
    Kim, Yun Jin
    Southern Univ Coll, Fac Chinese Med, Skudai, Malaysia.
    Kinfu, Yohannes
    Univ Canberra, Ctr Res & Action Publ Hlth, Canberra, ACT, Australia.
    Kissimova-Skarbek, Katarzyna A.
    Jagiellonian Univ Med Coll, Krakow, Poland.
    Koyanagi, Ai
    Parc Sanitari St Joan de Deu CIBERSAM, Res & Dev Unit, Barcelona, Spain.
    Larson, Heidi J.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA;London Sch Hyg & Trop Med, Dept Infect Dis Epidemiol, London, England.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Li, Yongmei
    San Francisco VA Med Ctr, San Francisco, CA USA.
    Lotufo, Paulo A.
    Univ Sao Paulo, Sao Paulo, Brazil.
    Lunevicius, Raimundas
    Aintree Univ Hosp Natl Hlth Serv Fdn Trust, Liverpool, Merseyside, England;Univ Liverpool, Sch Med, Liverpool, Merseyside, England.
    Majeed, Azeem
    Imperial Coll London, Dept Primary Care & Publ Hlth, London, England.
    Malekzadeh, Reza
    Univ Tehran Med Sci, Digest Dis Res Inst, Tehran, Iran.
    Malta, Deborah Carvalho
    Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil.
    Mazidi, Mohsen
    Chinese Acad Sci, Inst Genet & Dev Biol, Key State Lab Mol Dev Biol, Beijing, Peoples R China.
    Memish, Ziad A.
    Saudi Minist Hlth, Riyadh, Saudi Arabia;Alfaisal Univ, Coll Med, Riyadh, Saudi Arabia.
    Mendoza, Walter
    United Nations Populat Fund, Lima, Peru.
    Mengistie, Mubarek Abera
    Jimma Univ, Jimma, Oromia, Ethiopia.
    Mensah, George A.
    NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bethesda, MD USA.
    Mezgebe, Haftay Berhane
    Mekelle Univ, Mekelle, Tigray, Ethiopia.
    Miller, Ted R.
    Pacific Inst Res & Evaluat, Calverton, MD USA;Curtin Univ, Ctr Populat Hlth, Perth, WA, Australia.
    Mohammed, Muktar Sano Kedir
    Mizan Tepi Univ, Mizan Teferi, Ethiopia.
    Mohammed, Shafiu
    Heidelberg Univ, Inst Publ Hlth, Heidelberg, Germany;Ahmadu Bello Univ, Hlth Syst & Policy Res Unit, Zaria, Kaduna, Nigeria.
    Mueller, Ulrich O.
    Fed Inst Populat Res, Wiesbaden, Germany.
    Nagel, Gabriele
    Ulm Univ, Ulm, Germany.
    Nguyen, Cuong Tat
    Nguyen, Quyen Le
    Nong, Vuong Minh
    Noubiap, Jean Jacques N.
    Univ Cape Town, Cape Town, South Africa;Med Diagnost Ctr, Yaounde, Cameroon.
    Ogbo, Felix Akpojene
    Western Sydney Univ, Ctr Hlth Res, Sydney, NSW, Australia.
    Ortiz, Alberto
    IIS Fdn Jimenez Diaz UAM, Madrid, Spain.
    Ota, Erika
    St Lukes Int Univ, Tokyo, Tokyo, Japan.
    Patel, Tejas
    Mt Sinai Hlth Syst, New York, NY USA.
    Pearson-Stuttard, Jonathan
    Imperial Coll London, London, England.
    Perico, Norberto
    IRCCS Ist Ric Farmacol Mario Negri, Bergamo, Italy.
    Petzold, Max
    Univ Gothenburg, Hlth Metr Unit, Gothenburg, Sweden;Univ Witwatersrand, Johannesburg, South Africa.
    Pishgar, Farhad
    Univ Tehran Med Sci, Urooncol Res Ctr, Tehran, Iran;Univ Tehran Med Sci, Noncommunicable Dis Res Ctr, Tehran, Iran.
    Pourmalek, Farshad
    Univ British Columbia, Vancouver, BC, Canada.
    Qorbani, Mostafa
    Alborz Univ Med Sci, Noncommunicable Dis Res Ctr, Karaj, Iran.
    Rahimi-Movaghar, Vafa
    Univ Tehran Med Sci, Sina Trauma & Surg Res Ctr, Tehran, Iran.
    Rai, Rajesh Kumar
    Soc Hlth & Demog Surveillance, Suri, W Bengal, India.
    Rana, Saleem M.
    Contech Sch Publ Hlth, Lahore, Punjab, Pakistan;Contech Int Hlth Consultants, Lahore, Punjab, Pakistan.
    Rawaf, David Laith
    Imperial Coll London, WHO Collaborating Ctr, London, England;North Hampshire Hosp, Basingstroke, England;Univ Coll London Hosp, London, England.
    Rawaf, Salman
    Imperial Coll London, London, England.
    Remuzzi, Giuseppe
    IRCCS Ist Ric Farmacol Mario Negri, Bergamo, Italy;Azienda Socio Sanitaria Territoriale, Papa Giovanni23, Bergamo, Italy;Univ Milan, Dept Biomed & Clin Sci L Sacco, Milan, Italy.
    Renzaho, Andre M. N. N.
    Univ Western Sydney, Locked Bag 1797, Penrith, NSW 2751, Australia.
    Rezaei, Satar
    Kermanshah Univ Med Sci, Sch Publ Hlth, Kermanshah, Iran.
    Roshandel, Gholamreza
    Univ Tehran Med Sci, Digest Dis Res Inst, Tehran, Iran;Golestan Univ Med Sci, Golestan Res Ctr Gastroenterol & Hepatol, Gorgan, Iran.
    Bacher, Dietrich Rothen
    Ulm Univ, Inst Epidemiol & Med Biometry, Ulm, Germany.
    Safdarian, Mahdi
    Univ Tehran Med Sci, Sina Trauma & Surg Res Ctr, Tehran, Iran;Shahid Beheshti Univ Med Sci, Ophthalm Epidemiol Res Ctr, Tehran, Iran.
    Safi, Sare
    Safiri, Saeid
    Maragheh Univ Med Sci, Sch Nursing & Midwifery, Dept Publ Hlth, Managerial Epidemiol Res Ctr, Maragheh, Iran.
    Sahraian, Mohammad Ali
    Univ Tehran Med Sci, Res Ctr, Inst Neurosci, Tehran, Iran.
    Salamati, Payman
    Univ Tehran Med Sci, Sina Trauma & Surg Res Ctr, Tehran, Iran.
    Samy, Abdallah M.
    Ain Shams Univ, Cairo, Egypt.
    Sanabria, Juan Ramon
    Marshall Univ, J Edwards Sch Med, Huntington, WV USA;Case Western Reserve Univ, Cleveland, OH 44106 USA.
    Dolores Sanchez-Nino, Maria
    IIS Fdn Jimenez Diaz, Madrid, Spain.
    Milicevic, Milena M. Santric
    Univ Belgrade, Inst Social Med, Fac Med, Belgrade, Serbia;Univ Belgrade, Ctr Sch Publ Hlth & Hlth Management, Fac Med, Belgrade, Serbia.
    Sartorius, Benn
    Univ KwaZulu Natal, Sch Nursing & Publ Hlth, Publ Hlth Med, Durban, South Africa;SAMRC, UKZN Gastrointestinal Canc Res Ctr, Durban, South Africa.
    Sepanlou, Sadaf G.
    Univ Tehran Med Sci, Digest Dis Res Inst, Tehran, Iran.
    Shaikh, Masood Ali
    Santos Silva, Diego Augusto
    Univ Fed Santa Catarina, Florianopolis, SC, Brazil.
    Alves Silveira, Dayane Gabriele
    Brasilia Univ, Brasilia, DF, Brazil.
    Sobaih, Badr H. A.
    King Saud Univ, Riyadh, Saudi Arabia.
    Abdulkader, Rizwan Suliankatchi
    Minist Hlth, Riyadh, Saudi Arabia.
    Tabares-Seisdedos, Rafael
    Univ Valencia, Incliva Hlth Res Inst, Dept Med, Valencia, Spain;CIBERSAM, Valencia, Spain.
    Tehrani-Banihashemi, Arash
    Iran Univ Med Sci, Prevent Med & Publ Hlth Res Ctr, Tehran, Iran.
    Temsah, Mohamad-Hani
    King Saud Univ, Riyadh, Saudi Arabia;King Faisal Specialist Hosp & Res Ctr, Riyadh, Saudi Arabia.
    Topor-Madry, Roman
    Jagiellonian Univ Med Coll, Inst Publ Hlth, Fac Hlth Sci, Krakow, Poland;Wroclaw Med Univ, Fac Hlth Sci, Wroclaw, Poland.
    Tran, Bach Xuan
    Johns Hopkins Univ, Baltimore, MD USA;Hanoi Med Univ, Hanoi, Vietnam.
    Ukwaja, Kingsley Nnanna
    Fed Teaching Hosp, Dept Internal Med, Abakaliki, Ebonyi State, Nigeria.
    Uthman, Olalekan A.
    Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England.
    van Boven, Job F. M.
    Univ Groningen, Groningen, Netherlands.
    Wakayo, Tolassa
    Jimma Univ, Jimma, Oromia, Ethiopia.
    Werdecker, Andrea
    German Natl Cohort, Fed Inst Populat Res, Competence Ctr Mortal Follow Up, Wiesbaden, Germany.
    Workicho, Abdulhalik
    Jimma Univ, Jimma, Oromia, Ethiopia;Univ Ghent, Ghent, Belgium.
    Yaghoubi, Mohsen
    Univ Saskatchewan, Saskatoon, SK, Canada.
    Yano, Yuichiro
    Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA.
    Yaseri, Mehdi
    Shahid Beheshti Univ Med Sci, Ophthalm Epidemiol Res Ctr, Tehran, Iran;Univ Tehran Med Sci, Tehran, Iran.
    Yonemoto, Naohiro
    Kyoto Univ, Sch Publ Hlth, Dept Biostat, Kyoto, Japan.
    Younis, Mustafa Z.
    Jackson State Univ, Jackson, MS USA.
    Zhang, Anthony Lin
    RMIT Univ, Sch Hlth & Biomed Sci, Bundoora, Vic, Australia.
    Jumaan, Aisha O.
    Vos, Theo
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Naghavi, Mohsen
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Hay, Simon I.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA;Univ Oxford, Oxford Big Data Inst, LiKa Shing Ctr Hlth Informat & Discovery, Oxford, England.
    Murray, Christopher J. L.
    Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
    Diabetes mellitus and chronic kidney disease in the Eastern Mediterranean Region: findings from the Global Burden of Disease 2015 study2018In: International Journal of Public Health, ISSN 1661-8556, E-ISSN 1661-8564, Vol. 63, p. 177-186Article in journal (Refereed)
    Abstract [en]

    We used findings from the Global Burden of Disease 2015 study to update our previous publication on the burden of diabetes and chronic kidney disease due to diabetes (CKD-DM) during 1990-2015. We extracted GBD 2015 estimates for prevalence, mortality, and disability-adjusted life years (DALYs) of diabetes (including burden of low vision due to diabetes, neuropathy, and amputations and CKD-DM for 22 countries of the EMR from the GBD visualization tools. In 2015, 135,230 (95% UI 123,034-148,184) individuals died from diabetes and 16,470 (95% UI 13,977-18,961) from CKD-DM, 216 and 179% increases, respectively, compared to 1990. The total number of people with diabetes was 42.3 million (95% UI 38.6-46.4 million) in 2015. DALY rates of diabetes in 2015 were significantly higher than the expected rates based on Socio-demographic Index (SDI). Our study showed a large and increasing burden of diabetes in the region. There is an urgency in dealing with diabetes and its consequences, and these efforts should be at the forefront of health prevention and promotion.

  • 262. Morris, Andrew P
    et al.
    Le, Thu H
    Wu, Haojia
    Akbarov, Artur
    van der Most, Peter J
    Hemani, Gibran
    Smith, George Davey
    Mahajan, Anubha
    Gaulton, Kyle J
    Nadkarni, Girish N
    Valladares-Salgado, Adan
    Wacher-Rodarte, Niels
    Mychaleckyj, Josyf C
    Dueker, Nicole D
    Guo, Xiuqing
    Hai, Yang
    Haessler, Jeffrey
    Kamatani, Yoichiro
    Stilp, Adrienne M
    Zhu, Gu
    Cook, James P
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Blanton, Susan H
    de Borst, Martin H
    Bottinger, Erwin P
    Buchanan, Thomas A
    Cechova, Sylvia
    Charchar, Fadi J
    Chu, Pei-Lun
    Damman, Jeffrey
    Eales, James
    Gharavi, Ali G
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Heath, Andrew C
    Ipp, Eli
    Kiryluk, Krzysztof
    Kramer, Holly J
    Kubo, Michiaki
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lindgren, Cecilia M
    Lu, Yingchang
    Madden, Pamela A F
    Montgomery, Grant W
    Papanicolaou, George J
    Raffel, Leslie J
    Sacco, Ralph L
    Sanchez, Elena
    Stark, Holger
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Taylor, Kent D
    Xiang, Anny H
    Zivkovic, Aleksandra
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, Stanford Univ, Stanford Cardiovasc Inst, Stanford, USA; Stanford Univ, Stanford Diabet Res Ctr, Stanford, USA.
    Martin, Nicholas G
    Whitfield, John B
    Cai, Jianwen
    Laurie, Cathy C
    Okada, Yukinori
    Matsuda, Koichi
    Kooperberg, Charles
    Chen, Yii-Der Ida
    Rundek, Tatjana
    Rich, Stephen S
    Loos, Ruth J F
    Parra, Esteban J
    Cruz, Miguel
    Rotter, Jerome I
    Snieder, Harold
    Tomaszewski, Maciej
    Humphreys, Benjamin D
    Franceschini, Nora
    Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies2019In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, no 1, article id 29Article in journal (Refereed)
    Abstract [en]

    Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.

  • 263. Murray, Christopher J L
    et al.
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    Abubakar, Ibrahim
    Abu-Raddad, Laith J
    Abu-Rmeileh, Niveen M
    Achoki, Tom
    Ackerman, Ilana N
    Ademi, Zanfina
    Adou, Arsène K
    Adsuar, José C
    Afshin, Ashkan
    Agardh, Emilie E
    Alam, Sayed Saidul
    Alasfoor, Deena
    Albittar, Mohammed I
    Alegretti, Miguel A
    Alemu, Zewdie A
    Alfonso-Cristancho, Rafael
    Alhabib, Samia
    Ali, Raghib
    Alla, François
    Allebeck, Peter
    Almazroa, Mohammad A
    Alsharif, Ubai
    Alvarez, Elena
    Alvis-Guzman, Nelson
    Amare, Azmeraw T
    Ameh, Emmanuel A
    Amini, Heresh
    Ammar, Walid
    Anderson, H Ross
    Anderson, Benjamin O
    Antonio, Carl Abelardo T
    Anwari, Palwasha
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Arsenijevic, Valentina S Arsic
    Artaman, Al
    Asghar, Rana J
    Assadi, Reza
    Atkins, Lydia S
    Avila, Marco A
    Awuah, Baffour
    Bachman, Victoria F
    Badawi, Alaa
    Bahit, Maria C
    Balakrishnan, Kalpana
    Banerjee, Amitava
    Barker-Collo, Suzanne L
    Barquera, Simon
    Barregard, Lars
    Barrero, Lope H
    Basu, Arindam
    Basu, Sanjay
    Basulaiman, Mohammed O
    Beardsley, Justin
    Bedi, Neeraj
    Beghi, Ettore
    Bekele, Tolesa
    Bell, Michelle L
    Benjet, Corina
    Bennett, Derrick A
    Bensenor, Isabela M
    Benzian, Habib
    Bernabé, Eduardo
    Bertozzi-Villa, Amelia
    Beyene, Tariku J
    Bhala, Neeraj
    Bhalla, Ashish
    Bhutta, Zulfiqar A
    Bienhoff, Kelly
    Bikbov, Boris
    Biryukov, Stan
    Blore, Jed D
    Blosser, Christopher D
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    Bolliger, Ian W
    Başara, Berrak Bora
    Bornstein, Natan M
    Bose, Dipan
    Boufous, Soufiane
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    Brayne, Carol E
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    Breitborde, Nicholas J K
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    Brown, Jonathan C
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    Buckle, Geoffrey C
    Budke, Christine M
    Bulchis, Anne
    Bulloch, Andrew G
    Campos-Nonato, Ismael R
    Carabin, Hélène
    Carapetis, Jonathan R
    Cárdenas, Rosario
    Carpenter, David O
    Caso, Valeria
    Castañeda-Orjuela, Carlos A
    Castro, Ruben E
    Catalá-López, Ferrán
    Cavalleri, Fiorella
    Çavlin, Alanur
    Chadha, Vineet K
    Chang, Jung-Chen
    Charlson, Fiona J
    Chen, Honglei
    Chen, Wanqing
    Chiang, Peggy P
    Chimed-Ochir, Odgerel
    Chowdhury, Rajiv
    Christensen, Hanne
    Christophi, Costas A
    Cirillo, Massimo
    Coates, Matthew M
    Coffeng, Luc E
    Coggeshall, Megan S
    Colistro, Valentina
    Colquhoun, Samantha M
    Cooke, Graham S
    Cooper, Cyrus
    Cooper, Leslie T
    Coppola, Luis M
    Cortinovis, Monica
    Criqui, Michael H
    Crump, John A
    Cuevas-Nasu, Lucia
    Danawi, Hadi
    Dandona, Lalit
    Dandona, Rakhi
    Dansereau, Emily
    Dargan, Paul I
    Davey, Gail
    Davis, Adrian
    Davitoiu, Dragos V
    Dayama, Anand
    De Leo, Diego
    Degenhardt, Louisa
    Del Pozo-Cruz, Borja
    Dellavalle, Robert P
    Deribe, Kebede
    Derrett, Sarah
    Jarlais, Don C Des
    Dessalegn, Muluken
    Dharmaratne, Samath D
    Dherani, Mukesh K
    Diaz-Torné, Cesar
    Dicker, Daniel
    Ding, Eric L
    Dokova, Klara
    Dorsey, E Ray
    Driscoll, Tim R
    Duan, Leilei
    Duber, Herbert C
    Ebel, Beth E
    Edmond, Karen M
    Elshrek, Yousef M
    Endres, Matthias
    Ermakov, Sergey P
    Erskine, Holly E
    Eshrati, Babak
    Esteghamati, Alireza
    Estep, Kara
    Faraon, Emerito Jose A
    Farzadfar, Farshad
    Fay, Derek F
    Feigin, Valery L
    Felson, David T
    Fereshtehnejad, Seyed-Mohammad
    Fernandes, Jefferson G
    Ferrari, Alize J
    Fitzmaurice, Christina
    Flaxman, Abraham D
    Fleming, Thomas D
    Foigt, Nataliya
    Forouzanfar, Mohammad H
    Fowkes, F Gerry R
    Paleo, Urbano Fra
    Franklin, Richard C
    Fürst, Thomas
    Gabbe, Belinda
    Gaffikin, Lynne
    Gankpé, Fortuné G
    Geleijnse, Johanna M
    Gessner, Bradford D
    Gething, Peter
    Gibney, Katherine B
    Giroud, Maurice
    Giussani, Giorgia
    Dantes, Hector Gomez
    Gona, Philimon
    González-Medina, Diego
    Gosselin, Richard A
    Gotay, Carolyn C
    Goto, Atsushi
    Gouda, Hebe N
    Graetz, Nicholas
    Gugnani, Harish C
    Gupta, Rahul
    Gupta, Rajeev
    Gutiérrez, Reyna A
    Haagsma, Juanita
    Hafezi-Nejad, Nima
    Hagan, Holly
    Halasa, Yara A
    Hamadeh, Randah R
    Hamavid, Hannah
    Hammami, Mouhanad
    Hancock, Jamie
    Hankey, Graeme J
    Hansen, Gillian M
    Hao, Yuantao
    Harb, Hilda L
    Haro, Josep Maria
    Havmoeller, Rasmus
    Hay, Simon I
    Hay, Roderick J
    Heredia-Pi, Ileana B
    Heuton, Kyle R
    Heydarpour, Pouria
    Higashi, Hideki
    Hijar, Martha
    Hoek, Hans W
    Hoffman, Howard J
    Hosgood, H Dean
    Hossain, Mazeda
    Hotez, Peter J
    Hoy, Damian G
    Hsairi, Mohamed
    Hu, Guoqing
    Huang, Cheng
    Huang, John J
    Husseini, Abdullatif
    Huynh, Chantal
    Iannarone, Marissa L
    Iburg, Kim M
    Innos, Kaire
    Inoue, Manami
    Islami, Farhad
    Jacobsen, Kathryn H
    Jarvis, Deborah L
    Jassal, Simerjot K
    Jee, Sun Ha
    Jeemon, Panniyammakal
    Jensen, Paul N
    Jha, Vivekanand
    Jiang, Guohong
    Jiang, Ying
    Jonas, Jost B
    Juel, Knud
    Kan, Haidong
    Karch, André
    Karema, Corine K
    Karimkhani, Chante
    Karthikeyan, Ganesan
    Kassebaum, Nicholas J
    Kaul, Anil
    Kawakami, Norito
    Kazanjan, Konstantin
    Kemp, Andrew H
    Kengne, Andre P
    Keren, Andre
    Khader, Yousef S
    Khalifa, Shams Eldin A
    Khan, Ejaz A
    Khan, Gulfaraz
    Khang, Young-Ho
    Kieling, Christian
    Kim, Daniel
    Kim, Sungroul
    Kim, Yunjin
    Kinfu, Yohannes
    Kinge, Jonas M
    Kivipelto, Miia
    Knibbs, Luke D
    Knudsen, Ann Kristin
    Kokubo, Yoshihiro
    Kosen, Soewarta
    Krishnaswami, Sanjay
    Defo, Barthelemy Kuate
    Bicer, Burcu Kucuk
    Kuipers, Ernst J
    Kulkarni, Chanda
    Kulkarni, Veena S
    Kumar, G Anil
    Kyu, Hmwe H
    Lai, Taavi
    Lalloo, Ratilal
    Lallukka, Tea
    Lam, Hilton
    Lan, Qing
    Lansingh, Van C
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lawrynowicz, Alicia E B
    Leasher, Janet L
    Leigh, James
    Leung, Ricky
    Levitz, Carly E
    Li, Bin
    Li, Yichong
    Li, Yongmei
    Lim, Stephen S
    Lind, Maggie
    Lipshultz, Steven E
    Liu, Shiwei
    Liu, Yang
    Lloyd, Belinda K
    Lofgren, Katherine T
    Logroscino, Giancarlo
    Looker, Katharine J
    Lortet-Tieulent, Joannie
    Lotufo, Paulo A
    Lozano, Rafael
    Lucas, Robyn M
    Lunevicius, Raimundas
    Lyons, Ronan A
    Ma, Stefan
    Macintyre, Michael F
    Mackay, Mark T
    Majdan, Marek
    Malekzadeh, Reza
    Marcenes, Wagner
    Margolis, David J
    Margono, Christopher
    Marzan, Melvin B
    Masci, Joseph R
    Mashal, Mohammad T
    Matzopoulos, Richard
    Mayosi, Bongani M
    Mazorodze, Tasara T
    Mcgill, Neil W
    Mcgrath, John J
    Mckee, Martin
    Mclain, Abigail
    Meaney, Peter A
    Medina, Catalina
    Mehndiratta, Man Mohan
    Mekonnen, Wubegzier
    Melaku, Yohannes A
    Meltzer, Michele
    Memish, Ziad A
    Mensah, George A
    Meretoja, Atte
    Mhimbira, Francis A
    Micha, Renata
    Miller, Ted R
    Mills, Edward J
    Mitchell, Philip B
    Mock, Charles N
    Ibrahim, Norlinah Mohamed
    Mohammad, Karzan A
    Mokdad, Ali H
    Mola, Glen L D
    Monasta, Lorenzo
    Hernandez, Julio C Montañez
    Montico, Marcella
    Montine, Thomas J
    Mooney, Meghan D
    Moore, Ami R
    Moradi-Lakeh, Maziar
    Moran, Andrew E
    Mori, Rintaro
    Moschandreas, Joanna
    Moturi, Wilkister N
    Moyer, Madeline L
    Mozaffarian, Dariush
    Msemburi, William T
    Mueller, Ulrich O
    Mukaigawara, Mitsuru
    Mullany, Erin C
    Murdoch, Michele E
    Murray, Joseph
    Murthy, Kinnari S
    Naghavi, Mohsen
    Naheed, Aliya
    Naidoo, Kovin S
    Naldi, Luigi
    Nand, Devina
    Nangia, Vinay
    Narayan, K M Venkat
    Nejjari, Chakib
    Neupane, Sudan P
    Newton, Charles R
    Ng, Marie
    Ngalesoni, Frida N
    Nguyen, Grant
    Nisar, Muhammad I
    Nolte, Sandra
    Norheim, Ole F
    Norman, Rosana E
    Norrving, Bo
    Nyakarahuka, Luke
    Oh, In-Hwan
    Ohkubo, Takayoshi
    Ohno, Summer L
    Olusanya, Bolajoko O
    Opio, John Nelson
    Ortblad, Katrina
    Ortiz, Alberto
    Pain, Amanda W
    Pandian, Jeyaraj D
    Panelo, Carlo Irwin A
    Papachristou, Christina
    Park, Eun-Kee
    Park, Jae-Hyun
    Patten, Scott B
    Patton, George C
    Paul, Vinod K
    Pavlin, Boris I
    Pearce, Neil
    Pereira, David M
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    Perez-Ruiz, Fernando
    Perico, Norberto
    Pervaiz, Aslam
    Pesudovs, Konrad
    Peterson, Carrie B
    Petzold, Max
    Phillips, Michael R
    Phillips, Bryan K
    Phillips, David E
    Piel, Frédéric B
    Plass, Dietrich
    Poenaru, Dan
    Polinder, Suzanne
    Pope, Daniel
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    Poulton, Richie G
    Pourmalek, Farshad
    Prabhakaran, Dorairaj
    Prasad, Noela M
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    Quistberg, D Alex
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    Rahman, Sajjad U
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    Razavi, Homie
    Reddy, K Srinath
    Refaat, Amany
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    Scarborough, Peter
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    Seedat, Soraya
    Sepanlou, Sadaf G
    Serina, Peter T
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    Shaheen, Amira
    Shahraz, Saeid
    Levy, Teresa Shamah
    Shangguan, Siyi
    She, Jun
    Sheikhbahaei, Sara
    Shi, Peilin
    Shibuya, Kenji
    Shinohara, Yukito
    Shiri, Rahman
    Shishani, Kawkab
    Shiue, Ivy
    Shrime, Mark G
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    Silberberg, Donald H
    Simard, Edgar P
    Sindi, Shireen
    Singh, Abhishek
    Singh, Jasvinder A
    Singh, Lavanya
    Skirbekk, Vegard
    Slepak, Erica Leigh
    Sliwa, Karen
    Soneji, Samir
    Søreide, Kjetil
    Soshnikov, Sergey
    Sposato, Luciano A
    Sreeramareddy, Chandrashekhar T
    Stanaway, Jeffrey D
    Stathopoulou, Vasiliki
    Stein, Dan J
    Stein, Murray B
    Steiner, Caitlyn
    Steiner, Timothy J
    Stevens, Antony
    Stewart, Andrea
    Stovner, Lars J
    Stroumpoulis, Konstantinos
    Sunguya, Bruno F
    Swaminathan, Soumya
    Swaroop, Mamta
    Sykes, Bryan L
    Tabb, Karen M
    Takahashi, Ken
    Tandon, Nikhil
    Tanne, David
    Tanner, Marcel
    Tavakkoli, Mohammad
    Taylor, Hugh R
    Ao, Braden J Te
    Tediosi, Fabrizio
    Temesgen, Awoke M
    Templin, Tara
    Ten Have, Margreet
    Tenkorang, Eric Y
    Terkawi, Abdullah S
    Thomson, Blake
    Thorne-Lyman, Andrew L
    Thrift, Amanda G
    Thurston, George D
    Tillmann, Taavi
    Tonelli, Marcello
    Topouzis, Fotis
    Toyoshima, Hideaki
    Traebert, Jefferson
    Tran, Bach X
    Trillini, Matias
    Truelsen, Thomas
    Tsilimbaris, Miltiadis
    Tuzcu, Emin M
    Uchendu, Uche S
    Ukwaja, Kingsley N
    Undurraga, Eduardo A
    Uzun, Selen B
    Van Brakel, Wim H
    Van De Vijver, Steven
    van Gool, Coen H
    Van Os, Jim
    Vasankari, Tommi J
    Venketasubramanian, N
    Violante, Francesco S
    Vlassov, Vasiliy V
    Vollset, Stein Emil
    Wagner, Gregory R
    Wagner, Joseph
    Waller, Stephen G
    Wan, Xia
    Wang, Haidong
    Wang, Jianli
    Wang, Linhong
    Warouw, Tati S
    Weichenthal, Scott
    Weiderpass, Elisabete
    Weintraub, Robert G
    Wenzhi, Wang
    Werdecker, Andrea
    Westerman, Ronny
    Whiteford, Harvey A
    Wilkinson, James D
    Williams, Thomas N
    Wolfe, Charles D
    Wolock, Timothy M
    Woolf, Anthony D
    Wulf, Sarah
    Wurtz, Brittany
    Xu, Gelin
    Yan, Lijing L
    Yano, Yuichiro
    Ye, Pengpeng
    Yentür, Gökalp K
    Yip, Paul
    Yonemoto, Naohiro
    Yoon, Seok-Jun
    Younis, Mustafa Z
    Yu, Chuanhua
    Zaki, Maysaa E
    Zhao, Yong
    Zheng, Yingfeng
    Zonies, David
    Zou, Xiaonong
    Salomon, Joshua A
    Lopez, Alan D
    Vos, Theo
    Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013: quantifying the epidemiological transition2015In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 386, no 10009, p. 2145-2191Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development.

    METHODS:

    We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time.

    FINDINGS:

    Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6-6·6), from 65·3 years (65·0-65·6) in 1990 to 71·5 years (71·0-71·9) in 2013, HALE at birth rose by 5·4 years (4·9-5·8), from 56·9 years (54·5-59·1) to 62·3 years (59·7-64·8), total DALYs fell by 3·6% (0·3-7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6-29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries.

    INTERPRETATION:

    Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition-in which increasing sociodemographic status brings structured change in disease burden-is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

    FUNDING:

    Bill & Melinda Gates Foundation.

  • 264.
    Mutscher, Diana K
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Gustafsson, Urban
    Basu, Samar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, Anders O
    Department of Medical Sciences.
    Eriksson, Mats
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Ropivacaine may have advantates cmpared to bupivacaine in porcine endotoxemic shock2005Other (Other (popular scientific, debate etc.))
  • 265.
    Mutschler, Diana K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Eriksson, M. B.
    Wikström, B. G.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berggren-Kiiski, Ritva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Lagrange, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Nordgren, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Microdialysis-evaluated myocardial cyclooxygenase-mediated inflammation and early circulatory depression in porcine endotoxemia2003In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 31, no 6, p. 1780-1785Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the early myocardial biochemical inflammatory response with the microdialysis technique during porcine endotoxemia and to simultaneously monitor systemic hemodynamics.

    DESIGN: Prospective, randomized, placebo-controlled trial with parallel groups.

    SETTING: Animal research laboratory at the University Hospital of Uppsala, Sweden.

    SUBJECTS: Thirteen piglets aged 12-14 wks receiving general anesthesia.

    INTERVENTIONS: After thoracotomy and the insertion of microdialysis probes in standardized locations in the left ventricle of the heart and in the quadriceps muscle, seven pigs received a continuous infusion of endotoxin, initiating a severe endotoxemic shock. Six pigs received saline instead of endotoxin.

    MEASUREMENTS AND MAIN RESULTS: Endotoxemia caused a rapid and pronounced elevation of a metabolite obtained from prostaglandin degradation, 15-keto-dihydro-PGF(2alpha), in myocardial microdialysate fluid being specific of cyclooxygenase (COX)-mediated inflammation (p <.001 vs. saline-infused controls). Simultaneously, we observed a decrease in left ventricular stroke work index in the endotoxemic pigs (p <.01 vs. saline-infused controls). Endotoxemia did not alter 15-keto-dihydro-PGF(2alpha) levels in quadriceps muscle. Endotoxemia caused increases in taurine, hypoxanthine, and magnesium in myocardial microdialysate (p <.05 vs. saline-infused controls), whereas the contents of pyruvate, lactate, inosine, adenosine, and calcium were not significantly changed.

    CONCLUSION: Endotoxemia induced a myocardial COX-mediated inflammation without signs of ischemia. In parallel, a depletion of myocardial energy substrates and a deterioration in myocardial performance were seen.

  • 266.
    Mutschler, Diana K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Gustafsson, Urban
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Larsson, Anders O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Eriksson, Mats B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Ropivacaine may have advantages compared to bupivacaine in porcine endotoxemic shock2006In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 111, no 2, p. 189-199Article in journal (Refereed)
    Abstract [en]

    Patients that undergo major abdominal surgery often receive epidural postoperative analgesia. Septic complications are frequently seen in this cohort. In a porcine model of endotoxemic shock, resembling human gram-negative septic shock, we evaluated the effects of two widely used local anaesthetics, bupivacaine and ropivacaine given intravenously. In the endotoxin-ropivacaine group mixed venous saturation and platelet count were higher as compared to endotoxemic controls. Mean arterial blood pressure and platelet count were higher in ropivacaine-endotoxin pigs than in bupivacaine-endotoxin ones. Bupivacaine augmented endotoxin-mediated decrease in left ventricular stroke work index. Ropivacaine displays pathophysiological advantages compared to bupivacaine in septic shock, which may be explained by improved tissue perfusion by ropivacaine.

  • 267.
    Mutschler, Diana K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lagrange, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Etanercept reduces late endotoxin-induced pulmonary hypertension in the pig2006In: Journal of Interferon and Cytokine Research, ISSN 1079-9907, E-ISSN 1557-7465, Vol. 26, no 9, p. 661-667Article in journal (Refereed)
    Abstract [en]

    To evaluate whether etanercept, a tumor necrosis factor (TNF)-blocking agent, may counteract hemodynamic deterioration in endotoxemic shock, we designed a prospective, randomized placebo-controlled trial with parallel groups, consisting of 13 pigs aged 10-14 weeks receiving general anesthesia. Five pigs were given 25 mg of etanercept, 1 h before the start of a 4-h continuous infusion of endotoxin. Another 5 pigs were given the corresponding volume of saline, 1 h before the start of a 4-h continuous infusion of endotoxin. Three pigs were given 25 mg of etanercept, 1 hr before the start of a 4-h continuous infusion of saline. At 1 h of endotoxemia, mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) increased identically in both groups of pigs receiving endotoxin. Thereafter, two distinct different patterns in hemodynamics were observed. TNF-blocked pigs showed significantly lower MPAP and PVRI compared to controls. In the etanercept-treated endotoxemic pigs, Doppler analysis of the diastolic mitral inflow demonstrated a significantly increased E/A-ratio (early mitral wave inflow was divided by the atrial wave) at 2 h. The TNFblocking agent etanercept normalized two hemodynamic features of endotoxin-induced septic shock in pigs: (1) the sustained pulmonary hypertension and (2) diastolic dysfunction.

  • 268. Mårtensson, J
    et al.
    Vaara, S T
    Pettilä, V
    Ala-Kokko, T
    Karlsson, S
    Inkinen, O
    Uusaro, A
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Bell, M
    Assessment of plasma endostatin to predict acute kidney injury in critically ill patients.2017In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, no 10, p. 1286-1295Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We evaluated whether plasma endostatin predicts acute kidney injury (AKI), need for renal replacement therapy (RRT), or death.

    METHODS: Prospective, observational, multicenter study from 1 September 2011 to 1 February 2012 with data from 17 intensive care units (ICUs) in Finland.

    RESULTS: A total of 1112 patients were analyzed. We measured plasma endostatin within 2 h of ICU admission. Early AKI (KDIGO stage within 12 h of ICU admission) was found in 20% of the cohort, and 18% developed late AKI (KDIGO criteria > 12 h from ICU admission). Median (IQR) admission endostatin was higher in the early AKI group, 29 (19.1, 41.9) ng/ml as compared to 22.4 (16.1, 30.1) ng/ml for the late AKI group, and 18 (14.0, 23.6) ng/ml for non-AKI patients (P < 0.001). Endostatin level increased with increasing KDIGO stage. Significantly higher endostatin levels were found in patients with sepsis as compared to those without. Predictive properties for AKI, RRT, and mortality were low with corresponding areas under the receiver operating characteristic curve (AUC) of 0.62, 0.67, and 0.59. Sensitivity analyses among patients with chronic kidney disease or sepsis did not improve the predictive ability of endostatin. Adding endostatin to a clinical AKI prediction model (illness severity score, urine output, and age) insignificantly changed the AUC from 0.67 to 0.70 (P = 0.14).

    CONCLUSIONS: Endostatin increases with AKI severity but has limited value as a predictor of AKI, RRT and 90-day mortality in patients admitted to ICU. Moreover, endostatin does not improve AKI risk prediction when added to a clinical risk model.

  • 269.
    Mårtensson, Johan
    et al.
    Karolinska Institutet, Stockholm.
    Jonsson, Niklas
    Karolinska Institutet, Stockholm.
    Glassford, Neil J
    Austin Hospital, Australien.
    Bell, Max
    Karolinska Institutet, Stockholm.
    Martling, Claes-Roland
    Karolinska Institutet, Stockholm.
    Bellomo, Rinaldo
    Austin Hospital, Australien.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Plasma endostatin may improve acute kidney injury risk prediction in critically ill patients2016In: Annals of Intensive Care, ISSN 2110-5820, E-ISSN 2110-5820, Vol. 6, article id 6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Breakdown of renal endothelial, tubular and glomerular matrix collagen plays a major role in acute kidney injury (AKI) development. Such collagen breakdown releases endostatin into the circulation. The aim of this study was to compare the AKI predictive value of plasma endostatin with two previously suggested biomarkers of AKI, cystatin C and neutrophil gelatinase-associated lipocalin (NGAL).

    METHODS: We studied 93 patients without kidney disease who had a first plasma sample obtained within 48 h of ICU admission. We identified risk factors for AKI within the population and designed a predictive model. The individual ability and net contribution of endostatin, cystatin C and NGAL to predict AKI were evaluated by the area under the receiver operating characteristics curve (AUC), likelihood-ratio test, net reclassification improvement (NRI) and integrated discrimination improvement (IDI).

    RESULTS: In total, 21 (23 %) patients experienced AKI within 72 h. A three-parameter model (age, illness severity score and early oliguria) predicted AKI with an AUC of 0.759 (95 % CI 0.646-0.872). Adding endostatin to the predictive model significantly (P = 0.04) improved the AUC to 0.839 (95 % CI 0.752-0.925). In addition, endostatin significantly improved risk prediction using the likelihood-ratio test (P = 0.005), NRI analysis (0.27; P = 0.04) and IDI analysis (0.07; P = 0.04). In contrast, adding cystatin C or NGAL to the three-parameter model did not improve risk prediction in any of the four analyses.

    CONCLUSIONS: In this cohort of critically ill patients, plasma endostatin improved AKI prediction based on clinical risk factors, while cystatin C and NGAL did not.

  • 270. Naghavi, M,
    et al.
    Abajobir, AA,
    Abbafati, C
    Abbas, KM
    Abd-Allah, F
    Abera, SF
    Aboyans, V
    Adetokunboh, O
    Afshin, A
    Agrawal, A
    Ahmadi, A
    Ahmed, MB
    Ärnlöv, Johan
    Dalarna University; Karolinska institute.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Zaidi, Z
    Zaki, MES
    Zegeye, EA
    Zenebe, ZM
    Zerfu, TA
    Zhang, AL
    Zhang, X
    Zipkin, B
    Zodpey, S
    Lopez, AD,
    Murray, CJL
    Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016.2017In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 390, no 10100, p. 1151-1210Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Monitoring levels and trends in premature mortality is crucial to understanding how societies can address prominent sources of early death. The Global Burden of Disease 2016 Study (GBD 2016) provides a comprehensive assessment of cause-specific mortality for 264 causes in 195 locations from 1980 to 2016. This assessment includes evaluation of the expected epidemiological transition with changes in development and where local patterns deviate from these trends.

    METHODS: We estimated cause-specific deaths and years of life lost (YLLs) by age, sex, geography, and year. YLLs were calculated from the sum of each death multiplied by the standard life expectancy at each age. We used the GBD cause of death database composed of: vital registration (VR) data corrected for under-registration and garbage coding; national and subnational verbal autopsy (VA) studies corrected for garbage coding; and other sources including surveys and surveillance systems for specific causes such as maternal mortality. To facilitate assessment of quality, we reported on the fraction of deaths assigned to GBD Level 1 or Level 2 causes that cannot be underlying causes of death (major garbage codes) by location and year. Based on completeness, garbage coding, cause list detail, and time periods covered, we provided an overall data quality rating for each location with scores ranging from 0 stars (worst) to 5 stars (best). We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to generate estimates for each location, year, age, and sex. We assessed observed and expected levels and trends of cause-specific deaths in relation to the Socio-demographic Index (SDI), a summary indicator derived from measures of average income per capita, educational attainment, and total fertility, with locations grouped into quintiles by SDI. Relative to GBD 2015, we expanded the GBD cause hierarchy by 18 causes of death for GBD 2016.

    FINDINGS: The quality of available data varied by location. Data quality in 25 countries rated in the highest category (5 stars), while 48, 30, 21, and 44 countries were rated at each of the succeeding data quality levels. Vital registration or verbal autopsy data were not available in 27 countries, resulting in the assignment of a zero value for data quality. Deaths from non-communicable diseases (NCDs) represented 72·3% (95% uncertainty interval [UI] 71·2-73·2) of deaths in 2016 with 19·3% (18·5-20·4) of deaths in that year occurring from communicable, maternal, neonatal, and nutritional (CMNN) diseases and a further 8·43% (8·00-8·67) from injuries. Although age-standardised rates of death from NCDs decreased globally between 2006 and 2016, total numbers of these deaths increased; both numbers and age-standardised rates of death from CMNN causes decreased in the decade 2006-16-age-standardised rates of deaths from injuries decreased but total numbers varied little. In 2016, the three leading global causes of death in children under-5 were lower respiratory infections, neonatal preterm birth complications, and neonatal encephalopathy due to birth asphyxia and trauma, combined resulting in 1·80 million deaths (95% UI 1·59 million to 1·89 million). Between 1990 and 2016, a profound shift toward deaths at older ages occurred with a 178% (95% UI 176-181) increase in deaths in ages 90-94 years and a 210% (208-212) increase in deaths older than age 95 years. The ten leading causes by rates of age-standardised YLL significantly decreased from 2006 to 2016 (median annualised rate of change was a decrease of 2·89%); the median annualised rate of change for all other causes was lower (a decrease of 1·59%) during the same interval. Globally, the five leading causes of total YLLs in 2016 were cardiovascular diseases; diarrhoea, lower respiratory infections, and other common infectious diseases; neoplasms; neonatal disorders; and HIV/AIDS and tuberculosis. At a finer level of disaggregation within cause groupings, the ten leading causes of total YLLs in 2016 were ischaemic heart disease, cerebrovascular disease, lower respiratory infections, diarrhoeal diseases, road injuries, malaria, neonatal preterm birth complications, HIV/AIDS, chronic obstructive pulmonary disease, and neonatal encephalopathy due to birth asphyxia and trauma. Ischaemic heart disease was the leading cause of total YLLs in 113 countries for men and 97 countries for women. Comparisons of observed levels of YLLs by countries, relative to the level of YLLs expected on the basis of SDI alone, highlighted distinct regional patterns including the greater than expected level of YLLs from malaria and from HIV/AIDS across sub-Saharan Africa; diabetes mellitus, especially in Oceania; interpersonal violence, notably within Latin America and the Caribbean; and cardiomyopathy and myocarditis, particularly in eastern and central Europe. The level of YLLs from ischaemic heart disease was less than expected in 117 of 195 locations. Other leading causes of YLLs for which YLLs were notably lower than expected included neonatal preterm birth complications in many locations in both south Asia and southeast Asia, and cerebrovascular disease in western Europe.

    INTERPRETATION: The past 37 years have featured declining rates of communicable, maternal, neonatal, and nutritional diseases across all quintiles of SDI, with faster than expected gains for many locations relative to their SDI. A global shift towards deaths at older ages suggests success in reducing many causes of early death. YLLs have increased globally for causes such as diabetes mellitus or some neoplasms, and in some locations for causes such as drug use disorders, and conflict and terrorism. Increasing levels of YLLs might reflect outcomes from conditions that required high levels of care but for which effective treatments remain elusive, potentially increasing costs to health systems.

    FUNDING: Bill & Melinda Gates Foundation.

  • 271. Naghavi, Moshen
    et al.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Murray, Christopher JL
    Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.2015In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 385, no 9963, p. 117-171Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries.

    METHODS: We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions.

    FINDINGS: Global life expectancy for both sexes increased from 65·3 years (UI 65·0-65·6) in 1990, to 71·5 years (UI 71·0-71·9) in 2013, while the number of deaths increased from 47·5 million (UI 46·8-48·2) to 54·9 million (UI 53·6-56·3) over the same interval. Global progress masked variation by age and sex: for children, average absolute differences between countries decreased but relative differences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative differences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10·7%, from 4·3 million deaths in 1990 to 4·8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions.

    INTERPRETATION: For most countries, the general pattern of reductions in age-sex specific mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.

  • 272.
    Ndjole, Annaby Moussa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Bodolea, Constantin
    Nilsen, Tom
    Gentian AS, Moss, Norway.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Flodin, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Determination of cerebrospinal fluid cystatin C on Architect ci82002010In: JIM - Journal of Immunological Methods, ISSN 0022-1759, E-ISSN 1872-7905, Vol. 360, no 1-2, p. 84-88Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Human cystatin C is a cysteine protease inhibitor produced by all nucleated cells in the body and the protein is present in all body fluids. The concentration in cerebrospinal fluid (CSF) is considerably higher than in plasma. Cystatin C levels seem to influence the development of Alzheimer disease (AD) and low levels in the brain are associated with an increased risk for AD. The aim of this study was to develop a high throughput assay for the quantification of cystatin C in CSF. METHODS: Antigen excess, imprecision, interference, linearity, recovery, sample stability and reference values were evaluated on Architect ci8200 (Abbott Laboratories, Abbott Park, IL, USA). RESULTS: The assay had an antigen-excess limit at 23 mg/L and was linear over the range of 0.84 to 8.33 mg/L. Results > 8.33 mg/L were automatically rerun in a higher dilution. Within-run coefficient of variation (CV) was 1.71, 1.10 and 0.79%, between day CV was 1.71, 0.39 and 1.45%, between-run CV was 0.58, 0.66 and 0.48%, and total CV was 2.49, 1.34 and 1.72% at cystatin C concentrations of 1.39, 3.17 and 6.28 mg/L, respectively. The recovery was 97-102%. No interference at a 7.5% deviation level was observed for 8.5 g/L of hemoglobin or 800 mg/L (1368 micromol/L) of bilirubin. Reference values for cystatin C in cerebrospinal fluid obtained with this method were 2.42-14.33 mg/L.

  • 273.
    Nelander, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetric research.
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bergman, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetric research.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetric research. Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Cerebral Magnesium Levels in Preeclampsia; A Phosphorus Magnetic Resonance Spectroscopy Study2017In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 30, no 7, p. 667-672Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Magnesium sulfate (MgSO4) is used as a prophylaxis for eclamptic seizures. The exact mechanism of action is not fully established. We used phosphorus magnetic resonance spectroscopy (31P-MRS) to investigate if cerebral magnesium (Mg2+) levels differ between women with preeclampsia, normal pregnant, and nonpregnant women.

    METHODS: This cross-sectional study comprised 28 women with preeclampsia, 30 women with normal pregnancies in corresponding gestational week (range: 23-41 weeks) and 11 nonpregnant healthy controls. All women underwent 31P-MRS from the parieto-occipital region of the brain and were interviewed about cerebral symptoms. Differences between groups were assessed by analysis of variance and Tukey's post-hoc test. Correlations between Mg2+ levels and specific neurological symptoms were estimated with Spearman's rank test.

    RESULTS: Mean maternal cerebral Mg2+ levels were lower in women with preeclampsia (0.12 mM ± 0.02) compared to normal pregnant controls (0.14 mM ± 0.03) (P = 0.04). Nonpregnant and normal pregnant women did not differ in Mg2+ levels. Among women with preeclampsia, lower Mg2+ levels correlated with presence of visual disturbances (P = 0.04). Plasma levels of Mg2+ did not differ between preeclampsia and normal pregnancy.

    CONCLUSIONS: Women with preeclampsia have reduced cerebral Mg2+ levels, which could explain the potent antiseizure prophylactic properties of MgSO4. Within the preeclampsia group, women with visual disturbances have lower levels of Mg2+ than those without such symptoms.

  • 274.
    Nelander, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bergman, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Cerebral osmolytes and plasma osmolality in pregnancy and preeclampsia: a proton magnetic resonance spectroscopy study2018In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 31, no 7, p. 847-853Article in journal (Refereed)
    Abstract [en]

    Background: Cerebral complications contribute substantially to mortality in preeclampsia. Pregnancy calls for extensive maternal adaptations, some associated with increased propensity for seizures, but the pathophysiology behind the eclamptic seizures is not fully understood. Plasma osmolality and sodium levels are lowered in pregnancy. This could result in extrusion of cerebral organic osmolytes, including the excitatory neurotransmitter glutamate, but this remains to be determined. The hypothesis of this study was that cerebral levels of organic osmolytes are decreased during pregnancy, and that this decrease is even more pronounced in women with preeclampsia.

    Method: We used proton magnetic resonance spectroscopy to compare levels of cerebral organic osmolytes, in women with preeclampsia (n=30), normal pregnancy (n=32) and non-pregnant controls (n=16). Cerebral levels organic osmolytes were further correlated to plasma osmolality, and plasma levels of glutamate and sodium.

    Results: Compared to non-pregnant women, women with normal pregnancy and preeclampsia had lower levels of the cerebral osmolytes myo-inositol, choline and creatine (p=0.001 or less), and all these metabolites correlated with each other (p<0.05). Women with normal pregnancies and preeclampsia had similar levels of osmolytes, except for glutamate, which was significantly lower in preeclampsia. Cerebral and plasma glutamate levels were negatively correlated with each other (p<0.008), and cerebral myo-inositol, choline and creatine levels were all positively correlated with both plasma osmolality and sodium levels (p<0.05).

    Conclusion: Our results indicate that pregnancy is associated with extrusion of cerebral organic osmolytes. This includes the excitatory neurotransmitter glutamate, which may be involved in the pathophysiology of seizures in preeclampsia.

  • 275.
    Nerpin, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Jobs, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Ingelsson, Erik
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Inflammation, oxidative stress, glomerular filtration rate, and albuminuria in elderly men: a cross-sectional study2012In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 5, no 1, p. 537-Article in journal (Refereed)
    Abstract [en]

     BACKGROUND: The role of inflammation and oxidative stress in mild renal impairment in the elderly is not well studied. Accordingly, we aimed at investigating the associations between estimated glomerular filtration rate (eGFR), albumin/creatinine ratio (ACR), and markers of different inflammatory pathways and oxidative stress in a community based cohort of elderly men.

    FINDINGS: Cystatin C-based GFR, ACR, and biomarkers of cytokine-mediated inflammation (interleukin-6, high-sensitivity C-reactive protein[CRP], serum amyloid A[SAA]), cyclooxygenase-mediated inflammation (urinary prostaglandin F2alpha [PGF2alpha]), and oxidative stress (urinary F2 isoprostanes) were assessed in the Uppsala Longitudinal Study of Adult Men(n = 647, mean age 77 years).

    RESULTS: In linear regression models adjusting for age, BMI, smoking, blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, and treatment with statins, ACE-inhibitors, ASA, and anti-inflammatory agents, eGFR was inversely associated with CRP, interleukin-6, and SAA (beta-coefficient -0.13 to -0.19, p < 0.001 for all), and positively associated with urinary F2-isoprostanes (beta-coefficient 0.09, p = 0.02). In line with this, ACR was positively associated with CRP, interleukin-6, and SAA (beta- coefficient 0.09-0.12, p < 0.02 for all), and negatively associated with urinary F2-isoprostanes (beta-coefficient -0.12, p = 0.002). The associations were similar but with lower regression coefficients in a sub-sample with normal eGFR (>60 ml/min/1.73 m2, n = 514), with the exception that F2-isoprostane and SAA were no longer associated with eGFR.

    CONCLUSION: Our data indicate that cytokine-mediated inflammation is involved in the early stages of impaired kidney function in the elderly, but that cyclooxygenase-mediated inflammation does not play a role at this stage. The unexpected association between higher eGFR/lower albuminuria and increased F2-isoprostanes in urine merits further studies.

  • 276.
    Nerpin, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ingelsson, Erik
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Jobs, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Association between glomerular filtration rate and endothelial function in an elderly community cohort2012In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 224, no 1, p. 242-246Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Endothelial dysfunction is prevalent among individuals with chronic kidney disease. However, the association between glomerular filtration rate and endothelial function in the community is unclear and needs to be investigated in the general population.

    METHODS: In the community-based Prospective Investigation of the Vasculature of Uppsala Seniors study (PIVUS, n = 952, mean age 70, women 49.3%), we investigated cross-sectional associations between estimated cystatin C-based glomerular filtration rate (eGFR), and 3 measures representing different aspects of endothelial function (endothelial-dependent vasodilation [EDV], endothelial independent vasodilatation [EIDV], and flow-mediated dilatation [FMD]). We also performed pre-specified sub-group analyses in participants with normal eGFR (>60 ml/min/1.73 m(2)).

    RESULTS: In the whole cohort, 10 ml/min/1.73 m(2) higher eGFR was associated with 3% higher EDV (p = 0.001) and 2% higher EIDV (p = 0.007), adjusted for age and sex. The associations were attenuated and no longer statistically significant after adjusting for established cardiovascular risk factors. In participants with eGFR >60 ml/min/1.73 m(2), 10 ml higher eGFR was associated with 2% higher EDV (p = 0.04) after adjusting for sex and age. eGFR was not associated to FMD in any model or sub-sample.

    CONCLUSION: This community-based study suggests that eGFR is associated with endothelial function also in persons with normal kidney function, but that this association is largely explained by confounding by established cardiovascular risk factors. Thus, our data do not support the notion of a direct causal interplay between renal and vascular function prior to the development of CKD.

  • 277.
    Nerpin, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Högskolan Dalarna-Medicinsk vetenskap.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Andrén, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Jobs, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Högskolan Dalarna Medicinsk vetenskap.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Högskolan Dalarna Medicinsk vetenskap.
    The association between glomerular filtration rate and left ventricular function in two independent community-based cohorts of elderly2014In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, no 11, p. 2069-2074Article in journal (Refereed)
    Abstract [en]

    The cardiorenal syndrome, the detrimental bi-directional interplay between symptomatic heart failure and chronic kidney disease, is a major clinical challenge. Nonetheless, it is unknown if this interplay begins already at an asymptomatic stage. Therefore we investigated whether the glomerular filtration rate (GFR) is associated with left ventricular function in participants free from clinical heart failure and with a left ventricular ejection fraction (LVEF) > 40% and with pre-specified sub-group analyses in individuals with a GFR > 60 mL/min/m(2). Two independent community-based cohorts were used; the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 911; 50% women; mean age: 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 538; mean age: 71 years). We investigated cross-sectional association between cystatin C-based GFR (estimated glomerular function [eGFR]) and systolic (LVEF), diastolic- (isovolumic relaxation time [IVRT]) and global left ventricular function (myocardial performance index [MPI]) determined by echocardiography. In both PIVUS and ULSAM, higher eGFR was significantly associated with higher LVEF (P = 0.004 [PIVUS] and P = 0.005 [ULSAM]). In PIVUS, higher eGFR was significantly associated with lower IVRT (P = 0.001) and MPI (P = 0.006), in age- and sex-adjusted models. After further adjustment for cardiovascular risk factors, the association between higher eGFR and higher LVEF was still statistically significant (P = 0.008 [PIVUS] and P = 0.02 [ULSAM]). In PIVUS, the age- and sex-adjusted association between eGFR and left ventricular function was similar in participants with eGFR > 60 mL/min/m(2). Our data suggest that the interplay between kidney and heart function begins prior to the development of symptomatic heart failure and kidney disease.

  • 278.
    Nerpin, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jobs, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Jobs, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
    Hallan, Stein
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Arnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    The combined contribution of albuminuria and glomerular filtration rate to the prediction of cardiovascular mortality in elderly men2011In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 26, no 9, p. 2820-2827Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cardiovascular risk prediction is particularly important in the primary prevention of cardiovascular disease (CVD). Yet, data on whether the combined addition of albuminuria and estimated glomerular filtration rate (eGFR) improves cardiovascular risk prediction in individuals without CVD in the community is scarce.

    METHODS: We investigated associations between urinary albumin excretion rate (UAER), cystatin C-based eGFR and cardiovascular mortality in a community-based cohort of elderly men (ULSAM study; n = 1113, mean age 71 years, 208 cardiovascular deaths, median follow-up 12.9 years) with prespecified analyses in participants without CVD (n = 649, 86 cardiovascular deaths).

    RESULTS: Using multivariable Cox regression, higher UAER and lower eGFR were associated with increased risk for cardiovascular mortality independently of established cardiovascular risk factors in the whole sample and in men without CVD at baseline [subsample without CVD: UAER; hazard ratio (HR) per 1 SD 1.26, 95% confidence interval (CI) 1.05-1.51, P = 0.01; eGFR: HR per 1 SD 0.74, 95% CI 0.59-0.92, P = 0.007]. Analyses of model discrimination, calibration, reclassification and global fit suggested that UAER and eGFR also add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent CVD. Interestingly, established cutoffs used to diagnose microalbuminuria (UAER > 20 μg/min) and chronic kidney disease Stage 3 (eGFR < 60 mL/min/1.73m(2)), appeared less suitable for cardiovascular risk prediction [integrated discrimination improvement (IDI) 0.006, P = 0.11], while cutoffs UAER > 6 μg/min and eGFR < 45 mL/min/1.73m(2) significantly improved IDI (0.047, P < 0.001).

    CONCLUSIONS: UAER and eGFR improved cardiovascular risk prediction beyond established cardiovascular risk factors, suggesting that these kidney biomarkers may be useful in predicting cardiovascular death in elderly men.

  • 279. Nerpin, Elisabet
    et al.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jobs, Magnus
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Arnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Insulin sensitivity measured with euglycemic clamp is independently associated with glomerular filtration rate in a community-based cohort2008In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 31, no 8, p. 1550-1555Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the association between insulin sensitivity and glomerular filtration rate (GFR) in the community, with prespecified subgroup analyses in normoglycemic individuals with normal GFR. RESEARCH DESIGN AND METHODS: We investigated the cross-sectional association between insulin sensitivity (M/I, assessed using euglycemic clamp) and cystatin C-based GFR in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM], n = 1,070). We also investigated whether insulin sensitivity predicted the incidence of renal dysfunction at a follow-up examination after 7 years. RESULTS: Insulin sensitivity was directly related to GFR (multivariable-adjusted regression coefficient for 1-unit higher M/I 1.19 [95% CI 0.69-1.68]; P < 0.001) after adjusting for age, glucometabolic variables (fasting plasma glucose, fasting plasma insulin, and 2-h glucose after an oral glucose tolerance test), cardiovascular risk factors (hypertension, dyslipidemia, and smoking), and lifestyle factors (BMI, physical activity, and consumption of tea, coffee, and alcohol). The positive multivariable-adjusted association between insulin sensitivity and GFR also remained statistically significant in participants with normal fasting plasma glucose, normal glucose tolerance, and normal GFR (n = 443; P < 0.02). In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function (GFR <50 ml/min per 1.73 m(2)) during follow-up independently of glucometabolic variables (multivariable-adjusted odds ratio for 1-unit higher of M/I 0.58 [95% CI 0.40-0.84]; P < 0.004). CONCLUSIONS: Our data suggest that impaired insulin sensitivity may be involved in the development of renal dysfunction at an early stage, before the onset of diabetes or prediabetic glucose elevations. Further studies are needed in order to establish causality.

  • 280.
    Niemelä, Valter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Blennow, Kaj
    Zetterberg, Henrik
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Sundblom, Jimmy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Cerebrospinal fluid sCD27 levels indicate active T cell-mediated inflammation in premanifest Huntington's disease2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 2, article id e0193492Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Huntington's disease (HD) is a neurodegenerative disorder, but evidence also suggests neuroinflammation in the pathogenesis. The immune mechanisms involved and the timing of their activation need further clarification.

    METHODS: A clinically well-characterized HD cohort and gene negative controls were enrolled. YKL-40 reflecting innate immunity and sCD27, a marker of adaptive immunity, were measured across disease stages. Comparisons were made with markers of neurodegeneration: neurofilament light (NFL), total-tau (T-tau), and phospho-tau (P-tau).

    RESULTS: 52 cross-sectional cerebrospinal fluid samples and 23 follow-up samples were analyzed. sCD27 was elevated in manifest HD and premanifest gene expansion carriers, whereas controls mostly had undetectable levels. YKL-40 showed a trend toward increase in manifest HD. sCD27 correlated with YKL-40 which in turn was closely associated to all included markers of neurodegeneration. YKL-40, NFL, and both forms of tau could all independently predict HD symptoms, but only NFL levels differed between groups after age-adjustment.

    CONCLUSION: Increased sCD27 in premanifest HD is a sign of T cell-mediated neuroinflammation. This finding is novel since other reports almost exclusively have found early involvement of innate immunity. Validation of sCD27 in a larger HD cohort is needed. The role of adaptive immunity in HD needs further clarification, as it may hasten disease progression.

  • 281.
    Nilsen, Tom
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Gentian Technology AS, Moss, Norway.
    Haugen, SH
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Extraction,isolation, and concentration of calprotectin antigen (S100A8/S100A9) fromgranulocytes2018In: Health Science Reports, Vol. 1, no 5, article id e35Article in journal (Refereed)
    Abstract [en]

    Background

    Calprotectin is a promising biomarker for granulocyte activation. It is mainly measured in faeces as a marker for inflammatory bowel disease. A limitation is that there is no widely accepted calibrator.

    Aim

    To establish a method for purification of calprotectin from human granulocytes that is easily reproducible, reliable, and could contribute to a better agreement between different calprotectin methods.

    Methods and results

    Calprotectin was purified from granulocyte extracts using ion‐exchange chromatography. The granulocytes were separated from blood bags. The purity was analysed by analysing pixel density of a picture of the sodium dodecyl sulfate polyacrylamide gel electrophoresis and by size exclusion chromatography. The calprotectin concentration of the pure antigen solution was determined using Biuret method. The purity was >95% for 3 preparations, and their concentrations were 1079, 1080, and 1813 mg/L.

    Conclusion

    It is possible to reproducibly prepare highly purified calprotectin antigen from human granulocytes. The preparations can be used for preparing calibrators, controls for immunological calprotectin assays, and immunisation for raising antibodies against human calprotectin in hens.

  • 282.
    Nilsen, Tom
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Gentian AS, Moss, Norway.
    Sunde, Kathrin
    Gentian AS, Moss, Norway.
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Mandic Havelka, Aleksandra
    Karolinska Univ Hosp, Karolinska Inst & Clin Chem, Dept Mol Med & Surg, Stockholm, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    A novel turbidimetric immunoassay for fecal calprotectin optimized for routine chemistry analyzers2017In: Journal of clinical laboratory analysis (Print), ISSN 0887-8013, E-ISSN 1098-2825, Vol. 31, no 4, article id e22061Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Fecal calprotectin assays are widely used to exclude inflammatory bowel disease (IBD) in patients with suspected IBD. A problem with the fecal calprotectin assays is the rather long test-turnaround times. A particle enhanced turbidimetric immunoassays (PETIA) for fecal calprotectin would reduce test-turnaround times and would permit more laboratories to perform the measurements. The aim of this study was to evaluate a new feces calprotectin PETIA.

    METHOD: Using routine fecal samples the feces calprotectin PETIA was validated on two chemistry analyzers, Mindray BS-380 and Cobas 501.

    RESULTS: The assay is linear in the range 11-2000 μg/g, with a limit of quantitation of approximately 10 μg/g. No antigen excess hook effect was observed up to 10 000-15 000 μg/g depending on the instrument used. The turbidimetric method showed a good agreement with the Bühlmann ELISA. The total coefficient of variation was 3%-8% in the 50-100 μg/g range.

    CONCLUSION: The fecal calprotectin PETIA, fCal Turbo, is well suited for rapid analysis of fecal calprotectin on Mindray BS-380 or Cobas 501 clinical chemistry analyzers. The test results are commutable with Bühlmann fecal MRP8/14 ELISA.

  • 283.
    Nilsen, Tom
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sunde, Kathrin
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    A new turbidimetric immunoassay for serum calprotectin for fully automatized clinical analysers2015In: Journal of Inflammation, ISSN 1476-9255, E-ISSN 1476-9255, Vol. 12, article id 45Article in journal (Refereed)
    Abstract [en]

    Serum and plasma calprotectin concentration is shown to be elevated when neutrophils are activated, and may therefore be used as a marker for inflammatory diseases. A serum calprotectin immunoassay was developed based on calprotectin values observed in samples from the intensive care unit. The polyclonal avian antibodies were raised and affinity purified with calprotectin antigens. The performance was tested and it was observed that the assay was linear in the range 0.3-24.7 mg/L, the limit of quantitation was observed to be lower than 0.3 mg/L, no antigen excess was observed up to 54 mg/L, all CVs were lower than 1.8 % in the precision study, the calibration curve stability was longer than 6 weeks, and there was no significant interference detected for haemoglobin, intralipid or bilirubin. The serum calprotectin immunoassay presented in this paper performs well within the criteria carefully set from the limited clinical experience obtained in both serum and plasma. In addition it is commutable with Bühlmann MRP8/14 ELISA.

  • 284.
    Nilsen, Tom
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Serum calprotectin levels in elderly males and females without bacterial or viral infections2014In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 47, no 12, p. 1065-1068Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Calprotectin is released from activated leukocytes and calprotectin can thus be used as a marker for leukocyte activation. Faeces calprotectin is not only used as a marker for inflammatory bowel disease but can also be used to detect leukocyte activation in other body fluids. The aim of the present study was to study serum calprotectin levels in non-infected elderly individuals to establish reference intervals for the marker.

    METHODS: Serum calprotectin was analyzed by immunoturbidimetry in 75year old females and males without known infections. Individuals with CRP>20mg/L were excluded as this could indicate a subclinical infection. The calprotectin levels in the remaining 713 individuals were used to calculate reference values for this population. The Spearman rank correlations between calprotectin and 27 other laboratory biomarkers were also investigated.

    RESULTS: There was a strong positive Spearman rank correlation between calprotectin and CRP (p<0.000001) and alkaline phosphatase (p<0.000001). There were also significant negative correlations between calprotectin and ApoA1 and direct HDL-cholesterol.

    CONCLUSIONS: The reference interval for serum-calprotectin for all study subjects was 0.3-2.6mg/L. Leukocyte alkaline phosphatase contributes to serum alkaline phosphatase levels.

  • 285.
    Nilsson, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Amini, Ahmad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Wretlind, Bengt
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Pseudomonas aeruginosa infections are prevented in cystic fibrosis patients by avian antibodies binding Pseudomonas aeruginosa flagellin: Pseudomonas aeruginosa infections are prevented in cystic fibrosis patients by avian antibodies binding Pseudomonas aeruginosa flagellin2007In: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 856, no 1-2, p. 75-80Article in journal (Refereed)
    Abstract [en]

    Pseudomonas aeruginosa (PA) is the main cause of morbidity and mortality in cystic fibrosis (CF) patients. CF patients with chronic PA infections have a more rapid deterioration of their lung function and the bacteria become impossible to eradicate from the lungs. Antibiotic resistance among PA strains in CF patients is steadily increasing. Specific chicken (IgY) antibodies against PA have been shown to have potential to prevent PA infections in CF. Anti-Pseudomonas IgY reduces PA adhesion to epithelia, but the mechanism has not been fully elucidated. To gain further insight into the prophylactic effect of these antibodies, the immunoreactivity was investigated by 2D electrophoresis of PA strains, immunoblotting and MALDI-TOF-MS. To confirm the identity of the proteins, the tryptic peptides were analyzed by MALDI-TOF-MS to accurately measure their monoisotopic masses as well as determine their amino acid sequences. In order to facilitate fragmentation of the peptides they were N-terminally or C-terminally labeled. Several strains were investigated and anti-Pseudomonas IgY was immunoreactive against all of these strains, which strengthens its potential as a prophylactic treatment against PA. Flagellin was identified as the major antigen. Flagellin is the main protein of the flagella and is crucial for establishing infections in hosts as well as being involved in PA chemotaxis, motility, adhesion and inflammation. Furthermore, secreted flagellin elicits an inflammatory response. In conclusion, anti-Pseudomonas IgY binds flagellin, which may prevent PA infections in CF patients by hindering host invasion.

  • 286.
    Nilsson, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Bodolea, Constantin
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Cerebrospinal fluid cathepsin B and S2013In: Neurological Sciences, ISSN 1590-1874, E-ISSN 1590-3478, Vol. 34, no 4, p. 445-448Article in journal (Refereed)
    Abstract [en]

    Cathepsins are increased in the brain of elderly animals. We investigate the presence of cathepsin B and S in human cerebrospinal fluid (CSF) plasma and the associations with cystatin C, age and sex. We measured cathepsin B and S concentrations in CSFs from 118 persons, undergoing elective surgical procedures, with ELISA. Both cathepsin B and cathepsin S were positively correlated with age. No correlation was observed between cathepsin B or S and length, height or body mass index. Both cathepsin B and S were positively correlated to the cystatin C concentration in CSF. Calculated reference intervals were 4,893–17,636 pg/mL for cathepsin B and 2,681–11,459 pg/mL for cathepsin S. Elderly individuals had significantly higher levels of both cathepsin B (r s = 0.38, p = 0.00002) and cathepsin S (r s = 0.35, p = 0.0001) in CSF.

  • 287.
    Nilsson, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Kollberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Johannesson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wejåker, Per-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Carlander, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    More than 10 years' continuous oral treatment with specific immunoglobulin Y for the prevention of Pseudomonas aeruginosa infections: a case report2007In: Journal of Medicinal Food, ISSN 1096-620X, E-ISSN 1557-7600, Vol. 10, no 2, p. 375-378Article in journal (Refereed)
    Abstract [en]

    Immunotherapy with specific antibodies is an alternative to antibiotics for the prevention of infections in humans and animals. We have used orally administered immunoglobulin Y (IgY) preparations, purified from eggs of hens immunized with Pseudomonas aeruginosa bacteria, to prevent pulmonary P. aeruginosa infections in a group of patients with cystic fibrosis (CF). Respiratory infections are major problems for CF patients because of the thick mucus in the airways, and chronic P. aeruginosa lung infections occur in virtually all CF patients and cause morbidity and mortality. The IgY-treated group had only 2.5 P. aeruginosa-positive sputum cultures per 100 months, and none of the IgY-treated patients became chronically colonized with P. aeruginosa. In the control group, 13.7 of the cultures per 100 months were positive for P. aeruginosa, and 24% of patients became chronically colonized with P. aeruginosa. The first enrolled patient in this study has now been treated continuously for more than 10 years. During the first 8 years she only had four P. aeruginosa-positive cultures. After 8 years she became chronically infected, but still after 10 years the bacteria have not turned mucoid. No negative side effects of IgY treatment have been noted during these 10 years. To our knowledge this is the longest treatment with specific yolk antibodies for therapeutic purposes.

  • 288.
    Nilsson, Elin
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. klinisk kemi.
    Larsson, Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. klinisk kemi.
    Chicken anti-protein L for the detection of small amounts of protein L in the presence of IgG.2005In: Hybridoma (Larchmt), ISSN 1554-0014, Vol. 24, no 2, p. 112-4Article in journal (Refereed)
  • 289.
    Nilsson, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Stability of chicken IgY antibodies freeze-dried in the presence of lactose, sucrose and trehalose2007In: Journal of Poultry Science, ISSN 1349-0486, Vol. 44, no 1, p. 58-62Article in journal (Refereed)
    Abstract [en]

    Freeze-drying is used as a method to stabilize proteins. The process itself may however cause protein unfolding and denaturation, but the risk is reduced if a stabilizing agent is added prior to freeze-drying. Here chicken antibody (IgY) preparations were freeze-dried in the presence or absence of lactose, sucrose and threalose as stabilizing agent at 0.3, 0.06 and 0.012M. The activity of freeze-dried IgY batches in the absence of stabilizing agent was similar before and after freeze-drying, but decreased slowly during eight weeks at 37°C. Addition of disaccharide resulted in a preserved activity after eight weeks in 37°C, compared to samples with no sugar added. The results were similar irrespective of sugar type and concentration (0.012-0.3M). This shows that IgY freeze-dried in the presence of disaccharide is very stable and a method to reduce the cost and simplify transport, storage and use of avian antibodies.

  • 290.
    Nilsson, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Olesen, Hanne V.
    Wejåker, Per-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kollberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Good effect of IgY against Pseudomonas aeruginosa infections in cystic fibrosis patients2008In: Pediatric Pulmonology, ISSN 8755-6863, E-ISSN 1099-0496, Vol. 43, no 9, p. 892-899Article in journal (Refereed)
    Abstract [en]

    This is an extended open study of oral prophylactic treatment with egg yolk antibodies against Pseudomonas aeruginosa, Anti-Pseudomonas IgY, of 17 Swedish patients with cystic fibrosis. They have been on prophylactic IgY treatment for up to 12 years and altogether for 114 patient years. A group of 23 Danish CF patients served as control. There has been a total absence of adverse events. Only 29 cultures have been positive for P. aeruginosa (cultures after chronic colonization not included), that is, 2.3/100 treatment months compared to 7.0/100 months in the control group (P = 0.028). In the IgY treated group only one pair of siblings (2/17) has been chronically colonized with P. aeruginosa compared to seven patients (7/23) in the control group. Atypical mycobacteria, S. maltophilia, A. xylosoxidans, and A. fumigatus have appeared only sporadically. There have been no cultures positive for B. cepacia. There was no decrease in pulmonary functions (P = 0.730) within the IgY group. Body mass index values were normal or close to normal for all IgY treated patients. In conclusion, Anti-Pseudomonas IgY has great potential to prevent P. aeruginosa infections.

  • 291.
    Nilsson, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Stålberg, Johan
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    IgY stability in eggs stored at room temperature or at +4°C2012In: British Poultry Science, ISSN 0007-1668, E-ISSN 1466-1799, Vol. 53, no 1, p. 42-46Article in journal (Refereed)
    Abstract [en]

    1. The aim of this study was to investigate the stability of immunoglobulin-Y (IgY) in stored eggs from immunised hens.

    2. Eggs from individual hens were randomised and stored for up to one month at room temperature, or for up to 6 months at +4°C. IgY was extracted from the egg yolks and the antibody activities were tested by ELISA.

    3. There was no significant reduction in antibody titres with egg storage under these conditions.

    4. Egg yolks of immunised chickens provide an inexpensive source of large amounts of polyclonal antibodies for use in immunotherapy and immunoassays. By collecting eggs from different immunised hens and pooling their yolks, it should be possible to reduce batch-to-batch variation.

  • 292. Nitsch, Dorothea
    et al.
    Grams, Morgan
    Sang, Yingying
    Black, Corri
    Cirillo, Massimo
    Djurdjev, Ognjenka
    Iseki, Kunitoshi
    Jassal, Simerjot K
    Kimm, Heejin
    Kronenberg, Florian
    Oien, Cecilia M
    Levey, Andrew S
    Levin, Adeera
    Woodward, Mark
    Hemmelgarn, Brenda R
    Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: a meta-analysis2013In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 346, p. f324-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess for the presence of a sex interaction in the associations of estimated glomerular filtration rate and albuminuria with all-cause mortality, cardiovascular mortality, and end stage renal disease.

    DESIGN: Random effects meta-analysis using pooled individual participant data.

    SETTING: 46 cohorts from Europe, North and South America, Asia, and Australasia.

    PARTICIPANTS: 2,051,158 participants (54% women) from general population cohorts (n=1,861,052), high risk cohorts (n=151,494), and chronic kidney disease cohorts (n=38,612). Eligible cohorts (except chronic kidney disease cohorts) had at least 1000 participants, outcomes of either mortality or end stage renal disease of ≥ 50 events, and baseline measurements of estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology Collaboration equation (mL/min/1.73 m(2)) and urinary albumin-creatinine ratio (mg/g).

    RESULTS: Risks of all-cause mortality and cardiovascular mortality were higher in men at all levels of estimated glomerular filtration rate and albumin-creatinine ratio. While higher risk was associated with lower estimated glomerular filtration rate and higher albumin-creatinine ratio in both sexes, the slope of the risk relationship for all-cause mortality and for cardiovascular mortality were steeper in women than in men. Compared with an estimated glomerular filtration rate of 95, the adjusted hazard ratio for all-cause mortality at estimated glomerular filtration rate 45 was 1.32 (95% CI 1.08 to 1.61) in women and 1.22 (1.00 to 1.48) in men (P(interaction)<0.01). Compared with a urinary albumin-creatinine ratio of 5, the adjusted hazard ratio for all-cause mortality at urinary albumin-creatinine ratio 30 was 1.69 (1.54 to 1.84) in women and 1.43 (1.31 to 1.57) in men (P(interaction)<0.01). Conversely, there was no evidence of a sex difference in associations of estimated glomerular filtration rate and urinary albumin-creatinine ratio with end stage renal disease risk.

    CONCLUSIONS: Both sexes face increased risk of all-cause mortality, cardiovascular mortality, and end stage renal disease with lower estimated glomerular filtration rates and higher albuminuria. These findings were robust across a large global consortium.

  • 293.
    Noraddin, Feria Hikmet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Flodin, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Fredricsson, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sohrabian, Azita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Measurement of urinary cystatin C with a particle-enhanced turbidimetric immunoassay on architect ci82002012In: Journal of clinical laboratory analysis (Print), ISSN 0887-8013, E-ISSN 1098-2825, Vol. 26, no 5, p. 358-364Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Cystatin C is a low-molecular-weight protein that is freely filtered by the glomerulus and catabolized after reabsorption by the proximal tubular cells in healthy subjects. Urinary cystatin C is a potential biomarker for tubular damage including acute kidney injury (AKI) in the acute phase when patients are submitted to the intensive care unit.

    METHODS:

    The aim of this study was to perform a method validation of urinary analysis of cystatin C by particle-enhanced turbidimetric immunoassay (PETIA) on a high-throughput chemical analyzer. Total assay time was 10 min. The antigen excess, linearity, lower limit of quantification (LoQ), recovery, assay precision, stability, and interference caused by hemoglobin were evaluated.

    RESULTS:

    The LoQ was calculated to 0.020 mg/l with a coefficient of variation (CV) ≤ 10%. No hook effect was observed and the assay was linear over the studied interval less than 0.020-0.950 mg/l with a regression of R(2) = 0.9994. The assay had a recovery between 93-100% and the assay precision had a total CV of less than 3.5%. Cystatin C was stable for 3 days in room temperature and 14 days in +4C. The assay did not show any major interference with hemoglobin at a hemoglobin concentration of 10 g/L. The reference interval for urine cystatin C was less than 0.166 mg/l.

    CONCLUSION:

    The urinary cystatin C PETIA showed good precision and performance characteristics including short test turnaround times that are necessary qualifications for a biomarker at a routine laboratory.

  • 294. Nordin, A
    et al.
    Björnådal, L
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Svenungsson, E
    Jensen-Urstad, K
    Electrocardiography in 110 patients with systemic sclerosis: a cross-sectional comparison with population-based controls2014In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, no 3, p. 221-225Article in journal (Refereed)
    Abstract [en]

    Objectives:

    Patchy fibrosis of the myocardium is thought to cause conduction abnormalities in patients with systemic sclerosis (SSc). We compared the prevalence and type of rhythm/conduction disturbances in 74% of the SSc patients in Stockholm County and controls.

    Method: A total of 110 SSc patients (age 62 ± 12 years) fulfilling the American College of Rheumatology (ACR) criteria for SSc and 105 gender- and age-matched controls participated in this study. A 12-lead resting electrocardiogram (ECG) was performed in all participants. The first 49 patients and 42 controls also underwent a 22-24-h Holter ECG recording. Associations with disease subsets, autoantibodies, cardiovascular risk factors, and left ventricular ejection fraction (LVEF), as estimated by echocardiography, were investigated.

    Results:

    Abnormal ECGs were found in 28% of patients and 17% of controls (p = 0.05). Atrioventricular (AV) and/or intraventricular (IV) conduction abnormalities were found in 15% of patients and 5% of controls (p < 0.01). Four patients, but no controls, had low anteroseptal R-wave/septal Q-wave patterns with narrow QRS complexes, simulating a septal wall infarction pattern. Patients had more abnormal Holter ECG recordings than controls (38% vs. 17%, p = 0.05). All participants with a normal resting ECG had an LVEF ≥ 50%.

    Conclusions:

    Although ECGs are inexpensive, commonly available screening tools, to detect arrhythmias, such as frequent ventricular extrasystoles (VES), Holter tracings should be performed. The frequencies of AV and/or IV conduction abnormalities and septal Q waves/low R waves have not changed since 1985. The unmet need of anti-fibrotic treatment in SSc is underscored by these findings.

  • 295.
    Nordin, Gunnar
    et al.
    Equalis, Uppsala, Sweden.
    Ekvall, Sara
    Equalis, Uppsala, Sweden.
    Kristoffersson, Carolina
    Equalis, Uppsala, Sweden.
    Jonsson, Ann-Sofie
    Landstinget Varmland, Dept Clin Chem, Karlstad, Sweden.
    Bäck, Sten-Erik
    Lund Univ Hosp, Dept Clin Chem, Lund, Sweden.
    Rollborn, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Accuracy of determination of the glomerular filtration marker iohexol by European laboratories as monitored by external quality assessment2019In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 57, no 7, p. 1006-1011Article in journal (Refereed)
    Abstract [en]

    Background Glomerular filtration is the most important kidney function. The most accurate glomerular filtration rate (GFR) estimates are based on the clearance of exogenous filtration markers. Of these, iohexol is the only exogenous marker that is included in an external quality assessment (EQA) scheme. The aim of the present study was to evaluate the performance of the European laboratories participating in Equalis' EQA scheme for iohexol. Methods Weighed amounts of iohexol (Omnipaque) were added to plasma samples and distributed to laboratories participating in the EQA scheme for iohexol. All laboratories performed the assays in a blinded fashion. Results The number of participating laboratories varied between 27 and 34 during the study period. Iohexol was determined by HPLC in 77% of the laboratories and by UPLC/MS/MS methods in 15% of the laboratories. The mean interlaboratory coefficient of variation was 4.7% for the HPLC methods and 6.4% for the UPLC/MS/MS methods. The mean bias between calculated and measured iohexol values was -1.3 mg/L (95% confidence interval ±0.3) during the first part of the study period and 0.1 mg/L (±0.3) during the later part. Conclusions The low interlaboratory variation demonstrates that iohexol can be measured reliably by many laboratories and supports the use of iohexol as a GFR marker when there is a need for high quality GFR measurements.

  • 296.
    Nordmark, Gunnel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Bengtsson, Christine
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Karlsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sturfelt, Gunnar
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Effects of Dehydroepiandrosterone Supplement on Health-related Quality of Life in Glucocorticoid Treated Female Patients with Systemic Lupus Erythematosus2005In: Autoimmunity, ISSN 0891-6934, E-ISSN 1607-842X, Vol. 38, no 7, p. 531-540Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to evaluate the efficacy of low dose dehydroepiandrosterone (DHEA) on health-related quality of life (HRQOL) in glucocorticoid treated female patients with systemic lupus erythematosus (SLE). Forty one women ( >or= 5 mg prednisolone/day) were included in a double-blind, randomized, placebo-controlled study for 6 months where DHEA was given at 30 mg/20 mg ( or= 46 years) daily, or placebo, followed by 6 months open DHEA treatment to all patients. HRQOL was assessed at baseline, 6 and 12 months, using four validated questionnaires and the patients' partners completed a questionnaire assessing mood and behaviour at 6 months. DHEA treatment increased serum levels of sulphated DHEA from subnormal to normal. The DHEA group improved in SF-36 "role emotional" and HSCL-56 total score (both p<0.05). During open DHEA treatment, the former placebo group improved in SF-36 "mental health" (p<0.05) with a tendency for improvement in HSCL-56 total score (p=0.10). Both groups improved in McCoy's Sex Scale during active treatment (p<0.05). DHEA replacement decreased high-density lipoprotein (HDL) cholesterol and increased insulin-like growth factor I (IGF-I) and haematocrit. There were no effects on bone density or disease activity and no serious adverse events. Side effects were mild. We conclude that low dose DHEA treatment improves HRQOL with regard to mental well-being and sexuality and can be offered to women with SLE where mental distress and/or impaired sexuality constitutes a problem.

  • 297. Nylander, Martina
    et al.
    Osman, Abdimajid
    Ramström, Sofia
    Aklint, Emma
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindahl, Tomas L
    The role of thrombin receptors PAR1 and PAR4 for PAI-1 storage, synthesis and secretion by human platelets2012In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 129, no 4, p. e51-e58Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    Arterial thrombi contain more platelets than venous thrombi and are more resistant to fibrinolysis. This resistance could partly be due to plasminogen activator inhibitor 1 (PAI-1) secreted by platelets. The aim of this study was to elucidate differences between thrombin receptors protease-activated receptor (PAR) 1 and 4 and platelet storage, secretion and synthesis of platelet PAI-1, as compared to other platelet α-granule proteins such as VEGF and endostatin.

    MATERIALS AND METHODS:

    Human isolated platelets were incubated with thrombin (0.5U/ml), PAR1-activating peptide (AP) (0.4-30μM) or PAR4-AP (1.5-300μM) for up to 24hours. ELISA, western blot and fluorescence microscopy were used to measure secretion, contents and localization of PAI-1, VEGF and endostatin.

    RESULTS:

    Our results show that PAI-1 and VEGF might be co-localized and that endostatin does not co-localize with either PAI-1 or VEGF. PAI-1 and VEGF show a similar secretion pattern, being more sensitive to low grade PAR1 activation, but secretion was also observed with higher concentrations of PAR4-APs. PAI-1 is secreted in an active form. PAI-1 mRNA was found in platelets, and elevated levels of PAI-1 were detected after 24hours incubation of platelets.

    CONCLUSIONS:

    PAI-1 and VEGF, but not endostatin, might be stored in the same α-granule in human platelets. PAI-1 and VEGF also show a similar secretion pattern, being more sensitive to PAR1 than to PAR4 activation, but the secretion is not exclusively selective. Our results also show that platelet PAI-1 is increased if incubated for 24hours, both with addition of PAR1-activating peptide and without activation, which could indicate de novo synthesis.

  • 298.
    Nylander, Ruta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Arnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Relation between Cardiovascular Disease Risk Markers and Brain Infarcts Detected by Magnetic Resonance Imaging in an Elderly Population2015In: Journal of Stroke & Cerebrovascular Diseases, ISSN 1052-3057, E-ISSN 1532-8511, Vol. 24, no 2, p. 312-318Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Established cardiovascular risk markers, such as hypertension, are associated with increased risk of brain infarcts. The newer markers N-terminal pro-brain natriuretic peptide, troponin I, C-reactive protein, and cystatin C may affect the risk of cardiovascular events and potentially, thereby, also stroke. We investigated the association between established and new risk markers for cardiovascular disease and brain infarcts detected by magnetic resonance imaging (MRI) at age 75.

    METHODS:

    Four hundred six randomly selected subjects from the Prospective Investigation of the Vasculature in Uppsala Seniors study were examined with MRI of the brain at age 75. Blood samples, measurements, and dedicated questionnaires at age 70 were used for analysis of risk markers. A history of diseases had been obtained at age 70 and 75. MRI was evaluated regarding lacunar and cortical infarcts. Univariate associations between outcomes and risk markers were assessed with logistic regression models.

    RESULTS:

    One or more infarcts were seen in 23% of the subjects (20% had only lacunar infarcts, 1% had only cortical infarcts, and 2% had both). Hypertension (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.4, 4.7) and obesity (OR 1.3; CI 1.0, 1.8) were significantly associated with increased risk of brain infarction. The newer risk markers were not significantly associated with the brain infarcts.

    CONCLUSIONS:

    The new markers were not associated with the predominantly lacunar infarcts in our 75-year-old population, why troponin I and NT-proBNP may be associated mainly with cardioembolic infarcts as shown recently.

  • 299. Nyman, Ulf
    et al.
    Grubb, Anders
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Flodin, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Nordin, Gunnar
    Equalis, Uppsala, Sweden.
    Lindström, Veronica
    Björk, Jonas
    The revised Lund-Malmö GFR estimating equation outperforms MDRD and CKD-EPI across GFR, age and BMI intervals in a large Swedish population2014In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 52, no 6, p. 815-824Article in journal (Refereed)
    Abstract [en]

     Background:

    The performance of creatinine-based glomerular filtration rate (GFR) estimating equations may vary in subgroups defined by GFR, age and body mass index (BMI). This study compares the performance of the Modification of Diet in Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations with the revised Lund-Malmö equation (LM Revised), a new equation that can be expected to handle changes in GFR across the life span more accurately.

    Methods:

    The study included 3495 examinations in 2847 adult Swedish patients referred for measurement of GFR (mGFR) 2008-2010 by plasma clearance of iohexol (median 52 mL/min/1.73 m2). Bias, precision [interquartile range (IQR)] and accuracy [percentage of estimates ±10% (P10) and ±30% (P30) of mGFR] were compared.

    Results:

    The overall results of LM Revised/MDRD/CKD-EPI were: median bias 2%/8%/11%, IQR 12/14/14 mL/min/1.73 m2, P10 40%/35%/35% and P30 84%/75%/76%. LM Revised was the most stable equation in terms of bias, precision and accuracy across mGFR, age and BMI intervals irrespective of gender. MDRD and CKD-EPI overestimated mGFR in patients with decreased kidney function, young adults and elderly. All three equations overestimated mGFR and had low accuracy in patients with BMI <20 kg/m2, most pronounced among men.

    Conclusions:

    In settings similar to the investigated cohort LM Revised should be preferred to MDRD and CKD-EPI due to its higher accuracy and more stable performance across GFR, age and BMI intervals.

  • 300.
    Oke, V.
    et al.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Brauner, S.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gustafsson, J.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Zickert, A.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Gunnarsson, I.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Svenungsson, E.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Increased Serum Levels Of IFN-Lambda 1 Correlate With TH17 Axis Cytokines And Independently To IFN-Alpha Identify Patient Group With Higher Organ Damage2016In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 34, no 4, p. S45-S45Article in journal (Refereed)
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