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  • 24351.
    Zhao, Ying
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Left ventricular dyssynchrony is associated with reduced heart rate variability in familial amyloidotic polyneuropathy2012In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 155, no 2, p. 272-278Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cardiac complications are common in familial amyloidotic polyneuropathy (FAP), in which heart rate variability (HRV) is reduced. Although autonomic disturbances are well-established, mechanisms for reduced HRV, their relationship with left ventricular (LV) function in FAP are not well understood.

    METHODS: Twenty-nine FAP patients and 29 healthy controls were studied using Doppler echocardiography. Patients' and controls' HRV were studied using power spectral analysis from 24-hour Holter-ECG recordings.

    RESULTS: In FAP patients, all HRV parameters were lower (p<0.01 for all) than those in controls. Echocardiography showed a normal LV systolic function in patients. Relative filling time (FT/RR) was shorter (p<0.01) and total isovolumic time (t-IVT) was longer (p<0.01) in patients than in controls. E/Em was higher (p<0.01), as was Tei index (p=0.02) as compared to controls. T-IVT and Tei index correlated with stroke volume (SV) (r=-0.54, p<0.01 and r=-0.44, p<0.05, respectively) in patients. HRV was reduced in 9/29 (31%) patients, who had shorter FT/RR (p<0.01), longer t-IVT (p<0.01), higher Tei index (p=0.05), A wave (p<0.01) and E/Em (p<0.05) than in subjects without reduced HRV. FT/RR and t-IVT correlated with HRV spectral parameters (p<0.05 for all). The correlation between t-IVT and SV was stronger in patients with reduced HRV (r=-0.80, p<0.01) than in those without. QRS duration was not different in the two subgroups of patients.

    CONCLUSIONS: In a subset of patients with FAP, HRV was significantly reduced and appeared to be associated with shortened LV filling time and prolonged t-IVT, which reflect ventricular dyssynchrony, despite normal QRS. Thus, in addition to autonomic disturbances in FAP, ventricular dyssynchrony is another factor associated with reduced HRV. Correction of such disturbed ventricular function by cardiac resynchronization therapy may control patients' symptom.

  • 24352. Zhao, Ying
    et al.
    Li, Zhi-An
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    PDA with Eisenmenger complicated by pulmonary artery dissection.2010In: European Journal of Echocardiography, ISSN 1525-2167, E-ISSN 1532-2114Article in journal (Refereed)
    Abstract [en]

    A 49-year-old lady, known to have Eisenmenger PDA, careful transthoracic echocardiogram, showed clear evidence for pulmonary trunk dissection with a flap across the pulmonary trunk and this finding was confirmed by a CT scan.

  • 24353.
    Zhao, Ying
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Centre.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Centre.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå Heart Centre.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Centre.
    Accentuated left ventricular lateral wall function compensates for septal dyssynchrony after valve replacement for aortic stenosis2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 164, no 3, p. 339-344Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The interventricular septal motion becomes reversed after aortic valve replacement (AVR) for aortic stenosis (AS) despite maintained stroke volume (SV). We hypothesis that left ventricular (LV) lateral wall compensates for such disturbances, in order to secure normal SV. METHODS: We studied 29 severe AS patients (age 63±11years, 18 males) with normal ejection fraction (EF) before, 6months and 12months after AVR and compared them with 29 age- and gender-matched controls, using speckle tracking echocardiography. RESULTS: In patients, the LVEF and SV remained unchanged throughout. Before AVR, the septal radial motion, septal and lateral strain were reduced (p<0.001). Peak septal and lateral displacements, times from QRS to peak displacement were all not different from controls. Six months after AVR, septal radial motion reversed (p<0.001), lateral strain increased (p<0.05), peak septal displacement reduced (p<0.01) while lateral displacement increased (p<0.05). Time to peak septal displacement delayed (p<0.01) in contrast to lateral displacement which became early (p<0.05), resulting in a significant septal-lateral time delay (p<0.01). The accentuation of LV lateral wall correlated with septal displacement time delay (r=0.60, p<0.001) and septal-lateral time delay (r=0.64, p<0.001). SV correlated with lateral displacement (r=0.39, p<0.05). The systolic strain was correlated with opposite wall displacement (p<0.05 for both). There was no correlation between these measurements before and 12month after AVR. CONCLUSIONS: Accentuated lateral wall displacement compensates for septal dyssynchrony in order to maintain normal LVEF and SV. The continuing recovery of these disturbances 12months after complete mass regression suggests an ongoing reverse remodeling.

  • 24354.
    Zhao, Ying
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Nilsson, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Trans-catheter aortic valve implantation: early recovery of left and preservation of right ventricular function2011In: Interactive Cardiovascular and Thoracic Surgery, ISSN 1569-9293, E-ISSN 1569-9285, Vol. 12, no 1, p. 35-39Article in journal (Refereed)
    Abstract [en]

    This study aimed to assess the early effect of trans-catheter aortic valve implantation (TAVI) on right (RV) and left ventricular (LV) function in severe aortic stenosis (AS) patients. Twenty AS patients (age 79±6 years) were examined before, one week and six weeks after TAVI using Doppler echocardiography. LV ejection fraction (EF), long-axis [mitral annular plane systolic excursion (MAPSE)] and RV long-axis [tricuspid annular plane systolic excursion (TAPSE)] function, septal radial motion were studied. Results were compared with 30 AS patients before and one week after aortic valve replacement (AVR) as well as 30 normals (reference group). Before TAVI, LVEF was reduced and E/A was higher than the reference and AVR groups (P<0.05 for all). MAPSE, TAPSE and septal motion were equally reduced in TAVI and AVR patients (P<0.05 for all). One week after the TAVI, EF increased in patients with values <50% before the procedure. In contrast, AVR resulted in reversed septal motion (P<0.001) and depressed TAPSE (P<0.001). The extent of reversed septal motion correlated with that of TAPSE in the patients group as a whole after procedures (r=0.78, P<0.001). Six weeks after TAVI, RV function remained unchanged, but LVEF increased and E/A decreased (P<0.05 for both). Thus, TAVI procedure results in significant early improvement of LV systolic and diastolic function particularly in patients with reduced EF and preserves RV systolic function.

  • 24355. Zhao, Ying
    et al.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    He, Yi Hua
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    The effect of statins on valve function and calcification in aortic stenosis: A meta-analysis2016In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 246, p. 318-324Article in journal (Refereed)
    Abstract [en]

    Background: Aortic calcification has been shown to share the same risk factors as atherosclerosis which suggested a potential benefit from statins therapy. In view of the existing conflicting results, we aimed to provide objective evidence on the effect of statins in aortic stenosis (AS).

    Methods and results: A meta-analysis of eligible studies that used statins in AS was performed. Fourteen studies were identified, 5 randomized controlled trials (RCTs) and 9 observational studies. In the 14 studies as a whole, no significant differences were found in all cause mortality (OR = 0.98, p = 0.91), cardiovascular mortality (OR = 0.80, P = 0.23) or the need for valve replacement (OR = 0.93, p = 0.45) between the statins and the control groups. LDL-cholesterol dropped in the statins groups in both <24 months and ≥24 months follow-up (p < 0.001 for both) but not in controls (p = 0.35 and p = 0.33, respectively). In the <24 months statins group, the annual increase in peak aortic velocity and peak gradient was less (p < 0.0001 and p = 0.004, respectively), but the mean gradient, valve area and calcification score were not different from controls. In the ≥24 months statins group, none of the above parameters was different from controls.

    Conclusions: Despite the consistent beneficial effect of statins on LDL-cholesterol levels, the available evidence showed no effect on aortic valve structure, function or calcification and no benefit for clinical outcomes.

  • 24356. Zhao, Ying
    et al.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    He, Yi Hua
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    The effect of statins therapy in aortic stenosis: Meta-analysis comparison data of RCTs and observationals.2016In: Data in brief, ISSN 2352-3409, Vol. 7, p. 357-361Article in journal (Refereed)
    Abstract [en]

    Aortic stenosis has been shown to share the same risk factors as atherosclerosis which suggested a potential benefit from statins therapy. Fourteen studies which provided the effect of statins treatment on aortic stenosis (AS) were meta-analyzed, including 5 randomized controlled trials (RCTs) and 9 observational studies. In the RCTs, statins did not have any influence on peak aortic valve velocity, peak valve gradient, mean valve gradient, aortic valve area and aortic calcification compared to controls. In the observational studies, the peak valve velocity, peak gradient and aortic valve area showed less progression in the statins group compared to controls. This article describes data related article title "The effect of statins on valve function and calcification in aortic stenosis: a meta-analysis" (Zhao et al., 2016) [1].

  • 24357.
    Zhao, Ying
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Centre and Ultrasound Department, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
    Owen, Andrew
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Centre and Canterbury Christ Church University.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Centre.
    Early valve replacement for aortic stenosis irrespective of symptoms results in better clinical survival: a meta-analysis of the current evidence2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 168, no 4, p. 3560-3563Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Patients with severe, but asymptomatic aortic stenosis (AS) present a difficult clinical challenge. The conventional strategy is 'wait for symptoms' approach. However, some observational studies have suggested early aortic valve replacement (AVR) results in better outcome compared to late surgery. There are no randomised controlled trials comparing clinical outcome of early and late AVR. This meta-analysis is to examine the effect of the two approaches on clinical outcome in such patients. METHODS: We searched the PubMed for published studies on asymptomatic AS and treatment. Four observational studies (N=976 patients) were suitable for inclusion in the analysis. RESULTS: All four studies provided sufficient details. Using the subgroup of asymptomatic patients who underwent early surgery together or separately from the subgroup who had surgery after developing symptoms resulted in ORs of 0.17 and 0.16 respectively (p<0.00001) in favour of early AVR compared with conservational or late surgery. CONCLUSION: Meta-analysis of the available observational studies has demonstrated highly significant clinical outcome in favour of early AVR compared with late surgery, suggesting that early surgical approach offers substantial survival benefit for severe asymptomatic AS patients.

  • 24358. Zheng, Guang
    et al.
    Tian, Liting
    Liang, Yihuai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Broberg, Karin
    Lei, Lijian
    Guo, Weijun
    Nilsson, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Bergdahl, Ingvar A
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Skerfving, Staffan
    Jin, Taiyi
    δ-Aminolevulinic acid dehydratase genotype predicts toxic effects of lead on workers' peripheral nervous system2011In: Neurotoxicology, ISSN 0161-813X, E-ISSN 1872-9711, Vol. 32, no 4, p. 374-382Article in journal (Refereed)
    Abstract [en]

    There is a wide variation in sensitivity to lead (Pb) exposure, which may be due to genetic susceptibility towards Pb. We investigated whether a polymorphism (rs1800435) in the δ-aminolevulinic acid dehydratase (ALAD) gene affected the toxicokinetics and toxicodynamics of Pb. Among 461 Chinese Pb-exposed storage battery and 175 unexposed workers, allele frequencies for the ALAD1 and ALAD2 alleles were 0.968 and 0.032, respectively. The Pb-exposed workers had a higher fraction of the ALAD1-2/2-2 genotype than unexposed workers (7.8% vs. 2.3%, p=0.01). The Pb levels in blood (B-Pb) and urine (U-Pb) were higher in Pb-exposed workers carrying the ALAD2 allele compared to homozygotes for ALAD1 (median B-Pb: 606 vs. 499 μg/L; U-Pb: 233 vs. 164 μg/g creatinine), while there was no statistically significant difference in the unexposed controls (median: 24 vs. 37 μg/L, and 3.9 vs. 6.4μg/g creatinine, respectively). High B-Pb and U-Pb were associated with statistically significantly lower sensory and motor conduction velocities in the median, ulnar and peroneal nerves. At the same B-Pb and U-Pb, ALAD1 homozygotes had lower conduction velocities than the ALAD2 carriers. There were similar trends for toxic effects on haem synthesis (zinc protoporphyrin and haemoglobin in blood) and renal function (albumin and N-acetyl-d-β-acetylglucosaminidase in urine), but without statistical significance. There was no difference in Pb toxicokinetics and toxicodynamics associated with VDR BsmI polymorphism. Our results show that the ALAD genotype modifies the relationship between Pb and its toxic effects on the peripheral nervous system. This must be considered in the assessment of risks at Pb exposure.

  • 24359. Zheng, Hou-Feng
    et al.
    Duncan, Emma
    Eriksson, Joel
    Bergström, Ulrica
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Yerges-Armstrong, Laura M.
    Leo, Paul J.
    Vandenput, Liesbeth
    Nicholson, Geoffrey
    Ladouceur, Martin
    Prince, Richard L.
    Leslie, William D.
    Eisman, John A.
    Goltzman, David
    Jones, Graeme
    Xiao, Yongjun
    Liu, Jeff
    Reid, Lanr
    Sambrook, Philip N.
    Dennison, Elaine M.
    Danoy, Patrick
    Wilson, Scott G.
    McCloskey, Eugene
    Eastell, Richard
    Spector, Tim
    Mitchell, Braxton D.
    Streeten, Elizabeth A.
    Brommage, Robert
    Lorentzon, Mattias
    Pettersson, Ulrika
    Brown, Matthew A.
    Ohlsson, Claes
    Richards, J. Brent
    WNT16 is associated with bone mineral density, osteoporotic fracture and bone strength: a large-scale meta-analysis of genomewide association studies2012In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 23, no Suppl 2, p. S402-S403Article in journal (Other academic)
  • 24360. Zheng, Hou-Feng
    et al.
    Duncan, Emma L.
    Yerges-Armstrong, Laura M.
    Eriksson, Joel
    Bergström, Ulrica
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Leo, Paul J.
    Leslie, William D.
    Goltzman, David
    Blangero, John
    Hanley, David A.
    Carless, Melanie A.
    Streeten, Elizabeth A.
    Lorentzon, Mattias
    Brown, Matthew A.
    Spector, Tim D.
    Pettersson-Kymmer, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Ohlsson, Claes
    Mitchell, Braxton D.
    Richards, J. Brent
    Meta-analysis of genome-wide studies identifies MEF2C SNPs associated with bone mineral density at forearm2013In: Journal of Medical Genetics, ISSN 0022-2593, E-ISSN 1468-6244, Vol. 50, no 7, p. 473-478Article in journal (Refereed)
    Abstract [en]

    Background Forearm fractures affect 1.7 million individuals worldwide each year and most occur earlier in life than hip fractures. While the heritability of forearm bone mineral density (BMD) and fracture is high, their genetic determinants are largely unknown. Aim To identify genetic variants associated with forearm BMD and forearm fractures. Methods BMD at distal radius, measured by dual-energy x-ray absorptiometry, was tested for association with common genetic variants. We conducted a meta-analysis of genome-wide association studies for BMD in 5866 subjects of European descent and then selected the variants for replication in 715 Mexican American samples. Gene-based association was carried out to supplement the single-nucleotide polymorphism (SNP) association test. We then tested the BMD-associated SNPs for association with forearm fracture in 2023 cases and 3740 controls. Results We found that five SNPs in the introns of MEF2C were associated with forearm BMD at a genome-wide significance level (p<5x10(-8)) in meta-analysis (lead SNP, rs11951031[T] -0.20 SDs per allele, p=9.01x10(-9)). The gene-based association test suggested an association between MEF2C and forearm BMD (p=0.003). The association between MEF2C variants and risk of fracture did not achieve statistical significance (SNP rs12521522[A]: OR=1.14 (95% CI 0.92 to 1.35), p=0.14). Meta-analysis also revealed two genome-wide suggestive loci at CTNNA2 and 6q23.2. Conclusions These findings demonstrate that variants at MEF2C were associated with forearm BMD, implicating this gene in the determination of BMD at forearm.

  • 24361. Zheng, Hou-Feng
    et al.
    Forgetta, Vincenzo
    Hsu, Yi-Hsiang
    Estrada, Karol
    Rosello-Diez, Alberto
    Leo, Paul J.
    Dahia, Chitra L.
    Park-Min, Kyung Hyun
    Tobias, Jonathan H.
    Kooperberg, Charles
    Kleinman, Aaron
    Styrkarsdottir, Unnur
    Liu, Ching-Ti
    Uggla, Charlotta
    Evans, Daniel S.
    Nielson, Carrie M.
    Walter, Klaudia
    Pettersson-Kymmer, Ulrika
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    McCarthy, Shane
    Eriksson, Joel
    Kwan, Tony
    Jhamai, Mila
    Trajanoska, Katerina
    Memari, Yasin
    Min, Josine
    Huang, Jie
    Danecek, Petr
    Wilmot, Beth
    Li, Rui
    Chou, Wen-Chi
    Mokry, Lauren E.
    Moayyeri, Alireza
    Claussnitzer, Melina
    Cheng, Chia-Ho
    Cheung, Warren
    Medina-Gomez, Carolina
    Ge, Bing
    Chen, Shu-Huang
    Choi, Kwangbom
    Oei, Ling
    Fraser, James
    Kraaij, Robert
    Hibbs, Matthew A.
    Gregson, Celia L.
    Paquette, Denis
    Hofman, Albert
    Wibom, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Tranah, Gregory J.
    Marshall, Mhairi
    Gardiner, Brooke B.
    Cremin, Katie
    Auer, Paul
    Hsu, Li
    Ring, Sue
    Tung, Joyce Y.
    Thorleifsson, Gudmar
    Enneman, Anke W.
    van Schoor, Natasja M.
    de Groot, Lisette C. P. G. M.
    van der Velde, Nathalie
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Kemp, John P.
    Christiansen, Claus
    Sayers, Adrian
    Zhou, Yanhua
    Calderari, Sophie
    van Rooij, Jeroen
    Carlson, Chris
    Peters, Ulrike
    Berlivet, Soizik
    Dostie, Josee
    Uitterlinden, Andre G.
    Williams, Stephen R.
    Farber, Charles
    Grinberg, Daniel
    LaCroix, Andrea Z.
    Haessler, Jeff
    Chasman, Daniel I.
    Giulianini, Franco
    Rose, Lynda M.
    Ridker, Paul M.
    Eisman, John A.
    Nguyen, Tuan V.
    Center, Jacqueline R.
    Nogues, Xavier
    Garcia-Giralt, Natalia
    Launer, Lenore L.
    Gudnason, Vilmunder
    Mellstrom, Dan
    Vandenput, Liesbeth
    Amin, Najaf
    van Duijn, Cornelia M.
    Karlsson, Magnus K.
    Ljunggren, Osten
    Svensson, Olle
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Rousseau, Francois
    Giroux, Sylvie
    Bussiere, Johanne
    Arp, Pascal P.
    Koromani, Fjorda
    Prince, Richard L.
    Lewis, Joshua R.
    Langdahl, Bente L.
    Hermann, A. Pernille
    Jensen, Jens-Erik B.
    Kaptoge, Stephen
    Khaw, Kay-Tee
    Reeve, Jonathan
    Formosa, Melissa M.
    Xuereb-Anastasi, Angela
    Akesson, Kristina
    McGuigan, Fiona E.
    Garg, Gaurav
    Olmos, Jose M.
    Zarrabeitia, Maria T.
    Riancho, Jose A.
    Ralston, Stuart H.
    Alonso, Nerea
    Jiang, Xi
    Goltzman, David
    Pastinen, Tomi
    Grundberg, Elin
    Gauguier, Dominique
    Orwoll, Eric S.
    Karasik, David
    Davey-Smith, George
    Smith, Albert V.
    Siggeirsdottir, Kristin
    Harris, Tamara B.
    Zillikens, M. Carola
    van Meurs, Joyce B. J.
    Thorsteinsdottir, Unnur
    Maurano, Matthew T.
    Timpson, Nicholas J.
    Soranzo, Nicole
    Durbin, Richard
    Wilson, ScottG.
    Ntzani, Evangelia E.
    Brown, Matthew A.
    Stefansson, Kari
    Hinds, David A.
    Spector, Tim
    Cupples, L. Adrienne
    Ohlsson, Claes
    Greenwood, Celia M. T.
    Jackson, Rebecca D.
    Rowe, David W.
    Loomis, Cynthia A.
    Evans, David M.
    Ackert-Bicknell, Cheryl L.
    Joyner, Alexandra L.
    Duncan, Emma L.
    Kiel, Douglas P.
    Rivadeneira, Fernando
    Richards, J. Brent
    Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 526, no 7571, p. 112-+Article in journal (Refereed)
    Abstract [en]

    The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.

  • 24362. Zheng, Hou-Feng
    et al.
    Tobias, Jon H
    Duncan, Emma
    Evans, David M
    Eriksson, Joel
    Paternoster, Lavinia
    Yerges-Armstrong, Laura M
    Lehtimäki, Terho
    Bergström, Ulrica
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Kähönen, Mika
    Leo, Paul J
    Raitakari, Olli
    Laaksonen, Marika
    Nicholson, Geoffrey C
    Viikari, Jorma
    Ladouceur, Martin
    Lyytikäinen, Leo-Pekka
    Medina-Gomez, Carolina
    Rivadeneira, Fernando
    Prince, Richard L
    Sievanen, Harri
    Leslie, William D
    Mellström, Dan
    Eisman, John A
    Movérare-Skrtic, Sofia
    Goltzman, David
    Hanley, David A
    Jones, Graeme
    St Pourcain, Beate
    Xiao, Yongjun
    Timpson, Nicholas J
    Smith, George Davey
    Reid, Ian R
    Ring, Susan M
    Sambrook, Philip N
    Karlsson, Magnus
    Dennison, Elaine M
    Kemp, John P
    Danoy, Patrick
    Sayers, Adrian
    Wilson, Scott G
    Nethander, Maria
    McCloskey, Eugene
    Vandenput, Liesbeth
    Eastell, Richard
    Liu, Jeff
    Spector, Tim
    Mitchell, Braxton D
    Streeten, Elizabeth A
    Brommage, Robert
    Pettersson-Kymmer, Ulrika
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Brown, Matthew A
    Ohlsson, Claes
    Richards, J Brent
    Lorentzon, Mattias
    WNT16 influences bone mineral density, Cortical bone thickness, bone strength, and Osteoporotic fracture risk2012In: PLoS genetics, ISSN 1553-7404, Vol. 8, no 7, p. e1002745-Article in journal (Refereed)
    Abstract [en]

    We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ∼2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2×10(-9)). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3×10(-12), and -0.16 SD per G allele, P = 1.2×10(-15), respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3×10(-9)), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9×10(-6) and rs2707466: OR = 1.22, P = 7.2×10(-6)). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16(-/-) mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5×10(-13)<P<5.9×10(-4)) at both femur and tibia, compared with their wild-type littermates. Natural variation in humans and targeted disruption in mice demonstrate that WNT16 is an important determinant of CBT, BMD, bone strength, and risk of fracture.

  • 24363. Zheng, Jiaojiao
    et al.
    Rutegård, Martin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Santoni, Giola
    Wallner, Bengt
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Xie, Shao-Hua
    Lagergren, Jesper
    Prediabetes and diabetes in relation to risk of gastric adenocarcinoma2019In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 120, no 12, p. 1147-1152Article in journal (Refereed)
    Abstract [en]

    Background: Whether prediabetes or diabetes increases the risk of gastric adenocarcinoma is not clear.

    Methods: This cohort study included 111,198 participants in the Northern Swedish Health and Disease Study. The participants were followed up from November 1985 to April 2017. The exposure to prediabetes or diabetes was assessed by oral glucose tolerance tests and self-reports. The incidence of the outcome gastric adenocarcinoma was identified from the Swedish Cancer Registry. Multivariable Cox regressions were used to analyse the associations between prediabetes or diabetes and the risk of gastric adenocarcinoma, providing hazard ratios (HR) with 95% confidence intervals (CI), with adjustment for sex, age, calendar year, body mass index, tobacco smoking and education level.

    Results: Compared with normoglycaemic participants, the risk of gastric adenocarcinoma was not increased among participants with prediabetes (HR 1.07, 95% CI 0.79–1.44), diabetes (HR 0.77, 95% CI 0.46–1.29) or any of these exposures (HR 0.96, 95% CI 0.73–1.27). No associations were identified between prediabetes or diabetes and the risk of gastric adenocarcinoma in stratified analyses or in analyses separating cardia and non-cardia gastric adenocarcinoma.

    Conclusions: This study does not support the hypothesis that prediabetes or diabetes increases the risk of gastric adenocarcinoma.

  • 24364. Zheng, Ju-Sheng
    et al.
    Imamura, Fumiaki
    Sharp, Stephen J.
    van der Schouw, Yvonne T.
    Sluijs, Ivonne
    Gundersen, Thomas E.
    Ardanaz, Eva
    Boeing, Heiner
    Bonet, Catalina
    Humberto Gomez, Jesus
    Dow, Courtney
    Fagherazzi, Guy
    Franks, Paul W.
    Jenab, Mazda
    Kuehn, Tilman
    Kaaks, Rudolf
    Key, Timothy J.
    Khaw, Kay-Tee
    Lasheras, Cristina
    Mokoroa, Olatz
    Mancini, Francesca Romana
    Nilsson, Peter M.
    Overvad, Kim
    Panico, Salvatore
    Palli, Domenico
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sieri, Sabina
    Salamanca-Fernandez, Elena
    Sacerdote, Carlotta
    Spijkerman, Annemieke M. W.
    Stepien, Magdalena
    Tjonneland, Anne
    Tumino, Rosario
    Butterworth, Adam S.
    Riboli, Elio
    Danesh, John
    Langenberg, Claudia
    Forouhi, Nita G.
    Wareham, Nicholas J.
    Association of Plasma Vitamin D Metabolites With Incident Type 2 Diabetes: EPIC-InterAct Case-Cohort Study2019In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 104, no 4, p. 1293-1303Article in journal (Refereed)
    Abstract [en]

    Background: Existing evidence for the prospective association of vitamin D status with type 2 diabetes (T2D) is focused almost exclusively on circulating total 25-hydroxyvitamin D [25(OH)D] without distinction between its subtypes: nonepimeric and epimeric 25(OH)D3 stereoisomers, and 25(OH)D2, the minor component of 25(OH)D. We aimed to investigate the prospective associations of circulating levels of the sum and each of these three metabolites with incident T2D.

    Methods: This analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC)–InterAct case-cohort study for T2D included 9671 incident T2D cases and 13,562 subcohort members. Plasma vitamin D metabolites were quantified by liquid chromatography–mass spectrometry. We used a multivariable Prentice-weighted Cox regression to estimate hazard ratios (HRs) of T2D for each metabolite. Analyses were performed separately within country, and estimates were combined across countries using random-effects meta-analysis.

    Results: The mean concentrations (SD) of total 25(OH)D, nonepimeric 25(OH)D3, epimeric 25(OH)D3, and 25(OH)D2 were 41.1 (17.2), 40.7 (17.3), 2.13 (1.31), and 8.16 (6.52) nmol/L, respectively. Plasma total 25(OH)D and nonepimeric 25(OH)D3 were inversely associated with incident T2D [multivariable-adjusted HR per 1 SD = 0.81 (95% CI, 0.77, 0.86) for both variables], whereas epimeric 25(OH)D3 was positively associated [per 1 SD HR = 1.16 (1.09, 1.25)]. There was no statistically significant association with T2D for 25(OH)D2 [per 1 SD HR = 0.94 (0.76, 1.18)].

    Conclusions: Plasma nonepimeric 25(OH)D3 was inversely associated with incident T2D, consistent with it being the major metabolite contributing to total 25(OH)D. The positive association of the epimeric form of 25(OH)D3 with incident T2D provides novel information to assess the biological relevance of vitamin D epimerization and vitamin D subtypes in diabetes etiology.

  • 24365. Zheng, Ju-Sheng
    et al.
    Sharp, Stephen J.
    Imamura, Fumiaki
    Koulman, Albert
    Schulze, Matthias B.
    Ye, Zheng
    Griffin, Jules
    Guevara, Marcela
    María Huerta, José
    Kröger, Janine
    Sluijs, Ivonne
    Agudo, Antonio
    Barricarte, Aurelio
    Boeing, Heiner
    Colorado-Yohar, Sandra
    Dow, Courtney
    Dorronsoro, Miren
    Dinesen, Pia T.
    Fagherazzi, Guy
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Lund University, Malmö, Sweden.
    Feskens, Edith J. M.
    Kühn, Tilman
    Katzke, Verena Andrea
    Key, Timothy J.
    Khaw, Kay-Tee
    de Magistris, Maria Santucci
    Romana Mancini, Francesca
    Molina-Portillo, Elena
    Nilsson, Peter M.
    Olsen, Anja
    Overvad, Kim
    Palli, Domenico
    Ramón Quirós, Jose
    Rolandsson, Olov
    Ricceri, Fulvio
    Spijkerman, Annemieke M. W.
    Slimani, Nadia
    Tagliabue, Giovanna
    Tjonneland, Anne
    Tumino, Rosario
    van der Schouw, Yvonne T.
    Langenberg, Claudia
    Riboli, Elio
    Forouhi, Nita G.
    Wareham, Nicholas J.
    Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries: a cross-sectional analysis in the EPIC-InterAct study2017In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 15, article id 203Article in journal (Refereed)
    Abstract [en]

    Background: Accumulating evidence suggests that individual circulating saturated fatty acids (SFAs) are heterogeneous in their associations with cardio-metabolic diseases, but evidence about associations of SFAs with metabolic markers of different pathogenic pathways is limited. We aimed to examine the associations between plasma phospholipid SFAs and the metabolic markers of lipid, hepatic, glycaemic and inflammation pathways. Methods: We measured nine individual plasma phospholipid SFAs and derived three SFA groups (odd-chain: C15:0 + C17:0, even-chain: C14:0 + C16:0 + C18:0, and very-long-chain: C20:0 + C22:0 + C23:0 + C24:0) in individuals from the subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study across eight European countries. Using linear regression in 15,919 subcohort members, adjusted for potential confounders and corrected for multiple testing, we examined cross-sectional associations of SFAs with 13 metabolic markers. Multiplicative interactions of the three SFA groups with pre-specified factors, including body mass index (BMI) and alcohol consumption, were tested. Results: Higher levels of odd-chain SFA group were associated with lower levels of major lipids (total cholesterol (TC), triglycerides, apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB)) and hepatic markers (alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT)). Higher even-chain SFA group levels were associated with higher levels of low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C) ratio, triglycerides, ApoB, ApoB/A1 ratio, ALT, AST, GGT and CRP, and lower levels of HDL-C and ApoA1. Very-long-chain SFA group levels showed inverse associations with triglycerides, ApoA1 and GGT, and positive associations with TC, LDL-C, TC/HDL-C, ApoB and ApoB/A1. Associations were generally stronger at higher levels of BMI or alcohol consumption. Conclusions: Subtypes of SFAs are associated in a differential way with metabolic markers of lipid metabolism, liver function and chronic inflammation, suggesting that odd-chain SFAs are associated with lower metabolic risk and even-chain SFAs with adverse metabolic risk, whereas mixed findings were obtained for very-long-chain SFAs. The clinical and biochemical implications of these findings may vary by adiposity and alcohol intake.

  • 24366. Zheng, S. Lilly
    et al.
    Sun, Jielin
    Wiklund, Fredrik
    Gao, Zhengrong
    Stattin, Pär
    Department of Surgical and Perioperative sciences, Urology and Andrology, Umeå University Hospital, Umeå.
    Purcell, Lina D.
    Adami, Hans-Olov
    Hsu, Fang-Chi
    Zhu, Yi
    Adolfsson, Jan
    Johansson, Jan-Erik
    Turner, Aubrey R.
    Adams, Tamara S.
    Liu, Wennuan
    Duggan, David
    Carpten, John D.
    Chang, Bao-Li
    Isaacs, William B.
    Xu, Jianfeng
    Grönberg, Henrik
    Genetic variants and family history predict prostate cancer similar to prostate-specific antigen2009In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 15, no 3, p. 1105-1111Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Although prostate-specific antigen (PSA) is the best biomarker for predicting prostate cancer, its predictive performance needs to be improved. Results from the Prostate Cancer Prevention Trial revealed the overall performance measured by the areas under curve of the receiver operating characteristic at 0.68. The goal of the present study is to assess the ability of genetic variants as a PSA-independent method to predict prostate cancer risk. EXPERIMENTAL DESIGN: We systematically evaluated all prostate cancer risk variants that were identified from genome-wide association studies during the past year in a large population-based prostate cancer case-control study population in Sweden, including 2,893 prostate cancer patients and 1,781 men without prostate cancer. RESULTS: Twelve single nucleotide polymorphisms were independently associated with prostate cancer risk in this Swedish study population. Using a cutoff of any 11 risk alleles or family history, the sensitivity and specificity for predicting prostate cancer were 0.25 and 0.86, respectively. The overall predictive performance of prostate cancer using genetic variants, family history, and age, measured by areas under curve was 0.65 (95% confidence interval, 0.63-0.66), significantly improved over that of family history and age (0.61%; 95% confidence interval, 0.59-0.62; P = 2.3 x 10(-10)). CONCLUSION: The predictive performance for prostate cancer using genetic variants and family history is similar to that of PSA. The utility of genetic testing, alone and in combination with PSA levels, should be evaluated in large studies such as the European Randomized Study for Prostate Cancer trial and Prostate Cancer Prevention Trial.

  • 24367. Zhou, Bin
    et al.
    Bentham, James
    Di Cesare, Mariachiara
    Bixby, Honor
    Danaei, Goodarz
    Cowan, Melanie J.
    Paciorek, Christopher J.
    Singh, Gitanjali
    Hajifathalian, Kaveh
    Bennett, James E.
    Taddei, Cristina
    Bilano, Ver
    Carrillo-Larco, Rodrigo M.
    Djalalinia, Shirin
    Khatibzadeh, Shahab
    Lugero, Charles
    Peykari, Niloofar
    Zhang, Wan Zhu
    Lu, Yuan
    Stevens, Gretchen A.
    Riley, Leanne M.
    Bovet, Pascal
    Elliott, Paul
    Gu, Dongfeng
    Ikeda, Nayu
    Jackson, Rod T.
    Joffres, Michel
    Kengne, Andre Pascal
    Laatikainen, Tiina
    Lam, Tai Hing
    Laxmaiah, Avula
    Liu, Jing
    Miranda, J. Jaime
    Mondo, Charles K.
    Neuhauser, Hannelore K.
    Sundstrom, Johan
    Smeeth, Liam
    Soric, Maroje
    Woodward, Mark
    Ezzati, Majid
    Abarca-Gomez, Leandra
    Abdeen, Ziad A.
    Rahim, Hanan Abdul
    Abu-Rmeileh, Niveen M.
    Acosta-Cazares, Benjamin
    Adams, Robert
    Aekplakorn, Wichai
    Afsana, Kaosar
    Aguilar-Salinas, Carlos A.
    Agyemang, Charles
    Ahmadvand, Alireza
    Ahrens, Wolfgang
    Al Raddadi, Rajaa
    Al Woyatan, Rihab
    Ali, Mohamed M.
    Alkerwi, Ala'a
    Aly, Eman
    Amouyel, Philippe
    Amuzu, Antoinette
    Andersen, Lars Bo
    Anderssen, Sigmund A.
    Angquist, Lars
    Anjana, Ranjit Mohan
    Ansong, Daniel
    Aounallah-Skhiri, Hajer
    Araujo, Joana
    Ariansen, Inger
    Aris, Tahir
    Arlappa, Nimmathota
    Aryal, Krishna
    Arveiler, Dominique
    Assah, Felix K.
    Assuncao, Maria Cecilia F.
    Avdicova, Maria
    Azevedo, Ana
    Azizi, Fereidoun
    Babu, Bontha V.
    Bahijri, Suhad
    Balakrishna, Nagalla
    Bandosz, Piotr
    Banegas, Jose R.
    Barbagallo, Carlo M.
    Barcelo, Alberto
    Barkat, Amina
    Barros, Aluisio J. D.
    Barros, Mauro V.
    Bata, Iqbal
    Batieha, Anwar M.
    Baur, Louise A.
    Beaglehole, Robert
    Ben Romdhane, Habiba
    Benet, Mikhail
    Benson, Lowell S.
    Bernabe-Ortiz, Antonio
    Bernotiene, Gailute
    Bettiol, Heloisa
    Bhagyalaxmi, Aroor
    Bharadwaj, Sumit
    Bhargava, Santosh K.
    Bi, Yufang
    Bikbov, Mukharram
    Bjerregaard, Peter
    Bjertness, Espen
    Bjokelund, Cecilia
    Blokstra, Anneke
    Bo, Simona
    Bobak, Martin
    Boeing, Heiner
    Boggia, Jose G.
    Boissonnet, Carlos P.
    Bongard, Vanina
    Braeckman, Lutgart
    Brajkovich, Imperia
    Branca, Francesco
    Breckenkamp, Juergen
    Brenner, Hermann
    Brewster, Lizzy M.
    Bruno, Graziella
    Bueno-de-Mesquita, H. B. (as)
    Bugge, Anna
    Burns, Con
    Bursztyn, Michael
    de Leon, Antonio Cabrera
    Cameron, Christine
    Can, Gunay
    Candido, Ana Paula C.
    Capuano, Vincenzo
    Cardoso, Viviane C.
    Carlsson, Axel C.
    Carvalho, Maria J.
    Casanueva, Felipe F.
    Casas, Juan-Pablo
    Caserta, Carmelo A.
    Chamukuttan, Snehalatha
    Chan, Angelique W.
    Chan, Queenie
    Chaturvedi, Himanshu K.
    Chaturvedi, Nishi
    Chen, Chien-Jen
    Chen, Fangfang
    Chen, Huashuai
    Chen, Shuohua
    Chen, Zhengming
    Cheng, Ching-Yu
    Dekkaki, Imane Cherkaoui
    Chetrit, Angela
    Chiolero, Arnaud
    Chiou, Shu-Ti
    Chirita-Emandi, Adela
    Cho, Belong
    Cho, Yumi
    Chudek, Jerzy
    Cifkova, Renata
    Claessens, Frank
    Clays, Els
    Concin, Hans
    Cooper, Cyrus
    Cooper, Rachel
    Coppinger, Tara C.
    Costanzo, Simona
    Cottel, Dominique
    Cowell, Chris
    Craig, Cora L.
    Crujeiras, Ana B.
    Cruz, Juan J.
    D'Arrigo, Graziella
    d'Orsi, Eleonora
    Dallongeville, Jean
    Damasceno, Albertino
    Dankner, Rachel
    Dantoft, Thomas M.
    Dauchet, Luc
    De Backer, Guy
    de Gaetano, Giovanni
    De Henauw, Stefaan
    De Smedt, Delphine
    Deepa, Mohan
    Dehghan, Abbas
    Delisle, Helene
    Deschamps, Valerie
    Dhana, Klodian
    Di Castelnuovo, Augusto F.
    Dias-da-Costa, Juvenal Soares
    Diaz, Alejandro
    Dickerson, Ty T.
    Do, Ha T. P.
    Dobson, Annette J.
    Donfrancesco, Chiara
    Donoso, Silvana P.
    Doering, Angela
    Doua, Kouamelan
    Drygas, Wojciech
    Dulskiene, Virginija
    Dzakula, Aleksandar
    Dzerve, Vilnis
    Dziankowska-Zaborszczyk, Elzbieta
    Eggertsen, Robert
    Ekelund, Ulf
    El Ati, Jalila
    Ellert, Ute
    Elosua, Roberto
    Erasmus, Rajiv T.
    Erem, Cihangir
    Eriksen, Louise
    Escobedo-de la Pena, Jorge
    Evans, Alun
    Faeh, David
    Fall, Caroline H.
    Farzadfar, Farshad
    Felix-Redondo, Francisco J.
    Ferguson, Trevor S.
    Fernandez-Berges, Daniel
    Ferrante, Daniel
    Ferrari, Marika
    Ferreccio, Catterina
    Ferrieres, Jean
    Finn, Joseph D.
    Fischer, Krista
    Foeger, Bernhard
    Foo, Leng Huat
    Forslund, Ann-Sofie
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Forsner, Maria
    Umeå University, Faculty of Medicine, Department of Nursing. Högskolan Dalarna.
    Fortmann, Stephen P.
    Fouad, Heba M.
    Francis, Damian K.
    Franco, Maria do Carmo
    Franco, Oscar H.
    Frontera, Guillermo
    Fuchs, Flavio D.
    Fuchs, Sandra C.
    Fujita, Yuki
    Furusawa, Takuro
    Gaciong, Zbigniew
    Gareta, Dickman
    Garnett, Sarah P.
    Gaspoz, Jean-Michel
    Gasull, Magda
    Gates, Louise
    Gavrila, Diana
    Geleijnse, Johanna M.
    Ghasemian, Anoosheh
    Ghimire, Anup
    Giampaoli, Simona
    Gianfagna, Francesco
    Giovannelli, Jonathan
    Goldsmith, Rebecca A.
    Goncalves, Helen
    Gonzalez Gross, Marcela
    Gonzalez Rivas, Juan P.
    Gottrand, Frederic
    Graff-Iversen, Sidsel
    Grafnetter, Dusan
    Grajda, Aneta
    Gregor, Ronald D.
    Grodzicki, Tomasz
    Grontved, Anders
    Gruden, Grabriella
    Grujic, Vera
    Guan, Ong Peng
    Gudnason, Vilmundur
    Guerrero, Ramiro
    Guessous, Idris
    Guimaraes, Andre L.
    Gulliford, Martin C.
    Gunnlaugsdottir, Johanna
    Gunter, Marc
    Gupta, Prakash C.
    Gureje, Oye
    Gurzkowska, Beata
    Gutierrez, Laura
    Gutzwiller, Felix
    Hadaegh, Farzad
    Halkjaer, Jytte
    Hambleton, Ian R.
    Hardy, Rebecca
    Harikumar, Rachakulla
    Hata, Jun
    Hayes, Alison J.
    He, Jiang
    Hendriks, Marleen Elisabeth
    Henriques, Ana
    Hernandez Cadena, Leticia
    Herqutanto,
    Herrala, Sauli
    Heshmat, Ramin
    Hihtaniemi, Ilpo Tapani
    Ho, Sai Yin
    Ho, Suzanne C.
    Hobbs, Michael
    Hofman, Albert
    Dinc, Gonul Horasan
    Hormiga, Claudia M.
    Horta, Bernardo L.
    Houti, Leila
    Howitt, Christina
    Htay, Thein Thein
    Htet, Aung Soe
    Hu, Yonghua
    Maria Huerta, Jose
    Husseini, Abdullatif S.
    Huybrechts, Inge
    Hwalla, Nahla
    Iacoviello, Licia
    Iannone, Anna G.
    Ibrahim, M. Mohsen
    Ikram, M. Arfan
    Irazola, Vilma E.
    Islam, Muhammad
    Ivkovic, Vanja
    Iwasaki, Masanori
    Jacobs, Jeremy M.
    Jafar, Tazeen
    Jamrozik, Konrad
    Janszky, Imre
    Jasienska, Grazyna
    Jelakovic, Bojan
    Jiang, Chao Qiang
    Johansson, Mattias
    Jonas, Jost B.
    Jorgensen, Torben
    Joshi, Pradeep
    Juolevi, Anne
    Jurak, Gregor
    Juresa, Vesna
    Kaaks, Rudolf
    Kafatos, Anthony
    Kalter-Leibovici, Ofra
    Kamaruddin, Nor Azmi
    Kasaeian, Amir
    Katz, Joanne
    Kauhanen, Jussi
    Kaur, Prabhdeep
    Kavousi, Maryam
    Kazakbaeva, Gyulli
    Keil, Ulrich
    Boker, Lital Keinan
    Keinanen-Kiukaanniemi, Sirkka
    Kelishadi, Roya
    Kemper, Han C. G.
    Kersting, Mathilde
    Key, Timothy
    Khader, Yousef Saleh
    Khalili, Davood
    Khang, Young-Ho
    Khaw, Kay-Tee
    Kiechl, Stefan
    Killewo, Japhet
    Kim, Jeongseon
    Klumbiene, Jurate
    Kolle, Elin
    Kolsteren, Patrick
    Korrovits, Paul
    Koskinen, Seppo
    Kouda, Katsuyasu
    Koziel, Slawomir
    Kristensen, Peter Lund
    Krokstad, Steinar
    Kromhout, Daan
    Kruger, Herculina S.
    Kubinova, Ruzena
    Kuciene, Renata
    Kuh, Diana
    Kujala, Urho M.
    Kula, Krzysztof
    Kulaga, Zbigniew
    Kumar, R. Krishna
    Kurjata, Pawel
    Kusuma, Yadlapalli S.
    Kuulasmaa, Kari
    Kyobutungi, Catherine
    Lachat, Carl
    Landrove, Orlando
    Lanska, Vera
    Lappas, Georg
    Larijani, Bagher
    Laugsand, Lars E.
    Bao, Khanh Le Nguyen
    Le, Tuyen D.
    Leclercq, Catherine
    Lee, Jeannette
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    Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19.1 million participants2017In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 389, no 10064, p. 37-55Article in journal (Refereed)
    Abstract [en]

    Methods: For this analysis, we pooled national, subnational, or community population-based studies that had measured blood pressure in adults aged 18 years and older. We used a Bayesian hierarchical model to estimate trends from 1975 to 2015 in mean systolic and mean diastolic blood pressure, and the prevalence of raised blood pressure for 200 countries. We calculated the contributions of changes in prevalence versus population growth and ageing to the increase in the number of adults with raised blood pressure.

    Findings: We pooled 1479 studies that had measured the blood pressures of 19·1 million adults. Global age-standardised mean systolic blood pressure in 2015 was 127·0 mm Hg (95% credible interval 125·7–128·3) in men and 122·3 mm Hg (121·0–123·6) in women; age-standardised mean diastolic blood pressure was 78·7 mm Hg (77·9–79·5) for men and 76·7 mm Hg (75·9–77·6) for women. Global age-standardised prevalence of raised blood pressure was 24·1% (21·4–27·1) in men and 20·1% (17·8–22·5) in women in 2015. Mean systolic and mean diastolic blood pressure decreased substantially from 1975 to 2015 in high-income western and Asia Pacific countries, moving these countries from having some of the highest worldwide blood pressure in 1975 to the lowest in 2015. Mean blood pressure also decreased in women in central and eastern Europe, Latin America and the Caribbean, and, more recently, central Asia, Middle East, and north Africa, but the estimated trends in these super-regions had larger uncertainty than in high-income super-regions. By contrast, mean blood pressure might have increased in east and southeast Asia, south Asia, Oceania, and sub-Saharan Africa. In 2015, central and eastern Europe, sub-Saharan Africa, and south Asia had the highest blood pressure levels. Prevalence of raised blood pressure decreased in high-income and some middle-income countries; it remained unchanged elsewhere. The number of adults with raised blood pressure increased from 594 million in 1975 to 1·13 billion in 2015, with the increase largely in low-income and middle-income countries. The global increase in the number of adults with raised blood pressure is a net effect of increase due to population growth and ageing, and decrease due to declining age-specific prevalence.

    Interpretation: During the past four decades, the highest worldwide blood pressure levels have shifted from high-income countries to low-income countries in south Asia and sub-Saharan Africa due to opposite trends, while blood pressure has been persistently high in central and eastern Europe.

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    Wu, Aleksander Giwercman
    Wu, Frederick C.
    Wu, Shouling
    Xu, Haiquan
    Yan, Weili
    Yang, Xiaoguang
    Ye, Xingwang
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    Yoshihara, Akihiro
    Younger-Coleman, Novie O.
    Yusoff, Ahmad Faudzi
    Zainuddin, Ahmad Ali
    Zambon, Sabina
    Zampelas, Antonis
    Zdrojewski, Tomasz
    Zeng, Yi
    Zhao, Dong
    Zhao, Wenhua
    Zheng, Wei
    Zheng, Yingfeng
    Zhu, Dan
    Zhussupov, Baurzhan
    Zimmermann, Esther
    Cisneros, Julio Zuniga
    Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: a pooled analysis of 1018 population-based measurement studies with 88.6 million participants2018In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 47, no 3, p. 872-883iArticle in journal (Refereed)
    Abstract [en]

    Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure.

    Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probit-transformed) prevalence of raised blood pressure and age-group-and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure.

    Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the high-income Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association.

    Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups.

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    Mursu, Jaakko
    Nagel, Gabriele
    Namesna, Jana
    Nang, Ei Ei K.
    Nangia, Vinay B.
    Maria Navarrete-Munoz, Eva
    Ndiaye, Ndeye Coumba
    Nenko, Ilona
    Nervi, Flavio
    Nguyen, Nguyen D.
    Nguyen, Quang Ngoc
    Nieto-Martinez, Ramfi S. E.
    Ning, Guang
    Ninomiya, Toshiharu
    Noale, Marianna
    Noto, Davide
    Al Nsour, Mohannad
    Ochoa-Aviles, Angelica M.
    Oh, Kyungwon
    Ordunez, Pedro
    Osmond, Clive
    Otero, Johanna A.
    Owusu-Dabo, Ellis
    Pahomova, Elena
    Palmieri, Luigi
    Panda-Jonas, Songhomitra
    Panza, Francesco
    Parsaeian, Mahboubeh
    Peixoto, Sergio Viana
    Peltonen, Markku
    Peters, Annette
    Peykari, Niloofar
    Pham, Son Thai
    Pilav, Aida
    Pitakaka, Freda
    Piwonska, Aleksandra
    Piwonski, Jerzy
    Plans-Rubio, Pedro
    Porta, Miquel
    Portegies, Marileen L. P.
    Poustchi, Hossein
    Pradeepa, Rajendra
    Price, Jacqueline F.
    Punab, Margus
    Qasrawi, Radwan F.
    Qorbani, Mostafa
    Radisauskas, Ricardas
    Rahman, Mahmudur
    Raitakari, Olli
    Rao, Sudha Ramachandra
    Ramke, Jacqueline
    Ramos, Rafel
    Rampal, Sanjay
    Rathmann, Wolfgang
    Redon, Josep
    Reganit, Paul Ferdinand M.
    Rigo, Fernando
    Robinson, Sian M.
    Robitaille, Cynthia
    Rodriguez-Artalejo, Fernando
    del Cristo Rodriguez-Perez, Maria
    Rodriguez-Villamizar, Laura A.
    Rojas-Martinez, Rosalba
    Ronkainen, Kimmo
    Rosengren, Annika
    Rubinstein, Adolfo
    Rui, Ornelas
    Sandra Ruiz-Betancourt, Blanca
    Russo Horimoto, Andrea R. V.
    Rutkowski, Marcin
    Sabanayagam, Charumathi
    Sachdev, Harshpal S.
    Saidi, Olfa
    Sakarya, Sibel
    Salanave, Benoit
    Salonen, Jukka T.
    Salvetti, Massimo
    Sanchez-Abanto, Jose
    Santos, Diana
    dos Santos, Renata Nunes
    Santos, Rute
    Saramies, Jouko L.
    Sardinha, Luis B.
    Sarrafzadegan, Nizal
    Saum, Kai-Uwe
    Scazufca, Marcia
    Schargrodsky, Herman
    Scheidt-Nave, Christa
    Sein, Aye Aye
    Sharma, Sanjb K.
    Shaw, Jonathan E.
    Shibuya, Kenji
    Shin, Youchan
    Shiri, Rahman
    Siantar, Rosalynn
    Sibai, Abla M.
    Simon, Mary
    Simons, Judith
    Simons, Leon A.
    Sjostrom, Michael
    Slowikowska-Hilczer, Jolanta
    Slusarczyk, Przemyslaw
    Smeeth, Liam
    Snijder, Marieke B.
    So, Hung-Kwan
    Sobngwi, Eugene
    Söderberg, Stefan
    Umeå University.
    Solfrizzi, Vincenzo
    Sonestedt, Emily
    Soumare, Aicha
    Staessen, Jan A.
    Stathopoulou, Maria G.
    Steene-Johannessen, Jostein
    Stehle, Peter
    Stein, Aryeh D.
    Stessman, Jochanan
    Stoeckl, Doris
    Stokwiszewski, Jakub
    Stronks, Karien
    Strufaldi, Maria Wany
    Sun, Chien-An
    Sundstrom, Johan
    Sung, Yn-Tz
    Suriyawongpaisal, Paibul
    Sy, Rody G.
    Tai, E. Shyong
    Tamosiunas, Abdonas
    Tang, Line
    Tarawneh, Mohammed
    Tarqui-Mamani, Carolina B.
    Taylor, Anne
    Theobald, Holger
    Thijs, Lutgarde
    Thuesen, Betina H.
    Tolonen, Hanna K.
    Tolstrup, Janne S.
    Topbas, Murat
    Torrent, Maties
    Traissac, Pierre
    Trinh, Oanh T. H.
    Tulloch-Reid, Marshall K.
    Tuomainen, Tomi-Pekka
    Turley, Maria L.
    Tzourio, Christophe
    Ueda, Peter
    Ukoli, Flora A. M.
    Ulmer, Hanno
    Uusitalo, Hannu M. T.
    Valdivia, Gonzalo
    Valvi, Damaskini
    van Rossem, Lenie
    van Valkengoed, Irene G. M.
    Vanderschueren, Dirk
    Vanuzzo, Diego
    Vega, Tomas
    Velasquez-Melendez, Gustavo
    Veronesi, Giovanni
    Verschuren, W. M. Monique
    Verstraeten, Roosmarijn
    Viet, Lucie
    Vioque, Jesus
    Virtanen, Jyrki K.
    Viswanathan, Bharathi
    Vollenweider, Peter
    Voutilainen, Sari
    Vrijheid, Martine
    Wade, Alisha N.
    Wagner, Aline
    Walton, Janette
    Mohamud, Wan Nazaimoon Wan
    Wang, Feng
    Wang, Ming-Dong
    Wang, Qian
    Wang, Ya Xing
    Wannamethee, S. Goya
    Weerasekera, Deepa
    Whincup, Peter H.
    Widhalm, Kurt
    Wijga, Alet H.
    Wilks, Rainford J.
    Willeit, Johann
    Wilsgaard, Tom
    Wojtyniak, Bogdan
    Wong, Tien Yin
    Woo, Jean
    Woodward, Mark
    Wu, Frederick C.
    Wu, Shou Ling
    Xu, Haiquan
    Yan, Weili
    Yang, Xiaoguang
    Ye, Xingwang
    Yoshihara, Akihiro
    Younger-Coleman, Novie O.
    Zambon, Sabina
    Zargar, Abdul Hamid
    Zdrojewski, Tomasz
    Zhao, Wenhua
    Zheng, Yingfeng
    Zuniga Cisneros, Julio
    Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants2016In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 387, no 10027, p. 1513-1530Article in journal (Refereed)
    Abstract [en]

    Background One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes. Methods We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue. Findings We used data from 751 studies including 4 372 000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-7.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target. Interpretation Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults affected, has increased faster in low-income and middle-income countries than in high-income countries. Funding Wellcome Trust. Copyright (C) NCD Risk Factor Collaboration. Open Access article distributed under the terms of CC BY.

  • 24370.
    Zhou, Kaixin
    et al.
    Division of Cardiovascular & Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee, U.K..
    Donnelly, Louise A.
    Division of Cardiovascular & Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee, U.K..
    Morris, Andrew D.
    Division of Cardiovascular & Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee, U.K..
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Science, Genetic & Molecular Epidemiology Unit, Lund University, Malmö, Sweden ; Department of Nutrition, Harvard University, School of Public Health, Boston, MA.
    Jennison, Chris
    Department of Mathematical Sciences, University of Bath, Bath, U.K..
    Palmer, Colin N. A.
    Division of Cardiovascular & Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee, U.K..
    Pearson, Ewan R.
    Division of Cardiovascular & Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee, U.K..
    Clinical and genetic determinants of progression of type 2 diabetes: a DIRECT study2014In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 37, no 3, p. 718-724Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To identify the clinical and genetic factors that explain why the rate of diabetes progression is highly variable between idividuals following diagnosis of type 2 diabetes.

    RESEARCH DESIGN AND METHODS: We studied 5,250 patients with type 2 diabetes using comprehensive electronic medical records in Tayside, Scotland, from 1992 onward. We investigated the association of clinical, biochemical, and genetic factors with the risk of progression of type 2 diabetes from diagnosis to the requirement of insulin treatment (defined as insulin treatment or HbA(1c) 8.5% [69 mmol/mol] treated with two or more noninsulin therapies).RESULTSRisk of progression was associated with both low and high BMI. In an analysis stratified by BMI and HbA(1c) at diagnosis, faster progression was independently associated with younger age at diagnosis, higher log triacylglyceride (TG) concentrations (hazard ratio [HR] 1.28 per mmol/L [95% CI 1.15-1.42]) and lower HDL concentrations (HR 0.70 per mmol/L [95% CI 0.55-0.87]). A high Genetic Risk Score derived from 61 diabetes risk variants was associated with a younger age at diagnosis and a younger age when starting insulin but was not associated with the progression rate from diabetes to the requirement of insulin treatment.

    CONCLUSIONS: Increased TG and low HDL levels are independently associated with increased rate of progression of diabetes. The genetic factors that predispose to diabetes are different from those that cause rapid progression of diabetes, suggesting a difference in biological process that needs further investigation.

  • 24371.
    Zhou, Yang
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Chen, Changchun
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Johansson, Marcus J. O.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    The pre-mRNA retention and splicing complex controls tRNA maturation by promoting TAN1 expression2013In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 41, no 11, p. 5669-5678Article in journal (Refereed)
    Abstract [en]

    The conserved pre-mRNA retention and splicing (RES) complex, which in yeast consists of Bud13p, Snu17p and Pml1p, is thought to promote nuclear retention of unspliced pre-mRNAs and enhance splicing of a subset of transcripts. Here, we find that the absence of Bud13p or Snu17p causes greatly reduced levels of the modified nucleoside N-4-acetylcytidine (ac(4)C) in tRNA and that a lack of Pml1p reduces ac(4)C levels at elevated temperatures. The ac(4)C nucleoside is normally found at position 12 in the tRNA species specific for serine and leucine. We show that the tRNA modification defect in RES-deficient cells is attributable to inefficient splicing of TAN1 pre-mRNA and the effects of reduced Tan1p levels on formation of ac(4)C. Analyses of cis-acting elements in TAN1 pre-mRNA showed that the intron sequence between the 5' splice site and branchpoint is necessary and sufficient to mediate RES dependency. We also show that in RES-deficient cells, the TAN1 pre-mRNA is targeted for degradation by the cytoplasmic nonsense-mediated mRNA decay pathway, indicating that poor nuclear retention may contribute to the tRNA modification defect. Our results demonstrate that TAN1 pre-mRNA processing has an unprecedented requirement for RES factors and that the complex controls the formation of ac(4)C in tRNA.

  • 24372.
    Zhu, Jijia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    The Risk Factors of Depression among older people in China2012Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
  • 24373. Zhu, Lijun
    et al.
    Hou, Miao
    Sun, Bin
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Zhang, Li
    Yi, Jun
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Li, Xiaonan
    Testosterone Stimulates Adipose Tissue 11 beta-Hydroxysteroid Dehydrogenase Type 1 Expression in a Depot-Specific Manner in Children2010In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 95, no 7, p. 3300-3308Article in journal (Refereed)
    Abstract [en]

    Context: Activation of the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in adipose tissue results in the production of excess tissue glucocorticoids and the induction of adiposity and visceral obesity in particular. Androgens may affect body fat distribution by regulating the local metabolism of cortisol.

    Objective: Our objective was to study 11beta-HSD1 mRNA expression in abdominal sc and omental (om) adipose tissue in children after in vitro testosterone and cortisol treatment.

    Subjects and Methods: Paired fat biopsies (sc and om) were obtained from 19 boys (age 6-14 yr, body mass index 14.6-25.3 kg/m(2), BMI SD score SDS -1.6-3.1) undergoing open abdominal surgery. Pieces of adipose tissue were incubated with testosterone, cortisol, or both hormones for 24 h, whereupon mRNA expression of 11beta-HSD1 and hexose-6-phosphate dehydrogenase (H6PDH) were measured by real-time PCR, and 11beta-HSD1 enzyme activity was determined.

    Results: Testosterone treatment up-regulated 11beta-HSD1 mRNA expression compared with control incubations in the absence of testosterone (P < 0.05) in om adipose tissue. Testosterone and cortisol both increased 11beta-HSD1 mRNA expression in om but not sc adipose tissue in a depot-specific manner by 2.5- and 2.9-fold, respectively (P < 0.001). However, there was no synergistic effect of the two hormones. 11beta-HSD1 enzyme activity correlated positively to mRNA expression (r = 0.610; P = 0.001). Adipose tissue mRNA expression of H6PDH was affected in a similar fashion to 11beta-HSD1 after hormonal treatment.

    Conclusions: Testosterone and cortisol stimulated 11beta-HSD1 and H6PDH mRNA expression and 11beta-HSD1 activity in om but not in sc adipose tissue. This suggests that these hormones may contribute to fat distribution and accumulation during childhood.

  • 24374.
    Zhu, Shaochun
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Wuolikainen, Anna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wu, Junfang
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Öhman, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Wingsle, Gunnar
    Moritz, Thomas
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Trupp, Miles
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Targeted Multiple Reaction Monitoring Analysis of CSF Identifies UCHL1 and GPNMB as Candidate Biomarkers for ALS2019In: Journal of Molecular Neuroscience, ISSN 0895-8696, E-ISSN 1559-1166, Vol. 69, no 4, p. 643-657Article in journal (Refereed)
    Abstract [en]

    The neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) share some common molecular deficits including disruption of protein homeostasis leading to disease-specific protein aggregation. While insoluble protein aggregates are the defining pathological confirmation of diagnosis, patient stratification based on early molecular etiologies may identify distinct subgroups within a clinical diagnosis that would respond differently in therapeutic development programs. We are developing targeted multiple reaction monitoring (MRM) mass spectrometry methods to rigorously quantify CSF proteins from known disease genes involved in lysosomal, ubiquitin-proteasomal, and autophagy pathways. Analysis of CSF from 21 PD, 21 ALS, and 25 control patients, rigorously matched for gender, age, and age of sample, revealed significant changes in peptide levels between PD, ALS, and control. In patients with PD, levels of two peptides for chromogranin B (CHGB, secretogranin 1) were significantly reduced. In CSF of patients with ALS, levels of two peptides from ubiquitin carboxy-terminal hydrolase like protein 1 (UCHL1) and one peptide each for glycoprotein non-metastatic melanoma protein B (GPNMB) and cathepsin D (CTSD) were all increased. Analysis of patients with ALS separated into two groups based on length of survival after CSF sampling revealed that the increases in GPNMB and UCHL1 were specific for short-lived ALS patients. While analysis of additional cohorts is required to validate these candidate biomarkers, this study suggests methods for stratification of ALS patients for clinical trials and identifies targets for drug efficacy measurements during therapeutic development.

  • 24375.
    Zhu, Yan-He
    et al.
    Institute of Endemic Diseases, Health Science Center, School of Public Health, Xi'an Jiaotong University, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, China.
    Wang, Xin-Feng
    Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
    Yang, Guang
    Second Department of Cardiology, Shaanxi Province People's Hospital, Xi'an, China.
    Wei, Jin
    Department of Cardiology, Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China..
    Tan, Wu-Hong
    Institute of Endemic Diseases, Health Science Center, School of Public Health, Xi'an Jiaotong University, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, China.
    Wang, Li-Xin
    Institute of Endemic Diseases, Health Science Center, School of Public Health, Xi'an Jiaotong University, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, China.
    Guo, Xiong
    Institute of Endemic Diseases, Health Science Center, School of Public Health, Xi'an Jiaotong University, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, China.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Institute of Endemic Diseases, Health Science Center, School of Public Health, Xi'an Jiaotong University, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, China.
    Xu, Jie-Hua
    Department of Human Anatomy and Histo-Embryology, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
    Efficacy of long-term selenium supplementation in the treatment of chronic Keshan disease with congestive heart failure2019In: Current medical science, ISSN 2096-5230, Vol. 39, no 2, p. 237-242Article in journal (Refereed)
    Abstract [en]

    Few effective treatments for chronic Keshan disease have been available till now. The efficacy of long-term selenium supplementation in the treatment of chronic Keshan disease with congestive heart failure is inconclusive. This study aimed to determine whether selenium supplementation is associated with a decreased risk of cardiac death in chronic Keshan disease with congestive heart failure by ten years of follow-up. A retrospective long-term follow-up analysis was performed on a monitored cohort consisting of 302 chronic Keshan disease patients with a mean age of 40.8±11.4 years. Of the 302 chronic Keshan disease patients, 170 (56.3%) were given selenium supplementation until the end point of follow-up. Cox proportional hazards regression models were used to identify the independent predictors of cardiac events. Our results showed that during the follow-up, there were 101 deaths of patients with chronic Keshan disease in the selenium supplementation group (101/170, 59.4%) and 98 in non-selenium supplementation group (98/132, 74.2%). Multivariate analyses suggested that selenium supplementation was associated with a decreased risk of cardiac death (HR 0.39, 95% CI 0.28-0.53) after adjustment for baseline age, sex, cigarette smoking, family history of Keshan disease, body mass index (BMI), heart rate, electrocardiogram (ECG) abnormalities, blood pressure, initial cardiothoracic ratio, left ventricular ejection fractions (LVEF) and whole-blood selenium concentration. Our ten-year follow-up analysis indicated that selenium supplementation, specifically combined with the use of angiotensin-converting enzyme inhibitor and beta blocker therapy, improved the survival of patients with chronic Keshan disease with congestive heart failure. BMI, selenium deficiency, male, combined ECG abnormalities, LVEF, and fast heart rate increased the risk of cardiac events.

  • 24376. Zhu, Ying
    et al.
    Wei, Yongyue
    Zhang, Ruyang
    Dong, Xuesi
    Shen, Sipeng
    Zhao, Yang
    Bai, Jianling
    Albanes, Demetrius
    Caporaso, Neil E.
    Landi, Maria Teresa
    Zhu, Bin
    Chanock, Stephen J.
    Gu, Fangyi
    Lam, Stephen
    Tsao, Ming-Sound
    Shepherd, Frances A.
    Tardon, Adonina
    Fernandez-Somoano, Ana
    Fernandez-Tardon, Guillermo
    Chen, Chu
    Barnett, Matthew J.
    Doherty, Jennifer
    Bojesen, Stig E.
    Johansson, Mattias
    Brennan, Paul
    Mckay, James D.
    Carreras-Torres, Robert
    Muley, Thomas
    Risch, Angela
    Wichmann, Heunz-Erich
    Bickeboeller, Heike
    Rosenberger, Albert
    Rennert, Gad
    Saliba, Walid
    Arnold, Susanne M.
    Field, John K.
    Davies, Michael P. A.
    Marcus, Michael W.
    Wu, Xifeng
    Ye, Yuanqing
    Le Marchand, Loic
    Wilkens, Lynne R.
    Melander, Olle
    Manjer, Jonas
    Brunnstrom, Hans
    Hung, Rayjean J.
    Liu, Geoffrey
    Brhane, Yonathan
    Kachuri, Linda
    Andrew, Angeline S.
    Duell, Eric J.
    Kiemeney, Lambertus A.
    van der Heijden, Erik H. F. M.
    Haugen, Aage
    Zienolddiny, Shanbeh
    Skaug, Vidar
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Woll, Penella J.
    Cox, Angela
    Taylor, Fiona
    Teare, Dawn M.
    Lazarus, Philip
    Schabath, Matthew B.
    Aldrich, Melinda C.
    Houlston, Richard S.
    McLaughlin, John
    Stevens, Victoria L.
    Shen, Hongbing
    Hu, Zhibin
    Dai, Juncheng
    Amos, Christopher I.
    Han, Younghun
    Zhu, Dakai
    Goodman, Gary E.
    Chen, Feng
    Christiani, David C.
    Elevated Platelet Count Appears to Be Causally Associated with Increased Risk of Lung Cancer: A Mendelian Randomization Analysis2019In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 28, no 5, p. 935-942Article in journal (Refereed)
    Abstract [en]

    Background: Platelets are a critical element in coagulation and inflammation, and activated platelets are linked to cancer risk through diverse mechanisms. However, a causal relationship between platelets and risk of lung cancer remains unclear. Methods: We performed single and combined multiple instrumental variable Mendelian randomization analysis by an inverse-weighted method, in addition to a series of sensitivity analyses. Summary data for associations between SNPs and platelet count are from a recent publication that included 48,666 Caucasian Europeans, and the International Lung Cancer Consortium and Transdisciplinary Research in Cancer of the Lung data consisting of 29,266 cases and 56,450 controls to analyze associations between candidate SNPs and lung cancer risk. Results: Multiple instrumental variable analysis incorporating six SNPs showed a 62% increased risk of overall nonsmall cell lung cancer [NSCLC; OR, 1.62; 95% confidence interval (CI), 1.15-2.27; P = 0.005] and a 200% increased risk for small-cell lung cancer (OR, 3.00; 95% CI, 1.27-7.06; P = 0.01). Results showed only a trending association with NSCLC histologic subtypes, which may be due to insufficient sample size and/or weak effect size. A series of sensitivity analysis retained these findings. Conclusions: Our findings suggest a causal relationship between elevated platelet count and increased risk of lung cancer and provide evidence of possible antiplatelet interventions for lung cancer prevention. Impact: These findings provide a better understanding of lung cancer etiology and potential evidence for antiplatelet interventions for lung cancer prevention.

  • 24377. Zhuo, Lang
    et al.
    Xu, Ling
    Ye, Jingtao
    Sun, Sun
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Health Outcomes and Economic Evaluation Research Group, Stockholm, Sweden; Centre for Healthcare Ethics, Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, Sweden.
    Zhang, Yaoguang
    Burstrom, Kristina
    Chen, Jiaying
    Time Trade-Off Value Set for EQ-5D-3L Based on a Nationally Representative Chinese Population Survey2018In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 21, no 11, p. 1330-1337Article in journal (Refereed)
    Abstract [en]

    Objectives: To obtain a nationally representative Chinese three-level EuroQol five-dimensional questionnaire value set based on the time trade-off (TTO) method.

    Methods: A multistage, stratified, clustered random nationally representative Chinese sample was used. The study design followed an adapted UK Measurement and Valuation of Health protocol. Each respondent valued 11 random states plus state 33333 and "unconscious" using the TTO method in face-to-face interviews. Three types of models were explored: ordinary least squares, general least squares, and weighted least squares models.

    Results: In total, 5939 inhabitants aged 15 years and older were interviewed. Of these, 5503 satisfactorily interviewed participants were included in constructing models. An ordinary least squares model including 10 dummies without constant and N3 had a mean absolute error of 0.083 and a correlation coefficient of 0.899 between the predicted and mean values. Goodness-of-fit indices of two models based on split subsample were similar.

    Conclusions: TTO values were higher in our study compared with those in a study carried out in urban areas, which is mirrored by the higher values in rural areas. Several other aspects, in addition to the valuation procedure, might have influenced the results, such as factors beyond demographic factors such as view on life and death and believing in an afterlife, which need further investigation. Future studies using the three-level EuroQol five-dimensional questionnaire should consider using this value set based on a nationally representative sample of the Chinese population.

  • 24378. Zhuravleva, Z. D.
    et al.
    Lebedeva, A. V.
    Volnova, A. B.
    Mukhina, I. V.
    Druzin, Michael Ya.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    The effect of glycine microinjections in the medial preoptic area of the hypothalamus on the sexual behavior of male rats2015In: Neurochemical Journal, ISSN 1819-7124, Vol. 9, no 2, p. 141-145Article in journal (Refereed)
    Abstract [en]

    The mechanisms that underlie the early loss of the male reproductive function are still unknown. Therefore, investigation of this problem is an important task. The medial preoptic nucleus takes part in the regulation of sexual behavior; however, the role of glycine transmission in this nucleus has not yet been studied. Our study focuses on these questions.

  • 24379. Zhuravleva, Z.
    et al.
    Titova, N.
    Mukhina, I.
    Druzin, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Preoptic glycine receptors: possible mediators of neuron-glial interaction affecting social behavior in male rats2017In: Glia, ISSN 0894-1491, E-ISSN 1098-1136, Vol. 65, p. E298-E299Article in journal (Refereed)
  • 24380. Ziaei, Maryam
    et al.
    Salami, Alireza
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Aging Research Center (ARC) at Karolinska Institute and Stockholm University, Stockholm, Sweden.
    Persson, Jonas
    Age-related alterations in functional connectivity patterns during working memory encoding of emotional items2017In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 94, p. 1-12Article in journal (Refereed)
    Abstract [en]

    Previous findings indicate age-related differences in frontal-amygdala connectivity during emotional processing. However, direct evidence for age differences in brain functional activation and connectivity during emotional processing and concomitant behavioral implications is lacking. In the present study, we examined the impact of aging on the neural signature of selective attention to emotional information during working memory (WM) encoding. Participants completed an emotional WM task in which they were asked to attend to emotional targets and ignore irrelevant distractors. Despite an overall reduction in accuracy for older relative to younger adults, no behavioral age effect was observed as a function of emotional valence. The functional connectivity patterns of left ventrolateral prefrontal cortex showed that younger adults recruited one network for encoding of both positive and negative emotional targets and this network contributed to higher memory accuracy in this cohort. Older adults, on the other hand, engaged two distinct networks for encoding of positive and negative targets. The functional connectivity analysis using left amygdala further demonstrated that older adults recruited one single network during encoding of positive as well as negative targets whereas younger adults recruited this network only for encoding of negative items. The engagement of amygdala functional network also contributed to higher memory performance and faster response times in older adults. Our findings provide novel insights into the differential roles of functional brain networks connected to the medial PFC and amygdala during encoding of emotionally-valenced items with advancing age.

  • 24381.
    Zickerman, Caroline
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Hult, Ann-Catrin
    Umeå University.
    Hedlund, Lars
    Umeå University.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Midazolam is better than clonidine in preventing negative postoperative behaviour in children age 2-42017In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, no 8, p. 976-977Article in journal (Other academic)
  • 24382. Zidan, Mamdouh
    et al.
    Nicoll, Rachel
    Schmermund, Axel
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Cardiac multi-detector CT: its unique contribution to cardiology practice.2009In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 132, no 1, p. 25-29Article in journal (Refereed)
    Abstract [en]

    Medical practice is moving fast towards non-invasive and non-surgical disease management. While significant progress has been made with coronary artery disease prevention, MDCT stands as an ideal non-invasive tool for its progression. It accurately assesses both arterial lumen and wall disease. Although the main concern of current cardiology practice is the coronary stenotic disease, arterial wall calcification itself may significantly contribute to patients' symptoms. Thus, in addition to the beneficial use of MDCT in patients with mild to moderate risk for coronary disease, the unique information it provides on wall disease may assist the management of symptomatic patients with no flow-limiting lesions.

  • 24383.
    Zidén, Lena
    et al.
    Vårdalinstitutet, University of Gothenburg, Dep of Clinical Neuroscience and Rehabil, Sahlgrenska Academy Univerasity odf Gothenburg.
    Häggblom-Kronlöf, Greta
    Vårdalinstitutet, University of Gothenburg, Dep of Clinical Neuroscience and Rehabil, Sahlgrenska Academy Univerasity odf Gothenburg.
    Gustafsson, Susanne
    Vårdalinstitutet, University of Gothenburg, Dep of Clinical Neuroscience and Rehabil, Sahlgrenska Academy Univerasity odf Gothenburg.
    Lundin-Olsson, Lillemor
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Dahlin-Ivanoff, Synneve
    Vårdalinstitutet, University of Gothenburg, Dep of Clinical Neuroscience and Rehabil, Sahlgrenska Academy Univerasity odf Gothenburg.
    Physical Function and Fear of Falling 2 Years After the Health-Promoting Randomized Controlled Trial: Elderly Persons in the Risk Zone2014In: The Gerontologist, ISSN 0016-9013, E-ISSN 1758-5341, Vol. 54, no 3, p. 387-397Article in journal (Refereed)
    Abstract [en]

    Purpose of the study: To investigate the effects of 2 different health-promoting interventions on physical performance, fear of falling, and physical activity at 3-month, 1-year, and 2-year follow-ups of the study Elderly Persons in the Risk Zone.

    Design and Methods: A randomized, three-armed, single-blind, and controlled study in which 459 independent and community-dwelling people aged 80 years or older were included. A single preventive home visit including health-promoting information and advice and 4 weekly senior group meetings focused on health strategies and peer learning, with a follow-up home visit, were compared with control. Functional balance, walking speed, fear of falling, falls efficacy, and frequency of physical activities were measured 3 months, 1 year, and 2 years after baseline.

    Results There were no or limited differences between the groups at the 3-month and 1-year follow-ups. At 2 years, the odds ratio for having a total score of 48 or more on the Berg Balance scale compared with control was 1.80 (confidence interval 1.11-2.90) for a preventive home visit and 1.96 (confidence interval 1.21-3.17) for the senior meetings. A significantly larger proportion of intervention participants than controls maintained walking speed and reported higher falls efficacy. At 1 and 2 years, a significantly higher proportion of intervention participants performed regular physical activities than control.

    Implications: Both a preventive home visit and senior meetings reduced the deterioration in functional balance, walking speed, and falls efficacy after 2 years. The long-term effects of both interventions indicate a positive impact on postponement of physical frailty among independent older people.

  • 24384. Ziebland, Sue
    et al.
    Rasmussen, Birgit
    MacArtney, John
    Hajdarevic, Senada
    Umeå University, Faculty of Medicine, Department of Nursing.
    Sand Andersen, Rikke
    How wide is the Goldilocks Zone in your health system?2019In: Journal of Health Services Research and Policy, ISSN 1355-8196, E-ISSN 1758-1060, Vol. 24, no 1, p. 52-56Article in journal (Refereed)
    Abstract [en]

    In astrophysics, the 'Goldilocks Zone' describes the circumstellar habitable zone, in which planets, sufficiently similar to Earth, could support human life. The children's story of Goldilocks and the Three Bears, one of the most popular fairy tales in the English language, uses this metaphor to describe conditions for life that are neither too hot nor too cold and neither too close to the sun nor too far from its warmth. We propose that the 'Goldilocks Zone' also offers an apt metaphor for the struggle that people face when deciding if and when to consult a health care provider with a possible health problem. Drawing on decades of research in Denmark, England and Sweden on people's accounts of their experiences of accessing health care, this essay considers the ambivalence of health care seeking that individuals face in identifying when it is 'just right' to consult a general practitioner and the steps that health systems and individual clinicians might take to widen the zone.

  • 24385. Ziegelasch, Michael
    et al.
    Forslind, Kristina
    Skogh, Thomas
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Kastbom, Alf
    Berglin, Ewa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Decrease in bone mineral density during three months after diagnosis of early rheumatoid arthritis measured by digital X-ray radiogrammetry predicts radiographic joint damage after one year2017In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 19, no 1, article id 195Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Periarticular osteopenia is an early sign of incipient joint injury in rheumatoid arthritis (RA), but cannot be accurately quantified using conventional radiography. Digital X-ray radiogrammetry (DXR) is a computerized technique to estimate bone mineral density (BMD) from hand radiographs. The aim of this study was to evaluate whether decrease in BMD of the hands (BMD loss), as determined by DXR 3 months after diagnosis, predicts radiographic joint damage after 1 and 2 years in patients with early RA.

    METHODS: Patients (n = 176) with early RA (<12 months after onset of symptoms) from three different Swedish rheumatology centers were consecutively included in the study, and 167 of these patients were included in the analysis. Medication was given in accordance with Swedish guidelines, and the patients were followed for 2 years. Rheumatoid factor and antibodies to cyclic citrullinated peptides (anti-CCP) were measured at baseline, and 28-joint Disease Activity Score (DAS28) was assessed at each visit. Radiographs of the hands and feet were obtained at baseline, 3 months (hands only) and 1 and 2 years. Baseline and 1-year and 2-year radiographs were evaluated by the Larsen score. Radiographic progression was defined as a difference in Larsen score above the smallest detectable change. DXR-BMD was measured at baseline and after 3 months. BMD loss was defined as moderate when the decrease in BMD was between 0.25 and 2.5 mg/cm2/month and as severe when the decrease was greater than 2.5 mg/cm2/month. Multivariate regression was applied to test the association between DXR-BMD loss and radiographic damage, including adjustments for possible confounders.

    RESULTS: DXR-BMD loss during the initial 3 months occurred in 59% of the patients (44% moderate, 15% severe): 32 patients (19%) had radiographic progression at 1 year and 45 (35%) at 2 years. In multiple regression analyses, the magnitude of DXR-BMD loss was significantly associated with increase in Larsen score between baseline and 1 year (p = 0.033, adjusted R-squared = 0.069).

    CONCLUSION: DXR-BMD loss during the initial 3 months independently predicted radiographic joint damage at 1 year in patients with early RA. Thus, DXR-BMD may be a useful tool to detect ongoing joint damage and thereby to improve individualization of therapy in early RA.

  • 24386.
    Zijnge, Vincent
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Ammann, Thomas
    Institute of Oral Biology, Section of Oral Microbiology and Immunology, University of Zürich, Zürich, Switzerland.
    Thurnheer, Thomas
    Institute of Oral Biology, Section of Oral Microbiology and Immunology, University of Zürich, Zürich, Switzerland.
    Gmuer, Rudolf
    Institute of Oral Biology, Section of Oral Microbiology and Immunology, University of Zürich, Zürich, Switzerland.
    Subgingival Biofilm Structure2012In: Periodontal Disease / [ed] Kinane D.F. (Philadelphia, Pa.), Mombelli A. (Geneva), S. Karger, 2012, p. 1-16Chapter in book (Refereed)
    Abstract [en]

    Periodontitis is an inflammatory disease of the oral cavity initiated by a microbial biofilm (or 'dental plaque'). Subgingival biofilms in periodontal pockets are not easily analyzed without the loss of structural integrity. These subgingival plaques are structured communities of microorganisms with great phylogenetic diversity embedded in a self-produced extracellular polymeric matrix. For almost three decades, knowledge of the structure of plaque located below the gingival margin has been limited to landmark studies from the 1970s that were unaware of the breadth of microbial diversity we appreciate now. Only recently has technical progress - combining histology, confocal scanning fluorescent microscopy and fluorescent in situ hybridization to localize the most abundant species from different phyla and species associated with periodontitis - provided new insights into the architecture of subgingival biofilms. This review focuses on the structure and composition of subgingival biofilms and discusses current knowledge on the nature of the extracellular matrix. We describe further structural aspects of 'subgingival' biofilms produced in vitro that are gaining considerable interest as we search for models to investigate biofilm development, resistance to antibiotics, extracellular polymeric matrix composition and function, and reciprocal host-cell-to-biofilm interactions.

  • 24387. Zijnge, Vincent
    et al.
    Kieselbach, Thomas
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Oscarsson, Jan
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Proteomics of protein secretion by aggregatibacter actinomycetemcomitans2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 7, p. e41662-Article in journal (Refereed)
    Abstract [en]

    The extracellular proteome (secretome) of periodontitis-associated bacteria may constitute a major link between periodontitis and systemic diseases. To obtain an overview of the virulence potential of Aggregatibacter actinomycetemcomitans, an oral and systemic human pathogen implicated in aggressive periodontitis, we used a combined LC-MS/MS and bioinformatics approach to characterize the secretome and protein secretion pathways of the rough-colony serotype a strain D7S. LC-MS/MS revealed 179 proteins secreted during biofilm growth. Further to confirming the release of established virulence factors (e.g. cytolethal distending toxin [CDT], and leukotoxin [LtxA]), we identified additional putative virulence determinants in the secretome. These included DegQ, fHbp, LppC, Macrophage infectivity protein (MIP), NlpB, Pcp, PotD, TolB, and TolC. This finding indicates that the number of extracellular virulence-related proteins is much larger than previously demonstrated, which was also supported by in silico analysis of the strain D7S genome. Moreover, our LC-MS/MS and in silico data revealed that at least Type I, II, and V secretion are actively used to excrete proteins directly into the extracellular space, or via two-step pathways involving the Sec/Tat systems for transport across the inner membrane, and outer membrane factors, secretins and auto-transporters, respectively for delivery across the outer membrane. Taken together, our results provide a molecular basis for further elucidating the role of A. actinomycetemcomitans in periodontal and systemic diseases.

  • 24388. Zimmerman, Malin
    et al.
    Enes, Sara Rolandsson
    Skarstrand, Hanna
    Pourhamidi, Kaveh
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Gottsater, Anders
    Wollmer, Per
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Westergren-Thorsson, Gunilla
    Dahlin, Lars B.
    Temporal trend of autonomic nerve function and HSP27, MIF and PAI-1 in type 1 diabetes2017In: Journal of clinical and translational endocrinology, ISSN 2214-6237, Vol. 8, p. 15-21Article in journal (Refereed)
    Abstract [en]

    Aim: Diabetes mellitus type 1 (T1D) has numerous complications including autonomic neuropathy, i.e. dysfunction of the autonomous nervous system. This study focuses on Heat Shock Protein 27 (HSP27), Macrophage Migration Inhibitory Factor (MIF), Plasminogen Activator Inhibitor-1 (PAI-1) and HbA1c and their possible roles in effects of diabetes on the autonomic nervous system.

    Methods: Patients with T1D (n = 32, 41% women) were recruited in 1985 and followed up on four occasions (1989, 1993, 1998, and 2005). Autonomic function was tested using expiration/inspiration (E/I-ratio). Blood samples, i.e. HSP27 (last three occasions), MIF, PAI-1 (last two occasions) and HbA1c (five occasions), were analyzed.

    Results: Autonomic nerve function deteriorated over time during the 20-year-period, but levels of HSP27, MIF, and PAI-1 were not associated with cardiovascular autonomic neuropathy. MIF and PAI-1 were lower in T1D than in healthy controls in 2005. Increased HbA1c correlated with a decrease in E/I-ratio.

    Conclusions: Neither the neuroprotective substance HSP27 nor the inflammatory substances, MIF and PAI-1 were associated with measures of cardiovascular autonomic nerve function, but a deterioration of such function was observed in relation to increasing HbA1c in T1D during a 20-year follow-up period. Improved glucose control might be associated with protection against autonomic neuropathy in T1D.

  • 24389. Zimmerman, Malin
    et al.
    Pourhamidi, Kaveh
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Dahlin, Lars B.
    Autonomic Neuropathy: a Prospective Cohort Study of Symptoms and E/I Ratio in Normal Glucose Tolerance, Impaired Glucose Tolerance, and Type 2 Diabetes2018In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 9, article id 154Article in journal (Refereed)
    Abstract [en]

    Background: Autonomic neuropathy in diabetes, in addition to causing a range of symptoms originating from the autonomic nervous system, may increase cardiovascular morbidity. Our aim was to study the progression of autonomic neuropathy, based on symptom score and evaluation of an autonomic test, in persons with normal and impaired glucose tolerance and in patients with type 2 diabetes (T2D).

    Methods: Participants were recruited in 2003/2004 with a follow-up in 2014. The participants' glucose tolerance was categorized using oral glucose tolerance tests. Symptoms were evaluated using an autonomic symptom score (ASS), ECG was used to test cardiac autonomic function based on the expiration/inspiration ratio (E/I ratio), and blood samples were taken on both occasions.

    Results: ASSs were higher at follow-up in the T2D patients than in the normal glucose tolerance group (mean 1.21 +/- 1.30 vs. 0.79 +/- 0.7; p < 0.05). E/I ratio did not deteriorate more than could be expected as an aging effect in well-controlled T2D. No relationship was found between E/I ratio and HbA1c or ASS.

    Conclusion: The presence of autonomic symptoms increased over time in T2D patients, but the symptoms did not correlate with the Ell ratio in this metabolically well-controlled cohort. ASSs can be a useful clinical tool when assessing the progression of autonomic dysfunction in patients with abnormal glucose metabolism.

  • 24390.
    Zingmark, Lisa
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Holmqvist, Anna-Sara
    Umeå University, Faculty of Medicine, Department of Nursing.
    ”Jag försöker att vara som en syster för dem”: Kulturdoulans erfarenheter av att möta nyanlända kvinnor före, under och efter förlossning2017Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Objective: To illuminate the cultural doula’s experiences of meeting newly arrived women before, during and after childbirth. Design: A qualitative method with inductive approach was used. Data was collected through qualitative semistructured interviews and analyzed by qualitative content analysis.

    Settings: The womens clinic in a city in northern Sweden. Participants: Cultural doulas who continuously participated in childbirth. Findings: The analysis resulted in three main categories: The influence of culture, A driving force to help and wanting to develop oneself, The cultural doula is a link between language and emotions Key conclusions: According to the cultural doula, she is a link between language and culture. It is common that the cultural doula has given birth her self as well as assisted other in childbirth. Through her own experience and education she has good knowledge of care during childbirth. This combined with being able to talk several languages and being present throughout the the childbirth creates a sense of safety for the woman according to the cultural doula. She always take sides with the woman and does the utmost for her to have a positive experience. The cultural doula can often fill the role of a close female relative or friend. Implications for practice: The number of asylum seekers in Sweden is expected to remain at a high level. This will mean that midwives will meet many women born outside of Nordic countries from different cultures. The maternety mortality in Sweden is low, however, of those affected, women born abroad are in majority, which has been shown to be caused mostly by language barriers. The cultural doula project is relatively new and local but will hopefully expand to include the antenatal care and the period after the childbirth and to be more widely distributed nationally. 

  • 24391.
    Zingmark, Magnus
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Occupation-focused and occupation-based interventions for community-dwelling older people: Intervention effects in relation to facets of occupational engagement and cost effectiveness2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background

     Occupation-focused and occupation-based interventions can potentially promote occupational engagement among community-dwelling older people, but there is limited evidence to identify the most effective and cost-effective interventions. For independent-living older people, there is a lack of evidence to determine if occupation-focused and occupation-based interventions have an effect on their occupational engagement. For older people who need assistance because of bathing disabilities, there is limited evidence of the effects of occupation-focused and occupation-based interventions on their occupational engagement or for reducing or omitting their need for assistance. Finally, there is limited evidence to determine if occupation-focused and occupation-based interventions implemented for community-dwelling older people are cost effective.

    Aim

    The aim of this thesis was to evaluate the effects and cost effectiveness of occupation-focused and occupation-based interventions for two groups of community-dwelling older people, independent-living, community-dwelling older people and older people with bathing disabilities.

    Method

    Studies I and II were based on an exploratory randomized controlled trial. One hundred and seventy seven persons, 77–82 years, single living, and without need for home help were randomized to a no-intervention control group or to one of three occupational therapy interventions focused on promoting occupational engagement: an individual intervention, an activity group or a discussion group. In study I, effect sizes for leisure engagement and ability to perform activities of daily living (ADL) tasks were estimated for each intervention in relation to the control group to identify the most effective intervention at 3 and 12 months after baseline. In study II, the effects on quality adjusted life years (QALYs) and the total costs for the intervention, social services provided by the municipality and health care were used evaluate cost-effectiveness.

    Study III was a quasi-experimental clinical trial and included 95 persons, 65+, who had applied for municipality-based home help with bathing. For participants in the intervention group, occupational therapists implemented occupation-focused and occupation-based interventions. No occupational therapy intervention was implemented for those in the control group, but they were allocated home help services if judged to need it based on an assessment by a municipality care manager. Evaluations of ADL ability, self-rated health and allocated home help were implemented at baseline and after 15 weeks.

    Study IV involved the use of decision-modeling based on a five state Markov model that included levels of dependency in ADLs, place of residency and death. Probabilities for transitions between states in the model, QoL scores and societal costs for each state were derived from previous research. Overall, the model was based on research indicating that more severe levels of dependency reduced QALY scores and increased societal costs. Previous trials have provided evidence that an occupation-focused and occupation-based intervention implemented to reduce bathing disabilities increased the probability of independence of home help. The Markov model was used to evaluate cost-effectiveness over 8 years for an intervention compared to no intervention.

    Results

    The results of study I indicated that each intervention had a small positive effect on minimizing a decline in leisure engagement and/or ADL, but no intervention was clearly superior. In study II, the results indicated that the interventions delivered in a group format positively affected self-rated health. The discussion group was the most cost-effective intervention. The results of study III indicated that the intervention had no effect on ADL ability or self-rated health. There was, however, a large difference in the allocation of home help at follow up, indicating that the intervention was effective in reducing dependency on home help for bathing. The results of study IV indicated that compared to no intervention, the intervention resulted in a positive accumulation of QALYs and lower costs for every year during the entire 8 year period.

    Conclusion

    This thesis provides evidence to support the implementation of occupation-focused and occupation-based interventions for independent-living, community-dwelling older people in order to reduce their decline in occupational engagement and improve their self-rated health; the interventions also have the potential to be cost effective. This thesis also provides evidence that an occupation-focused and occupation-based intervention implemented for older people with bathing disabilities was effective in promoting independence from home help for bathing. Finally, an occupation-focused and occupation-based intervention that increased the probability of being independent of home help for bathing had a positive impact on the long term accumulation of QALYs and reduced societal costs and, therefore, can be considered very cost effective.

  • 24392.
    Zingmark, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy. Community Care Administration, Municipality of Östersund, Östersund.
    Bernspång, Birgitta
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Meeting the needs of elderly with bathing disability2011In: Australian Occupational Therapy Journal, ISSN 0045-0766, E-ISSN 1440-1630, Vol. 58, no 3, p. 164-71Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIMS: Difficulties with bathing are frequent among older people and are associated with an increasing need for societal support. As loss of independence has a negative impact on health and wellbeing, it is important to study interventions that can provide the required support for people to be able to remain independent. Occupational therapy interventions can improve clients' abilities enabling them to bathe themselves, thus reducing the need for other, more long-term societal support from, e.g. a home help. In this study, two groups of elderly people with difficulties in bathing were compared; the clients in the intervention group were engaged in occupational therapy.

    METHODS: A quasi-experimental non-equivalent control group design was used, in which participants with reported difficulties in bathing were recruited consecutively from two municipalities. The clients in the intervention group routinely received occupational therapy, whereas clients in the control group received assistance from a home help for bathing. Activities of daily living, quality of life and home-help allocation were assessed at the baseline and after 15 weeks.

    RESULTS: Clients in the intervention group received less than three home visits on average, with majority of interventions consisting of graded activity and the use of an encouraging approach. Seventy per cent of the interventions were adaptive. Activities of daily living and quality of life of both groups improved, but the differences of being allocated a home help were significant.

    CONCLUSION: Occupational therapy interventions seem beneficial in terms of supporting older people in becoming independent of home help in bathing but the results must be interpreted with caution as there were differences at baseline between the groups.

  • 24393.
    Zingmark, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health. Head of Research and Development Health and Social Care Administration, Municipality of Östersund, Östersund, Sweden.
    Evertsson, Bodil
    Haak, Maria
    Characteristics of occupational therapy and physiotherapy within the context of reablement in Swedish municipalities: A national survey2019In: Health & Social Care in the Community, ISSN 0966-0410, E-ISSN 1365-2524Article in journal (Refereed)
    Abstract [en]

    Reablement is a multidisciplinary, home-based intervention implemented for people at risk of functional decline and losing independence aiming to optimise functioning and independence in activities of daily living. There is limited knowledge about what characterises the intervention and the role of different professionals. The purpose of this study was to explore the characteristics and differences of occupational therapy and physiotherapy interventions in terms of focus, content and duration within the context of reablement in Swedish municipalities. Web-based surveys were used to collect data from 43 municipalities representing 25% of the population in Sweden. Data on intervention characteristics were reported for all cases receiving occupational therapy (n = 1,395) and physiotherapy (n = 1,006) over a 15-week period. Data were presented descriptively, and differences between occupational therapy and physiotherapy were analysed using Chi-square tests. The results indicated that reablement in Sweden was implemented for adults in all ages (19-103 years, median 81.0 years); 72% had home help. For both professions, a baseline assessment was made in fewer than half of all cases. There were significant differences between occupational therapists and physiotherapists regarding the focus and content as well as the number of contacts and duration of the intervention. For occupational therapists, walking indoors and self-care were the largest focus areas, whereas for physiotherapists walking indoors and body function were the largest focus areas. For most cases, the intervention was completed within five sessions over a 6-week period. This study provides the first picture of occupational therapy and physiotherapy within Swedish reablement contexts. In relation to the results, the focus of interventions, how assessments are made and how the intervention is implemented over time are issues that can be further elaborated.

  • 24394.
    Zingmark, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Health and Social Care Administration, Municipality of Östersund, Sweden.
    Evertsson, Bodil
    Haak, Maria
    The content of reablement: Exploring occupational and physiotherapy interventions2019In: British Journal of Occupational Therapy, ISSN 0308-0226, E-ISSN 1477-6006, Vol. 82, no 2, p. 122-126Article in journal (Refereed)
    Abstract [en]

    Statement of context: Occupational therapists and physiotherapists in a Swedish municipality answered a web-based survey about their reablement interventions.

    Critical reflection on practice: There were overlapping areas as well as differences regarding the focus of occupational and physiotherapy interventions. Regarding the duration of interventions, occupational therapy was implemented over a short time span in contrast to physiotherapy, which had a longer duration. Both professions used valid and reliable instruments to a very limited extent.

    Implications for practice: If other areas than self-care and mobility are to be addressed within reablement there is a need to critically reflect on the focus, content and duration of reablement interventions. Valid and reliable assessments can be utilised to a greater extent to guide goal-setting, the focus of interventions and to evaluate effects.mited extent.

  • 24395.
    Zingmark, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Fisher, Anne G.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Nilsson, Ingeborg
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Occupation-focused interventions for well older people: an exploratory randomized controlled trial2014In: Scandinavian Journal of Occupational Therapy, ISSN 1103-8128, E-ISSN 1651-2014, Vol. 21, no 6, p. 447-457Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this exploratory randomised controlled trial (RCT) was to evaluate three different occupation-focused interventions for well older people by estimating effect sizes for leisure engagement and ability in activities of daily living (ADL) and thereby identifying the most effective interventions.

    Methods: One hundred and seventy seven persons, 77-82 years old, living alone and without home help, were randomized to a control group (CG), an individual intervention (IG), an activity group (AG), and a one-meeting discussion group (DG). All interventions focused on occupational engagement and how persons can cope with age-related activity restrictions in order to enhance occupational engagement. Data were collected by blinded research assistants at baseline, three, and 12 months. Ordinal outcome data were converted, using Rasch measurement methods, to linear measures of leisure engagement and ADL ability. Standardized between-group effect sizes, Cohen's d, were calculated.

    Results: While all groups showed a decline in leisure engagement and ADL over time, the IG and the DG were somewhat effective in minimizing the decline at both three and 12 months. However, the effect sizes were small.

    Conclusions: The findings indicate that occupation-focused interventions intended to minimize a decline in leisure engagement and ADL were sufficiently promising to warrant their further research.

  • 24396.
    Zingmark, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy. Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Nilsson, Ingeborg
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Fisher, Anne G.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Department of Occupational Therapy, College of Health and Human Sciences, Colorado State University, Fort Collins, USA.
    Lindholm, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Occupation-focused health promotion for well older people: a cost-effectiveness analysis2016In: British Journal of Occupational Therapy, ISSN 0308-0226, E-ISSN 1477-6006, Vol. 79, no 3, p. 153-162Article in journal (Refereed)
    Abstract [en]

    Introduction The aim of this study was to evaluate three occupational therapy interventions, focused on supporting continued engagement in occupation among older people, to determine which intervention was most cost effective, evaluated as the incremental cost/quality adjusted life year gained. Method The study was based on an exploratory randomized controlled trial. Participants were 77-82 years, single living and without home help. One hundred and seventy seven persons were randomized to an individual intervention, an activity group, a discussion group or a no intervention control group. All interventions focused on supporting the participants to maintain or improve occupational engagement. Outcomes were evaluated at baseline, three and 12 months and included general health and costs (intervention, municipality and health care). Based on linear regression models, we evaluated how outcomes had changed at each follow-up for each intervention group in relation to the control group. Results Both group interventions resulted in quality adjusted life years gained at three months. A sustained effect on quality adjusted life years gained and lower total costs indicated that the discussion group was the most cost-effective intervention. Conclusion Short-term, occupation-focused occupational therapy intervention delivered in group formats for well older people resulted in quality-adjusted life years gained. A one-session discussion group was most cost effective.

  • 24397.
    Zingmark, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Nilsson, Ingeborg
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Fisher, Anne
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Lindholm, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Occupation-focused health promotion for well older people - a cost-effectiveness analysisIn: Article in journal (Other academic)
  • 24398.
    Zingmark, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy. Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Community Care Administration, Municipality of Östersund, 83182 Östersund, Sweden.
    Nilsson, Ingeborg
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy. Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Norström, Fredrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Sahlén, Klas-Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Umeå University, Faculty of Medicine, Department of Nursing.
    Lindholm, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Cost effectiveness of an intervention focused on reducing bathing disability2017In: European Journal of Ageing, ISSN 1613-9372, E-ISSN 1613-9380, Vol. 14, no 3, p. 233-241Article in journal (Refereed)
    Abstract [en]

    The onset of bathing disability among older people is critical for a decline in functioning and has implications for both the individuals’ quality of life and societal costs. The aim of this study was to evaluate longterm cost effectiveness of an intervention targeting bathing disability among older people. For hypothetical cohorts of community-dwelling older people with bathing disability, transitions between states of dependency and death were modelled over 8 years including societal costs. A five-state Markov model based on states of dependency was used to evaluate Quality-adjusted life years (QALYs) and costs from a societal perspective. An intervention group was compared with a no intervention control group. The intervention focused on promoting safe and independent performance of bathing-related tasks. The intervention effect, based on previously published trials, was applied in the model as a 1.4 increased probability of recovery during the first year. Over the full follow-up period, the intervention resulted in QALY gains and reduced societal cost. After 8 years, the intervention resulted in 0.052 QALYs gained and reduced societal costs by €2410 per person. In comparison to the intervention cost, the intervention effect was a more important factor for the magnitude of QALY gains and long-term societal costs. The intervention cost had only minor impact on societal costs. The conclusion was that an intervention targeting bathing disability among older people presents a cost-effective use of resources and leads to both QALY gains and reduced societal costs over 8 years.

  • 24399.
    Zingmark, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health. Health and Social Care Administration, Municipality of Östersund, 83182 Östersund, Sweden.
    Norström, Fredrik
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Lindholm, Lars
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Dahlin-Ivanoff, Synneve
    Göteborgs universitet.
    Gustafsson, Susanne
    Göteborgs universitet.
    Modelling long-term cost-effectiveness of health promotion for community-dwelling older people2019In: European Journal of Ageing, ISSN 1613-9372, E-ISSN 1613-9380, Vol. 16, no 4, p. 395-404Article in journal (Refereed)
    Abstract [en]

    The effectiveness of health promotion for community-dwelling older people is well documented; however, there is a general lack of health economic evaluations. The aim of the present study was to evaluate long-term cost-effectiveness over 4 years of two health promoting interventions: senior meetings and a preventive home visit, for community-dwelling older people in relation to no intervention. We applied a Markov model including five states defined in relation to level of dependency of home help and place of residency. The model included transitions between dependency states, scores for quality of life and societal costs for each state, intervention costs and intervention effects for two formats of health promoting interventions. For each intervention and a no-intervention control group, we calculated the accumulated quality-adjusted life years (QALYs) and societal costs over 4 years. Sensitivity analyses included higher intervention costs, lower intervention effects and additional intervention costs and effects related to booster sessions. The results of all analyses indicated that health promotion implemented for community-dwelling older people in the format of senior meetings or a preventive home visit was cost-effective. Both interventions lead to QALY gains and reduce societal costs at any follow-up over 4 years, and thus, resources can be used to implement other interventions. The most important factor for the magnitude of QALY gains and cost savings was the intervention effect. Yearly booster sessions implemented for those persons who maintained their level of functioning extended the intervention effects adding additional QALYs and further reducing societal costs.

  • 24400. Zirakzadeh, A Ali
    et al.
    Kinn, Johan
    Krantz, David
    Rosenblatt, Robert
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Urology, Stockholm South General Hospital, Karolinska Institutet, Stockholm, Sweden.
    Winerdal, Malin E
    Hu, Jin
    Hartana, Ciputra Adijaya
    Lundgren, Christian
    Bergman, Emma Ahlén
    Johansson, Markus
    Holmström, Benny
    Hansson, Johan
    Sidikii, Alexander
    Vasko, Janos
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Marits, Per
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Winqvist, Ola
    Doxorubicin enhances the capacity of B cells to activate T cells in urothelial urinary bladder cancer2017In: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 176, p. 63-70Article in journal (Refereed)
    Abstract [en]

    Cancer is currently treated by a combination of therapies, including chemotherapy which is believed to suppress the immune system. Combination of immunotherapy and chemotherapy correlates with improved survival but needs careful planning in order to achieve a synergistic effect. In this study, we have demonstrated that doxorubicin treatment of B cells resulted in increased expression of CD86 and concordantly increased CD4(+) T cell activation in the presence of superantigen, an effect that was inhibited by the addition of a CD86 blocking antibody. Furthermore, doxorubicin resulted in decreased expression of the anti-inflammatory cytokines IL-10 and TNF-α. Finally, B cells from urinary bladder cancer patients, treated with a neoadjuvant regiment containing doxorubicin, displayed increased CD86-expression. We conclude that doxorubicin induces CD86 expression on B cells and hence enhances their antigen-presenting ability in vitro, a finding verified in patients. Development of tailored time and dose schedules may increase the effectiveness of combining chemotherapy and immunotherapy.

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