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  • 1.
    Friberg, Orjan
    et al.
    Örebro University Hospital.
    Svedjeholm, Rolf
    Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Soderquist, Bo
    Örebro University Hospital.
    Letter: Treating Sternal Wound Infections After Cardiac Surgery With an Implantable Gentamicin-Collagen Sponge2010In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 304, no 19, p. 2123-2124Article in journal (Other academic)
    Abstract [en]

    n/a

  • 2.
    Gheorghiade, Mihai
    et al.
    Northwestern University Feinberg School of Medicine, Chicago, USA.
    Greene, Stephen J
    Duke University Medical Center, Durham, North Carolina, USA.
    Butler, Javed
    Stony Brook University, Stony Brook, New York, USA.
    Filippatos, Gerasimos
    Athens University Hospital Attikon and Kapodistrian University of Athens, Athens, Greece.
    Lam, Carolyn S P
    National Health Center, Singapore and Duke, National University of Singapore, Singapore.
    Maggioni, Aldo P
    Associazione Nazionale Medici Cardiologi Ospedalieri Research Center, Florence, Italy.
    Ponikowski, Piotr
    Medical University, Wroclaw, Poland.
    Shah, Sanjiv J
    Northwestern University Feinberg School of Medicine, Chicago, USA.
    Solomon, Scott D
    Brigham and Women's Hospital Boston, Massachusetts, USA.
    Kraigher-Krainer, Elisabeth
    Charite University Medicine Berlin-Campus Virchow Klinikum, Berlin, Germany.
    Samano, Eliana T
    Bayer, Sao Paulo, Brazil.
    Müller, Katharina
    Bauer Pharma, Wuppertal, Germany.
    Roessig, Lothar
    Bauer Pharma, Wuppertal, Germany.
    Burkert, Pieske
    Charité University Medicine Berlin–Campus Virchow Klinikum and German Heart Center Berlin, Germany.
    Effect of Vericiguat, a Soluble Guanylate Cyclase Stimulator, on Natriuretic Peptide Levels in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction: The SOCRATES-REDUCED Randomized Trial.2015In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 314, no 21, p. 2251-2262Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: Worsening chronic heart failure (HF) is a major public health problem.

    OBJECTIVE: To determine the optimal dose and tolerability of vericiguat, a soluble guanylate cyclase stimulator, in patients with worsening chronic HF and reduced left ventricular ejection fraction (LVEF).

    DESIGN, SETTING, AND PARTICIPANTS: Dose-finding phase 2 study that randomized 456 patients across Europe, North America, and Asia between November 2013 and January 2015, with follow-up ending June 2015. Patients were clinically stable with LVEF less than 45% within 4 weeks of a worsening chronic HF event, defined as worsening signs and symptoms of congestion and elevated natriuretic peptide level requiring hospitalization or outpatient intravenous diuretic.

    INTERVENTIONS: Placebo (n = 92) or 1 of 4 daily target doses of oral vericiguat (1.25 mg [n = 91], 2.5 mg [n = 91], 5 mg [n = 91], 10 mg [n = 91]) for 12 weeks.

    MAIN OUTCOMES AND MEASURES: The primary end point was change from baseline to week 12 in log-transformed level of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The primary analysis specified pooled comparison of the 3 highest-dose vericiguat groups with placebo, and secondary analysis evaluated a dose-response relationship with vericiguat and the primary end point.

    RESULTS: Overall, 351 patients (77.0%) completed treatment with the study drug with valid 12-week NT-proBNP levels and no major protocol deviation and were eligible for primary end point evaluation. In primary analysis, change in log-transformed NT-proBNP levels from baseline to week 12 was not significantly different between the pooled vericiguat group (log-transformed: baseline, 7.969; 12 weeks, 7.567; difference, -0.402; geometric means: baseline, 2890 pg/mL; 12 weeks, 1932 pg/mL) and placebo (log-transformed: baseline, 8.283; 12 weeks, 8.002; difference, -0.280; geometric means: baseline, 3955 pg/mL; 12 weeks, 2988 pg/mL) (difference of means, -0.122; 90% CI, -0.32 to 0.07; ratio of geometric means, 0.885, 90% CI, 0.73-1.08; P = .15). The exploratory secondary analysis suggested a dose-response relationship whereby higher vericiguat doses were associated with greater reductions in NT-proBNP level (P < .02). Rates of any adverse event were 77.2% and 71.4% among the placebo and 10-mg vericiguat groups, respectively.

    CONCLUSIONS AND RELEVANCE: Among patients with worsening chronic HF and reduced LVEF, compared with placebo, vericiguat did not have a statistically significant effect on change in NT-proBNP level at 12 weeks but was well-tolerated. Further clinical trials of vericiguat based on the dose-response relationship in this study are needed to determine the potential role of this drug for patients with worsening chronic HF.

    TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01951625.

  • 3.
    Hanberger, Håkan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Garcia-Rodriguez, J-A
    Gobernado, M
    Goossens, H
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment.
    Struelens, MJ
    French and Portuguese ICU Stud,
    French and Portuguese ICU, Study Groups
    Antibiotic suseptibility among aerobic gram-negative bacilli in intensive care units in 5 European countries. 1999In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 281, p. 67-71Article in journal (Refereed)
  • 4.
    Knip, Mikael
    et al.
    University of Helsinki, Finland; Helsinki University Hospital, Finland.
    Akerblom, Hans K.
    University of Helsinki, Finland.
    Al Taji, Eva
    Charles University of Prague, Czech Republic.
    Becker, Dorothy
    University of Pittsburgh, PA USA.
    Bruining, Jan
    Sophia Childrens University Hospital, Netherlands.
    Castano, Luis
    University of Basque Country, Spain.
    Danne, Thomas
    Kinder-und Jugendkrankenhaus–Auf der Bult, Hannover, Germany.
    de Beaufort, Carine
    Centre Hospital Luxembourg, Luxembourg.
    Dosch, Hans-Michael
    University of Toronto, Canada.
    Dupre, John
    University of Western Ontario, Canada.
    Fraser, William D.
    University of Sherbrooke, Canada.
    Howard, Neville
    Childrens Hospital Westmead, Australia.
    Ilonen, Jorma
    University of Turku, Finland; Turku University Hospital, Finland.
    Konrad, Daniel
    Kinder and Jugendkrankenhaus Auf Der Bult, Germany; University of Childrens Hospital Zurich, Switzerland.
    Kordonouri, Olga
    Kinder and Jugendkrankenhaus Auf Der Bult, Germany.
    Krischer, Jeffrey P.
    University of S Florida, FL USA.
    Lawson, Margaret L.
    Childrens Hospital Eastern Ontario, Canada.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Madacsy, Laszlo
    Semmelweis University, Hungary.
    Mahon, Jeffrey L.
    University of Western Ontario, Canada.
    Ormisson, Anne
    Tartu University, Estonia.
    Palmer, Jerry P.
    University of Washington, WA USA.
    Pozzilli, Paolo
    University of Campus Biomed Rome, Italy.
    Savilahti, Erkki
    University of Helsinki, Finland.
    Serrano-Rios, Manuel
    CIBERDEM, Spain.
    Songini, Marco
    St Michelle Hospital, Italy.
    Taback, Shayne
    University of Manitoba, Canada.
    Vaarala, Outi
    University of Helsinki, Finland; AstraZeneca, Sweden.
    White, Neil H.
    Washington University, MO USA.
    Virtanen, Suvi M.
    National Institute Health and Welf, Finland.
    Wasikowa, Renata
    Medical Academic Wroclaw, Poland.
    Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes The TRIGR Randomized Clinical Trial2018In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 319, no 1, p. 38-48Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cows milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. MAIN OUTCOMES AND MEASURES Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8%[95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes.

  • 5.
    Knip, Mikael
    et al.
    University of Helsinki, Helsinki, Finland.
    Åkerblom, Hans K
    University of Helsinki, Helsinki, Finland.
    Becker, Dorothy
    University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
    Dosch, Hans-Michael
    University of Toronto, Toronto, Ontario, Canada.
    Dupre, John
    University of Western Ontario, London, Canada.
    Fraser, William
    University of Montréal, Montréal, Québec, Canada.
    Howard, Neville
    Children’s Hospital of Westmead, Sydney, Australia.
    Ilonen, Jorma
    University of Turku, Turku, Finland.
    Krischer, Jeffrey P
    University of South Florida, Tampa, USA.
    Kordonouri, Olga
    Kinder- und Jugendkrankenhaus AUF DER BULT, Hannover, Germany.
    Lawson, Margaret L
    Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada .
    Palmer, Jerry P
    University of Washington, Seattle, USA.
    Savilahti, Erkki
    University of Helsinki, Helsinki, Finland.
    Vaarala, Outi
    National Institute for Health and Welfare, Helsinki, Finland.
    Virtanen, Suvi M
    National Institute for Health and Welfare, Helsinki, Finland.
    Hydrolyzed infant formula and early β-cell autoimmunity: a randomized clinical trial.2014In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 311, no 22, p. 2279-2287Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: The disease process leading to clinical type 1 diabetes often starts during the first years of life. Early exposure to complex dietary proteins may increase the risk of β-cell autoimmunity in children at genetic risk for type 1 diabetes. Extensively hydrolyzed formulas do not contain intact proteins.

    OBJECTIVE: To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of diabetes-associated autoantibodies in young children.

    DESIGN, SETTING, AND PARTICIPANTS: A double-blind randomized clinical trial of 2159 infants with HLA-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1078 were randomized to be weaned to the extensively hydrolyzed casein formula and 1081 were randomized to be weaned to a conventional cows' milk-based formula. The participants were observed to April 16, 2013.

    INTERVENTIONS: The participants received either a casein hydrolysate or a conventional cows' milk formula supplemented with 20% of the casein hydrolysate.

    MAIN OUTCOMES: AND MEASURES: Primary outcome was positivity for at least 2 diabetes-associated autoantibodies out of 4 analyzed. Autoantibodies to insulin, glutamic acid decarboxylase, and the insulinoma-associated-2 (IA-2) molecule were analyzed using radiobinding assays and islet cell antibodies with immunofluorescence during a median observation period of 7.0 years (mean, 6.3 years).

    RESULTS: The absolute risk of positivity for 2 or more islet autoantibodies was 13.4% among those randomized to the casein hydrolysate formula (n = 139) vs 11.4% among those randomized to the conventional formula (n = 117). The unadjusted hazard ratio for positivity for 2 or more autoantibodies among those randomized to be weaned to the casein hydrolysate was 1.21 (95% CI, 0.94-1.54), compared with those randomized to the conventional formula, while the hazard ratio adjusted for HLA risk, duration of breastfeeding, vitamin D use, study formula duration and consumption, and region was 1.23 (95% CI, 0.96-1.58). There were no clinically significant differences in the rate of reported adverse events between the 2 groups.

    CONCLUSIONS AND RELEVANCE: Among infants at risk for type 1 diabetes, the use of a hydrolyzed formula, when compared with a conventional formula, did not reduce the incidence of diabetes-associated autoantibodies after 7 years. These findings do not support a benefit from hydrolyzed formula. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00179777.

  • 6.
    Kurt Schultz, Johannes
    et al.
    Akershus University Hospital, Norway; University of Oslo, Norway.
    Yaqub, Sheraz
    Oslo University Hospital, Norway.
    Wallon, Conny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Blecic, Ljiljana
    Ostfold Hospital, Norway.
    Mjorud Forsmo, Havard
    Haukeland Hospital, Norway.
    Folkesson, Joakim
    Uppsala University, Sweden.
    Buchwald, Pamela
    Helsingborg Hospital, Sweden.
    Korner, Hartwig
    Stavanger University Hospital, Norway.
    Dahl, Fredrik A.
    Akershus University Hospital, Norway.
    Oresland, Tom
    Akershus University Hospital, Norway; University of Oslo, Norway.
    Laparoscopic Lavage vs Primary Resection for Acute Perforated Diverticulitis The SCANDIV Randomized Clinical Trial2015In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 314, no 13, p. 1364-1375Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Perforated colonic diverticulitis usually requires surgical resection, which is associated with significant morbidity. Cohort studies have suggested that laparoscopic lavage may treat perforated diverticulitis with less morbidity than resection procedures. OBJECTIVE To compare the outcomes from laparoscopic lavage with those for colon resection for perforated diverticulitis. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized clinical superiority trial recruiting participants from 21 centers in Sweden and Norway from February 2010 to June 2014. The last patient follow-up was in December 2014 and final review and verification of the medical records was assessed in March 2015. Patients with suspected perforated diverticulitis, a clinical indication for emergency surgery, and free air on an abdominal computed tomography scan were eligible. Of 509 patients screened, 415 were eligible and 199 were enrolled. INTERVENTIONS Patients were assigned to undergo laparoscopic peritoneal lavage (n = 101) or colon resection (n = 98) based on a computer-generated, center-stratified block randomization. All patients with fecal peritonitis (15 patients in the laparoscopic peritoneal lavage group vs 13 in the colon resection group) underwent colon resection. Patients with a pathology requiring treatment beyond that necessary for perforated diverticulitis (12 in the laparoscopic lavage group vs 13 in the colon resection group) were also excluded from the protocol operations and treated as required for the pathology encountered. MAIN OUTCOMES AND MEASURES The primary outcome was severe postoperative complications (Clavien-Dindo score greater thanIlla) within 90 days. Secondary outcomes included other postoperative complications, reoperations, length of operating time, length of postoperative hospital stay, and quality of life. RESULTS The primary outcome was observed in 31 of 101 patients (30.7%) in the laparoscopic lavage group and 25 of 96 patients (26.0%) in the colon resection group (difference, 4.7% [95% CI, -7.9% to 17.0%]; P = .53). Mortality at 90 days did not significantly differ between the laparoscopic lavage group (14 patients [13.9%]) and the colon resection group (11 patients [11.5%]; difference, 2.4% [95% CI, -7.2% to 11.9%]; P = .67). The reoperation rate was significantly higher in the laparoscopic lavage group (15 of 74 patients [20.3%]) than in the colon resection group (4 of 70 patients [5.7%]; difference, 14.6% [95% CI, 3.5% to 25.6%]; P = .01) for patients who did not have fecal peritonitis. The length of operating time was significantly shorter in the laparoscopic lavage group; whereas, length of postoperative hospital stay and quality of life did not differ significantly between groups. Four sigmoid carcinomas were missed with laparoscopic lavage. CONCLUSIONS AND RELEVANCE Among patients with likely perforated diverticulitis and undergoing emergency surgery, the use of laparoscopic lavage vs primary resection did not reduce severe postoperative complications and led to worse outcomes in secondary end points. These findings do not support laparoscopic lavage for treatment of perforated diverticulitis.

  • 7.
    Lund, Lars H
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Benson, Lina
    Karolinska Institutet, Stockholm, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Edner, Magnus
    Karolinska Institutet, Stockholm, Sweden.
    Association Between Use of Renin-Angiotensin System Antagonists and Mortality in Patients With Heart Failure and Preserved Ejection Fraction2012In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 308, no 20, p. 2108-2117Article in journal (Refereed)
    Abstract [en]

    CONTEXT:

    Heart failure with preserved ejection fraction (HFPEF) may be as common and as lethal as heart failure with reduced ejection fraction (HFREF). Three randomized trials of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ie, renin-angiotensin system [RAS] antagonists) did not reach primary end points but may have had selection bias or been underpowered.

    OBJECTIVE:

    To test the hypothesis that use of RAS antagonists is associated with reduced all-cause mortality in an unselected population with HFPEF.

    DESIGN, SETTING, AND PATIENTS:

    Prospective study using the Swedish Heart Failure Registry of 41,791 unique patients registered from 64 hospitals and 84 outpatient clinics between 2000 and 2011. Of these, 16,216 patients with HFPEF (ejection fraction ≥40%; mean [SD] age, 75 [11] years; 46% women) were either treated (n = 12,543) or not treated (n = 3673) with RAS antagonists. Propensity scores for RAS antagonist use were derived from 43 variables. The association between use of RAS antagonists and all-cause mortality was assessed in a cohort matched 1:1 based on age and propensity score and in the overall cohort with adjustment for propensity score as a continuous covariate. To assess consistency, separate age and propensity score-matched analyses were performed according to RAS antagonist dose in patients with HFPEF and in 20,111 patients with HFREF (ejection fraction <40%) in the same registry.

    MAIN OUTCOME MEASURE:

    All-cause mortality.

    RESULTS:

    In the matched HFPEF cohort, 1-year survival was 77% (95% CI, 75%-78%) for treated patients vs 72% (95% CI, 70%-73%) for untreated patients, with a hazard ratio (HR) of 0.91 (95% CI, 0.85-0.98; P = .008). In the overall HFPEF cohort, crude 1-year survival was 86% (95% CI, 86%-87%) for treated patients vs 69% (95% CI, 68%-71%) for untreated patients, with a propensity score-adjusted HR of 0.90 (95% CI, 0.85-0.96; P = .001). In the HFPEF dose analysis, the HR was 0.85 (95% CI, 0.78-0.83) for 50% or greater of target dose vs no treatment (P < .001) and 0.94 (95% CI, 0.87-1.02) for less than 50% of target dose vs no treatment (P = .14). In the age and propensity score-matched HFREF analysis, the HR was 0.80 (95% CI, 0.74-0.86; P < .001).

    CONCLUSION:

    Among patients with heart failure and preserved ejection fraction, the use of RAS antagonists was associated with lower all-cause mortality.

  • 8.
    Lund, Lars H.
    et al.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Benson, Lina
    Soder Sjukhuset, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Edner, Magnus
    Karolinska Institute, Sweden.
    Friberg, Leif
    Danderyd Hospital, Sweden; Danderyd Hospital, Sweden.
    Association Between Use of beta-Blockers and Outcomes in Patients With Heart Failure and Preserved Ejection Fraction2014In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 312, no 19, p. 2008-2018Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Heart failure with preserved ejection fraction (HFPEF) may be as common and may have similar mortality as heart failure with reduced ejection fraction (HFREF). beta-Blockers reduce mortality in HFREF but are inadequately studied in HFPEF. OBJECTIVE To test the hypothesis that beta-blockers are associated with reduced all-cause mortality in HFPEF. DESIGN Propensity score-matched cohort study using the Swedish Heart Failure Registry. Propensity scores for beta-blacker use were derived from 52 baseline clinical and socioeconomic variables. SETTING Nationwide registry of 67 hospitals with inpatient and outpatient units and 95 outpatient primary care clinics in Sweden with patients entered into the registry between July 1, 2005, and December 30, 2012, and followed up until December 31, 2012. PARTICIPANTS From a consecutive sample of 41 976 patients, 19 083 patients with HFPEF (mean [SD] age, 76 [12] years; 46% women). Of these, 8244 were matched 2:1 based on age and propensity score for beta-blocker use, yielding 5496 treated and 2748 untreated patients with HFPEF. Also we conducted a positive-control consistency analysis involving 22 893 patients with HFREF, of whom 6081 were matched yielding 4054 treated and 2027 untreated patients. EXPOSURES beta-Blockers prescribed at discharge from the hospital or during an outpatient visit, analyzed 2 ways: without consideration of crossover and per-protocol analysis with censoring at crossover, if applicable. MAIN OUTCOMES AND MEASURES The prespecified primary outcome was all-cause mortality and the secondary outcome was combined all-cause mortality or heart failure hospitalization. RESULTS Median follow-up in HFPEF was 755 days, overall; 709 days in the matched cohort; no patients were lost to follow-up. In the matched HFPEF cohort, 1-year survival was 80% vs 79% for treated vs untreated patients, and 5-year survival was 45% vs 42%, with 2279(41%) vs 1244(45%) total deaths and 177 vs 191 deaths per 1000 patient-years (hazard ratio [HR], 0.93; 95% Cl, 0.86-0.996; P =.04). beta-Blockers were not associated with reduced combined mortality or heart failure hospitalizations: 3368(61%) vs 1753(64%) total for first events, with 371 vs 378 first events per 1000 patient-years (HR, 0.98; 95% Cl, 0.92-1.04; P = .46). In the matched HFREF cohort, beta-blockers were associated with reduced mortality (HR, 0.89; 95% Cl, 0.82-0.97, P=.005) and also with reduced combined mortality or heart failure hospitalization (HR, 0.89; 95% Cl, 0.84-0.95; P =.001). CONCLUSIONS AND RELEVANCE In patients with HFPEF, use of beta-blockers was associated with lower all-cause mortality but not with combined all-cause mortality or heart failure hospitalization. beta-Blockers in HFPEF should be examined in a large randomized clinical trial.

  • 9.
    Mattsson, Niklas
    et al.
    University of Gothenburg.
    Zetterberg, Henrik
    University of Gothenburg.
    Hansson, Oskar
    Lund University.
    Andreasen, Niels
    Karolinska Institutet, Huddinge University Hospital, Stockholm.
    Parnetti, Lucilla
    University of Perugia, Italy.
    Jonsson, Michael
    University of Gothenburg.
    Herukka, Sanna-Kaisa
    University of Kuopio, Finland.
    van der Flier, Wiesje M.
    Vrije University Medical Center, Amsterdam, the Netherlands.
    Blankenstein, Marinus A.
    Vrije University Medical Center, Amsterdam, the Netherlands.
    Ewers, Michael
    University of Dublin, Ireland.
    Rich, Kenneth
    New York University, USA.
    Kaiser, Elmar
    University of Heidelberg, Germany.
    Verbeek, Marcel
    Radboud University Medical Centre, Nijmegen, the Netherlands.
    Tsolaki, Magda
    Aristotle University of Thessaloniki, Greece .
    Mulugeta, Ezra
    Stavanger University Hospital, Norway.
    Rosén, Erik
    University of Gothenburg.
    Aarsland, Dag
    Stavanger University Hospital, Norway.
    Jelle Visser, Pieter
    University of Maastricht, the Netherlands.
    Schroeder, Johannes
    University of Heidelberg, Germany.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    de Leon, Mony
    New York University, USA.
    Hampel, Harald
    University of Dublin, Ireland.
    Scheltens, Philip
    Vrije University Medical Center, Amsterdam, the Netherlands.
    Pirttilae, Tuula
    University of Kuopio, Finland.
    Wallin, Anders
    University of Gothenburg.
    Eriksdotter Jönhagen, Maria
    Karolinska Institutet, Huddinge University Hospital, Stockholm.
    Minthon, Lennart
    Lund University.
    Winblad, Bengt
    Karolinska Institutet, Huddinge University Hospital, Stockholm.
    Blennow, Kaj
    University of Gothenburg.
    CSF Biomarkers and Incipient Alzheimer Disease in Patients With Mild Cognitive Impairment2009In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 302, no 4, p. 385-393Article in journal (Refereed)
    Abstract [en]

    CONTEXT:

    Small single-center studies have shown that cerebrospinal fluid (CSF) biomarkers may be useful to identify incipient Alzheimer disease (AD) in patients with mild cognitive impairment (MCI), but large-scale multicenter studies have not been conducted.

    OBJECTIVE:

    To determine the diagnostic accuracy of CSF beta-amyloid(1-42) (Abeta42), total tau protein (T-tau), and tau phosphorylated at position threonine 181 (P-tau) for predicting incipient AD in patients with MCI.

    DESIGN, SETTING, AND PARTICIPANTS:

    The study had 2 parts: a cross-sectional study involving patients with AD and controls to identify cut points, followed by a prospective cohort study involving patients with MCI, conducted 1990-2007. A total of 750 individuals with MCI, 529 with AD, and 304 controls were recruited by 12 centers in Europe and the United States. Individuals with MCI were followed up for at least 2 years or until symptoms had progressed to clinical dementia.

    MAIN OUTCOME MEASURES:

    Sensitivity, specificity, positive and negative likelihood ratios (LRs) of CSF Abeta42, T-tau, and P-tau for identifying incipient AD.

    RESULTS:

    During follow-up, 271 participants with MCI were diagnosed with AD and 59 with other dementias. The Abeta42 assay in particular had considerable intersite variability. Patients who developed AD had lower median Abeta42 (356; range, 96-1075 ng/L) and higher P-tau (81; range, 15-183 ng/L) and T-tau (582; range, 83-2174 ng/L) levels than MCI patients who did not develop AD during follow-up (579; range, 121-1420 ng/L for Abeta42; 53; range, 15-163 ng/L for P-tau; and 294; range, 31-2483 ng/L for T-tau, P < .001). The area under the receiver operating characteristic curve was 0.78 (95% confidence interval [CI], 0.75-0.82) for Abeta42, 0.76 (95% CI, 0.72-0.80) for P-tau, and 0.79 (95% CI, 0.76-0.83) for T-tau. Cut-offs with sensitivity set to 85% were defined in the AD and control groups and tested in the MCI group, where the combination of Abeta42/P-tau ratio and T-tau identified incipient AD with a sensitivity of 83% (95% CI, 78%-88%), specificity 72% (95% CI, 68%-76%), positive LR, 3.0 (95% CI, 2.5-3.4), and negative LR, 0.24 (95% CI, 0.21-0.28). The positive predictive value was 62% and the negative predictive value was 88%.

    CONCLUSIONS:

    This multicenter study found that CSF Abeta42, T-tau, and P-tau identify incipient AD with good accuracy, but less accurately than reported from single-center studies. Intersite assay variability highlights a need for standardization of analytical techniques and clinical procedures.

  • 10.
    Nilsson, Peter M.
    et al.
    Lund University, Skåne University Hospital, Sweden.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Self-titration of antihypertensive therapy in high-risk patients: bringing it home2014In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 312, no 8, p. 795-796Article in journal (Other academic)
  • 11.
    Norman, Mikael
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Umea Univ Hosp, Sweden.
    Hallberg, Boubou
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Abrahamsson, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Bjorklund, Lars J.
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Domellof, Magnus
    Umea Univ, Sweden.
    Farooqi, Aijaz
    Umea Univ, Sweden; Umea Univ, Sweden.
    Foyn Bruun, Cathrine
    Umea Univ, Sweden.
    Gadsboll, Christian
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Hellstrom-Westas, Lena
    Uppsala Univ, Sweden.
    Ingemansson, Fredrik
    Ryhov Cty Hosp, Sweden.
    Kallen, Karin
    Lund Univ, Sweden.
    Ley, David
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Marsal, Karel
    Lund Univ, Sweden.
    Normann, Erik
    Uppsala Univ, Sweden.
    Serenius, Fredrik
    Uppsala Univ, Sweden.
    Stephansson, Olof
    Karolinska Inst, Sweden.
    Stigson, Lennart
    Gothenburg Univ, Sweden.
    Um-Bergstrom, Petra
    Karolinska Inst, Sweden; Soder Sjukhuset, Sweden.
    Hakansson, Stellan
    Umea Univ, Sweden.
    Association Between Year of Birth and 1-Year Survival Among Extremely Preterm Infants in Sweden During 2004-2007 and 2014-20162019In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 321, no 12, p. 1188-1199Article in journal (Refereed)
    Abstract [en]

    Importance  Since 2004-2007, national guidelines and recommendations have been developed for the management of extremely preterm births in Sweden. If and how more uniform management has affected infant survival is unknown.

    Objective  To compare survival of extremely preterm infants born during 2004-2007 with survival of infants born during 2014-2016.

    Design, Setting and Participants  All births at 22-26 weeks’ gestational age (n = 2205) between April 1, 2004, and March 31, 2007, and between January 1, 2014, and December 31, 2016, in Sweden were studied. Prospective data collection was used during 2004-2007. Data were obtained from the Swedish pregnancy, medical birth, and neonatal quality registries during 2014-2016.

    Exposures  Delivery at 22-26 weeks’ gestational age.

    Main Outcomes and Measures  The primary outcome was infant survival to the age of 1 year. The secondary outcome was 1-year survival among live-born infants who did not have any major neonatal morbidity (specifically, without intraventricular hemorrhage grade 3-4, cystic periventricular leukomalacia, necrotizing enterocolitis, retinopathy of prematurity stage 3-5, or severe bronchopulmonary dysplasia).

    Results  During 2004-2007, 1009 births (3.3/1000 of all births) occurred at 22-26 weeks’ gestational age compared with 1196 births (3.4/1000 of all births) during 2014-2016 (P = .61). One-year survival among live-born infants at 22-26 weeks’ gestational age was significantly lower during 2004-2007 (497 of 705 infants [70%]) than during 2014-2016 (711 of 923 infants [77%]) (difference, −7% [95% CI, −11% to −2.2%], P = .003). One-year survival among live-born infants at 22-26 weeks’ gestational age and without any major neonatal morbidity was significantly lower during 2004-2007 (226 of 705 infants [32%]) than during 2014-2016 (355 of 923 infants [38%]) (difference, −6% [95% CI, −11% to −1.7%], P = .008).

    Conclusions and Relevance  Among live births at 22-26 weeks’ gestational age in Sweden, 1-year survival improved between 2004-2007 and 2014-2016.

  • 12.
    Nystrom, Fredrik H.
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Wijkman, Magnus
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Fredriksson, Mats
    Linkoping Univ, Linkoping, Sweden.
    Letter: Supine Systolic Blood Pressure and 1-Year Mortality in Patients With Acute Chest Pain Reply2010In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 304, no 1, p. 40-41Article in journal (Other academic)
    Abstract [en]

    n/a

  • 13. ODonoghue, M
    et al.
    Boden, WE
    Braunwald, E
    Cannon, CP
    Clayton, TC
    de Winter, RJ
    Fox, KA
    Lagerqvist, B
    McCullough, PA
    Murphy, SA
    Spacek, R
    Swahn, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Wallentin, L
    Windhausen, F
    Sabatine, MS
    Early invasive vs conservative treatment strategies in women and men with unstable angina and non-ST-segment elevation myocardial infarction: A meta-analysis2008In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 300, no 1, p. 71-80Article in journal (Refereed)
    Abstract [en]

    Context: Although an invasive strategy is frequently used in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS), data from some trials suggest that this strategy may not benefit women. Objective: To conduct a meta-analysis of randomized trials to compare the effects of an invasive vs conservative strategy in women and men with NSTE ACS. Data Sources: Trials were identified through a computerized literature search of the MEDLINE and Cochrane databases (1970-April 2008) using the search terms invasive strategy, conservative strategy, selective invasive strategy, acute coronary syndromes, non-ST-elevation myocardial infarction, and unstable angina. Study Selection: Randomized clinical trials comparing an invasive vs conservative treatment strategy in patients with NSTE ACS. Data Extraction: The principal investigators for each trial provided the sex-specific incidences of death, myocardial infarction (MI), and rehospitalization with ACS through 12 months of follow-up. Data Synthesis: Data were combined across 8 trials (3075 women and 7075 men). The odds ratio (OR) for the composite of death, MI, or ACS for invasive vs conservative strategy in women was 0.81 (95% confidence interval [CI], 0.65-1.01, 21.1% vs 25.0%) and in men was 0.73 (95% CI, 0.55-0.98, 21.2% vs 26.3%) without significant heterogeneity between sexes (P for interaction = .26). Among biomarker-positive women, an invasive strategy was associated with a 33% lower odds of death, MI, or ACS (OR, 0.67, 95% CI, 0.50-0.88) and a nonsignificant 23% lower odds of death or MI (OR, 0.77, 95% CI, 0.47-1.25). In contrast, an invasive strategy was not associated with a significant reduction in the triple composite end point in biomarker-negative women (OR, 0.94, 95% CI, 0.61-1.44, P for interaction = .36) and was associated with a nonsignificant35%higher odds of death or MI (OR, 1.35, 95% CI, 0.78-2.35, P for interaction = .08). Among men, the OR for death, MI, or ACS was 0.56 (95% CI, 0.46-0.67) if biomarker-positive and 0.72 (95% CI, 0.51-1.01) if biomarker-negative (P for interaction = .09). Conclusions: In NSTE ACS, an invasive strategy has a comparable benefit in men and high-risk women for reducing the composite end point of death, MI, or rehospitalization with ACS. In contrast, our data provide evidence supporting the new guideline recommendation for a conservative strategy in low-risk women. ©2008 American Medical Association. All rights reserved.

  • 14.
    Pedersen, T R
    et al.
    Ullevål University Hospital.
    Faergeman, O
    Århus University Hospital.
    Kastelein, JJP
    Academic Hospital Amsterdam.
    Olsson, Anders
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Tikkanen, MJ
    Helsinki University Central Hospital.
    Holme, I
    Ullevål University Hospital.
    Larsen, ML
    Århus University Hospital.
    Bendiksen, FS
    Hamar, Norway.
    Lindahl, C
    Pfizer Sweden.
    Szarek, M
    Pfizer Inc, New York.
    Tsai, J
    Pfizer Inc, New York.
    High-dose atorvastatin vs usual dose simvastatin for secondary prevention after myocardial infarction - The IDEAL study: A randomized controlled trial2005In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 294, no 19, p. 2437-2445Article in journal (Refereed)
    Abstract [en]

    Context Evidence suggests that more intensive lowering of low-density lipoprotein cholesterol (LDL-C) than is commonly applied clinically will provide further benefit in stable coronary artery disease. Objective To compare the effects of 2 strategies of lipid lowering on the risk of cardiovascular disease among patients with a previous myocardial infarction (MI). Design, Setting, and Participants The IDEAL study, a prospective, randomized, open-label, blinded end-point evaluation trial conducted at 190 ambulatory cardiology care and specialist practices in northern Europe between March 1999 and March 2005 with a median follow-up of 4.8 years, which enrolled 8888 patients aged 80 years or younger with a history of acute MI. Interventions Patients were randomly assigned to receive a high dose of atorvastatin (80 mg/d; n=4439), or usual-dose simvastatin (20 mg/d; n=4449). Main Outcome Measure Occurrence of a major coronary event, defined as coronary death, confirmed nonfatal acute MI, or cardiac arrest with resuscitation. Results During treatment, mean LDL-C levels were 104 (SE, 0.3) mg/dL in the simvastatin group and 81 (SE, 0.3) mg/dL in the atorvastatin group. A major coronary event occurred in 463 simvastatin patients (10.4%) and in 411 atorvastatin patients (9.3%) (hazard ratio [HR], 0.89; 95% Cl, 0.78-1.01; P=.07). Nonfatal acute MI occurred in 321 (7.2%) and M7 (6.0%) in the 2 groups (HR, 0.83; 95% Cl, 0.71-0.98; P=.02), but no differences were seen in the 2 other components of the primary end point. Major cardiovascular events occurred in 608 and 533 in the 2 groups, respectively (HR, 0.87; 95% Cl, 0.77-0.98; P=.02). Occurrence of any coronary event was reported in 1059 simvastatin and 898 atorvastatin patients (HR, 0.84; 95% Cl, 0.76-0.91; Pless than.001). Non-cardiovascular death occurred in 156 (3.5%) and 143 (3.2%) in the 2 groups (HR, 0.92; 95% Cl, 0.73-1.15; P=.47). Death from any cause occurred in 374 (8.4%) in the simvastatin group and 366 (8.2%) in the atorvastatin group (HR, 0.98; 95% Cl, 0.85-1.13; P=.81). Patients in the atorvastatin group had higher rates of drug discontinuation due to nonserious adverse events; transaminase elevation resulted in 43 (1.0%) vs 5 (0.1%) withdrawals (Pless than.001). Serious myopathy and rhabdomyolysis were rare in both groups. Conclusions In this study of patients with previous MI, intensive lowering of LDL-C did not result in a significant reduction in the primary outcome of major coronary events, but did reduce the risk of other composite secondary end points and nonfatal acute MI. There were no differences in cardiovascular or all-cause mortality. Patients with MI may benefit from intensive lowering of LDL-C without an increase in noncardiovascular mortality or other serious adverse reactions.

  • 15.
    Pedersen, T.R.
    et al.
    Center of Preventive Medicine, Ullevål University Hospital, Oslo, Norway.
    Faergeman, O.
    Department of Medicine-Cardiology A, Århus University Hospital, Århus, Denmark.
    Kastelein, J.J.P.
    Academic Hospital Amsterdam, Amsterdam, Netherlands.
    Olsson, Anders
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Tikkanen, M.J.
    Medical Clinic, Helsinki University Hospital, Helsinki, Finland.
    Holme, I.
    Center of Preventive Medicine, Ullevål University Hospital, Oslo, Norway.
    Larsen, M.L.
    Department of Medicine-Cardiology A, Århus University Hospital, Århus, Denmark.
    Bendiksen, F.S.
    Bendiksen, F.S..
    High-dose statins and the IDEAL study: Reply2006In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 295, no 21, p. 2478-2479p. 2478-2479Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 16.
    Rebagliato, Marisa
    et al.
    Department of Public Health, Miguel Hernandez University, Alicante, Spain .
    Cuttini, Marina
    Units of Epidemiology and Neonatal Intensive Care, Burlo Garofolo Children's Hospital.
    Broggin, Lara
    Units of Epidemiology and Neonatal Intensive Care, Burlo Garofolo Children's Hospital.
    Berbik, Istvan
    Department of Obstetrics and Gynaecology, Vaszary Kolos Hospital, Tergoti, Hungary .
    de Vonderweid, Umberto
    Units of Epidemiology and Neonatal Intensive Care, Burlo Garofolo Children's Hospital.
    Hansen, Gesine
    Department of Pediatrics, Martin-Luther University, Halle, Germany .
    Kaminski, Monique
    Epidemiological Research Unit on Perinatal and Women's Health U.149 INSERM.
    Kollée, Louis A. A.
    Department of Neonatology, University Hospital of Nijmegen, Nijmegen, the Netherlands.
    Kucinskas, Audrunas
    Neonatal Clinic, Vilnius University, Lithuania .
    Lenoir, Sylvie
    Villejuif, and Unit of Research on Reproduction, INSERM CJF 89-08 .
    Levin, Adik
    Newborn and Premature Children's Department, Tallinn Hospital, Estonia .
    Persson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment.
    Reid, Margaret
    Department of Public Health, University of Glasgow.
    Saracci, Rodolfo
    Trieste, and Division of Epidemiology, IFC, National Research Council .
    Neonatal end-of-life decision making: physicians' attitudes and relationship with self-reported practices in 10 European countries2000In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 284, no 19, p. 2451-2459Article in journal (Refereed)
    Abstract [en]

    Context: The ethical issues surrounding end-of-life decision making for infants with adverse prognoses are controversial. Little empirical evidence is available on the attitudes and values that underlie such decisions in different countries and cultures. Objective: To explore the variability of neonatal physicians' attitudes among 10 European countries and the relationship between such attitudes and self-reported practice of end-of-life decisions. Design and Setting: Survey conducted during 1996-1997 in 10 European countries (France, Germany, Italy, the Netherlands, Spain, Sweden, the United Kingdom, Estonia, Hungary, and Lithuania). Participants: A total of 1391 physicians (response rate, 89%) regularly employed in 142 neonatal intensive care units (NICUs). Main Outcome Measures: Scores on an attitude scale, which measured views regarding absolute value of life (score of 0) vs value of quality of life (score of 10), self-report of having ever set limits to intensive neonatal interventions in cases of poor neurological prognosis. Results: Physicians more likely to agree with statements consistent with preserving life at any cost were from Hungary (mean attitude scores, 5.2 [95% confidence interval {Cl}, 4.9-5.5]), Estonia (4.9 [95% Cl, 4.3-5.5]), Lithuania (5.5 [95% Cl, 4.8-6.1]), and Italy (5.7 [95% Cl, 5.3-6.0]), while physicians more likely to agree with the idea that quality of life must be taken into account were from the United Kingdom (attitude scores, 7.4 [95% Cl, 7.1-7.7]), the Netherlands (7.3 [95% Cl, 7.1-7.5]), and Sweden (6.8 [95% Cl, 6.4-7.3]). Other factors associated with having a pro-quality-of-life view were being female, having had no children, being Protestant or having no religious background, considering religion as not important, and working in an NICU with a high number of very low-birth-weight newborns. Physicians with scores reflecting a more quality-of-life view were more likely to report that in their practice, they had set limits to intensive interventions in cases of poor neurological prognosis, with an adjusted odds ratio of 1.5 (95% Cl, 1.3-1.7) per unit change in attitude score. Conclusions: In our study, physicians' likelihood of reporting setting limits to intensive neonatal interventions in cases of poor neurological prognosis is related to their attitudes. After adjusting for potential confounders, country remained the most important predictor of physicians' attitudes and practices.

  • 17. Schwartz, GG
    et al.
    Olsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Ezekowitz, MD
    Ganz, P
    Oliver, MF
    Waters, D
    Zeiher, A
    Chaitman, BR
    Atorvastatin for acute coronary syndromes2001In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 286, no 5, p. 533-533Other (Other academic)
  • 18. Schwartz, GG
    et al.
    Olsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Ezekowitz, MD
    Ganz, P
    Oliver, MF
    Waters, D
    Zeiher, A
    Chaitman, BR
    Atorvastatin for acute coronary syndromes - Reply2001In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 286, no 5, p. 533-534Other (Other academic)
  • 19. Schwartz, Gregory
    et al.
    Olsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Ezekowitz, Michael
    Ganz, Peter
    Oliver, Michael
    Waters, David
    Zeither, Andreas
    Chaitman, Bernard
    Leslie, Sally
    Stern, Theresa
    Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes. The MIRACL study: A randomized controlled trial.2001In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 285, p. 1711-1718Article in journal (Refereed)
  • 20.
    Serenius, Fredrik
    et al.
    Uppsala University, Sweden Umeå University, Sweden .
    Källén, Karin
    Lund University, Sweden .
    Blennow, Mats
    Karolinska Institute, Stockholm, Sweden.
    Ewald, Uwe
    Uppsala University, Sweden .
    Fellman, Vineta
    Lund University, Sweden .
    Holmström, Gerd
    Uppsala University, Sweden .
    Lindberg, Eva
    Örebro University, Sweden .
    Lundqvist, Pia
    Lund University, Sweden .
    Marsal, Karel
    Lund University, Sweden .
    Norman, Mikael
    Karolinska Institute, Stockholm, Sweden.
    Olhager, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Stigson, Lennart
    University of Gothenburg, Sweden .
    Stjernqvist, Karin
    Lund University, Sweden .
    Vollmer, Brigitte
    Karolinska Institute, Stockholm, Sweden .
    Strömberg, Bo
    Uppsala University, Sweden .
    Neurodevelopmental Outcome in Extremely Preterm Infants at 2.5 Years After Active Perinatal Care in Sweden2013In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 309, no 17, p. 1810-1820Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE:

    Active perinatal care increases survival of extremely preterm infants; however, improved survival might be associated with increased disability among survivors.

    OBJECTIVE:

    To determine neurodevelopmental outcome in extremely preterm children at 2.5 years (corrected age).

    DESIGN, SETTING, AND PARTICIPANTS:

    Population-based prospective cohort of consecutive extremely preterm infants born before 27 weeks of gestation in Sweden between 2004 and 2007. Of 707 live-born infants, 491 (69%) survived to 2.5 years. Survivors were assessed and compared with singleton control infants who were born at term and matched by sex, ethnicity, and municipality. Assessments ended in February 2010 and comparison estimates were adjusted for demographic differences.

    MAIN OUTCOMES AND MEASURES:

    Cognitive, language, and motor development was assessed with Bayley Scales of Infant and Toddler Development (3rd edition; Bayley-lll), which are standardized to mean (SD) scores of 100 (15). Clinical examination and parental questionnaires were used for diagnosis of cerebral palsy and visual and hearing impairments. Assessments were made by week of gestational age.

    RESULTS:

    At a median age of 30.5 months (corrected), 456 of 491 (94%) extremely preterm children were evaluated (41 by chart review only). For controls, 701 had information on health status and 366 had Bayley-lll assessments. Mean (SD) composite Bayley-III scores (cognition, 94 [12.3]; language, 98 [16.5]; motor, 94 [15.9]) were lower than the corresponding mean scores for controls (cognition, 104 [10.6]; P < .001; adjusted difference in mean scores, 9.2 [99% CI, 6.9-11.5]; language, 109 [12.3]; P < .001; adjusted difference in mean scores, 9.3 [99% Cl, 6.4-12.3]; and motor, 107 [13.7]; P < .001; adjusted difference in mean scores, 12.6 [99% Cl, 9.5-15.6]). Cognitive disability was moderate in 5% of the extremely preterm group vs 0.3% in controls (P < .001) and it was severe in 6.3% of the extremely preterm group vs 0.3% in controls (P < .001). Language disability was moderate in 9.4% of the extremely preterm group vs 2.5% in controls (P < .001) and severe in 6.6% of the extremely preterm group vs 0% in controls (P < .001). Other comparisons between the extremely preterm group vs controls were for cerebral palsy (7.0% vs 0.1%; P < .001), for blindness (0.9% vs 0%; P = .02), and for hearing impairment (moderate and severe, 0.9% vs 0%; P = .02, respectively). Overall, 42% (99% CI, 36%-48%) of extremely preterm children had no disability, 31% (99% CI, 25%-36%) had mild disability, 16% (99% CI, 12%-21%) had moderate disability, and 11% (99% CI, 7.2%-15%) had severe disability. Moderate or severe overall disability decreased with gestational age at birth (22 weeks, 60%; 23 weeks, 51%; 24 weeks, 34%; 25 weeks, 27%; and 26 weeks, 17%; P for trend < .001).

    CONCLUSIONS AND RELEVANCE:

    Of children born extremely preterm and receiving active perinatal care, 73% had mild or no disability and neurodevelopmental outcome improved with each week of gestational age. These results are relevant for clinicians counseling families facing extremely preterm birth.

  • 21.
    Stenestrand, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Lindbäck, Johan
    Wallentin, Lars
    Long-term outcome of primary percutaneous coronary intervention vs prehospital and in-hospital thrombolysis for patients with ST-elevation myocardial infarction2006In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 296, no 14, p. 1749-1756Article in journal (Refereed)
    Abstract [en]

    Context: Whether the superior results of percutaneous coronary intervention (PCI) reported in clinical trials in which patients with ST-segment elevation myocardial infarction (STEMI) received reperfusion treatment can be replicated in daily practice has been questioned, especially whether it is superior to prehospital thrombolysis (PHT). Objective: To evaluate the outcome of different reperfusion strategies in consecutive STEMI patients. Design, Setting, and Patients: A prospective observational cohort study of 26 205 consecutive STEMI patients in the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA) who received reperfusion therapy within 15 hours of symptom onset. The registry includes more than 95% of all Swedish patients, of all ages, who were treated in a coronary intensive care unit between 1999 and 2004. Interventions: Seven thousand eighty-four patients underwent primary PCI, 3078, PHT, and 16 043, in-hospital thrombolysis (IHT). Main Outcome Measures: Mortality, reinfarction, and readmissions as reported in the National Health Registries through December 31, 2005. Results: After adjusting for younger age and less comorbidity, primary PCI was associated with lower mortality than IHT at 30 days (344 [4.9%] vs 1834 [11.4%], hazard ratio [HR], 0.61, 95% confidence interval [CI], 0.53-0.71) and at 1 year (541 [7.6%] vs 2555 [15.9%], HR, 0.68, 95% CI, 0.60-0.76). Also primary PCI correlated with lower mortality than PHT at 30 days (344 [4.9%] vs 234 [7.6%], HR, 0.70, 95% CI, 0.58-0.85) and 1 year (541 [7.6%] vs 317 [10.3%], HR, 0.81, 95% CI, 0.69-0.94). Prehospital thrombolysis predicted a lower mortality than IHT at 30 days (HR, 0.87, 95% CI, 0.76-1.01) and at 1 year (HR, 0.84, CI 0.74-0.95). Beyond 2 hours' treatment delay, the observed mortality reductions with PHT tended to decrease while the benefits with primary PCI seemed to remain regardless of time delay. Primary PCI was also associated with shorter hospital stay and less reinfarction than either PHT or IHT. Conclusions: In unselected patients with STEMI, primary PCI, which compared favorably with IHT and PHT, was associated with reduced duration of hospital stay, readmission, reinfarction, and mortality. ©2006 American Medical Association. All rights reserved.

  • 22.
    Stenestrand, Ulf
    et al.
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Lindbäck, Johan
    Uppsala University.
    Wallentin, Lars
    Uppsala University.
    Percutaneous coronary intervention vs thrombolysis for ST-elevation myocardial infarction - Reply2007In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 297, no 12, p. 1314-1315Article in journal (Other academic)
    Abstract [en]

      

  • 23.
    Stenestrand, Ulf
    et al.
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Wallentin, Lars
    Department of Cardiology, University Hospital of Uppsala, Uppsala, Sweden.
    Early statin treatment following acute myocardial infarction and 1-year survival2001In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 285, no 4, p. 430-436Article in journal (Refereed)
    Abstract [en]

    CONTEXT:

    Randomized trials have established statin treatment as secondary prevention in coronary artery disease, but it is unclear whether early treatment with statins following acute myocardial infarction (AMI) influences survival.

    OBJECTIVE:

    To evaluate the association between statin treatment initiated before or at the time of hospital discharge and 1-year mortality after AMI.

    DESIGN AND SETTING:

    Prospective cohort study using data from the Swedish Register of Cardiac Intensive Care on patients admitted to the coronary care units of 58 Swedish hospitals in 1995-1998. One-year mortality data were obtained from the Swedish National Cause of Death Register.

    PATIENTS:

    Patients with first registry-recorded AMI who were younger than 80 years and who were discharged alive from the hospital, including 5528 who received statins at or before discharge and 14 071 who did not.

    MAIN OUTCOME MEASURE:

    Relative risk of 1-year mortality according to statin treatment.

    RESULTS:

    At 1 year, unadjusted mortality was 9.3% (1307 deaths) in the no-statin group and 4.0% (219 deaths) in the statin treatment group. In regression analysis adjusting for confounding factors and propensity score for statin use, early statin treatment was associated with a reduction in 1-year mortality (relative risk, 0.75; 95% confidence interval, 0.63-0.89; P =.001) in hospital survivors of AMI. This reduction in mortality was similar among all subgroups based on age, sex, baseline characteristics, previous disease manifestations, and medications.

    CONCLUSIONS:

    Early initiation of statin treatment in patients with AMI is associated with reduced 1-year mortality. These results emphasize the importance of implementing the results of randomized statin trials in unselected AMI patients.

  • 24.
    Stenestrand, Ulf
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Wijkman, Magnus
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Nystrom, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Association between admission supine systolic blood pressure and 1-year mortality in patients admitted to the intensive care unit for acute chest pain.2010In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 303, no 12, p. 1167-1172Article in journal (Refereed)
    Abstract [en]

    CONTEXT: High resting blood pressure (BP) is among the best studied and established risk factors for cardiovascular disease. However, little is known about the relationship between BP under acute stress, such as in acute chest pain, and subsequent mortality. OBJECTIVE: To study long-term mortality related to supine BP in patients admitted to the medical intensive care unit (ICU) for acute chest pain. DESIGN, SETTING, AND PARTICIPANTS: Data from the RIKS-HIA (Registry of Information and Knowledge About Swedish Heart Intensive Care Admissions) was used to analyze the mortality in relation to supine admission systolic BP in 119,151 participants who were treated at the ICU for the symptom of chest pain from 1997 through 2007. Results from this prospective cohort study were presented according to systolic BP quartiles: Q1, less than 128 mm Hg; Q2, from 128 to 144 mm Hg; Q3, from 145 to 162 mm Hg; and Q4, at or above 163 mm Hg. MAIN OUTCOME MEASURE: Total mortality. RESULTS: Mean (SD) follow-up time was 2.47 (1.5) years (range, 1-10 years). One-year mortality rate by Cox proportional hazard model (adjusted for age, sex, smoking, diastolic BP, use of antihypertensive medication at admission and discharge, and use of lipid-lowering and antiplatelet medication at discharge) showed that participants in Q4 had the best prognosis (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.72-0.80, Q4 compared with Q2; corresponding risks for Q1 were HR, 1.46; 95% CI, 1.39-1.52, and for Q3, HR, 0.83; 95% CI, 0.79-0.87). Patients in Q4 had a 21.7% lower absolute risk compared with Q2, patients in Q3 had a 15.2% lower risk than in Q2, and patients in Q1 had a 40.3% higher risk for mortality than in Q2. The worse prognosis in Q2 compared with Q4 was independent of body mass index and previous diagnoses and similar when analysis was restricted to patients with a final diagnosis of angina or myocardial infarction (HR, 0.75; 95% CI, 0.71-0.80, Q4 compared with Q2). CONCLUSION: Among patients admitted to the ICU for chest pain, there is an inverse association between admission supine systolic BP and 1-year mortality rate.

  • 25.
    Sullivan, David
    et al.
    Royal Prince Alfred Hospital, Australia .
    Olsson, Anders
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL. Stockholm Heart Center, Stockholm, Sweden.
    Scott, Rob
    Amgen Inc, CA USA .
    Kim, Jae B
    Amgen Inc, CA USA .
    Xue, Allen
    Amgen Inc, CA USA .
    Gebski, Val
    University of Sydney, Australia .
    Wasserman, Scott M
    Amgen Inc, CA USA .
    Stein, Evan A
    Metab and Atherosclerosis Research Centre, OH 45227 USA .
    Effect of a Monoclonal Antibody to PCSK9 on Low-Density Lipoprotein Cholesterol Levels in Statin-Intolerant Patients The GAUSS Randomized Trial2012In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 308, no 23, p. 2497-2506Article in journal (Refereed)
    Abstract [en]

    Context An estimated 10% to 20% of patients cannot tolerate statins or adequate doses to achieve treatment goals. Plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, promoting their degradation and increasing LDL cholesterol levels. In phase 1 studies, a human monoclonal antibody to PCSK9, AMG145, was well tolerated and reduced LDL cholesterol levels. less thanbrgreater than less thanbrgreater thanObjective To assess the efficacy and tolerability of AMG145 in patients with statin intolerance due to muscle-related side effects. less thanbrgreater than less thanbrgreater thanDesign, Setting, and Patients A 12-week, randomized, double-blind, placebo- and ezetimibe-controlled, dose-ranging study conducted between July 2011 and May 2012 in statin-intolerant adult patients at 33 international sites. less thanbrgreater than less thanbrgreater thanIntervention Patients were randomized equally to 1 of 5 groups: AMG145 alone at doses of 280 mg, 350 mg, or 420 mg; AMG145 at 420 mg plus 10 mg of ezetimibe; or 10 mg of ezetimibe plus placebo. AMG145 or placebo was administered subcutaneously every 4 weeks. less thanbrgreater than less thanbrgreater thanMain Outcome Measures The primary end point was percentage change from baseline to week 12 in ultracentrifugation-measured LDL cholesterol. Other end points included measures of safety and tolerability of different doses of AMG145 and AMG145 plus ezetimibe. less thanbrgreater than less thanbrgreater thanResults Of 236 patients screened, 160 were randomized (mean age, 62 years; 64% female; mean baseline LDL cholesterol, 193 mg/dL); all patients had intolerance to 1 or more statins because of muscle-related events. At week 12, mean changes in LDL cholesterol levels were -67 mg/dL (-41%; 95% CI, -49% to -33%) for the AMG145, 280-mg, group; -70 mg/dL (-43%; 95% CI, -51% to -35%) for the 350-mg group; -91 mg/dL (-51%; 95% CI, -59% to -43%) for the 420-mg group; and -110 mg/dL (-63%; 95% CI, -71% to -55%) for the 420-mg/ezetimibe group compared with -14 mg/dL (-15%; 95% CI, -23% to -7.0%) for the placebo/ezetimibe group (Pandlt;.001). Four serious adverse events were reported with AMG145 (coronary artery disease, acute pancreatitis, hip fracture, syncope). Myalgia was the most common treatment-emergent adverse event during the study, occurring in 5 patients (15.6%) in the 280-mg group (n=32); 1 patient (3.2%) in the 350-mg group (n=31), 1 patient (3.1%) in the 420-mg group (n=32), 6 patients (20.0%) receiving 420-mg AMG145/ezetimibe, and 1 patient (3.1%) receiving placebo/ezetimibe. less thanbrgreater than less thanbrgreater thanConclusion In this phase 2 study in statin-intolerant patients, subcutaneous administration of a monoclonal antibody to PCSK9 significantly reduced LDL cholesterol levels and was associated with short-term tolerability.

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