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  • 101. Celiker, Shemal
    et al.
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Wilhelmsson, Bo
    A radiofrequency vs topical steroid treatment of chronic nasal obstruction: A prospective randomized study of 84 cases2011In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 131, no 1, p. 79-83Article in journal (Refereed)
    Abstract [en]

    Conclusions:

    Nasal congestion caused by mucosal swelling and conch hypertrophy impairs breathing and causes snoring and headaches. Treatment of conch hypertrophy with radiofrequency (RF) allows reduction of mucosal swelling, minimization of hyperplasia, and decreased mucus production. This treatment provides a clinically significant improvement in snoring, headaches, and mouth breathing.

    Objective:

    To compare the efficacy of RF surgery to nasal steroid; each method used separately and both in combination.

    Methods:

    This was a consecutive randomized study, which included 84 patients with 3 outpatient visits, where the first visit included a complete medical history, assessment of ENT status, and skin tests. Nasal flow measured with rhinomanometry was done at the first visit and then before and after each treatment. Patients were asked to respond to a questionnaire at the first visit and after each subsequent treatment. Thereafter the variables were analyzed with established statistical methods.

    Results:

    Measurement of variables and patient questionnaire responses showed a clear improvement in several symptoms, such as sneezing and headache, and a clinically significant improvement in nasal congestion and snoring.

  • 102.
    Chabok, Abbas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Colonic Diverticulitis: Diagnostic and Therapeutic Aspects2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The overall aims of this thesis were to evaluate diagnostic and therapeutic aspects of colonic diverticulitis.

    In the first study, a systematic review of the literature was performed to evaluate radiological diagnostics for patients with acute left-sided diverticulitis. Forty-nine relevant articles were found and read in full and data were extracted or calculated. Twenty-nine of these were excluded. The best evidence for the diagnosis of diverticulitis in the literature was to be found with US. Only one small study of good quality was found for both CT and MRI.

    In the second paper, a prospective multicentre study was performed to determine the faecal carriage of antibiotic-resistant bacteria and antibiotic treatment in 208 surgical patients with acute intra-abdominal infections. The highest rates of resistance among Enterobacteriaceae were detected for ampicillin (54%), tetracycline (26%), cefuroxime (26%) and trimethoprim-sulfamethoxazole (20%). The prevalence of decreased susceptibility (I + R) for the other antibiotics tested was for ciprofloxacin 20%, piperacillin-tazobactam 17%, cefotaxime 14%, ertapenem 12%, gentamicin 3% and imipenem 0%. ESBL- and AmpC producing Enterobacteriaceae were found in samples from 13 patients (6.3%).  We found high rates of resistance among Enterobacteriaceae against antibiotics which were commonly used in Sweden.

    In the third paper, a multicentre randomized study was performed to investigate the need of antibiotic treatment in acute uncomplicated diverticulitis. Six hundred and twenty-three patients were randomized to treatment with (314 patients) or without (309 patients) antibiotics. Complications were found in six patients (1.9%) in the no antibiotic and three (1.0%) in the antibiotic group (p=0.302). The median hospital stay was three days in both groups. Recurrent diverticulitis follow-up was similar in both groups (16%, p=0.895). We conclude that antibiotic treatment for acute uncomplicated diverticulitis neither accelerated recovery nor prevented complications or recurrence. Based on the results, antibiotics should therefore be reserved mainly for the treatment of complicated diverticulitis.

    The fourth paper presents a prospective observational study performed in two centres to evaluate CT colonography in the follow-up of acute diverticulitis as regards patient acceptance and diagnostic accuracy in 108 patients. Patients experienced colonoscopy as more painful (p<0.001) and uncomfortable (p<0.001). Diverticulosis and polyps were detected in 94% and 20% with colonoscopy and in 94% and 29% with CTC, respectively. Sensitivity and specificity for CTC in the detection of diverticulosis was 99% and 67%, with a level of relatively good agreement (К= 0.71). Regarding detection of polyps, the sensitivity and specificity were 47% and 75%, with a poor agreement (К= 0.17). We concluded that CTC was less painful and unpleasant. CTC detected diverticulosis with good accuracy while the accuracy of detection of small polyps was poor. CTC could be an alternative, especially in cases of incomplete colonoscopy or in a situation with limited colonoscopy resources.

  • 103.
    Chabok, Abbas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Andreasson, Kalle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nikberg, Maziar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Low risk of complications in patients with first-time acute uncomplicated diverticulitis2017In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 32, no 12, p. 1699-1702Article in journal (Refereed)
    Abstract [en]

    First-time acute uncomplicated diverticulitis (AUD) has been considered to have an increased risk of complication, but the level of evidence is low. The aim of the present study was to evaluate the risk of complications in patients with first-time AUD and in patients with a history of diverticulitis. This paper is a population-based retrospective study at Vastmanland's Hospital, VasterA<yen>s, Sweden, where all patients were identified with a diagnosis of colonic diverticular disease ICD-10 K57.0-9 from January 2010 to December 2014. The records of all patients were surveyed and patients with a computed tomography (CT)-verified AUD were included. Complications defined as CT-verified abscess, perforation, colonic obstruction, fistula, or sepsis within 1 month from the diagnosis of AUD were registered. Of 809 patients with AUD, 642 (79%) had first-time AUD and 167 (21%) had a previous history of AUD with no differences in demographic or clinical characteristics. In total, 16 (2%) patients developed a complication within 1 month irrespective of whether they had a previous history of diverticulitis (P = 0.345). In the binary logistic regression analysis, first-time diverticulitis was not associated with increased risk of complications (OR 1.58; CI 0.52-4.81). The rate of antibiotic therapy was about 7-10% during the time period and outpatient management increased from 7% in 2010 to 61% in 2014. The risk for development of complications is low in AUD with no difference between patients with first-time or recurrent diverticulitis. This result strengthens existing evidence on the benign disease course of AUD.

  • 104.
    Chabok, Abbas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Hjern, F.
    Haapaniemi, S.
    Smedh, Kennet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis2012In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 99, no 4, p. 532-539Article in journal (Refereed)
    Abstract [en]

    Background: The standard of care for acute uncomplicated diverticulitis today is antibiotic treatment, although there are no controlled studies supporting this management. The aim was to investigate the need for antibiotic treatment in acute uncomplicated diverticulitis, with the endpoint of recovery without complications after 12 months of follow-up.

    Methods: This multicentre randomized trial involving ten surgical departments in Sweden and one in Iceland recruited 623 patients with computed tomography-verified acute uncomplicated left-sided diverticulitis. Patients were randomized to treatment with (314 patients) or without (309 patients) antibiotics.

    Results: Age, sex, body mass index, co-morbidities, body temperature, white blood cell count and C-reactive protein level on admission were similar in the two groups. Complications such as perforation or abscess formation were found in six patients (1.9 per cent) who received no antibiotics and in three (1.0 per cent) who were treated with antibiotics (P = 0.302). The median hospital stay was 3 days in both groups. Recurrent diverticulitis necessitating readmission to hospital at the 1-year follow-up was similar in the two groups (16 per cent, P = 0.881).

    Conclusion: Antibiotic treatment for acute uncomplicated diverticulitis neither accelerates recovery nor prevents complications or recurrence. It should be reserved for the treatment of complicated diverticulitis.

  • 105.
    Chabok, Abbas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Smedh, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nilsson, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Stenson, Marianne
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    CT-colonography in the follow-up of acute diverticulitis: patient acceptance and diagnostic accuracy2013In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 48, no 8, p. 979-986Article in journal (Refereed)
    Abstract [en]

    Objective. The aim of this study was to assess CT-colonography (CTC) in the follow-up of diverticulitis regarding patient acceptance and diagnostic accuracy for diverticular disease, adenomas and cancer, with colonoscopy as a reference standard. Methods. A prospective comparative study where half of the patients underwent colonoscopy first, followed immediately by CTC. The other half had the examinations in the reverse order. Patient experiences and findings were registered after every examination, blinded to the examiner. Results. Of a total of 110 consecutive patients, 108 were included in the study, with a median age of 56 years (range 27-84). The success rate was 91% for colonoscopy and 86% for CTC. Examination time was 25 mm for both methods. The mean time for CTC evaluation was 20 mm. Eighty-three per cent of the patients received sedation during colonoscopy. Despite this, patients experienced colonoscopy as more painful (p < 0.001) and uncomfortable (p < 0.001). Diverticulosis and polyps were detected in 94% and 20% with colonoscopy and in 94% and 29% with CTC, respectively. Sensitivity and specificity for CTC in the detection of diverticulosis was 99% and 67%, with a good agreement (kappa = 0.71). Regarding detection of polyps, the sensitivity and specificity were 47% and 75%, with a poor agreement (kappa = 0.17). No cancer was found. Conclusion. CTC was less painful and unpleasant and can be used for colonic investigation in the follow-up of diverticulitis. CTC detected diverticulosis with good accuracy while the detection accuracy of small polyps was poor. CTC is a viable alternative, especially in case of incomplete colonoscopy or in a situation with limited colonoscopy resources.

  • 106.
    Chabok, Abbas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Tärnberg, Maria
    Smedh, Kennet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nilsson, Lennart E
    Lindberg, Christian
    Hanberger, Håkan
    Prevalence of fecal carriage of antibiotic-resistant bacteria in patients with acute surgical abdominal infections2010In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 45, no 10, p. 1203-1210Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Antibiotic resistance is increasing worldwide. The aims of the current study were to determine the fecal carriage of antibiotic-resistant bacteria and antibiotic treatment in surgical patients admitted to hospital due to acute intra-abdominal infections.

    MATERIALS AND METHODS:

    Eight Swedish surgical units participated in this prospective multicenter investigation. Rectal swabs were obtained on admission to hospital. Cultures were performed on chromogenic agar and antibiotic susceptibility testing was performed using the disk diffusion method. Extended-spectrum beta-lactamase (ESBL)-phenotype was confirmed by Etest.

    RESULTS:

    Rectal samples were obtained and analyzed from 208 patients with intra-abdominal surgical infections. Surgery was performed in 134 patients (65%). Cephalosporins were the most frequently used empirical antibiotic therapy. The highest rates of resistance among Enterobacteriaceae were detected for ampicillin (54%), tetracycline (26%), cefuroxime (26%) and trimethoprim-sulfamethoxazole (20%). The prevalence of decreased susceptibility (I + R) for the other antibiotics tested was for ciprofloxacin 20%, piperacillin-tazobactam 17%, cefotaxime 14%, ertapenem 12%, gentamicin 3% and imipenem 0%. ESBL-producing Enterobacteriaceae were found in samples from 10 patients (5%). Three patients had five E. coli isolates producing AmpC enzymes.

    CONCLUSIONS:

    This study shows a high rate of resistance among Enterobacteriaceae against antibiotics which are commonly used in Sweden and should have implications for the future choice of antibiotics for surgical patients.

  • 107.
    Checknita, Dave
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden;Karolinska Univ Sjukhuset, Psychiat Bldg R5 00 C-O Jari Tiihonen, S-17176 Stockholm, Sweden.
    Ekström, Tomas J.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Nilsson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Tiihonen, Jari
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Hodgins, Sheilagh
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden;Univ Montreal, Inst Univ Sante Mentale Montreal, Montreal, PQ, Canada.
    Associations of monoamine oxidase A gene first exon methylation with sexual abuse and current depression in women2018In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 125, no 7, p. 1053-1064Article in journal (Refereed)
    Abstract [en]

    Childhood physical abuse (PA) and sexual abuse (SA) interact with monoamine oxidase A (MAOA) gene polymorphism to modify risk for mental disorders. In addition, PA and SA may alter gene activity through epigenetic mechanisms such as DNA methylation, thereby further modifying risk for disorders. We investigated whether methylation in a region spanning the MAOA first exon and part of the first intron was associated with PA and/or SA, MAOA genotype, alcohol dependence, drug dependence, depression disorders, anxiety disorders, and conduct disorder. 114 Swedish women completed standardized diagnostic interviews and questionnaires to report PA and SA, and provided saliva samples for DNA extraction. DNA was genotyped for MAOA-uVNTR polymorphisms, and methylation of a MAOA region of interest (chrX: 43,515,544-43,515,991) was measured. SA, not PA, was associated with hypermethylation of the MAOA first exon relative to no-abuse, and the association was robust to adjustment for psychoactive medication, alcohol and drug dependence, and current substance use. SA and MAOA-uVNTR genotype, but not their interaction, was associated with MAOA methylation. SA associated with all measured mental disorders. Hypermethylation of MAOA first exon mediated the association of SA with current depression, and both methylation levels and SA independently predicted lifetime depression. Much remains to be learned about the independent effects of SA and MAOA-uVNTR genotypes on methylation of the MAOA first exon.

  • 108.
    Cloodt, Erika
    et al.
    Lund Univ, Dept Hlth Sci Lund, Div Physiotherapy, Lund, Sweden..
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Rodby-Bousquet, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Lund Univ, Dept Clin Sci Lund, Orthopaed, Lund, Sweden..
    Demographic and modifiable factors associated with knee contracture in children with cerebral palsy2018In: Developmental Medicine & Child Neurology, ISSN 0012-1622, E-ISSN 1469-8749, Vol. 60, no 4, p. 391-396Article in journal (Refereed)
    Abstract [en]

    AimTo identify the prevalence of knee contracture and its association with gross motor function, age, sex, spasticity, and muscle length in children with cerebral palsy (CP). MethodCross-sectional data for passive knee extension were analysed in 3045 children with CP (1756 males, 1289 females; mean age 8y 1mo [SD 3.84]). CP was classified using the Gross Motor Function Classification System (GMFCS) levels I (n=1330), II (n=508), III (n=280), IV (n=449), and V (n=478). Pearson's chi(2) test and multiple binary logistic regression were applied to analyse the relationships between knee contracture and GMFCS level, sex, age, spasticity, hamstring length, and gastrocnemius length. ResultsKnee contracture greater than or equal to 5 degrees occurred in 685 children (22%). The prevalence of knee contracture was higher in older children and in those with higher GMFCS levels. Odds ratios (ORs) for knee contracture were significantly higher for children at GMFCS level V (OR=13.17), with short hamstring muscles (OR=9.86), and in the oldest age group, 13 years to 15 years (OR=6.80). InterpretationKnee contracture is associated with higher GMFCS level, older age, and shorter muscle length; spasticity has a small effect. Maintaining muscle length, especially of the hamstrings, is important for reducing the risk of knee contracture.

  • 109.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Berglund, Kenneth
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Nilsson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Why Do Adolescents Drink?: Motivational Patterns Related to Alcohol Consumption and Alcohol-Related Problems2010In: Substance Use & Misuse, ISSN 1082-6084, E-ISSN 1532-2491, Vol. 45, no 10, p. 1589-1604Article in journal (Refereed)
    Abstract [en]

    The present study was designed to investigate motivational patterns for drinking alcohol and their relation about alcohol consumption and problems related to alcohol consumption. Data were collected by semistructured interviews and questionnaires, containing questions about reasons for drinking, alcohol consumption, and problems related to alcohol consumption during the years 2001, 2004, and 2005. Three independent population samples from two different counties of central Sweden were included. A total of 11,167 adolescents participated. Data on reasons for drinking were analyzed by factor analysis to extract components explaining drinking motives. Relationships between motivational patterns and alcohol use were examined with correlation analysis. Three drinking motives emerged (social-enhancement, coping, and dominance motives) and related to alcohol consumption and problems related to alcohol consumption. Limitations of the study are noted and discussed.

  • 110.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Nordquist, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Göktürk, Camilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Hallman, Jarmila
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Nilsson, Kent W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    The clock gene PER2 and sleep problems: association with alcohol consumption among Swedish adolescents2010In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 115, no 1, p. 41-48Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Alcohol abuse is associated with sleep problems, which are often linked to circadian rhythm disturbances. Previous studies have separately examined the effects of mutations in the clock gene PER2 on alcohol consumption and sleep problems. Here we hypothesized that an allelic variation in the PER2 gene is associated with alcohol consumption in interaction with sleep problems among adolescents. METHODS: The Survey of Adolescent Life and Health in Västmanland 2006, a Swedish county, including 1254 students 17-18 years old, was used as a population-representative sample of adolescents. We investigated the PER2 Single Nucleotide polymorphism (SNP) 10870 (A/G) in the cohort together with an assessment of alcohol consumption according to the AUDIT-C questionnaire, and sleep problems using a survey consisting of 18 items. Furthermore, we carried out an exploratory analysis on the PER2 Single Nucleotide Polymorphism 10870 polymorphism in a group of severely alcoholic females. RESULTS: We found a significant association of the SNP 10870 in adolescent boys, where the genotype AA, in the presence of several and frequent sleep problems, was associated with increased alcohol consumption. Among adolescent girls, only sleep problems were related to alcohol consumption. A non-significant trend was observed among the severely alcoholic females, with the G allele being over-represented in the severely alcoholic females group in comparision to the control females. CONCLUSION: These results indicate that PER2 gene variation is associated with alcohol consumption in interaction with sleep problems among Swedish adolescent boys.

  • 111.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Nordquist, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Kronstrand, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Alling, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Nilsson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Adolescent alcohol consumption: Biomarkers PEth and FAEE in relation to interview and questionnaire data2009In: Journal of Studies on Alcohol and Drugs, ISSN 1937-1888, E-ISSN 1938-4114, Vol. 70, no 5, p. 797-804Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE

     The aim of this study was to investigate the congruence of biomarkers, questionnaires, and interviews as instruments to assess adolescent alcohol consumption.

    METHOD

     The methodology used was a cross-sectional study with a randomized sample. Four different methods were used to estimate high adolescent alcohol consumption. The concordance of the results was investigated. Surveys were performed, and biological specimens were collected at all schools in the county of Västmanland, Sweden, in 2001. Eighty-one boys and 119 girls from a population of 16- and 19-year-old adolescents were randomly selected from quartiles of volunteers representing various degrees of psychosocial risk behaviors. Using a questionnaire (for a 1-hour session) and in-depth interviews, subjects were assessed regarding their alcohol-use habits. Blood and hair samples were analyzed for phosphatidylethanol (PEth) and fatty acid ethyl esters (FAEEs), respectively.

    RESULTS

     High alcohol consumption was underreported in the questionnaire compared with the interviews. PEth and FAEE analyses weakly confirmed the self-reports, and the results of the two biochemical tests did not overlap. The PEth blood test was the most specific but the least sensitive, whereas the FAEE hair test revealed low specificity and an overrepresentation of positive results in girls.

    CONCLUSIONS

    The expected higher self-report of high alcohol consumption by interview rather than by questionnaire was confirmed partly because of the influence of a bogus pipeline procedure. The absence of overlap between PEth and FAEE results and their poor agreement with self-reports suggested that biomarkers are unsuitable as screening tools for alcohol consumption in adolescents.

  • 112.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Sylvén, Sara M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Papadopoulos, Fotios C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Postpartum depression symptoms: a case-control study on monoaminergic functional polymorphisms and environmental stressors2011In: Psychiatric Genetics, ISSN 0955-8829, E-ISSN 1473-5873, Vol. 21, no 1, p. 19-28Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Postpartum depression (PPD) is an under diagnosed and under treated mood disorder, with negative impact on both the mother and the infant's health. The aim of this study is to examine whether genetic variations in the monoaminergic neurotransmitter system, together with environmental stressors, contribute to the development of PPD symptoms.

    METHODS:

    This nested case-control study included 275 women from a population-based cohort of delivering women in Sweden. A questionnaire containing the Edinburgh Postnatal Depression Scale was collected at 6 weeks and 6 months postpartum. Three functional polymorphisms were genotyped, catechol-O-methyltransferase (COMT)-ValMet, monoamine oxidase A (MAOA)-upstream variable number tandem repeat (uVNTR) and serotonin transporter linked polymorphic region (5HTT-LPR). Stressful life events, maternity stressors and previous psychiatric contact were considered as potential risk factors.

    RESULTS:

    COMT-ValMet was significantly associated with PPD symptoms at 6 weeks, but not at 6 months postpartum. A significant gene-gene interaction effect was present between COMT-ValMet and MAOA-uVNTR. In a gene-environment multivariate model, COMT-ValMet, psychiatric contact and maternity stressors were significantly associated with PPD symptoms. Among those with history of psychiatric problems, the COMT-ValMet and 5HTT-LPR risk variants were associated with PPD symptoms, whereas in the absence of previous psychiatric contact only maternity stressors were related to PPD symptoms.

    CONCLUSION:

    The interaction effect between monoaminergic genes and environmental stressors is likely to contribute to vulnerability for PPD. The different patterns of association according to history of psychiatric problems, if replicated, might be helpful in screening strategies.

  • 113.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Todkar, Aniruddha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Granholm, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nilsson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nylander, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Alpha 2a-Adrenoceptor Gene Expression and Early Life Stress-Mediated Propensity to Alcohol Drinking in Outbred Rats2015In: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 12, no 7, p. 7154-7171Article in journal (Refereed)
    Abstract [en]

    Stressful events early in life, later high alcohol consumption and vulnerability to alcohol use disorder (AUD) are tightly linked. Norepinephrine is highly involved in the stress response and the alpha 2A-adrenoceptor, which is an important regulator of norepinephrine signalling, is a putative target in pharmacotherapy of AUD. The aim of the present study was to investigate the effects of early-life stress and adult voluntary alcohol drinking on the alpha 2A-adrenoceptor. The relative expression and promoter DNA methylation of the Adra2a gene were measured in the hypothalamus, a key brain region in stress regulation. A well-characterized animal model of early-life stress was used in combination with an episodic voluntary drinking in adulthood. Alcohol drinking rats with a history of early-life stress had lower Adra2a expression than drinking rats not exposed to stress. Alcohol intake and Adra2a gene expression were negatively correlated in high-drinking animals, which were predominantly rats subjected to early-life stress. The results provide support for a link between early-life stress, susceptibility for high alcohol consumption, and low Adra2a expression in the hypothalamus. These findings can increase our understanding of the neurobiological basis for vulnerability to initiate risk alcohol consumption and individual differences in the response to 2A-adrenoceptor agonists.

  • 114.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Todkar, Aniruddha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Mujtaba, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Granholm, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nilsson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nylander, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    EXPERIMENTAL EVIDENCE OF A LINK BETWEEN THE alpha 2A-ADRENERGIC RECEPTOR GENE, EARLY LIFE STRESS, AND ETHANOL DRINKING2015In: Alcohol and Alcoholism, ISSN 0735-0414, E-ISSN 1464-3502, Vol. 50Article in journal (Other academic)
  • 115.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Nilsson, Kent W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Three-way interaction effect of 5-HTTLPR, BDNF Val66Met, and childhood adversity on depression: A replication study2013In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 23, no 10, p. 1300-1306Article in journal (Refereed)
    Abstract [en]

    Both the serotonin transporter linked promoter region (5-HTTLPR) and the brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms have been shown to interact with unfavourable environment in relation to depression symptoms and to depression diagnosis. Several attempts have been made to study a three-way interaction effect of these factors on depression, however with contradictory results. We aimed to test the hypothesis of a three-way interaction effect and to attempt at replication in an independent population-based sample. Family maltreatment, sexual abuse and depression were self-reported by an adolescent population-based cohort (N=1393) from the county of Västmanland, Sweden. DNA was isolated from saliva, and used for genotyping of the 5-HTTLPR and BDNF Val66Met polymorphisms. Neither 5-HTTLPR or BDNF genotypes separately, nor in interaction with each other had any relation to depression, however in an environment adjusted model a two-way interaction and a three-way interaction effect was found. Both 5-HTTLPR and BDNF Val66Met interacted with unfavourable environment in relation to depressive symptoms (Adj R2=0.19). Depressive symptoms and depression were more common among carriers of either the ss/sl+Val/Val or the ll+Met genotypes in the presence of early-life adversities. This three-way effect was more pronounced among girls. The current study, with a virtually similar set-up compared to previous studies, can partially confirm previous findings and their generalizability. The study also shows the importance of genetic plasticity in individuals with different environmental exposure, for different phenotypic expression.

  • 116.
    Conden, Emelie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Type D personality is a risk factor for psychosomatic symptoms and musculoskeletal pain among adolescents: a cross-sectional study of a large population-based cohort of Swedish adolescents2013In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 13, p. 11-Article in journal (Refereed)
    Abstract [en]

    Background: Type D personality, or the "distressed personality", is a psychosocial factor associated with negative health outcomes, although its impact in younger populations is unclear. The purpose of this study was to investigate the prevalence of Type D personality and the associations between Type D personality and psychosomatic symptoms and musculoskeletal pain among adolescences. Methods: A population-based, self-reported cross-sectional study conducted in Vastmanland, Sweden with a cohort of 5012 students in the age between 15-18 years old. The participants completed the anonymous questionnaire Survey of Adolescent Life in Vastmanland 2008 during class hour. Psychosomatic symptoms and musculoskeletal pain were measured through index measuring the presence of symptoms and how common they were. DS14 and its two component subscales of negative affectivity (NA) and social inhibition (SI) were measured as well. Results: There was a difference depending on sex, where 10.4% among boys and 14.6% among girls (p = < 0.001) were defined as Type D personality. Boys and girls with a Type D personality had an approximately 2-fold increased odds of musculoskeletal pain and a 5-fold increased odds of psychosomatic symptoms. The subscale NA explained most of the relationship between Type D personality and psychosomatic symptoms and musculoskeletal pain. No interaction effect of NA and SI was found. Conclusions: There was a strong association between Type D personality and both psychosomatic symptoms and musculoskeletal pain where adolescent with a type D personality reported more symptoms. The present study contributes to the mapping of the influence of Type D on psychosomatic symptoms and musculoskeletal pain among adolescents.

  • 117.
    Condén, Emelie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Type D personality and ill-health among Swedish adolescents2013Licentiate thesis, comprehensive summary (Other academic)
  • 118.
    Condén, Emelie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Type D Personality: Psychometric Properties of the DS14 and Associations with Ill Health and Coronary Heart Disease in General and Clinical Populations2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Type D personality, or distressed personality, refers to the joint tendency to experience negative emotions and to inhibit self-expression in social interactions. The overall aims of this thesis were to examine the impact of Type D personality on adolescents’ self-perceived health, to examine the factorial and temporal stability of the Type D personality construct DS14, and to clarify whether type D personality is an independent risk factor for recurrent myocardial infarction and all-cause mortality among patients with myocardial infarction.

    The prevalence of Type D personality in the adolescent population was 10.4% for boys and 14.6% for girls. Boys and girls with Type D personality were approximately twice as likely to report musculoskeletal pain and five times as likely to report psychosomatic symptoms.

    Adolescents with Type D personality were four times more likely to have sleep disturbances and to sleep fewer hours, especially on school nights.

    Among patients with myocardial infarction, the Swedish DS14 had stable structural validity. Our measurements confirmed the two-factor model of the DS14. However, the DS14 exhibited low temporal stability, especially when comparing the measurement obtained during hospitalization with the 1- and 12-month follow-up measurements.

    Among patients with myocardial infarction, the Framingham risk score had a strong predictive value for recurrent myocardial infarction, and a somewhat weaker predictive value for all-cause mortality. However, none of the previously proposed methods for the analysis of the DS14 Type D personality measurement predicted recurrent myocardial infarction or all-cause mortality, either in univariable analyses or in addition to the Framingham risk score.

    In conclusion, the present thesis found significant associations between the DS14 and psychosomatic symptoms in adolescents. However, the measurement exhibited a low stability over time and no predictive value for recurrent myocardial infarction and mortality among patients with myocardial infarction. Taken together, these results raise the question of whether the Swedish DS14 really is a measure of personality. An alternative explanation for the strong cross-sectional associations observed between the DS14 and psychosomatic symptoms might be that the DS14 functions as a pseudo-measure of ill health, or co-varies with depressive or psychosomatic characteristics.

  • 119.
    Condén, Emelie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Type D personality is associated with sleep problems in adolescents. Results from a population-based cohort study of Swedish adolescents2013In: Journal of Psychosomatic Research, ISSN 0022-3999, E-ISSN 1879-1360, Vol. 74, no 4, p. 290-295Article in journal (Refereed)
    Abstract [en]

    Objective: Sleep problems are associated with an increased risk of psychiatric and somatic diseases. Type D personality, or the distressed personality, refers to the joint tendency to experience negative emotions and to inhibit self-expression in social interaction. Type D personality is associated with an increased number of health complaints including cardiovascular diseases. The present study investigated whether Type D personality was associated with sleep problems among adolescents. Methods: The study was part of the Survey of Adolescent Life in Vastmanland 2008 (SALVe 2008). A total of 5012 adolescents (age 15-18 years old) completed a questionnaire including the Type D measurement DS14 and questions on sleep disturbances, sleep hours during school nights, and sleep hours during weekend nights. Results: Adolescents with a Type D personality had an approximately four times increased risk of having sleep disturbances. Moreover, Type D personality was associated with sleeping fewer hours. Conclusion: As adolescence represents a formative period for development it is critical to identify sleep disorders early. The presence of Type D personality associated with poor sleep demands attention because sleep problems may be an early stage in the development of later diseases.

  • 120.
    Condén, Emelie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Philippe, Wagner
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Type D personality as an independent risk factor for recurrent myocardial infarction and all-cause mortality in addition to theFramingham risk score: a prospective cohort-study2014In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754Article in journal (Refereed)
  • 121.
    Condén, Emelie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp Vasteras, Dept Med, Vasteras, Sweden..
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Insomnia predicts long-term all-cause mortality after acute myocardial infarction: A prospective cohort study2016In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 215, p. 217-222Article in journal (Refereed)
    Abstract [en]

    Background: Sleep impairment such as insomnia is an established risk factor for the development of cardiovascular disease and acute myocardial infarction (AMI). The aim of the current study was to examine the association between insomnia and all-cause mortality among AMI patients. Methods: This prospective cohort study used data on n = 732 patients recruited from September 2006 to May 2011 as part of the Vastmanland Myocardial Infarction Study (VaMIS), a prospective cohort study of AMI patients living in Vastmanland County, Sweden. Participants were followed up for all-cause mortality until December 9, 2015. The outcome of interest was time-to-death (TTD), with the presence of insomnia being the risk factor of main interest. Data were analyzed using a piecewise Cox regression model with change point for insomnia at two years of follow-up, adjusted for socioeconomic, lifestyle and clinical risk factors. Results: In total, n = 175 (23.9%) of the participants suffered from insomnia. During a mean (SD) follow-up time of 6.0 (2.5) years (4392 person-years), a total of n = 231 (31.6%) participants died, n = 77 (44.0%) in the insomnia group and n= 154 (27.6%) in the non-insomnia group (log-rank test p < 0.001). In a multiple adjusted piecewise Cox regression model, insomnia did not imply a higher risk of death during the first two years after AMI (HR 0.849; 95% CI 0.508-1.421; p = 0.534). During the period after the first two years, however, insomnia implied a 1.6 times higher risk of death (HR 1.597; 95% CI 1.090-2.341; p = 0.016). Conclusions: Insomnia implies a higher risk of death among AMI patients in the long term.

  • 122.
    Condén, Emelie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Prevalence of Type D Personality and Factorial and Temporal Stability of the DS14 after Myocardial Infarction in a Swedish Population2014In: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 55, no 6, p. 601-610Article in journal (Refereed)
    Abstract [en]

    This study examined the prevalence of Type D personality and the temporal stability, internal consistency, and construct validity of the DS14 at three time points after myocardial infarction. The prevalence of Type D personality was 14.0% during hospitalization, 25.1% at 1 month, and 19.2% at 12 months. A total of 6.1% of patients were classified as Type D personality at all three assessments, whereas 68.4% were stable non-Type D and 25.6% changed between personality classifications. The DS14 had stable structural validity, but low temporal stability over time, especially from hospitalization to the 1-month and 12-month follow-ups (k = 0.365 and 0.397, respectively).

  • 123.
    Condén, Emelie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Malardalen Univ, Sch Hlth Care & Social Welf, Vasteras, Sweden..
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Wagner, Philippe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Is type D personality an independent risk factor for recurrent myocardial infarction or all-cause mortality in post-acute myocardial infarction patients?2017In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 24, no 5, p. 522-533Article in journal (Refereed)
    Abstract [en]

    Background: Type D personality refers to a combination of simultaneously high levels of negative affectivity and social inhibition. The present study aimed to examine whether type D personality was independently associated with recurrent myocardial infarction or all-cause mortality in post-acute myocardial infarction patients, using any of the previously proposed methods for measuring type D personality. Design: This was a prospective cohort study. Methods: Utilising data from the Vastmanland Myocardial Infarction Study, 946 post-acute myocardial infarction patients having data on the DS14 instrument used to measure type D personality were followed-up for recurrent myocardial infarction and all-cause mortality until 9 December 2015. Data were analysed using Cox regression, adjusted for established risk factors. Results: In total, 133 (14.1%) patients suffered from type D personality. During a mean follow-up time for recurrent myocardial infarction of 5.7 (3.2) years, 166 (17.5%) patients were affected by recurrent myocardial infarction, of which 26 (15.7%) had type D personality, while during a mean follow-up time for all-cause mortality of 6.3 (2.9) years, 321 (33.9%) patients died, of which 42 (13.1%) had type D personality. After adjusting for established risk factors, type D personality was not significantly associated with recurrent myocardial infarction or all-cause mortality using any of the previously proposed methods for measuring type D personality. A weak association was found between the social inhibition part of type D personality and a decreased risk of all-cause mortality, but this association was not significant after taking missing data into account in a multiple imputation analysis. Conclusions: No support was found for type D personality being independently associated with recurrent myocardial infarction or all-cause mortality in post-acute myocardial infarction patients, using any of the previously proposed methods for measuring type D personality.

  • 124.
    Culverhouse, R. C.
    et al.
    Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.;Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA..
    Saccone, N. L.
    Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.;Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA..
    Horton, A. C.
    Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA..
    Ma, Y.
    Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA..
    Anstey, K. J.
    Australian Natl Univ, Ctr Res Ageing Hlth & Wellbeing, Canberra, ACT, Australia..
    Banaschewski, T.
    Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Child & Adolescent Psychiat & Psychotherapy, Mannheim, Germany..
    Burmeister, M.
    Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA..
    Cohen-Woods, S.
    Flinders Univ S Australia, Sch Psychol, Fac Social & Behav Sci, Adelaide, SA, Australia..
    Etain, B.
    Univ Paris Diderot, Sorbonne Paris Cite, UMR S 1144, Paris, France.;AP HP, Grp St Louis Lariboisiere F, Paris, France.;INSERM, U1144, Paris, France..
    Fisher, H. L.
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, London, England..
    Goldman, N.
    Princeton Univ, Off Populat Res, Princeton, NJ 08544 USA..
    Guillaume, S.
    Univ Montpellier, Montpellier, France.;INSERM, Neuropsychiat U1061, Montpellier, France.;CHU Montpellier, Dept Emergency Psychiat & Acute Care, Montpellier, France..
    Horwood, J.
    Univ Otago Christchurch, Dept Psychol Med, Christchurch, New Zealand..
    Juhasz, G.
    Semmelweis Univ, Hungarian Acad Sci, MTA SE NAP Genet Brain Imaging Migraine Res Grp B, Budapest, Hungary.;Semmelweis Univ, Dept Pharmacodynam, Budapest, Hungary.;Univ Manchester, Neurosci & Psychiat Unit, Manchester, Lancs, England.;Semmelweis Univ, NAP A SE New Antidepressant Target Res Grp, Budapest, Hungary..
    Lester, K. J.
    Univ Sussex, Sch Psychol, Brighton, E Sussex, England..
    Mandelli, L.
    Univ Bologna, Dept Biomed & NeuroMotor Sci, Bologna, Italy..
    Middeldorp, C. M.
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Neurosci Campus Amsterdam, Amsterdam, Netherlands..
    Olie, E.
    Univ Montpellier, Montpellier, France.;INSERM, Neuropsychiat U1061, Montpellier, France.;CHU Montpellier, Dept Emergency Psychiat & Acute Care, Montpellier, France..
    Villafuerte, S.
    Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA..
    Air, T. M.
    Univ Adelaide, Discipline Psychiat, Adelaide, SA, Australia..
    Araya, R.
    London Sch Hyg & Trop Med, Ctr Global Mental Hlth, London, England..
    Bowes, L.
    Univ Oxford, Dept Expt Psychol, Oxford, England..
    Burns, R.
    Australian Natl Univ, Ctr Res Ageing Hlth & Wellbeing, Canberra, ACT, Australia..
    Byrne, E. M.
    Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Coffey, C.
    Murdoch Childrens Res Inst, Ctr Adolescent Hlth, Melbourne, Vic, Australia..
    Coventry, W. L.
    Univ New England, Discipline Psychol, Armidale, NSW, Australia..
    Gawronski, K. A. B.
    Univ Penn, Dept Genet, Perelman Sch Med, Philadelphia, PA 19104 USA..
    Glei, D.
    Georgetown Univ, Ctr Populat & Hlth, Washington, DC USA..
    Hatzimanolis, A.
    Univ Athens, Sch Med, Eginit Hosp, Dept Psychiat, Athens, Greece.;Theodor Theohari Cozzika Fdn, Neurobiol Res Inst, Athens, Greece..
    Hottenga, J-J
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.;VU Med Ctr Amsterdam, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands..
    Jaussent, I.
    INSERM, Neuropsychiat U1061, Montpellier, France..
    Jawahar, C.
    Univ Adelaide, Discipline Psychiat, Adelaide, SA, Australia..
    Jennen-Steinmetz, C.
    Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Biostat, Mannheim, Germany..
    Kramer, J. R.
    Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA..
    Lajnef, M.
    INSERM, U955, Creteil, France..
    Little, K.
    Murdoch Childrens Res Inst, Melbourne, Vic, Australia.;Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia.;Univ Melbourne, Sch Psychol Sci, Melbourne, Vic, Australia..
    zu Schwabedissen, H. M.
    Univ Basel, Dept Pharmaceut Sci, Biopharm, Basel, Switzerland..
    Nauck, M.
    Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany..
    Nederhof, E.
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands..
    Petschner, P.
    Semmelweis Univ, Dept Pharmacodynam, Budapest, Hungary.;Semmelweis Univ, NAP A SE New Antidepressant Target Res Grp, Budapest, Hungary.;Semmelweis Univ, Hungarian Acad Sci, MTA SE Neuropsychopharmacol & Neurochem Res Grp, Budapest, Hungary..
    Peyrot, W. J.
    Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands.;GGZ InGeest, Amsterdam, Netherlands..
    Schwahn, C.
    Univ Med Greifswald, Dept Prosthet Dent Gerostomatol & Dent Mat, Greifswald, Germany..
    Sinnamon, G.
    Univ Adelaide, Discipline Psychiat, Adelaide, SA, Australia..
    Stacey, D.
    Univ Adelaide, Discipline Psychiat, Adelaide, SA, Australia..
    Tian, Y.
    Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA..
    Toben, C.
    Univ Adelaide, Discipline Psychiat, Adelaide, SA, Australia..
    Van der Auwera, S.
    Univ Med Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany..
    Wainwright, N.
    Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge, England..
    Wang, J-C
    Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA..
    Willemsen, G.
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.;VU Med Ctr Amsterdam, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands..
    Anderson, I. M.
    Univ Manchester, Neurosci & Psychiat Unit, Manchester, Lancs, England.;Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England..
    Arolt, V.
    Univ Munster, Dept Psychiat & Psychotherapy, Munster, Germany..
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Västmanland Cty Hosp Västerås, Västerås, Sweden..
    Bagdy, G.
    Semmelweis Univ, Dept Pharmacodynam, Budapest, Hungary.;Semmelweis Univ, NAP A SE New Antidepressant Target Res Grp, Budapest, Hungary.;Semmelweis Univ, Hungarian Acad Sci, MTA SE Neuropsychopharmacol & Neurochem Res Grp, Budapest, Hungary..
    Baune, B. T.
    Univ Adelaide, Discipline Psychiat, Adelaide, SA, Australia..
    Bellivier, F.
    Univ Paris Diderot, Sorbonne Paris Cite, UMR S 1144, Paris, France.;AP HP, Grp St Louis Lariboisiere F, Paris, France.;INSERM, U1144, Paris, France..
    Boomsma, D. I.
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Neurosci Campus Amsterdam, Amsterdam, Netherlands.;VU Med Ctr Amsterdam, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands..
    Courtet, P.
    Univ Montpellier, Montpellier, France.;INSERM, Neuropsychiat U1061, Montpellier, France.;CHU Montpellier, Dept Emergency Psychiat & Acute Care, Montpellier, France..
    Dannlowski, U.
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.;VU Med Ctr Amsterdam, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.;Univ Munster, Dept Psychiat & Psychotherapy, Munster, Germany..
    de Geus, E. J. C.
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.;VU Med Ctr Amsterdam, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands..
    Deakin, J. F. W.
    Univ Manchester, Neurosci & Psychiat Unit, Manchester, Lancs, England.;Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England..
    Easteal, S.
    Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT, Australia..
    Eley, T.
    Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England..
    Fergusson, D. M.
    Univ Otago Christchurch, Dept Psychol Med, Christchurch, New Zealand..
    Goate, A. M.
    Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA..
    Gonda, X.
    Semmelweis Univ, Dept Pharmacodynam, Budapest, Hungary.;Semmelweis Univ, NAP A SE New Antidepressant Target Res Grp, Budapest, Hungary.;Semmelweis Univ, Hungarian Acad Sci, MTA SE Neuropsychopharmacol & Neurochem Res Grp, Budapest, Hungary.;Semmelweis Univ, Kutvolgyi Clin Ctr, Dept Psychiat & Psychotherapy, Budapest, Hungary..
    Grabe, H. J.
    Univ Med Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany..
    Holzman, C.
    Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA..
    Johnson, E. O.
    RTI Int, Fellow Program, Res Triangle Pk, NC USA.;RTI Int, Behav Hlth & Criminal Justice Div, Res Triangle Pk, NC USA..
    Kennedy, M.
    Univ Otago, Dept Pathol, Christchurch, New Zealand..
    Laucht, M.
    Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Child & Adolescent Psychiat & Psychotherapy, Mannheim, Germany..
    Martin, N. G.
    QIMR Berghofer, Genet Epidemiol, Brisbane, Qld, Australia..
    Munafo, M. R.
    Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England.;Univ Bristol, Sch Expt Psychol, UK Ctr Tobacco & Alcohol Studies, Bristol, Avon, England..
    Nillson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Västmanland Cty Hosp Västerås, Västerås, Sweden..
    Oldehinkel, A. J.
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands..
    Olsson, C. A.
    Deakin Univ Geelong, Ctr Social & Early Emot Dev, Sch Psychol, Fac Hlth, Burwood, Vic, Australia.;Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia.;Univ Melbourne, Sch Psychol Sci, Melbourne, Vic, Australia.;Murdoch Childrens Res Inst, Ctr Adolescent Hlth, Melbourne, Vic, Australia..
    Ormel, J.
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands..
    Otte, C.
    Charite, Klin Psychiat & Psychotherapie Campus Benjamin Fr, Berlin, Germany..
    Patton, G. C.
    Univ Melbourne, Murdoch Childrens Res Inst, Dept Paediat, Melbourne, Vic, Australia..
    Penninx, B. W. J. H.
    Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands.;GGZ InGeest, Amsterdam, Netherlands..
    Ritchie, K.
    INSERM, Neuropsychiat U1061, Montpellier, France..
    Sarchiapone, M.
    Univ Molise, Dept Hlth Sci, Campobasso, Italy..
    Scheid, J. M.
    Michigan State Univ, Dept Psychiat, E Lansing, MI 48824 USA..
    Serretti, A.
    Univ Bologna, Dept Biomed & NeuroMotor Sci, Bologna, Italy..
    Smit, J. H.
    Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands.;GGZ InGeest, Amsterdam, Netherlands..
    Stefanis, N. C.
    Univ Athens, Sch Med, Eginit Hosp, Dept Psychiat, Athens, Greece.;Theodor Theohari Cozzika Fdn, Neurobiol Res Inst, Athens, Greece..
    Surtees, P. G.
    Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge, England..
    Voelzke, H.
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany..
    Weinstein, M.
    Georgetown Univ, Ctr Populat & Hlth, Washington, DC USA..
    Whooley, M.
    Vet Affairs Hlth Care Syst, San Francisco, CA USA.;Univ Calif San Francisco, San Francisco, CA 94143 USA..
    Nurnberger, J. I., Jr.
    Indiana Univ Sch Med, Dept Psychiat, Inst Psychiat Res, Indianapolis, IN 46202 USA.;Indiana Univ Sch Med, Dept Med & Mol Genet, Inst Psychiat Res, Indianapolis, IN 46202 USA..
    Breslau, N.
    Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA..
    Bierut, L. J.
    Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA..
    Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression2018In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 23, no 1, p. 133-142Article in journal (Refereed)
    Abstract [en]

    The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.

  • 125. Culverhouse, Robert C
    et al.
    Bowes, Lucy
    Breslau, Naomi
    Nurnberger, John I
    Burmeister, Margit
    Fergusson, David M
    Munafò, Marcus
    Saccone, Nancy L
    Bierut, Laura J
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nilsson, Kent W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Protocol for a collaborative meta-analysis of 5-HTTLPR, stress, and depression.2013In: BMC psychiatry, ISSN 1471-244X, Vol. 13, p. 304-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Debate is ongoing about what role, if any, variation in the serotonin transporter linked polymorphic region (5-HTTLPR) plays in depression. Some studies report an interaction between 5-HTTLPR variation and stressful life events affecting the risk for depression, others report a main effect of 5-HTTLPR variation on depression, while others find no evidence for either a main or interaction effect. Meta-analyses of multiple studies have also reached differing conclusions.

    METHODS/DESIGN: To improve understanding of the combined roles of 5-HTTLPR variation and stress in the development of depression, we are conducting a meta-analysis of multiple independent datasets. This coordinated approach utilizes new analyses performed with centrally-developed, standardized scripts. This publication documents the protocol for this collaborative, consortium-based meta-analysis of 5-HTTLPR variation, stress, and depression.

    STUDY ELIGIBILITY CRITERIA: Our goal is to invite all datasets, published or unpublished, with 5-HTTLPR genotype and assessments of stress and depression for at least 300 subjects. This inclusive approach is to minimize potential impact from publication bias.

    DATA SOURCES: This project currently includes investigators from 35 independent groups, providing data on at least N = 33,761 participants.The analytic plan was determined prior to starting data analysis. Analyses of individual study datasets will be performed by the investigators who collected the data using centrally-developed standardized analysis scripts to ensure a consistent analytical approach across sites. The consortium as a group will review and interpret the meta-analysis results.

    DISCUSSION: Variation in 5-HTTLPR is hypothesized to moderate the response to stress on depression. To test specific hypotheses about the role of 5-HTTLPR variation on depression, we will perform coordinated meta-analyses of de novo results obtained from all available data, using variables and analyses determined a priori. Primary analyses, based on the original 2003 report by Caspi and colleagues of a GxE interaction will be supplemented by secondary analyses to help interpret and clarify issues ranging from the mechanism of effect to heterogeneity among the contributing studies. Publication of this protocol serves to protect this project from biased reporting and to improve the ability of readers to interpret the results of this specific meta-analysis upon its completion.

  • 126. Dahl, K
    et al.
    Westlin, J
    Kraaz, W
    Winqvist, O
    Bergkvist, L
    Uppsala University, Interfaculty Units, Centre for Clinical Research.
    Thörn, M
    Identification of sentinel nodes in patients with colon cancer.2005In: Eur J Surg Oncol, ISSN 0748-7983, Vol. 31, no 4, p. 381-5Article in journal (Refereed)
  • 127.
    Dalberg, K
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Johansson, H
    Signomklao, T
    Rutqvist, L E
    Bergkvist, Leif
    Interfaculty Units, Centre for Clinical Research.
    Frisell, J
    Liljegren, G
    Ambre, T
    Sandelin, K
    A randomised study of axillary drainage and pectoral fascia preservation after mastectomy for breast cancer.2004In: Eur J Surg Oncol, ISSN 0748-7983, Vol. 30, no 6, p. 602-9Article in journal (Refereed)
  • 128.
    Damberg, M
    Uppsala University, Interfaculty Units, Centre for Clinical Research.
    Transcription factor AP-2 and monoaminergic functions in the central nervous system.2005In: J Neural Transm, ISSN 0300-9564, Vol. 112, no 10, p. 1281-96Article in journal (Refereed)
  • 129.
    de Boniface, J.
    et al.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden;Capio St Gorans Hosp, Breast Ctr, Dept Surg, Sankt Goransplan 1, SE-11281 Stockholm, Sweden.
    Frisell, J.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Univ Hosp, Dept Breast & Endocrine Surg, Stockholm, Sweden.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Surg, Vasteras, Sweden.
    Andersson, Yvette
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Surg, Vasteras, Sweden.
    Breast-conserving surgery followed by whole-breast irradiation offers survival benefits over mastectomy without irradiation2018In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 105, no 12, p. 1607-1614Article in journal (Refereed)
    Abstract [en]

    Background: The prognostic equivalence between mastectomy and breast-conserving surgery (BCS) followed by radiotherapy was shown in pivotal trials conducted decades ago. Since then, detection and treatment of breast cancer have improved substantially and recent retrospective analyses point towards a survival benefit for less extensive breast surgery. Evidence for the association of such survival data with locoregional recurrence rates is largely lacking.

    Methods: The Swedish Multicentre Cohort Study prospectively included clinically node-negative patients with breast cancer who had planned sentinel node biopsy between 2000 and 2004. Axillary lymph node dissection was undertaken only in patients with sentinel node metastases. For the present investigation, adjusted survival analyses were used to compare patients who underwent BCS and postoperative radiotherapy with those who received mastectomy without radiotherapy.

    Results: Of 3518 patients in the Swedish Multicentre Cohort Study, 2767 were included in the present analysis; 2338 had BCS with postoperative radiotherapy and 429 had mastectomy without radiotherapy. Median follow-up was 156 months. BCS followed by whole-breast irradiation was superior to mastectomy without irradiation in terms of both overall survival (79.5 versus 64.3 per cent respectively at 13 years; P < 0.001) and breast cancer-specific survival (90.5 versus 84.0 per cent at 13 years; P < 0.001). The local recurrence rate did not differ between the two groups. The axillary recurrence-free survival rate at 13 years was significantly lower after mastectomy without irradiation (98.3 versus 96.2 per cent; P < 0.001).

    Conclusion: The present data support the superiority or BCS with postoperative radiotherapy over mastectomy without radiotherapy. The axillary recurrence rate differed significantly, and could be one contributing factor in a complex explanatory model.

  • 130.
    de Boniface, J.
    et al.
    Karolinska Inst, Dept Mol Med & Surg, SE-17176 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Breast & Endocrine Surg, Stockholm, Sweden..
    Frisell, J.
    Karolinska Inst, Dept Mol Med & Surg, SE-17176 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Breast & Endocrine Surg, Stockholm, Sweden..
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Surg, Vasteras, Sweden..
    Andersson, Yvette
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Surg, Vasteras, Sweden..
    Ten-year report on axillary recurrence after negative sentinel node biopsy for breast cancer from the Swedish Multicentre Cohort Study2017In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 104, no 3, p. 238-247Article in journal (Refereed)
    Abstract [en]

    Background: The omission of axillary lymph node dissection (ALND) in patients with breast cancer with a negative finding on sentinel node biopsy (SNB) has reduced armmorbidity substantially. Early follow-up reports have shown the rate of axillary recurrence to be significantly lower than expected, with a median false-negative rate of 7 per cent for SNB. Long-term follow-up is needed as recurrences may develop late.

    Methods: The Swedish Multicentre Cohort Study included 3518 women with breast cancer and a clinically negative axilla, in whom SNB was planned. ALND was performed only in patients with sentinel node metastasis. Twenty-six centres contributed to enrolment between September 2000 and January 2004. The primary endpoint was the axillary recurrence rate and the secondary endpoint was breast cancer-specific survival, calculated using Kaplan-Meier survival estimates.

    Results: Some 2216 sentinel node-negative patients with 2237 breast cancers were analysed. The median follow-up time was 126 (range 0-174) months. Isolated axillary recurrence was found in 35 patients (1.6 per cent). High histological grade and multifocal tumours were risk factors for axillary recurrence, whereas the removal of more than two sentinel nodes decreased the risk. Fourteen (40 per cent) of 35 patients died as a consequence of axillary recurrence.

    Conclusion: The risk of axillary recurrence remains lower than expected after a negative finding on SNB at 10-year follow-up. Axillary recurrences may occur long after primary surgery, and lead to a significant risk of breast cancer death.

  • 131.
    de Boniface, Jana
    Uppsala University, Interfaculty Units, Centre for Clinical Research.
    Sentinel Node Biopsy in Breast Cancer: Clinical and Immunological Aspects2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The most important prognostic factor in breast cancer is the axillary lymph node status. The sentinel node biopsy (SNB) is reported to stage the axilla with an accuracy > 95 % in early breast cancer. Tumour-related perturbation of T-cell function has been observed in patients with malignancies, including breast cancer. The down-regulation of the important T-cell activation molecules CD3-ζ and CD28 may cause T-cell dysfunction, anergy, tolerance and deletion.

    The expression of CD3-ζ and CD28 was evaluated in 25 sentinel node biopsies. The most pronounced down-regulation was seen in the paracortical area, where the best agreement between both parameters was observed. CD28 expression was significantly more suppressed in CD4+ than in CD8+ T-cells.

    From the Swedish sentinel node database, 109 patients with breast cancer > 3 cm planned for both SNB and a subsequent axillary dissection were identified. The false negative rate (FNR) was 12.5%. Thirteen cases of tumour multifocality were detected on postoperative pathology. The FNR in this subgroup was higher (30.8%) than in patients with unifocal disease (7.8%; P = 0.012).

    From the Swedish SNB multicentre cohort trial, 2246 sentinel node-negative patients who had not undergone further axillary surgery were selected for analysis. After a median follow-up time of 37 months (range 0-75), 13 isolated axillary recurrences (13/2246; 0.6%) were found. In another 14 cases, local or distant failure preceded or coincided with axillary relapse (27/2246; 1.2%).

    In conclusion, the immunological analysis of the sentinel node might provide valuable prognostic information and aid selection of patients for immunotherapy. SNB is encouraged in breast cancer larger than 3 cm, if no multifocal growth pattern is present. The axillary recurrence rate after a negative SNB in Sweden is in accordance with international figures. However, a longer follow-up is mandatory before the true failure rate of the SNB can be determined.

  • 132.
    de Boniface, Jana
    et al.
    Capio St Gorans Hosp, Dept Surg, Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Frisell, Jan
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Breast & Endocrine Surg, Stockholm, Sweden..
    Andersson, Yvette
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Surg, Vasteras, Sweden.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Ahlgren, Johan
    Univ Orebro, Dept Oncol, Orebro, Sweden..
    Ryden, Lisa
    Lund Univ, Inst Clin Sci, Dept Surg, Lund, Sweden.;Skane Univ Hosp, Dept Surg, Lund, Sweden..
    Bagge, Roger Olofsson
    Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Clin Sci, Dept Surg,Sahlgrenska Acad, Gothenburg, Sweden..
    Sund, Malin
    Norrland Univ Hosp, Surg Ctr, Umea, Sweden.;Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden..
    Johansson, Hemming
    Karolinska Inst, Clin Trials Off, Dept Oncol Pathol, Stockholm, Sweden..
    Lundstedt, Dan
    Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden..
    Survival and axillary recurrence following sentinel node-positive breast cancer without completion axillary lymph node dissection: the randomized controlled SENOMAC trial2017In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 17, article id 379Article in journal (Refereed)
    Abstract [en]

    Background: The role of axillary lymph node dissection (ALND) has increasingly been called into question among patients with positive sentinel lymph nodes. Two recent trials have failed to show a survival difference in sentinel node-positive breast cancer patients who were randomized either to undergo completion ALND or not. Neither of the trials, however, included breast cancer patients undergoing mastectomy or those with tumors larger than 5 cm, and power was debatable to show a small survival difference.

    Methods: The prospective randomized SENOMAC trial includes clinically node-negative breast cancer patients with up to two macrometastases in their sentinel lymph node biopsy. Patients with T1-T3 tumors are eligible as well as patients prior to systemic neoadjuvant therapy. Both breast-conserving surgery and mastectomy, with or without breast reconstruction, are eligible interventions. Patients are randomized 1: 1 to either undergo completion ALND or not by a web-based randomization tool. This trial is designed as a non-inferiority study with breast cancer-specific survival at 5 years as the primary endpoint. Target accrual is 3500 patients to achieve 80% power in being able to detect a potential 2.5% deterioration of the breast cancer-specific 5-year survival rate. Follow-up is by annual clinical examination and mammography during 5 years, and additional controls after 10 and 15 years. Secondary endpoints such as arm morbidity and health-related quality of life are measured by questionnaires at 1, 3 and 5 years.

    Discussion: Several large subgroups of breast cancer patients, such as patients undergoing mastectomy or those with larger tumors, have not been included in key trials; however, the use of ALND is being questioned even in these groups without the support of high-quality evidence. Therefore, the SENOMAC Trial will investigate the need of completion ALND in case of limited spread to the sentinel lymph nodes not only in patients undergoing any breast surgery, but also in neoadjuvantly treated patients and patients with larger tumors.

  • 133. de Ridder, Lissy
    et al.
    Turner, Dan
    Wilson, David C.
    Koletzko, Sibylle
    Martin-de-Carpi, Javier
    Fagerberg, Ulrika L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Spray, Christine
    Sladek, Malgorzata
    Shaoul, Ron
    Roma-Giannikou, Eleftheria
    Bronsky, Jiri
    Serban, Daniela E.
    Cucchiara, Salvatore
    Veres, Gabor
    Ruemmele, Frank M.
    Hojsak, Iva
    Kolho, Kaija L.
    Davies, Ieuan H.
    Aloi, Marina
    Lionetti, Paolo
    Veereman-Wauters, Gigi
    Braegger, Christian P.
    Trindade, Eunice
    Wewer, Anne V.
    Hauer, Almuthe
    Levine, Arie
    Malignancy and Mortality in Pediatric Patients with Inflammatory Bowel Disease: A Multinational Study from the Porto Pediatric IBD Group2014In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 20, no 2, p. 291-300Article in journal (Refereed)
    Abstract [en]

    Background: The combination of the severity of pediatric-onset inflammatory bowel disease (IBD) phenotypes and the need for intense medical treatment may increase the risk of malignancy and mortality, but evidence regarding the extent of the problem is scarce. Therefore, the Porto Pediatric IBD working group of ESPGHAN conducted a multinational-based survey of cancer and mortality in pediatric IBD. Methods: A survey among pediatric gastroenterologists of 20 European countries and Israel on cancer and/or mortality in the pediatric patient population with IBD was undertaken. One representative from each country repeatedly contacted all pediatric gastroenterologists from each country for reporting retrospectively cancer and/or mortality of pediatric patients with IBD after IBD onset, during 2006-2011. Results: We identified 18 cases of cancers and/or 31 deaths in 44 children (26 males) who were diagnosed with IBD (ulcerative colitis, n = 21) at a median age of 10.0 years (inter quartile range, 3.0-14.0). Causes of mortality were infectious (n = 14), cancer (n = 5), uncontrolled disease activity of IBD (n = 4), procedure-related (n = 3), other non-IBD related diseases (n = 3), and unknown (n = 2). The most common malignancies were hematopoietic tumors (n = 11), of which 3 were hepatosplenic T-cell lymphoma and 3 Ebstein-Barr virus-associated lymphomas. Conclusions: Cancer and mortality in pediatric IBD are rare, but cumulative rates are not insignificant. Mortality is primarily related to infections, particularly in patients with 2 or more immunosuppressive agents, followed by cancer and uncontrolled disease. At least 6 lymphomas were likely treatment-associated by virtue of their phenotype.

  • 134. Deb, Siddhartha
    et al.
    Johansson, Ida
    Byrne, David
    Nilsson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Constable, Leonie
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Dobrovic, Alexander
    Hedenfalk, Ingrid
    Fox, Stephen B.
    Nuclear HIF1A expression is strongly prognostic in sporadic but not familial male breast cancer2014In: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 27, no 9, p. 1223-1230Article in journal (Refereed)
    Abstract [en]

    Male breast cancer is poorly understood with a large proportion arising in the familial context particularly with the BRCA2 germline mutation. As phenotypic and genotypic differences between sporadic and familial male breast cancers have been noted, we investigated the importance of a hypoxic drive in these cancers as this pathway has been shown to be of importance in familial female breast cancer. Expression of two major hypoxia-induced proteins, the hypoxia-inducible factor-1 alpha (HIF1A) and the carbonic anhydrase IX (CA9), examined within a large cohort including 61 familial (3 BRCA1, 28 BRCA2, 30 BRCAX) and 225 sporadic male breast cancers showed that 31% of all male breast cancers expressed either HIF1A (25%) and/or CA9 (8%) in the combined cohort. Expression of HIF1A correlated with an increased incidence of a second-major malignancy (P=0.04), histological tumor type (P=0.005) and basal phenotype (P=0.02). Expression of CA9 correlated with age (P=0.004) in sporadic cases and an increased tumor size (P=0.003). Expression of HIF1A was prognostic for disease-specific survival in sporadic male breast cancers (HR: 3.8, 95% CI: 1.5-9.8, P=0.006) but not within familial male breast cancer, whereas CA9 was only prognostic in familial male breast cancers (HR: 358.0, 95% CI: 9.3-13781.7, P=0.002) and not in sporadic male breast cancer. This study found that hypoxic drive is less prevalent in male breast cancer compared with female breast cancer, possibly due to a different breast microenvironment. The prognostic impact of HIF1A is greatest in sporadic male breast cancers with an alternate dominant mechanism for the oncogenic drivers suggested in high risk familial male breast cancers.

  • 135. Degraeuwe, Pieter L J
    et al.
    Beld, Monique P A
    Ashorn, Merja
    Canani, Roberto Berni
    Day, Andrew S
    Diamanti, Antonella
    Fagerberg, Ulrika L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Henderson, Paul
    Kolho, Kaija-Leena
    Van de Vijver, Els
    van Rheenen, Patrick F
    Wilson, David C
    Kessels, Alfons G H
    Faecal calprotectin in suspected paediatric inflammatory bowel disease.2015In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 60, no 3, p. 339-346Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The diagnostic accuracy of faecal calprotectin (FC) concentration for paediatric inflammatory bowel disease (IBD) is well described at the population level, but not at the individual level. We reassessed the diagnostic accuracy of FC in children with suspected IBD and developed an individual risk prediction rule using individual patient data.

    METHODS: MEDLINE, EMBASE, DARE, and MEDION databases were searched to identify cohort studies evaluating the diagnostic performance of FC in paediatric patients suspected of having IBD. A standard study-level meta-analysis was performed. In an individual patient data meta-analysis, we reanalysed the diagnostic accuracy on a merged patient dataset. Using logistic regression analysis we investigated whether and how the FC value and patient characteristics influence the diagnostic precision. A prediction rule was derived for use in clinical practice and implemented in a spreadsheet calculator.

    RESULTS: According to the study-level meta-analysis (9 studies, describing 853 patients), FC has a high overall sensitivity of 0.97 (95% confidence interval [CI] 0.92-0.99) and a specificity of 0.70 (0.59-0.79) for diagnosing IBD. In the patient-level pooled analysis of 742 patients from 8 diagnostic accuracy studies, we calculated that at an FC cutoff level of 50 μg/g there would be 17% (95% CI 15-20) false-positive and 2% (1-3) false-negative results. The final logistic regression model was based on individual data of 545 patients and included both FC level and age. The area under the receiver operating characteristic curve of this derived prediction model was 0.92 (95% CI 0.89-0.94).

    CONCLUSIONS: In high-prevalence circumstances, FC can be used as a noninvasive biomarker of paediatric IBD with only a small risk of missing cases. To quantify the individual patients' risk, we developed a simple prediction model based on FC concentration and age. Although the derived prediction rule cannot substitute the clinical diagnostic process, it can help in selecting patients for endoscopic evaluation.

  • 136.
    Doerstling, Steven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Västmanland Cty Hosp, Dept Clin Physiol, Västerås, Sweden.
    Öhrvik, John
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Henriksen, Egil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Västmanland Cty Hosp, Dept Clin Physiol, Västerås, Sweden.
    Growth differentiation factor 15 in a community-based sample: age-dependent reference limits and prognostic impact2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 2, p. 86-93Article in journal (Refereed)
    Abstract [en]

    Background: Despite the growing body of evidence on growth differentiation factor 15 (GDF-15) reference values for patients with existing cardiovascular disease, limited investigation has been dedicated to characterizing the distribution and prognostic impact of GDF-15 in predominantly healthy populations. Furthermore, current cutoff values for GDF-15 fail to account for the well-documented age-dependence of circulating GDF-15. Methods: From 810 community-dwelling older adults, we selected a group of apparently healthy participants (n = 268). From this sample, circulating GDF-15 was modeled using the generalized additive models for location scale and shape (GAMLSS) to develop age-dependent centile values. Unadjusted and adjusted Cox proportional hazards models were used to assess the association between the derived GDF-15 reference values (expressed as centiles) and all-cause mortality. Results: Smoothed centile curves showed increasing GDF-15 with age in the apparently healthy participants. An approximately three-fold difference was observed between the 95th and 5th GDF-15 centiles across ages. In a median 8.0 years of follow-up, 97 all-cause deaths were observed in 806 participants with eligible values. In unadjusted Cox regression analyses, the hazard ratio (95% CI) for all-cause mortality per 25-unit increase in GDF-15 centile was 1.80 (1.48-2.20) and dichotomized at the 95th centile, >= 95th versus <95th, was 3.04 (1.99-4.65). Age-dependent GDF-15 centiles remained a significant predictor of all-cause mortality in all subsequent adjusted models. Conclusions: Age-dependent GDF-15 centile values developed from a population of apparently healthy older adults are independently predictive of all-cause mortality. Therefore, GDF-15 reference values could be a useful tool for risk-stratification in a clinical setting.

  • 137. Dotevall, Annika
    et al.
    Rosengren, Annika
    Bartnik, Malgorzata
    Malmberg, Klas
    Ohrvik, John
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Simoons, Maarten
    Rydén, Lars
    Sex-related aspects on abnormal glucose regulation in patients with coronary artery disease2007In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 28, no 3, p. 310-315Article in journal (Refereed)
    Abstract [en]

    Aim To investigate the prevalence of diabetes and impaired glucose regulation (IGR) in a large cohort of men and women with coronary artery disease (CAD), and to describe the effect of abnormal glucose regulation by sex on symptoms, clinical course, and diagnosis.

    Methods and results A total of 4855 patients with CAD (median age 66 years; 29% women) were analysed within the framework of the Euro Heart Survey on Diabetes and the Heart. In all, 967 (28.1%) men and 528 (37.5%) women had diabetes. Of 3185 patients with unknown glucose regulation, 1835 (57.6%; 1400 men and 435 women) underwent an oral glucose tolerance test revealing that 17% of the men and 18% of the women had diabetes and 35 and 39% impaired glucose tolerance or impaired fasting glucose, respectively. Thus, only 19% of the women and 27% of the men had a normal glucose regulation. Women were more likely to have diabetes than men with an odds ratio (OR) of 1.32 (1.13–1.54). The corresponding OR for abnormal glucose regulation was 1.34 (1.11–1.62). Gender did not influence differences in clinical presentation between patients with diabetes or IGR and those with a normal glucose metabolism.

    Conclusion Abnormal glucose regulation was more common in women than men with CAD. However, the influence of diabetes on presenting symptoms and clinical course was similar in men and women.

  • 138.
    Drevin, Jennifer
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Kristiansson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Stern, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Sophiahemmet Univ, Dept Hlth Promoting Sci, Uppsala, Sweden.
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Measuring pregnancy planning: A psychometric evaluation and comparison of two scales2017In: Journal of Advanced Nursing, ISSN 0309-2402, E-ISSN 1365-2648, Vol. 73, no 11, p. 2765-2775Article in journal (Refereed)
    Abstract [en]

    Aims: To psychometrically test the London Measure of Unplanned Pregnancy and compare it with the Swedish Pregnancy Planning Scale. Background: The incidence of unplanned pregnancies is an important indicator of reproductive health. The London Measure of Unplanned Pregnancy measures pregnancy planning by taking contraceptive use, timing, intention to become pregnant, desire for pregnancy, partner agreement, and pre-conceptual preparations into account. It has, however, previously not been psychometrically evaluated using confirmatory factor analysis. The Likert-scored single-item Swedish Pregnancy Planning Scale has been developed to measure the woman's own view of pregnancy planning level. Design: Cross-sectional design. Methods: In 2012-2013, 5493 pregnant women living in Sweden were invited to participate in the Swedish Pregnancy Planning study, of whom 3327 (61%) agreed to participate and answered a questionnaire. A test-retest pilot study was conducted in 2011-2012. Thirty-two participants responded to the questionnaire on two occasions 14 days apart. Data were analysed using confirmatory factor analysis, Cohen's weighted kappa and Spearman's correlation. Results: All items of the London Measure of Unplanned Pregnancy contributed to measuring pregnancy planning, but four items had low item-reliability. The London Measure of Unplanned Pregnancy and Swedish Pregnancy Planning Scale corresponded reasonably well with each other and both showed good test-retest reliability. Conclusion: The London Measure of Unplanned Pregnancy may benefit from item reduction and its usefulness may be questioned. The Swedish Pregnancy Planning Scale is time-efficient and shows acceptable reliability and construct validity, which makes it more useful for measuring pregnancy planning.

  • 139.
    Dérand, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hirsch, Jan-Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Virtual bending of mandibular reconstruction plates using a computer-aided design2009In: Journal of oral and maxillofacial surgery (Print), ISSN 0278-2391, E-ISSN 1531-5053, Vol. 67, no 8, p. 1640-1643Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The purpose of this study was to investigate the possibility of virtually designing and manufacturing a template for reconstruction plate bending, to be used during treatment of congenital or acquired bony entities. The outcome was compared with plates bent by the freehand approach in a stereolithographic skull model. MATERIALS AND METHODS: From a computed tomography examination, a polygon skull was created and the corresponding stereolithographic model retrieved. A polygon mesh of a Compact UniLock 2.4-mm plate was obtained from Synthes (Bettlach, Switzerland). The polygon plate was bent virtually around the mandible and rendered in all 3 dimensions, and a template was created. Five 10-hole plates were bent using this template, and five 10-hole plates were bent using a stereolithographic model as the template. The 2 groups were compared using the Wilcoxon signed rank test. P values less than .001 was considered to be statistically significant. RESULTS: No statistical difference was seen between the 2 methods. The median discrepancy between the 2 groups was 0.1 mm. CONCLUSION: Within the constraints of this investigation, by use of a virtually produced template based on a virtually planned reconstruction, it is possible to bend a reconstruction plate with the same degree of accuracy as that of the traditional freehand approach.

  • 140.
    Eaker, Sonja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Dickman, Paul W.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Differences in management of older women influence breast cancer survival: results from a population-based database in Sweden2006In: PLoS Medicine, ISSN 1549-1676, Vol. 3, no 3, p. e25-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Several reports have shown that less aggressive patterns of diagnostic activity and care are provided to elderly breast carcinoma patients. We sought to investigate whether differences in the management of older women with breast cancer are associated with survival. METHODS AND FINDINGS: In an observational study using a population-based clinical breast cancer register of one health-care region in Sweden, we identified 9,059 women aged 50-84 y diagnosed with primary breast cancer between 1992 and 2002. The 5-y relative survival ratio was estimated for patients classified by age group, diagnostic activity, tumor characteristics, and treatment. The 5-y relative survival for breast cancer patients was lower (up to 13%) in women 70-84 y of age compared to women aged 50-69 y, and the difference was most pronounced in stage IIB-III and in the unstaged. Significant differences in disease management were found, as older women had larger tumors, had fewer nodes examined, and did not receive treatment by radiotherapy or by chemotherapy as often as the younger women. Adjustment for diagnostic activity, tumor characteristics, and treatment diminished the relative excess mortality in stages III and in the unstaged, whereas the excess mortality was only marginally affected in stage IIB. CONCLUSIONS: Less diagnostic activity, less aggressive treatment, and later diagnosis in older women are associated with poorer survival. The large differences in treatment of older women are difficult to explain by co-morbidity alone.

  • 141.
    Eaker, Sonja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Halmin, Märit
    Bellocco, Rino
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Ahlgren, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Research and Development, Gävleborg.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lambe, Mats
    Social differences in breast cancer survival in relation to patient management within a National Health Care System (Sweden)2009In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 124, no 1, p. 180-187Article in journal (Refereed)
    Abstract [en]

    Epidemiologic studies have shown that cancer survival is poorer in low compared with high socioeconomic groups. We investigated whether these differences were associated with disparities in tumour characteristics and management. This cohort study was based on 9,908 women aged 20-79 years at diagnosis with primary breast cancer identified in a Swedish population-based clinical register. Information on socioeconomic standing was obtained from a social database. The 5-year cause-specific survival (CSS) and mortality hazard ratios (HR) were estimated by Cox proportional hazard models to assess differences in survival between socioeconomic groups while adjusting for diagnostic intensity, tumour characteristics and treatment. Following adjustment for age, year and stage at diagnosis, the risk of dying of breast cancer was 35% lower among women with high education compared with that of low education (HR = 0.65, 95% CI 0.53-0.80). When compared with women with high education, a lower percentage of women with low education had been investigated for proliferation (84 vs. 76%) or hormone receptor status (89 vs. 81%), had tumours <or=20 mm (68 vs. 64%), were treated at a main hospital (75 vs. 68%) and had received radiation treatment (80 vs. 67%) or chemotherapy (31 vs. 18%). However, these proportional differences could not explain the observed social gradient in survival. To minimize social differences in breast cancer survival, further research should address not only factors leading to inequities in management but also focus on patient factors such as health awareness, comorbidity burden and compliance to adjuvant treatment.

  • 142.
    Eaker, Sonja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Wigertz, Annette
    Lambert, Paul C
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Ahlgren, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Research and Development, Gävleborg.
    Lambe, Mats
    Breast cancer, sickness absence, income and marital status: A study on life situation 1 year prior diagnosis compared to 3 and 5 years after diagnosis2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 3, p. e18040-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Improved cancer survival poses important questions about future life conditions of the survivor. We examined the possible influence of a breast cancer diagnosis on subsequent working and marital status, sickness absence and income.

    MATERIALS:

    We conducted a matched cohort study including 4,761 women 40-59 years of age and registered with primary breast cancer in a Swedish population-based clinical register during 1993-2003, and 2,3805 women without breast cancer. Information on socioeconomic standing was obtained from a social database 1 year prior and 3 and 5 years following the diagnosis. In Conditional Poisson Regression models, risk ratios (RRs) and 95% confidence intervals (CIs) were estimated to assess the impact of a breast cancer diagnosis.

    FINDINGS:

    Three years after diagnosis, women who had had breast cancer more often had received sickness benefits (RR = 1.49, 95% CI 1.40-1.58) or disability pension (RR = 1.47, 95% CI 1.37-1.58) than had women without breast cancer. We found no effect on income (RR = 0.99), welfare payments (RR = 0.98), or marital status (RR = 1.02). A higher use of sickness benefits and disability pension was evident in all stages of the disease, although the difference in use of sickness benefits decreased after 5 years, whereas the difference in disability pension increased. For woman with early stage breast cancer, the sickness absence was higher following diagnosis among those with low education, who had undergone mastectomy, and had received chemo- or hormonal therapy. Neither tumour size nor presence of lymph nodes metastasis was associated with sickness absence after adjustment for treatment.

    INTERPRETATION:

    Even in early stage breast cancer, a diagnosis negatively influences working capacity both 3 and 5 years after diagnosis, and it seems that the type of treatment received had the largest impact. A greater focus needs to be put on rehabilitation of breast cancer patients, work-place adaptations and research on long-term sequelae of treatment.

  • 143.
    Edmark, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Reducing Atelectasis during General Anaesthesia – the Importance of Oxygen Concentration, End-Expiratory Pressure and Patient Factors: A Clinical Study Exploring the Prevention of Atelectasis in Adults2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: The use of pure oxygen during preoxygenation and induction of general anaesthesia is a major cause of atelectasis. The interaction between reduced lung volume, resulting in airway closure, and varying inspiratory fractions of oxygen (FIO2) in determining the risk of developing atelectasis is still obscure.

    Methods: In this thesis, computed tomography (in studies I and II during anaesthesia, in studies III and IV postoperatively) was used to investigate the area of atelectasis in relation to FIO2 and varying levels of continuous positive airway pressure (CPAP) or positive end-expiratory pressure (PEEP).

    Study I investigated the short-term influence of reducing FIO2 during preoxygenation and induction of general anaesthesia, and the time to hypoxia during apnoea.

    Study II focused on the long-term effect of an FIO2 of 0.8 for preoxygenation.

    Study III applied CPAP/PEEP with an FIO2 of 1.0 or 0.8 for pre- and postoxygenation until extubation. After extubation, CPAP with an FIO2 of 0.3 was applied before the end of mask ventilation.

    Study IV compared two groups given CPAP/PEEP during anaesthesia and an FIO2 of 1.0 or 0.3 during postoxygenation, but without CPAP after extubation.

    Results: Study I showed a reduction in atelectasis with an FIO2 of 0.8 or 0.6, compared with 1.0, but the time to hypoxia decreased. In study II, atelectasis evolved gradually after preoxygenation. In study III, atelectasis was reduced with an FIO2 of 1.0 and CPAP/PEEP compared with an FIO2 of 1.0 without CPAP/PEEP. The intervention failed in the group given an FIO2 of 0.8, this group had more smokers. Atelectasis and age were correlated. In study IV, no difference was found between the groups. Post hoc analysis showed that smoking and ASA class increased the risk for atelectasis.

    Conclusion, the effect of reducing FIO2 during preoxygenation to prevent atelectasis might be short-lived. A lower FIO2 shortened the time to the appearance of hypoxia. Increasing lung volume by using CPAP/PEEP also decreased the risk of atelectasis, but the method might fail; for example in patients who are heavy smokers. In older patients care must be taken to reduce a high FIO2 before ending CPAP.

  • 144.
    Edmark, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Auner, U
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Enlund, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Post-operative atelectasis: a randomised trial investigating a ventilatory strategy and low oxygen fraction during recovery2014In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, no 6, p. 681-688Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Atelectasis is common during and after general anaesthesia. We hypothesized that a ventilation strategy with a combination of 1) continuous positive airway pressure (CPAP) or positive end-expiratory pressure (PEEP) and 2) a reduced end-expiratory oxygen concentration during recovery would reduce post-operative atelectasis.

    METHODS: Sixty patients were randomized into two groups. During anaesthesia induction, inspiratory oxygen fraction (FI O2 ) was 1.0, and depending on weight, CPAP 6, 7 or 8 cmH2 O was applied in both groups via facemask. During maintenance of anaesthesia, a laryngeal mask airway (LMA) was used, and PEEP was 6-8 cmH2 O in both groups. Before removal of the LMA, FI O2 was set to 0.3 in the intervention group and 1.0 in the control group. Atelectasis was studied by computed tomography (CT) approximately 14 min post-operatively.

    RESULTS: In one patient in the group given an FI O2 of 0.3 before removal of the LMA a CT scan could not be performed so the patient was excluded. The area of atelectasis was 5.5, 0-16.9 cm(2) (median and range), and 6.8, 0-27.5 cm(2) in the groups given FI O2 0.3 or FI O2 1.0 before removal of the LMA, a difference that was not statistically significant (P = 0.48). Post-hoc analysis showed dependence of atelectasis on smoking (despite all were clinically lung healthy) and American Society of Anesthesiologists class (P = 0.038 and 0.015, respectively).

    CONCLUSION: Inducing anaesthesia with CPAP/PEEP and FI O2 1.0 and deliberately reducing FI O2 during recovery before removal of the LMA did not reduce post-operative atelectasis compared with FI O2 1.0 before removal of the LMA.

  • 145.
    Edmark, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Auner, Udo
    Hallén, Jan
    Lassinantti-Olowsson, Lena
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Enlund, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    A ventilation strategy during general anaesthesia to reduce postoperative atelectasis2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 3, p. 242-250Article in journal (Refereed)
    Abstract [en]

    Background:

    Atelectasis is common during and after general anaesthesia. We hypothesized that a ventilation strategy, without recruitment manoeuvres, using a combination of continuous positive airway pressure (CPAP) or positive end-expiratory pressure (PEEP) and a reduced end-expiratory oxygen fraction (FETO2) before ending mask ventilation with CPAP after extubation would reduce the area of postoperative atelectasis.

    Methods:

    Thirty patients were randomized into three groups. During induction and emergence, inspiratory oxygen fractions (FIO2) were 1.0 in the control group and 1.0 or 0.8 in the intervention groups. No CPAP/PEEP was used in the control group, whereas CPAP/PEEP of 6 cmH2O was used in the intervention groups. After extubation, FIO2 was set to 0.30 in the intervention groups and CPAP was applied, aiming at FETO2 < 0.30. Atelectasis was studied by computed tomography 25 min postoperatively.

    Results:

    The median area of atelectasis was 5.2 cm(2) (range 1.6-12.2 cm(2)) and 8.5 cm(2) (3-23.1 cm(2)) in the groups given FIO2 1.0 with or without CPAP/PEEP, respectively. After correction for body mass index the difference between medians (2.9 cm(2)) was statistically significant (confidence interval 0.2-7.6 cm(2), p = 0.04). In the group given FIO2 0.8, in which seven patients were ex- or current smokers, the median area of atelectasis was 8.2 cm(2) (1.8-14.7 cm(2)).

    Conclusion:

    Compared with conventional ventilation, after correction for obesity, this ventilation strategy reduced the area of postoperative atelectasis in one of the intervention groups but not in the other group, which included a higher proportion of smokers.

  • 146.
    Edmark, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Auner, Udo
    Hallén, Jan
    Lassinantti-Olowsson, Lena
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Enlund, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Reduction in postoperative atelectasis by continuous positive airway pressure and low oxygen concentration after endotracheal extubationManuscript (preprint) (Other academic)
    Abstract [en]

    Background. Atelectasis is common during and after general anaesthesia. We hypothesized that a ventilation strategy using a combination of 1) continuous positive airway pressure (CPAP) or positive end-expiratory pressure (PEEP) and 2) a reduced end-expiratory oxygen fraction (FETO2) before commencing mask ventilation with CPAP after extubation would reduce the area of postoperative atelectasis.

    Methods. Thirty patients were randomized into three groups. During induction and emergence, inspiratory oxygen fractions (FIO2) were 1.0 in the control group and 1.0 or 0.8 in the intervention groups. No CPAP/PEEP was used in the control group, whereas CPAP/PEEP of 6 cmH2O was used in the intervention groups. After extubation, FIO2 was set to 0.30 in the intervention groups and CPAP was applied via a facemask, aiming at a FETO2 < 0.30. Atelectasis was studied by computed tomography 25 min postoperatively.

    Results. The median area of atelectasis was 5.2 cm2 (range 1.6–12.2 cm2) and 8.5 cm2 (3–23.1 cm2) in the groups given FIO2 1.0 with or without CPAP/PEEP, respectively. In the group given FIO2 0.8, in which 7 patients were ex- or current smokers, the median area of atelectasis was 8.2 cm2 (1.8–14.7 cm2). After correction for body mass index and age, the difference between the two groups given FIO2 1.0 was statistically significant (P = 0.016).

    Conclusion. Compared with conventional ventilation, this ventilation strategy reduced the area of postoperative atelectasis in one of the intervention groups but not in the other group, which included a higher proportion of smokers.

  • 147.
    Edmark, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Auner, Udo
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Enlund, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Atelectasis after anaesthesia: a randomised trial of positive airway pressure and low oxygen2013Article in journal (Other academic)
    Abstract [en]

    Background:

    Atelectasis is common during and after general anaesthesia. We hypothesized that a ventilation strategy with a combination of 1) continuous positive airway pressure (CPAP) or positive end-expiratory pressure (PEEP) and 2) a reduced end-expiratory oxygen fraction (FETO2) before extubation would reduce postoperative atelectasis.

    Methods:

    Sixty patients were randomized into two groups. During anaesthesia induction, inspiratory oxygen fractions (FIO2) were 1.0, and depending on weight, CPAP 6–8 cm H2O was applied in both groups via face mask. During maintenance of anaesthesia, a laryngeal mask airway was used, and depending on weight, PEEP was 6–8 cm H2O in both groups. Before extubation, FIO2 was set to 0.3 in the intervention groups and 1.0 in the control group. Atelectasis was studied by computed tomography approximately 13 min postoperatively.

    Results:

    The area of atelectasis was 5.5, 0–16.9 cm2 (median and range), and 6.8, 0–27.5 cm2 in the groups given FIO2 0.3 or FIO2 1.0 before extubation, a difference that was not statistically significant.

    Conclusion:

    Inducing anaesthesia with CPAP/PEEP and FIO2 1.0 and deliberately reducing FIO2 before extubation did not reduce postoperative atelectasis compared with FIO2 1.0 before extubation.

  • 148.
    Edmark, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Östberg, Erland
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Scheer, H
    Wallquist, W
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Zetterström, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Preserved oxygenation in obese patients receiving protective ventilation during laparoscopic surgery: a randomized controlled study2016In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 1, p. 26-35Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Venous admixture from atelectasis and airway closure impedes oxygenation during general anaesthesia. We tested the hypothesis that continuous positive airway pressure (CPAP) during pre-oxygenation and reduced fraction of inspiratory oxygen (FIO2 ) during emergence from anaesthesia can improve oxygenation in patients with obesity undergoing laparoscopic surgery.

    METHODS: In the intervention group (n = 20, median BMI 41.9), a CPAP of 10 cmH2 O was used during pre-oxygenation and induction of anaesthesia, but no CPAP was used in the control group (n = 20, median BMI 38.1). During anaesthesia, all patients were ventilated in volume-controlled mode with an FIO2 of 0.4 and a positive end-expiratory pressure (PEEP) of 10 cmH2 O. During emergence, before extubation, the control group was given an FIO2 of 1.0 and the intervention group was divided into two subgroups, which were given an FIO2 of 1.0 or 0.31. Oxygenation was assessed perioperatively by the estimated venous admixture (EVA).

    RESULTS: The median EVA before pre-oxygenation was about 8% in both groups. During anaesthesia after intubation, the median EVA was 8.2% in the intervention vs. 13.2% in the control group (P = 0.048). After CO2 pneumoperitoneum, the median EVA was 8.4% in the intervention vs. 9.9% in the control group (P > 0.05). One hour post-operatively, oxygenation had deteriorated in patients given an FIO2 of 1.0 during emergence but not in patients given an FIO2 of 0.31.

    CONCLUSIONS: A CPAP of 10 cmH2 O during pre-oxygenation and induction, followed by PEEP after intubation, seemed to preserve oxygenation during anaesthesia. Post-operative oxygenation depended on the FIO2 used during emergence.

  • 149.
    Ehrsson, Ylva Tiblom
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Stenhammar, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Tydén, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Self-reported sexually transmitted infections among female university students.2016In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 1, p. 45-49Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate the occurrence of self-reported sexually transmitted infections (STIs) and associated factors among female university students requesting contraceptive counselling.

    MATERIAL AND METHODS: Cross-sectional study. Female university students (n = 353) completed a waiting-room questionnaire in connection with contraceptive counselling at a Student Health Centre in Uppsala, Sweden.

    RESULTS: Ninety-three (26.3%) female students had experienced an STI. The three most frequently reported STIs were chlamydia trachomatis, condyloma, and genital herpes. The experience of an STI was significantly associated with the total number of sexual partners (OR 1.060, 95% CI 1.030-1.091, P < 0.001), being heterosexual (OR 4.640, 95% CI 1.321-16.290, P = 0.017), having experienced an abortion (OR 2.744, 95% CI 1.112-6.771, P = 0.028), not being HPV-vaccinated (OR 2.696, 95% CI 1.473-4.935, P = 0.001), and having had intercourse on first night without using a condom (OR 2.375, 95% CI 1.182-4.771, P = 0.015).

    CONCLUSIONS: Contraceptive counselling should also include information about primary and secondary prevention of STI, such as the importance of correct use of a condom and STI testing, to prevent a further spread of STIs.

  • 150. Eklund, A.
    et al.
    Carlsson, P.
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Montgomery, A.
    Bergkvist, L.
    Rudberg, C.
    Long-term cost-minimization analysis comparing laparoscopic with open (Lichtenstein) inguinal hernia repair2010In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 97, no 5, p. 765-771Article in journal (Refereed)
    Abstract [en]

    Background:

    Laparoscopic surgery has emerged as a new treatment modality for inguinal hernia repair. The aim of the present study was to analyse its long-term costs in relation to those of open repair.

    Methods:

    A randomized multicentre study comparing totally extraperitoneal laparoscopic repair (TEP) with open repair by the Lichtenstein procedure was performed on men with a primary inguinal hernia. Long-term data on recurrences and complications up to 5 years after operation were collected. Taking treatment costs into consideration, a cost-minimization analysis was conducted.

    Results:

    A total of 1370 patients had an inguinal hernia repair, 665 in the TEP and 705 in the Lichtenstein group. The total hospital cost for the index operation was €710·6 higher for TEP repair (P < 0·001). Including costs associated with recurrences and complications, this difference increased to €795·1 (P < 0·001). Taking community costs into account, the difference decreased by €503·1 to €292·0 (P = 0·024).

    Conclusion:

    This cost-minimization analysis, including complications, reoperations and community costs during follow-up of 5 years, showed that laparoscopic inguinal hernia repair had a small but significant increase in overall costs compared with open repair.

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