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  • 151.
    Al-Shamkhi, Nasrin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Dahlen, S. E.
    Karolinska Inst, Inst Environm Med, Expt Asthma & Allergy Res Unit, Stockholm, Sweden..
    Hedlin, G.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Middelveld, R.
    Karolinska Inst, Inst Environm Med, Expt Asthma & Allergy Res Unit, Stockholm, Sweden..
    Bjerg, A.
    Univ Gothenburg, Krefting Res Ctr, Dept Internal Med & Clin Nutr, Gothenburg, Sweden..
    Ekerljung, L.
    Univ Gothenburg, Krefting Res Ctr, Dept Internal Med & Clin Nutr, Gothenburg, Sweden..
    Olin, A. C.
    Univ Gothenburg, Sect Occupat & Environm Med, Dept Publ Hlth & Community Med, Inst Med,Sahlgrenska Acad, Gothenburg, Sweden..
    Sommar, J.
    Umea Univ, Dept Publ Hlth & Clin Med Occupat & Environm Med, Umea, Sweden..
    Forsberg, B.
    Umea Univ, Dept Publ Hlth & Clin Med Occupat & Environm Med, Umea, Sweden..
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Important non-disease-related determinants of exhaled nitric oxide levels in mild asthma - results from the Swedish GA(2)LEN study2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 9, p. 1185-1193Article in journal (Refereed)
    Abstract [en]

    Background Fractional exhaled nitric oxide (FeNO) has a potential clinical role in asthma management. Constitutive factors such as age, height and gender, as well as individual characteristics, such as IgE sensitization and smoking, affect the levels of FeNO in population-based studies. However, their effect on FeNO in subjects with asthma has been scarcely studied. Objective To study the effects on FeNO of these commonly regarded determinants, as demonstrated in healthy subjects, as well as menarche age and parental smoking, in a population of asthmatics. Material and Methods Fractional exhaled nitric oxide was measured in 557 subjects with asthma from the Swedish GA(2)LEN study. Allergic sensitization was assessed by skin prick tests to most common aeroallergens. Upper airway comorbidities, smoking habits, smoking exposure during childhood and hormonal status (for women) were questionnaire-assessed. Results Male gender (P < 0.001), greater height (P < 0.001) and sensitization to both perennial allergens and pollen (P < 0.001) are related to higher FeNO levels. Current smoking (P < 0.001) and having both parents smoking during childhood, vs. having neither (P < 0.001) or only one parent smoking (P = 0.002), are related to lower FeNO. Women with menarche between 9 and 11 years of age had lower FeNO than those with menarche between 12 and 14 years of age (P = 0.03) or 15 and 17 years of age (P = 0.003). Conclusions and Clinical relevance Interpreting FeNO levels in clinical practice is complex, and constitutional determinants, as well as smoking and IgE sensitisation, are of importance in asthmatic subjects and should be accounted for when interpreting FeNO levels. Furthermore, menarche age and parental smoking during childhood and their effects on lowering FeNO deserve further studies.

  • 152.
    Alsiö, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Stenhammar, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Hulting, Anna-Lena
    Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Karolinska Institutet, Stockholm.
    Montgomery, Scott M
    Clinical Research Centre; Örebro University Hospital, Örebro.
    Edlund, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Parental food preferences are associated with body weight disturbance in preschool childrenManuscript (preprint) (Other academic)
    Abstract [en]

    Parental factors such as stress induced by parenting and certain food preferences are suspected to promote obesity in preschool children. In this context, especially the intake of dietary fat is assumed to play a key role for the children’s risk to become obese. Here we analyzed eating behaviors in parents of 3-year-olds in order to identify parental traits that are associated with body weight in these children. We also tested for possible interactions between psychosocial factors such as stress induced by parenting and parental food cravings. Questionnaires were sent out to 1300 parents whose children’s body weight was measured during ambulatory medical care visits (parental response rate 70.4%). Using the Food Craving Inventory scale allowed examining parental preferences for the following food categories:  high-fat/high-protein, sweets, carbohydrates, and fast food. Psychosocial stress caused by parenting was assessed with the Swedish Parenthood Stress Questionnaire (SPSQ). Our main finding was that the parental preference for foods rich in high-fat/high-protein nutrients displayed an inverse U-shaped function to the children’s body weight such that low preference for this category was associated with both overweight and underweight in offspring. Parental preference for sweet-foods were associated with higher odds for developing overweight in early childhood. The level of parental food preferences was significantly modulated by stress induced by parenting. In conclusion, we show that parental food preference is affected by stress and is associated with the body weight status of their children. The results suggest that parental intake of high-fat/high-protein foods protects against weight disturbances in preschool children.

  • 153.
    Alsén, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Immunohistochemical evaluation of antibodies for staining of mouse spinal cord and mouse neuronal cells2013Independent thesis Basic level (university diploma), 10 credits / 15 HE creditsStudent thesis
  • 154. Althabe, Fernando
    et al.
    Belizan, Jose M
    Villar, Jose
    Alexander, Sophie
    Bergel, Eduardo
    Ramos, Silvina
    Romero, Mariana
    Donner, Allan
    Lindmark, Gunilla
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Langer, Ana
    Farnot, Ubaldo
    Cecatti, Jose G
    Carroli, Guillermo
    Kestler, Edgar
    Mandatory second opinion to reduce rates of unnecessary caesarean sections in Latin America: a cluster randomised controlled trial.2004In: Lancet, ISSN 1474-547X, Vol. 363, no 9425, p. 1934-40Article in journal (Other scientific)
  • 155. Altmae, Signe
    et al.
    Reimand, Jueri
    Hovatta, Outi
    Zhang, Pu
    Kere, Juha
    Laisk, Triin
    Saare, Merli
    Peters, Maire
    Vilo, Jaak
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Salumets, Andres
    Interactome of Human Embryo Implantation: Identification of Gene Expression Pathways, Regulation, and Integrated Regulatory Networks2012In: Molecular Endocrinology, ISSN 0888-8809, E-ISSN 1944-9917, Vol. 26, no 1, p. 203-217Article in journal (Refereed)
    Abstract [en]

    A prerequisite for successful embryo implantation is adequate preparation of receptive endometrium and the establishment and maintenance of a viable embryo. The success of implantation further relies upon a two-way dialogue between the embryo and uterus. However, molecular bases of these preimplantation and implantation processes in humans are not well known. We performed genome expression analyses of humanembryos (n = 128) andhumanendometria (n = 8). We integrated these data with protein-protein interactions in order to identify molecular networks within the endometrium and the embryo, and potential embryo-endometrium interactions at the time of implantation. For that, we applied a novel network profiling algorithm HyperModules, which combines topological module identification and functional enrichment analysis. We found a major wave of transcriptional down-regulation in preimplantation embryos. In receptive-stage endometrium, several genes and signaling pathways were identified, including JAK-STAT signaling and inflammatory pathways. The main curated embryo-endometrium interaction network highlighted the importance of cell adhesion molecules in the implantation process. We also identified cytokine-cytokine receptor interactions involved in implantation, where osteopontin (SPP1), leukemia inhibitory factor (LIF) and leptin (LEP) pathways were intertwining. Further, we identified a number of novel players in human embryo-endometrium interactions, such as apolipoprotein D (APOD), endothelin 1 (END1), fibroblast growth factor 7 (FGF7), gastrin (GAST), kringle containing trnasmembrane protein 1 (KREMEN1), neuropilin 1 (NRP1), serpin peptidase inhibitor clade A member 3 (SERPINA3), versican (VCAN), and others. Our findings provide a fundamental resource for better understanding of the genetic network that leads to successful embryo implantation. We demonstrate the first systems biology approach into the complex molecular network of the implantation process in humans.

  • 156.
    Altmae, Signe
    et al.
    Competence Ctr Hlth Technol, Tartu, Estonia.;Univ Granada, Sch Med, Dept Paediat, Granada, Spain..
    Tamm-Rosenstein, Karin
    Tallinn Univ Technol, Dept Gene Technol, EE-19086 Tallinn, Estonia..
    Esteban, Francisco J.
    Univ Jaen, Dept Expt Biol, Jaen, Spain..
    Simm, Jaak
    Tallinn Univ Technol, Dept Gene Technol, EE-19086 Tallinn, Estonia..
    Kolberg, Liis
    Univ Tartu, Inst Comp Sci, Ulikooli 18, EE-50090 Tartu, Estonia..
    Peterson, Hedi
    Univ Tartu, Inst Comp Sci, Ulikooli 18, EE-50090 Tartu, Estonia.;Quretec Ltd, Tartu, Estonia..
    Metsis, Madis
    Competence Ctr Hlth Technol, Tartu, Estonia.;Tallinn Univ, Sch Nat Sci & Hlth, EE-10120 Tallinn, Estonia..
    Haldre, Kai
    West Tallinn Cent Hosp Womens Clin, Ctr Reprod Med, Tallinn, Estonia..
    Horcajadas, Jose A.
    Hosp Miguel Servet, Araid I CS, Zaragoza, Spain..
    Salumets, Andres
    Competence Ctr Hlth Technol, Tartu, Estonia.;Univ Tartu, Dept Obstet & Gynaecol, Ulikooli 18, EE-50090 Tartu, Estonia..
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Endometrial transcriptome analysis indicates superiority of natural over artificial cycles in recurrent implantation failure patients undergoing frozen embryo transfer2016In: Reproductive Biomedicine Online, ISSN 1472-6483, E-ISSN 1472-6491, Vol. 32, no 6, p. 597-613Article in journal (Refereed)
    Abstract [en]

    Little consensus has been reached on the best protocol for endometrial preparation for frozen embryo transfer (FET). It is not known how, and to what extent, hormone supplementation in artificial cycles influences endometrial preparation for embryo implantation at a molecular level, especially in patients who have experienced recurrent implantation failure. Transcriptome analysis of 15 endometrial biopsy samples at the time of embryo implantation was used to compare two different endometrial preparation protocols, natural versus artificial cycles, for FET in women who have experienced recurrent implantation failure compared with fertile women. IPA and DAVID were used for functional analyses of differentially expressed genes. The TRANSFAC database was used to identify oestrogen and progesterone response elements upstream of differentially expressed genes. Cluster analysis demonstrated that natural cycles are associated with a better endometrial receptivity transcriptome than artificial cycles. Artificial cycles seemed to have a stronger negative effect on expression of genes and pathways crucial for endometrial receptivity, including ESR2, FSHR, LEP, and several interleukins and matrix metalloproteinases. Significant overrepresentation of oestrogen response elements among the genes with deteriorated expression in artificial cycles (P < 0.001) was found; progesterone response elements predominated in genes with amended expression with artificial cycles (P = 0.0052).

  • 157. Altmael, S.
    et al.
    Martinez-Conejero, J. A.
    Esteban, F. J.
    Horcajadas, J. A.
    Salumets, A.
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Endometrial gene expression analysis in infertile women in natural and hormone replacement cycles2012In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 27, no Suppl. 2, p. O-243-Article in journal (Other academic)
  • 158.
    Altman, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health. Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden;Stockholm Urogynecol Clin, Stockholm, Sweden.
    Geale, Kirk
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Falconer, Christian
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Div Obstet & Gynecol, S-18288 Stockholm, Sweden.
    Morcos, Edward
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Div Obstet & Gynecol, S-18288 Stockholm, Sweden.
    A generic health-related quality of life instrument for assessing pelvic organ prolapse surgery: correlation with condition-specific outcome measures2018In: International Urogynecology Journal, ISSN 0937-3462, E-ISSN 1433-3023, Vol. 29, no 8, p. 1093-1099Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate the use of a generic and globally accessible instrument for assessing health-related quality of life (HR-QoL) in pelvic organ prolapse (POP) surgery. In a prospective multicenter setting, 207 women underwent surgery for apical prolapse [stage ae<yen>2, Pelvic Organ Prolapse Quantificcation (POP-Q) system] with or without anterior wall defect. Demographic and surgical characteristics were collected before surgery. Results of the 15-dimensional (15D) instrument and condition-specific pelvic floor symptoms as assessed using the Pelvic Floor Distress Inventory questionnaire (PFDI-20), including its subscales Pelvic Organ Prolapse Distress Inventory-6 (POPDI-6), Colorectal-Anal Distress Inventory-8 (CRADI-8), and Urinary Distress Inventory-6 (UDI-6), were assessed preoperatively and 2 months and 1 year after surgery. HR-QoL as estimated by 15D was improved 1 year after surgery (p < 0.001). Prolapse-related 15D profile-index measures (excretion, discomfort, sexual activity, distress, and mobility) were significantly improved after surgery (p < 0.05-0.001). Significant inverse associations were detected between increased 15D scores and a decrease in PFDI-20 and subscale scores (p < 0.001), indicating improvements on both instruments. Generic HR-QoL as estimated by 15D improved significantly after apical POP surgery and correlated with improvements of condition-specific outcome measures. These results suggest that a comprehensive evaluation of global HR-QoL is valid in assessing pelvic reconstructive surgery and may provide novel and important insights into previously understudied areas, such as cost-utility and cost-effectiveness analysis after urogynecological surgery.

  • 159. Altman, Daniel
    et al.
    Ragnar, Inga
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ekström, Åsa
    Tydén, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Olsson, Sven-Eric
    Anal sphincter lacerations and upright delivery postures - a risk analysis from a randomized controlled trial2007In: International Urogynecology Journal, ISSN 0937-3462, E-ISSN 1433-3023, Vol. 18, no 2, p. 141-146Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate obstetric sphincter lacerations after a kneeling or sitting position at second stage of labor in a multivariate risk analysis model. MATERIALS AND METHODS: Two hundred and seventy-one primiparous women with normal pregnancies and spontaneous labor were randomized, 138 to a kneeling position and 133 to a sitting position. Medical data were retrieved from delivery charts and partograms. Risk factors were tested in a multivariate logistic regression model in a stepwise manner. RESULTS: The trial was completed by 106 subjects in the kneeling group and 112 subjects in the sitting group. There were no significant differences with regard to duration of second stage of labor or pre-trial maternal characteristics between the two groups. Obstetrical sphincter tears did not differ significantly between the two groups but an intact perineum was more common in the kneeling group (p<0.03) and episiotomy (mediolateral) was more common in the sitting group (p<0.05). Three grade IV sphincter lacerations occurred in the sitting group compared to none in the kneeling group (NS). Multivariate risk analysis indicated that prolonged duration of second stage of labor and episiotomy were associated with an increased risk of third- or fourth-degree sphincter tears (p<0.01 and p<0.05, respectively). Delivery posture, maternal age, fetal weight, use of oxytocin, and use of epidural analgesia did not increase the risk of obstetrical anal sphincter lacerations in the two upright postures. CONCLUSION: Obstetrical anal sphincter lacerations did not differ significantly between a kneeling or sitting upright delivery posture. Episiotomy was more common after a sitting delivery posture, which may be associated with an increased risk of anal sphincter lacerations. Upright delivery postures may be encouraged in healthy women with normal, full-term pregnancy.

  • 160.
    Altman, Maria
    et al.
    Dept of Medicine Solna, Clinical Epidemiological Unit, T2 Karolinska Institutet, Stockholm, Sweden.
    Edstedt Bonamy, Anna-Karin
    Dept of Medicine Solna, Clinical Epidemiological Unit, T2 Karolinska Institutet, Stockholm, Sweden.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Cnattingius, Sven
    Dept of Medicine Solna, Clinical Epidemiological Unit, T2 Karolinska Institutet, Stockholm, Sweden.
    Cause-specific infant mortality in a population-based Swedish study of term and post-term births: the contribution of gestational age and birth weight2012In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 2, no 4, article id e001152Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To investigate infant mortality and causes of infant death in relation to gestational age (GA) and birth weight for GA in non-malformed term and post-term infants.

    DESIGN:

    Observational, retrospective nationwide cohort study.

    SETTING:

    Sweden 1983-2006.

    PARTICIPANTS:

    2 152 738 singleton non-malformed infants born at 37 gestational weeks or later.

    MAIN OUTCOME MEASURES:

    Infant, neonatal and postneonatal mortality and causes of infant death.

    RESULTS:

    Infant mortality rate was 0.12% (n=2687). Compared with infants born at 40 weeks, risk of infant mortality was increased among early term infants (37 weeks, adjusted OR 1.70, 95% CI 1.43 to 2.02). Compared with infants with normal birth weight for GA, very small for gestational age (SGA; <3rd percentile) infants faced a doubled risk of infant mortality (adjusted OR 2.13, 95% CI 1.80 to 2.53), and corresponding risk was also increased among moderately SGA infants (3rd to <10th percentile; adjusted OR 1.46, 95% CI 1.26 to 1.68). Sudden infant death syndrome (SIDS) was the most common cause of death, accounting for 39% of all infant mortality. Compared with birth at 40 weeks, birth at 37 weeks was associated with increased risks of death by infections, cardiovascular disorders, SIDS and malignant neoplasms. Very and moderately SGA were associated with increased risks of death by neonatal respiratory disorders, infections, cardiovascular disorders, SIDS and neuromuscular disorders. High birth weight for GA was associated with increased risks of death by asphyxia and malignant neoplasms.

    CONCLUSION:

    Early term birth and very to moderately low birth weight for GA are independent risk factors for infant mortality among non-malformed term infants.

  • 161. Altmäe, Signe
    et al.
    Esteban, Francisco J
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Simón, Carlos
    Giudice, Linda
    Lessey, Bruce A
    Horcajadas, Jose A
    Macklon, Nick S
    D'Hooghe, Thomas
    Campoy, Cristina
    Fauser, Bart C
    Salamonsen, Lois A
    Salumets, Andres
    Guidelines for the design, analysis and interpretation of 'omics' data: focus on human endometrium2013In: Human Reproduction Update, ISSN 1355-4786, E-ISSN 1460-2369, Vol. 20, no 1, p. 12-28Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND 'Omics' high-throughput analyses, including genomics, epigenomics, transcriptomics, proteomics and metabolomics, are widely applied in human endometrial studies. Analysis of endometrial transcriptome patterns in physiological and pathophysiological conditions has been to date the most commonly applied 'omics' technique in human endometrium. As the technologies improve, proteomics holds the next big promise for this field. The 'omics' technologies have undoubtedly advanced our knowledge of human endometrium in relation to fertility and different diseases. Nevertheless, the challenges arising from the vast amount of data generated and the broad variation of 'omics' profiling according to different environments and stimuli make it difficult to assess the validity, reproducibility and interpretation of such 'omics' data. With the expansion of 'omics' analyses in the study of the endometrium, there is a growing need to develop guidelines for the design of studies, and the analysis and interpretation of 'omics' data.

    METHODS Systematic review of the literature in PubMed, and references from relevant articles were investigated up to March 2013.

    RESULTS The current review aims to provide guidelines for future 'omics' studies on human endometrium, together with a summary of the status and trends, promise and shortcomings in the high-throughput technologies. In addition, the approaches presented here can be adapted to other areas of high-throughput 'omics' studies.

    CONCLUSION A highly rigorous approach to future studies, based on the guidelines provided here, is a prerequisite for obtaining data on biological systems which can be shared among researchers worldwide and will ultimately be of clinical benefit.

  • 162.
    Altmäe, Signe
    et al.
    Dept of Biotechnolgy, Institute of Molecular and Cell Biology, Estonian Genome Foundation, University of Tartu, Estonia.
    Haller, Kadri
    Dep of Obstetrics and Gynaecology, University of Tartu, Estonia.
    Peters, Maire
    Dep of Obstetrics and Gynaecology, University of Tartu, Estonia.
    Saare, Merli
    Dep of Obstetrics and Gynaecology, University of Tartu, Estonia.
    Hovatta, Outi
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Velthut, Agne
    Nova Vita Clinic, Centre for Infertility Treament and Medical Genetics, Estonia.
    Karro, Helle
    Dep of Obstetrics and Gynaecology, University of Tartu, Estonia.
    Metspalu, Andres
    Dept of Biotechnolgy, Institute of Molecular and Cell Biology, Estonian Genome Foundation, University of Tartu, Estonia.
    Salumets, Andres
    Dept of Biotechnolgy, Institute of Molecular and Cell Biology, Estonian Genome Foundation, University of Tartu, Estonia.
    Aromatase gene (CYP19A1) variants, female infertility and ovarian stimulation outcome: a preliminary report2009In: Reproductive Biomedicine Online, ISSN 1472-6483, E-ISSN 1472-6491, Vol. 18, no 5, p. 651-657Article in journal (Refereed)
    Abstract [en]

    Progress has been made towards ascertaining the genetic predictors of ovarian stimulation in IVF. Aromatase cytochrome P450, encoded by the CYP19A1 gene, catalyses a key step in ovarian oestrogen biosynthesis. Hence, the aromatase gene is an attractive candidate for genetic studies. This study aimed to examine the genetic influences of CYP19A1 TCT trinucleotide insertion/deletion (Ins/Del) and (TTTA)(n) microsatellite intronic polymorphisms on ovarian stimulation outcome and aetiology of female infertility. IVF patients (n = 152) underwent ovarian stimulation according to recombinant FSH and gonadotrophin releasing hormone antagonist protocol. Del/Del homozygous patients with shorter TTTA repeats exhibited decreased ovarian FSH sensitivity in ovarian stimulation, which may reflect variations in aromatase gene expression during early antral follicle development. Accordingly, this study demonstrates correlations between Del allele and shorter (TTTA)(n) repeat sizes with smaller ovaries (r = -0.70, P = 0.047) and fewer antral follicles (r = 0.21, P = 0.018) on days 3-5 of spontaneous menstrual cycle, respectively. Furthermore, Del variation linked with low-repeat-number (TTTA)(n) alleles are involved in enhanced genetic susceptibility to unexplained infertility (adjusted OR = 4.33, P = 0.039) and endometriosis (r = -0.88, P = 0.026), which corroborates evidence on the overlapping patient profiles of ovarian dysfunction in both types of female infertility.

  • 163.
    Altmäe, Signe
    et al.
    Division of Obstetrics and Gynaecology, Dept of Clinical Science, Karolinska University Hospital Huddinge, Sweden.
    Hovatta, O.
    Division of Obstetrics and Gynaecology, Dept of Clinical Science, Karolinska University Hospital Huddinge, Sweden.
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Salumets, A.
    Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia.
    Genetic predictors of controlled ovarian hyperstimulation: where do we stand today?2011In: Human Reproduction Update, ISSN 1355-4786, E-ISSN 1460-2369, Vol. 17, no 6, p. 813-828Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND

    Nowadays, the use of IVF has improved the prospects of infertility treatment. The expected outcome of IVF depends greatly on the effectiveness of controlled ovarian hyperstimulation (COH), where exogenous gonadotrophins are used to induce folliculogenesis. The response to stimulation varies substantially among women and is difficult to predict. Several predictive markers of COH outcome have been proposed (e.g. maternal age and ovarian reserve), but the search for optimal predictors is ongoing. Pharmacogenetic studies demonstrate the effects of individual genetic variability on COH outcome and the potential for customizing therapy based on the patient's genome.

    METHODS

    MEDLINE, EMBASE, DARE, CINAHL and the Cochrane Library, and references from relevant articles were investigated up to February 2011 regarding any common genetic variation and COH/IVF outcome.

    RESULTS

    Several polymorphisms in genes involved in FSH signalling, estrogen biosynthesis, folliculogenesis, folate metabolism and other aspects influence the response to exogenous gonadotrophin administration, resulting in differences in COH and IVF outcomes. Nevertheless, the most studied polymorphism FSHR Asn680Ser is practically the only genetic marker, together with ESR1 PvuII T/C, that could be applied in clinical tests.

    CONCLUSIONS

    Although data are accumulating with evidence suggesting that the ovarian response to COH is mediated by various polymorphisms, the optimal biomarkers and the efficacy of the tests still remain to be evaluated.

  • 164.
    Altmäe, Signe
    et al.
    Dept of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Kallak, Theodora Kunovac
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Fridén, Barbro
    Dept of Women´s and Children´s Health, Obstetrics and Gynaecology, Karolinska Institutet, Stockholm, Sweden.
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Variation in Hyaluronan-Binding Protein 2 (HABP2) Promoter Region is Associated With Unexplained Female Infertility2011In: Reproductive Sciences, ISSN 1933-7191, Vol. 18, no 5, p. 485-492Article in journal (Refereed)
    Abstract [en]

    We set up to analyze polymorphisms in hyaluronan-binding protein 2 (HABP2) gene in healthy fertile women (n = 158) and in women with unexplained infertility (n = 116) and to investigate the potential role of HABP2 in receptive endometrium. Minor rs1157916 A and the major rs2240879 A alleles together with AA genotypes were significantly less frequent in infertile women than in controls. Immunohistochemistry analysis of endometrial HABP2 expression at the time of implantation identified significantly lower HABP2 protein level in infertile women in stroma and vessels than in fertile women. Migration assay analysis of cultured trophoblast and endothelial cells toward HABP2 protein referred to the function of HABP2 in endometrial endothelial cells. In conclusion, our results indicate that polymorphisms in the regulatory region of HABP2 gene could influence gene expression levels in the receptive endometrium and could thereby be one reason for infertility complications in women with unexplained infertility. Additionally, HABP2 protein involvement in endometrial angiogenesis is proposed.

  • 165.
    Altmäe, Signe
    et al.
    Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia.
    Martinez-Conejero, José A
    IVIOMICS, Valencia, Spain.
    Esteban, Francisco J
    Department of Experimental Biology, University of Jaen, Jaen, Spain.
    Ruiz-Alonso, Maria
    IVIOMICS, Valencia, Spain.
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Horcajadas, José A
    Araid at IþCS, Hospital Miguel Servet, Zaragoza, Spain.
    Salumets, Andres
    Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia.
    MicroRNAs miR-30b, miR-30d, and miR-494 Regulate Human Endometrial Receptivity2013In: Reproductive Sciences, ISSN 1933-7191, E-ISSN 1933-7205, Vol. 20, no 3, p. 308-317Article in journal (Refereed)
    Abstract [en]

    MicroRNAs (miRNAs) act as important epigenetic posttranscriptional regulators of gene expression. We aimed to gain more understanding of the complex gene expression regulation of endometrial receptivity by analyzing miRNA signatures of fertile human endometria. We set up to analyze miRNA signatures of receptive (LH + 7, n = 4) versus prereceptive (LH + 2, n = 5) endometrium from healthy fertile women. We found hsa-miR-30b and hsa-miR-30d to be significantly upregulated, and hsa-miR-494 and hsa-miR-923 to be downregulated in receptive endometrium. Three algorithms (miRanda, PicTar, and TargetScan) were used for target gene prediction. Functional analyses of the targets using Ingenuity Pathways Analysis and The Database for Annotation, Visualization and Integrated Discovery indicated roles in transcription, cell proliferation and apoptosis, and significant involvement in several relevant pathways, such as axon guidance, Wnt/β-catenin, ERK/MAPK, transforming growth factor β (TGF-β), p53 and leukocyte extravasation. Comparison of predicted miRNA target genes and our previous messenger RNA microarray data resulted in a list of 12 genes, including CAST, CFTR, FGFR2, and LIF that could serve as a panel of genes important for endometrial receptivity. In conclusion, we suggest that a subset of miRNAs and their target genes may play important roles in endometrial receptivity.

  • 166.
    Altmäe, Signe
    et al.
    Division of Obstetrics and Gynecology, Dept of Clinical Science, Karolinska Institutet, Stockholm, Sweden.
    Martínez-Conejero, J. A.
    Salumets, A.
    iGenomix, Valencia, Spain.
    Simón, C.
    Horcajadas, J. A.
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Endometrial gene expression analysis at the time of embryo implantation in women with unexplained infertility2010In: Molecular human reproduction, ISSN 1360-9947, E-ISSN 1460-2407, Vol. 16, no 3, p. 178-187Article in journal (Refereed)
    Abstract [en]

    Successful embryo implantation depends on the quality of the embryo, as well as on the receptivity of the endometrium. The aim of this study was to investigate the endometrial gene expression profile in women with unexplained infertility in comparison with fertile controls at the time of embryo implantation in order to find potential predictive markers of uterine receptivity and to identify the molecular mechanisms of infertility. High-density oligonucleotide gene arrays, comprising 44 000 gene targets, were used to define the endometrial gene expression profile in infertile (n = 4) and fertile (n = 5) women during the mid-secretory phase (day LH +7). Microarray results were validated using real-time PCR. Analyses of expression data were carried out using non-parametric methods. Hierarchical clustering and principal component analysis showed a clear distinction in endometrial gene expression between infertile and fertile women. In total we identified 145 significantly (>3-fold change) up-regulated and 115 down-regulated genes in infertile women versus controls. Via Database for Annotation, Visualization and Integrated Discovery functional analysis we detected a substantial number of dysregulated genes in the endometria of infertile women, involved in cellular localization (21.1%) and transport (18.8%) and transporter activity (13.1%) and with major localization in extracellular regions (19.2%). Ingenuity Pathways Analysis of the gene list showed dysregulation of gene pathways involved in leukocyte extravasation signalling, lipid metabolism and detoxification in the endometria of infertile women. In conclusion, endometrial gene expression in women with unexplained infertility at the time of embryo implantation is markedly different from that in fertile women. These results provide new information on genes and pathways that may have functional significance as regards to endometrial receptivity and subsequent embryo implantation.

  • 167.
    Altmäe, Signe
    et al.
    Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Salumets, Andres
    Department of Obstetrics and Gynaecology, University of Tartu, Tartu, Estonia.
    Bjuresten, Kerstin
    Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Kallak, Theodora Kunovac
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wånggren, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Landgren, Britt-Marie
    Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Hovatta, Outi
    Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Tissue Factor and Tissue Factor Pathway Inhibitors TFPI and TFPI2 in Human Secretory Endometrium - Possible Link to Female Infertility2011In: Reproductive Sciences, ISSN 1933-7191, E-ISSN 1933-7205, Vol. 18, no 7, p. 666-678Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate tissue factor (TF) and its inhibitors TFPI and TFPI2 in secretory endometrium of fertile women and in women with unexplained infertility in relation to endometrial receptivity. In addition, common variation in the regulatory area of TF and TFPI genes was studied. Immunostaining of TF and TFPI, together with the appearance of pinopodes, revealed similar expression pattern in fertile endometrium throughout the secretory phase, being highest at the time of implantation. When compared protein expression levels at the time of implantation, infertile women demonstrated significantly higher TFPI expression in luminal epithelium. Furthermore, polymorphism TF -603 A/G was associated with the endometrial protein level in infertile women, being highest in women with GG genotype, and variation TFPI -287 T/C was associated with unexplained infertility, where infertile women presented more frequently T allele than fertile women. Contrary to TF and TFPI, TFPI2 showed different mRNA and protein expression patterns in fertile endometrium, and no differences between fertile and infertile women were detected. We conclude that the TF pathway is involved in normal endometrial maturation, where TF and TFPI seem to have important roles at the time of embryo implantation. Higher TFPI expression level during the time of embryo implantation and TFPI -287 T allele could be risk factors for unexplained infertility. No distinct involvement of TFPI2 in the regulation of endometrial receptivity and unexplained infertility was found.

  • 168.
    Altmäe, Signe
    et al.
    Dept of Clinical Science, Inervention and Technology, Division of Obstetrics and Gynecology, karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ruiz, Jonatan R.
    Dept of Biosciences and Nutrition, Unit for Preventive Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Laanpere, Margit
    Syvänen, Tiina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Yngve, Agneta
    Salumets, Andres
    Nilsson, Torbjörn K.
    Dept of Clinical Chemistry, Örebro University Hospital, Örebro, Sweden.
    Variations in folate pathway genes are associated with unexplained female infertility2010In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 94, no 1, p. 130-137Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate associations between folate-metabolizing gene variations, folate status, and unexplained female infertility. DESIGN: An association study. SETTING: Hospital-based IVF unit and university-affiliated reproductive research laboratories. PATIENT(S): Seventy-one female patients with unexplained infertility. INTERVENTION(S): Blood samples for polymorphism genotyping and homocysteine, vitamin B12, and folate measurements. MAIN OUTCOME MEASURE(S): Allele and genotype frequencies of the following polymorphisms: 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C/T, 1298A/C, and 1793G/A, folate receptor 1 (FOLR1) 1314G/A, 1816delC, 1841G/A, and 1928C/T, transcobalamin II (TCN2) 776C/G, cystathionase (CTH) 1208G/T and solute carrier family 19, member 1 (SLC19A1) 80G/A, and concentrations of plasma homocysteine, vitamin B12, and serum folate. RESULT(S): MTHFR genotypes 677CT and 1793GA, as well as 1793 allele A were significantly more frequent among controls than in patients. The common MTHFR wild-type haplotype (677, 1298, 1793) CAG was less prevalent, whereas the rare haplotype CCA was more frequent in the general population than among infertility patients. The frequency of SLC19A1 80G/A genotypes differed significantly between controls and patients and the A allele was more common in the general population than in infertile women. Plasma homocysteine concentrations were influenced by CTH 1208G/T polymorphism among infertile women. CONCLUSION(S): Polymorphisms in folate pathway genes could be one reason for fertility complications in some women with unexplained infertility.

  • 169.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    FENO and suspected asthma: better to identify responsiveness to treatment than to label with a diagnosis2018In: The Lancet Respiratory Medicine, ISSN 2213-2600, E-ISSN 2213-2619, Vol. 6, no 1, p. 3-5Article in journal (Other academic)
  • 170.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    FeNO and the Prediction of Exercise-Induced Bronchoconstriction2018In: Journal of Allergy and Clinical Immunology: In Practice, ISSN 2213-2198, E-ISSN 2213-2201, Vol. 6, no 3, p. 863-864Article in journal (Other academic)
  • 171.
    Alving, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Anolik, Robert
    Crater, Glenn
    LaForce, Craig F.
    Rickard, Kathy
    Validation of a new portable exhaled nitric oxide analyzer, NIOX VERO®: Randomized studies in asthma2017In: Pulmonary Therapy, Vol. 3, p. 207-218Article in journal (Refereed)
  • 172.
    Alving, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Basic aspects of exhaled nitric oxide2010In: European Respiratory Monograph, ISSN 1025-448X, E-ISSN 2075-6674, Vol. 49, p. 1-31Article, review/survey (Refereed)
    Abstract [en]

    Nitric oxide (NO) in orally exhaled air mainly originates fromthe respiratory epithelium. NO is produced by inducible NOsynthase (iNOS), which is regulated by signal transducer andactivator of transcription (STAT)-1 under the influence ofhomeostatic interferon-c. In patients with asthma, iNOSexpression is upregulated by interleukin (IL)-4 and IL-13 viathe activation of STAT-6 in the bronchial epithelium. Thus,exhaled NO primarily signals local T-helper cell type 2-driveninflammation in the bronchial mucosa. With these character-istics, exhaled NO will be a suitable marker for predicting theresponse to inhaled corticosteroids, and to monitor the anti-inflammatory effect.The methodology for measuring exhaled NO has beenstandardised based on international consensus. The determi-nants of exhaled NO levels are fairly well characterised, withthe most important being cigarette smoking, nitrate intake, airpollution, allergen sensitisation and exposure, along withheight, sex and age. A future development may be the estima-tion of peripheral airway inflammation by measuring exhaledNO at multiple exhalation flow rates.

  • 173. Aman, J.
    et al.
    Hanson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Östlund, I.
    Wall, K.
    Persson, B.
    Increased Fat Mass and Cardiac Septal Hypertrophy in Newborn Infants of Mothers with Well-Controlled Diabetes during Pregnancy2011In: Neonatology, ISSN 1661-7800, Vol. 100, no 2, p. 147-154Article in journal (Refereed)
    Abstract [en]

    Background: Improved glycaemic control during pregnancy in mothers with type 1 diabetes (T1DM) and gestational diabetes (GDM) has resulted in a marked reduction of perinatal mortality and morbidity, but the prevalence of macrosomia is usually high. Objective: We used non-invasive anthropometric methods to estimate the body composition and the thickness of the interventricular heart septum in 18 infants of mothers with well-controlled T1DM, 10 infants of mothers with GDM and 28 infants of healthy control mothers matched for gestational age and mode of delivery. Methods: Skinfold measurements were obtained with a Harpenden calliper within 48 h after delivery. Echocardiography was also performed to measure the thickness of the interventricular septum. Cord blood was sampled for assays of C-peptide, leptin and IGF-I. Results: The rates of macrosomia (gestational age-adjusted birth weight >2 standard deviation score, SDS) were 56 and 30% in infants of mothers with T1DM and GDM, respectively, compared to 10% in control infants. The body fat content was 40% (0.2 kg) higher and the interventricular heart septum thickness was increased by 20% in both groups of infants of diabetic mothers. We found no associations between maternal levels of HbA1c during pregnancy and body composition or interventricular heart septum thickness. Cord levels of C-peptide and leptin were significantly higher in infants of T1DM mothers than in control infants. Cord leptin level was associated with birth weight SDS and percent body fat in infants of T1DM mothers. IGF-I was associated with percent body fat in infants of GDM mothers and control mothers. A multiple-regression analysis showed that 50% of the variation in body weight SDS could be determined, with IGF-I, leptin and C-peptide as independent variables. Conclusion: Both fat mass and cardiac septal thickness are increased in newborn infants of women with T1DM and GDM in spite of efforts to achieve good glycaemic control during pregnancy.

  • 174.
    Amaral, Rita
    et al.
    Univ Porto, Fac Med, CINTESIS Ctr Hlth Technol & Serv Res, Edificio Nascente,Piso 2,Rua Dr Placido Costa S-N, P-4200450 Porto, Portugal;Porto Hlth Sch, Dept Cardiovasc & Resp Sci, Porto, Portugal.
    Fonseca, Joao A.
    Univ Porto, Fac Med, CINTESIS Ctr Hlth Technol & Serv Res, Edificio Nascente,Piso 2,Rua Dr Placido Costa S-N, P-4200450 Porto, Portugal;Univ Porto, Fac Med, MEDCIDS Dept Community Med Informat & Hlth Sci, Porto, Portugal;Inst & Hosp CUF, Dept Allergy, Porto, Portugal.
    Jacinto, Tiago
    Univ Porto, Fac Med, CINTESIS Ctr Hlth Technol & Serv Res, Edificio Nascente,Piso 2,Rua Dr Placido Costa S-N, P-4200450 Porto, Portugal;Porto Hlth Sch, Dept Cardiovasc & Resp Sci, Porto, Portugal;Inst & Hosp CUF, Dept Allergy, Porto, Portugal.
    Pereira, Ana M.
    Univ Porto, Fac Med, CINTESIS Ctr Hlth Technol & Serv Res, Edificio Nascente,Piso 2,Rua Dr Placido Costa S-N, P-4200450 Porto, Portugal;Inst & Hosp CUF, Dept Allergy, Porto, Portugal.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Having concomitant asthma phenotypes is common and independently relates to poor lung function in NHANES 2007-20122018In: Clinical and Translational Allergy, ISSN 2045-7022, E-ISSN 2045-7022, Vol. 8, article id 13Article in journal (Refereed)
    Abstract [en]

    Background: Evidence for distinct asthma phenotypes and their overlap is becoming increasingly relevant to identify personalized and targeted therapeutic strategies. In this study, we aimed to describe the overlap of five commonly reported asthma phenotypes in US adults with current asthma and assess its association with asthma outcomes. Methods: Data from the National Health and Nutrition Examination Surveys (NHANES) 2007-2012 were used (n =30,442). Adults with current asthma were selected. Asthma phenotypes were: B-Eos-high [if blood eosinophils (B-Eos) >= 300/mm(3)]; FeNO-high (FeNO >= 35 ppb); B-Eos&FeNO-low (B-Eos < 150/mm(3) and FeNO < 20 ppb); asthma with obesity (AwObesity) (BMI >= 30 kg/m(2)); and asthma with concurrent COPD. Data were weighted for the US population and analyses were stratified by age (< 40 and >= 40 years old). Results: Of the 18,619 adults included, 1059 (5.6% [95% CI 5.1-5.9]) had current asthma. A substantial overlap was observed both in subjects aged < 40 years (44%) and >= 40 years (54%). The more prevalent specific overlaps in both age groups were AwObesity associated with either B-Eos-high (15 and 12%, respectively) or B-Eos&FeNO-low asthma (13 and 11%, respectively). About 14% of the current asthma patients were"non-classified". Regardless of phenotype classification, having concomitant phenotypes was significantly associated with (adjusted OR, 95% CI) >= 2 controller medications (2.03, 1.16-3.57), and FEV1 < LLN (3.21, 1.74-5.94), adjusted for confounding variables. Conclusions: A prevalent overlap of commonly reported asthma phenotypes was observed among asthma patients from the general population, with implications for objective asthma outcomes. A broader approach may be required to better characterize asthma patients and prevent poor asthma outcomes.

  • 175.
    Amaral, Rita
    et al.
    Univ Porto, CINTESIS Ctr Hlth Technol & Serv Res, Fac Med, Edificio Nascente,Piso 2, P-4200450 Porto, Portugal;Porto Hlth Sch, Dept Cardiovasc & Resp Sci, Porto, Portugal.
    Pereira, Ana M.
    Univ Porto, CINTESIS Ctr Hlth Technol & Serv Res, Fac Med, Edificio Nascente,Piso 2, P-4200450 Porto, Portugal;Inst & Hosp CUF, Dept Allergy, Porto, Portugal.
    Jacinto, Tiago
    Univ Porto, CINTESIS Ctr Hlth Technol & Serv Res, Fac Med, Edificio Nascente,Piso 2, P-4200450 Porto, Portugal;Porto Hlth Sch, Dept Cardiovasc & Resp Sci, Porto, Portugal.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Fonseca, Joao A.
    Univ Porto, CINTESIS Ctr Hlth Technol & Serv Res, Fac Med, Edificio Nascente,Piso 2, P-4200450 Porto, Portugal;Inst & Hosp CUF, Dept Allergy, Porto, Portugal;Univ Porto, MEDCIDS Dept Community Med Informat & Hlth Sci, Fac Med, Porto, Portugal.
    Comparison of hypothesis- and data-driven asthma phenotypes in NHANES 2007-2012: the importance of comprehensive data availability2019In: Clinical and Translational Allergy, ISSN 2045-7022, E-ISSN 2045-7022, Vol. 9, article id 17Article in journal (Refereed)
    Abstract [en]

    Background

    Half of the adults with current asthma among the US National Health and Nutrition Examination Survey (NHANES) participants could be classified in more than one hypothesis-driven phenotype. A data-driven approach applied to the same subjects may allow a more useful classification compared to the hypothesis-driven one.

    Aim

    To compare previously defined hypothesis-driven with newly derived data-driven asthma phenotypes, identified by latent class analysis (LCA), in adults with current asthma from NHANES 2007-2012.

    Methods

    Adults (18years) with current asthma from the NHANES were included (n=1059). LCA included variables commonly used to subdivide asthma. LCA models were derived independently according to age groups: <40 and 40years old.

    Results

    Two data-driven phenotypes were identified among adults with current asthma, for both age groups. The proportions of the hypothesis-driven phenotypes were similar among the two data-driven phenotypes (p>0.05). Class A <40years (n=285; 75%) and Class A 40years (n=462; 73%), respectively, were characterized by a predominance of highly symptomatic asthma subjects with poor lung function, compared to Class B <40years (n=94; 25%) and Class B 40years (n=170; 27%). Inflammatory biomarkers, smoking status, presence of obesity and hay fever did not markedly differ between the phenotypes.

    Conclusion

    Both data- and hypothesis-driven approaches using clinical and physiological variables commonly used to characterize asthma are suboptimal to identify asthma phenotypes among adults from the general population. Further studies based on more comprehensive disease features are required to identify asthma phenotypes in population-based studies.

  • 176.
    Amaratunga, Chanaki
    et al.
    NIAID, Lab Malaria & Vector Res, Div Intramural Res, NIH, Rockville, MD USA.
    Andrianaranjaka, Voahangy Hanitriniaina
    Inst Pasteur Madagascar, Malaria Res Unit, Antananarivo, Madagascar;Univ Antananarivo, Fac Sci, Antananarivo, Madagascar.
    Ashley, Elizabeth
    MOCRU, Yangon, Myanmar;Univ Oxford, Ctr Trop Med & Global Hlth, Oxford, England.
    Bethell, Delia
    Armed Forces Res Inst Med Sci, Bangkok, Thailand.
    Bjorkman, Anders
    Karolinska Inst, Dept Mol Tumor & Cell Biol, Stockholm, Sweden.
    Bonnington, Craig A.
    Shoklo Malaria Res Unit, Mae Sot, Thailand.
    Cooper, Roland A.
    Dominican Univ Calif, Dept Nat Sci & Math, San Rafael, CA USA.
    Dhorda, Mehul
    Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, WWARN, Oxford, England.
    Dondorp, Arjen
    Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, WWARN, Oxford, England;Mahidol Univ, Fac Trop Med, Mahidol Oxford Res Unit, Bangkok, Thailand.
    Erhart, Annette
    ITM Antwerp, Dept Publ Hlth, Antwerp, Belgium;Inst Trop Med, MRC Unit Gambia, Fajara, Gambia;Inst Trop Med, MRC Unit Gambia, Fajara, Gambia.
    Fairhurst, Rick M.
    NIAID, Lab Malaria & Vector Res, Div Intramural Res, NIH, Rockville, MD USA.
    Faiz, Abul
    Dev Care Fdn, Dhaka, Bangladesh.
    Fanello, Caterina
    Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England;Mahidol Oxford Res Unit, Bangkok, Thailand.
    Fukuda, Mark M.
    Armed Forces Res Inst Med Sci, Bangkok, Thailand.
    Guerin, Philippe
    Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, WWARN, Oxford, England.
    van Huijsduijnen, Rob Hooft
    Med Malaria Venture, Geneva, Switzerland.
    Hien, Tran Tinh
    Hong, N. V.
    Natl Inst Malariol Parasitol & Entomol, Hanoi, Vietnam.
    Htut, Ye
    Dept Med Res, Yangon, Myanmar.
    Huang, Fang
    Chinese Ctr Dis Control & Prevent, Natl Inst Parasit Dis, Shanghai, Peoples R China.
    Humphreys, Georgina
    Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, WWARN, Oxford, England.
    Imwong, Mallika
    Mahidol Univ, Fac Trop Med, Dept Mol Trop Med & Genet, Bangkok, Thailand;Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand.
    Kennon, Kalynn
    Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, WWARN, Oxford, England.
    Lim, Pharath
    NIAID, Lab Malaria & Vector Res, Div Intramural Res, NIH, Rockville, MD USA.
    Lin, Khin
    Dept Med Res, Pyin Oo Lwin Branch, Anesakhan, Myanmar.
    Lon, Chanthap
    Armed Forces Res Inst Med Sci, Bangkok, Thailand.
    Mårtensson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Mayxay, Mayfong
    Lao Oxford Mahosot Hospital, Wellcome Trust Res Unit, LOMWRU, Viangchan, Laos;Univ Hlth Sci, Minist Hlth, Fac Postgrad Studies, Viangchan, Laos;Churchill Hosp, Nuffield Dept Med, Ctr Trop Med & Global Hlth, Oxford, England.
    Mokuolu, Olugbenga
    Univ Ilorin, Coll Hlth Sci, Dept Paediat & Child Hlth, Ilorin, Nigeria;Univ Ilorin, Teaching Hosp, Ctr Malaria & Other Trop Dis Care, Ilorin, Nigeria.
    Morris, Ulrika
    Karolinska Inst, Dept Mol Tumor & Cell Biol, Stockholm, Sweden.
    Ngasala, Billy E.
    Muhimbili Univ Hlth & Allied Sci, Dept Parasitol & Med Entomol, Dar Es Salaam, Tanzania.
    Amambua-Ngwa, Alfred
    Inst Trop Med, MRC Unit Gambia, Fajara, Gambia.
    Noedl, Harald
    Med Univ Vienna, Inst Specif Prophylaxis & Trop Med, Vienna, Austria.
    Nosten, Francois
    Shoklo Malaria Res Unit, Mae Sot, Thailand;Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England;Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand.
    Onyamboko, Marie
    Mahidol Oxford Res Unit, Bangkok, Thailand;Kinshasa Sch Publ Hlth, Kinshasa, DEM REP CONGO.
    Phyo, Aung Pyae
    Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England;Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand.
    Plowe, Christopher V.
    Duke Univ, Duke Global Hlth Inst, Durham, NC USA.
    Pukrittayakamee, Sasithon
    Mahidol Univ, Dept Clin Trop Med, Bangkok, Thailand;Royal Soc Thailand, Bangkok, Thailand.
    Randrianarivelojosia, Milijaona
    Inst Pasteur Madagascar, Malaria Res Unit, Antananarivo, Madagascar;Univ Toliara, Fac Sci, Toliara, Madagascar.
    Rosenthal, Philip J.
    Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA;Univ Calif San Francisco, Div HIV Infect Dis & Global Med, San Francisco, CA 94143 USA.
    Saunders, David L.
    Armed Forces Res Inst Regenerat Med, Bangkok, Thailand;US Army Med Mat Dev Act, Ft Detrick, MD USA.
    Sibley, Carol Hopkins
    Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, WWARN, Oxford, England;Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
    Smithuis, Frank
    Myanmar Oxford Clin Res Unit, Yangon, Myanmar.
    Spring, Michele D.
    Armed Forces Res Inst Med Sci, Dept Immunol & Med, Bangkok, Thailand.
    Sondo, Paul
    Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, WWARN, Oxford, England;CRUN, Ouaga, Burkina Faso.
    Sreng, Sokunthea
    Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia.
    Starzengruber, Peter
    Med Univ Vienna, Inst Specif Prophylaxis & Trop Med, Vienna, Austria;Med Univ Vienna, Dept Lab Med, Div Clin Microbiol, Vienna, Austria.
    Stepniewska, Kasia
    Univ Oxford, Ctr Trop Med & Global Hlth, WWARN, Oxford, England.
    Suon, Seila
    Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia.
    Takala-Harrison, Shannon
    Univ Maryland, Sch Med, Inst Global Hlth, Div Malaria Res, Baltimore, MD 21201 USA.
    Thriemer, Kamala
    Inst Trop Med, Antwerp, Belgium;Menzies Sch Hlth Res, Darwin, NT, Australia.
    Thuy-Nhien, Nguyen
    Tun, Kyaw Myo
    Myanmar Oxford Clin Res Unit, Yangon, Myanmar;Def Serv Med Acad, Yangon, Myanmar.
    White, Nicholas J.
    Mahidol Univ, Fac Trop Med, Mahidol Oxford Res Unit, Bangkok, Thailand;Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England.
    Woodrow, Charles
    Mahidol Univ, Fac Trop Med, Mahidol Oxford Res Unit, Bangkok, Thailand;Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England.
    Association of mutations in the Plasmodium falciparum Kelch13 gene (Pf3D7_1343700) with parasite clearance rates after artemisinin-based treatments: a WWARN individual patient data meta-analysis2019In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 17, p. 1-20, article id 1Article in journal (Refereed)
    Abstract [en]

    Background: Plasmodium falciparum infections with slow parasite clearance following artemisinin-based therapies are widespread in the Greater Mekong Subregion. A molecular marker of the slow clearance phenotype has been identified: single genetic changes within the propeller region of the Kelch13 protein (pfk13; Pf3D7_1343700). Global searches have identified almost 200 different non-synonymous mutant pfk13 genotypes. Most mutations occur at low prevalence and have uncertain functional significance. To characterize the impact of different pfk13 mutations on parasite clearance, we conducted an individual patient data meta-analysis of the associations between parasite clearance half-life (PC1/2) and pfk13 genotype based on a large set of individual patient records from Asia and Africa.

    Methods: A systematic literature review following the PRISMA protocol was conducted to identify studies published between 2000 and 2017 which included frequent parasite counts and pfk13 genotyping. Four databases (Ovid Medline, PubMed, Ovid Embase, and Web of Science Core Collection) were searched. Eighteen studies (15 from Asia, 2 from Africa, and one multicenter study with sites on both continents) met inclusion criteria and were shared. Associations between the log transformed PC1/2 values and pfk13 genotype were assessed using multivariable regression models with random effects for study site.

    Results: Both the pfk13 genotypes and the PC1/2 were available from 3250 (95%) patients (n=3012 from Asia (93%), n=238 from Africa (7%)). Among Asian isolates, all pfk13 propeller region mutant alleles observed in five or more specific isolates were associated with a 1.5- to 2.7-fold longer geometric mean PC1/2 compared to the PC1/2 of wild type isolates (all p≤0.002). In addition, mutant allele E252Q located in the P. falciparum region of pfk13 was associated with 1.5-fold (95%CI 1.4-1.6) longer PC1/2. None of the isolates from four countries in Africa showed a significant difference between the PC1/2 of parasites with or without pfk13 propeller region mutations.Previously, the association of six pfk13 propeller mutant alleles with delayed parasite clearance had been confirmed. This analysis demonstrates that 15 additional pfk13 alleles are associated strongly with the slow-clearing phenotype in Southeast Asia.

    Conclusion: Pooled analysis associated 20 pfk13 propeller region mutant alleles with the slow clearance phenotype, including 15 mutations not confirmed previously.

  • 177.
    Amark, Hanna
    et al.
    Karolinska Institute, Department of Clinical Science and Education, Unit of Obstetrics and Gynecology, Södersjukhuset, Stockholm, Sweden.
    Millde-Luthander, Charlotte
    Karolinska Institute, Department of Clinical Science and Education, Unit of Obstetrics and Gynecology, Södersjukhuset, Stockholm, Sweden.
    Ajne, Gunilla
    Department of Obstetrics and Gynecology, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Högberg, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Pettersson, Hans
    Karolinska Institute, Department of Clinical Science and Education, Unit of Obstetrics and Gynecology, Södersjukhuset, Stockholm, Sweden.
    Wiklund, Ingela
    Department of Clinical Sciences, Division of Obstetrics and Gynecology, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Grunewald, Charlotta
    Karolinska Institute, Department of Clinical Science and Education, Unit of Obstetrics and Gynecology, Södersjukhuset, Stockholm, Sweden.
    Single versus pairwise interpretation of cardiotochography, a comparative study from six Swedish delivery units2014In: Sexual & Reproductive HealthCare, ISSN 1877-5756, E-ISSN 1877-5764, Vol. 5, no 4, p. 195-198Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of the study was to evaluate whether interpreting CTG pairwise brings about a higher level of correctly classified CTG recordings in a non-selected population of midwives and physicians.

    STUDY DESIGN: A comparative study.

    SETTING: Five delivery units in Stockholm and one delivery unit in Uppsala, with 1589, 3740, 3908, 4539, 6438, and 7331 deliveries in 2011, respectively.

    SUBJECTS: 536 midwives and physicians classified one randomly selected CTG recording individually followed by a pairwise classification. The pairs consisted of two midwives (119 pairs) or one midwife and one physician (149 pairs), a total of 268 pairs.

    MAIN OUTCOME MEASURE: The proportion of individually correctly classified CTG recordings versus the proportion of pairwise correctly classified CTG recordings.

    RESULTS: The proportion of individually correctly classified CTG's was 75% and the proportion of pairwise correctly classified CTG's was 80% (difference 5%, p = 0.12).

    CONCLUSIONS: There was no statistically significant difference when CTG's were classified pairwise compared to individual classifications. The proportion of individually correctly classified CTG's was high (75%). There were differences in the proportion of correctly classified CTG recordings between the delivery units, indicating potential areas of improvement.

  • 178.
    Ambrosi, Aurelie
    et al.
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Salomonsson, Stina
    Eliasson, Hakan
    Zeffer, Elisabeth
    Skog, Amanda
    Dzikaite, Vijole
    Bergman, Gunnar
    Fernlund, Eva
    Tingstrom, Joanna
    Theander, Elke
    Rydberg, Annika
    Skogh, Thomas
    Öhman, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Lundstrom, Ulla
    Mellander, Mats
    Winqvist, Ola
    Fored, Michael
    Ekbom, Anders
    Alfredsson, Lars
    Kallberg, Henrik
    Olsson, Tomas
    Gadler, Fredrik
    Jonzon, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kockum, Ingrid
    Sonesson, Sven-Erik
    Wahren-Herlenius, Marie
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Development of heart block in children of SSA/SSB-autoantibody-positive women is associated with maternal age and displays a season-of-birth pattern2012In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, no 3, p. 334-340Article in journal (Refereed)
    Abstract [en]

    Objective Congenital heart block may develop in the fetuses of Ro/SSA-positive and La/SSB-positive mothers. Recurrence rates of only 10-20% despite persisting maternal antibodies indicate that additional factors are critical for the establishment of heart block. The authors investigated the influence of other maternal and fetal factors on heart block development in a Swedish population-based cohort.

    Methods The influence of fetal gender, maternal age, parity and time of birth on heart block development was analysed in 145 families, including Ro/La-positive (n=190) and Ro/La-negative (n=165) pregnancies.

    Results There was a recurrence rate of 12.1% in Ro/La-positive women, and no recurrence in Ro/La-negative women. Fetal gender and parity did not influence the development of heart block in either group. Maternal age in Ro/La-positive pregnancies with a child affected by heart block was, however, significantly higher than in pregnancies resulting in babies without heart block (p<0.05). Seasonal timing of pregnancy influenced the outcome. Gestational susceptibility weeks 18-24 occurring during January-March correlated with a higher proportion of children with heart block and lower vitamin D levels during the same period in a representative sample of Swedish women and a corresponding higher proportion of children with heart block born in the summer (p<0.02). Maternal age or seasonal timing of pregnancy did not affect the outcome in Ro/La-negative pregnancies.

    Conclusion This study identifies maternal age and seasonal timing of pregnancy as novel risk factors for heart block development in children of Ro/La-positive women. These observations may be useful for counselling when pregnancy is considered.

  • 179. Amcoff, B
    et al.
    Bondestam, M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    School adjustment in grade one in relation to the result of a preschool health examination1998In: The Folke Bernadotte International Memorial Conference: Our children - their future, children and young persons with disabilities, StockholmArticle, book review (Other scientific)
  • 180. Amer-Wåhlin,
    et al.
    van den Berg,
    Berglund,
    Blennow,
    Dahlström,
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hagberg,
    Jonsson,
    Kierkegaard,
    Sjörs, Gunnar
    Sävman,
    Westas,
    Ågren, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Asfyxi och neonatal HLR, SFOG2013Report (Other academic)
  • 181.
    Amini, Hashem
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Fetal Anomalies: Surveillance and Diagnostic Accuracy of Ultrasound and Magnetic Resonance Imaging2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aims were to investigate the accuracy of ultrasound in diagnosis of structural fetal anomalies with special focus on false positive findings (I), to evaluate the additional value of second trimester fetal MRI on pregnancy management (II-III) and to estimate the ascertainment in the Swedish Birth Defects Registry and incidence of spina bifida and cleft lip/palate (IV).

    Retrospectively, 328 fetal autopsies were identified where pregnancies were terminated due to ultrasonographically diagnosed fetal anomalies. In 175 (53.4 %) cases ultrasound and fetal autopsy were identical, in 124 (37.8 %) ultrasound was almost correct, in 23 (7.0 %)  ultrasound diagnoses could not be verified, but fetal autopsy showed other anomalies with at least the same prognostic value and in six (1.8 %)  ultrasound diagnosis could not be verified and autopsy showed no or less severe anomalies (I).

    Prospectively, 29 pregnancies with CNS- (II) and 63 with non-CNS-anomalies (III) were included. In the CNS study MRI provided no additional information in 18 fetuses (62 %), additional information without changing the management in 8 (28 %) and additional information altering the pregnancy management in 3 (10%). In the non-CNS study the corresponding figures were 43 (68 %), 17 (27 %) and three (5 %), respectively. MRI in the second trimester might be a clinically valuable adjunct to ultrasound for the evaluation of CNS anomalies, especially when the ultrasound is inconclusive due to maternal obesity (II) and in non-CNS anomalies in cases of diaphragmatic hernia or oligohydramnios (III).

    In newborns, the ascertainments of birth defects are relatively high and assessable, but in pregnancy terminations they are lower or unknown. The incidence of newborns with spina bifida has decreased because of an increased rate of pregnancy terminations (>60%). There is room for improvement concerning the reporting of anomalies from terminated pregnancies (IV).

  • 182.
    Amini, Hashem
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Antonsson, Per
    Papadogiannakis, Nikos
    Ericson, Katharina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Pilo, Christina
    Eriksson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Westgren, Magnus
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Comparison of ultrasound and autopsy findings in pregnancies terminated due to fetal anomalies2006In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 85, no 10, p. 1208-1216Article in journal (Refereed)
    Abstract [en]

    Objective. To compare antenatal diagnoses with autopsy findings in pregnancies terminated after ultrasound detection of fetal anomalies. A second aim was to study the quality of antenatal fetal diagnosis over time. Design. Retrospective, multicenter study over two consecutive six-year periods in Uppsala and Stockholm. Setting. Cases were identified through fetal autopsy reports. Subjects. Three hundred and twenty-eight fetuses from pregnancies terminated between 1992 and 2003 because of ultrasonographically diagnosed anomalies. Main outcome measures. The findings at the last ultrasound examination were compared with the autopsy reports. Results. In 299 cases (91.2%) ultrasound findings either exactly matched or were essentially similar to the autopsy findings. In 23 cases (7%) ultrasound findings were not confirmed at autopsy, but the postnatal findings were at least as severe as the antenatal ones. In six cases (1.8%) termination was performed for an anomaly which proved to be less severe than was predicted by ultrasound. The number of such cases was the same in both six-year periods, while the total number of cases increased from 113 in the first to 215 in the second period. Fetal examination provided further diagnostic information in 47% of the cases. In 10% a syndrome was disclosed. Conclusion. Termination of pregnancy was not always based on a correct antenatal diagnosis. All fetuses but one from terminated pregnancies had evident anomalies. In six cases (1.8%) the decision to terminate was based on suboptimal prognostic and diagnostic information. Fetal autopsy by an experienced perinatal pathologist is essential to provide a definitive diagnosis.

  • 183.
    Amini, Hashem
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ollars, Birgitta
    Swedish Birth Defects Registry, National Board of Health and Welfare, Stockholm, Sweden.
    Annerén, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    The Swedish Birth Defects Registry: ascertainment and incidence of spina bifida and cleft lip/palate2009In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 88, no 6, p. 654-659Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To assess the ascertainment of spina bifida and cleft lip/palate (CLP) in newborns and in fetuses from terminated pregnancies (ToPs) in the Swedish Birth Defects Registry (BDR) and to estimate the true incidences of these two anomalies. DESIGN: Retrospective register study. SETTING: Center for Epidemiology at the Swedish National Board of Health and Welfare, and Uppsala University Hospital. POPULATION: Newborns and fetuses from ToPs with spina bifida (1999-2004) and CLP (1999-2002) in Sweden. METHODS: Data from four registries/sources were used to estimate ascertainment in BDR and incidences of spina bifida and CLP. Main outcome measure: Ascertainment, under-ascertainment, and true incidence. RESULTS: For newborns, under-ascertainment of spina bifida and CLP were 6 and 13%, respectively, in BDR after record linkage with the Medical Birth Registry. Ascertainment of cleft palate increased when accompanied by cleft lip. The under-ascertainment of spina bifida in ToPs after 18 gestational weeks was 27%. Ascertainment of CLP in all ToPs and of spina bifida in ToPs before the 18th gestational week could not be estimated. The majority (109/155, 70%) of ToPs with spina bifida occurred before the 18th week. The estimated incidence of spina bifida per 10,000 births was 6.1 (2.4 newborns and 3.7 ToPs) and of CLP 20.1 (18.9 newborns and 1.2 ToPs). CONCLUSION: The ascertainments are relatively high for newborns in BDR, but lower or unknown for ToPs, which has an impact on the surveillance of spina bifida in view of the high proportion of ToPs.

  • 184.
    Amini, Hashem
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Raiend, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    The Clinical Impact of Fetal Magnetic Resonance Imaging on Management of CNS Anomalies in the Second Trimester of Pregnancy2010In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 89, no 12, p. 20p. 1571-1581Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate the additional information of second trimester magnetic resonance imaging (MRI) compared to ultrasound in fetuses with identified or suspected CNS anomalies and to study the clinical impact of the information on pregnancy management.

    Design: Prospective study during 2004-2007. The fetal MRI examination was planned to be performed within three days after the ultrasound.

    Setting: Uppsala University hospital.    

    Subjects: Twenty-nine pregnant women where second trimester ultrasound identified or suspected fetal CNS anomalies.

    Main outcome measures: Evaluation of the additional information gained from MRI and the consequence it had on pregnancy management.

    Results: The mean interval between ultrasound and MRI was 1.6 days (range 0 –7). In 18 fetuses (62 %)  MRI verified the ultrasound diagnosis but provided no additional information, while in 8 (28 %) MRI gave additional information without changing the management. In 3 (10 %), MRI provided additional information that changed the management of the pregnancy. Two of these women were obese.

    Conclusions: Fetal MRI in the second trimester might be a clinically valuable adjunct to ultrasound for the evaluation of CNS anomalies, especially when ultrasound is inconclusive due to maternal obesity.

     

  • 185.
    Amini, Hashem
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Second trimester fetal magnetic resonance imaging improves diagnosis of non-central nervous system anomalies2011In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 90, no 4, p. 380-389Article in journal (Refereed)
    Abstract [en]

    Objectives. To evaluate the additional information of second trimester magnetic resonance imaging (MRI) compared to ultrasound in fetuses with identified or suspected non-CNS anomalies and to study the clinical impact of the MRI information on pregnancy management. Design. Prospective study during 2003-2007. The fetal MRI examination was planned to be performed within three days after the ultrasound. Setting. Uppsala University hospital. Material and methods. Sixty-three women, where the second trimester ultrasound identified or raised suspicion of fetal anomalies were included. Ultrasound was compared to MRI in relation to the final diagnosis, which was based on the assessment of all available data including post-partum clinical follow-up and autopsy results. Main outcome measures. Evaluation of the additional information gained from MRI and the consequences it had on pregnancy management. Results. The mean interval between ultrasound and MRI was 2.6 days (range 0-15). In 42 (67%) cases MRI was performed within three days. All MRI examinations were assessable. In 43 (68%) fetuses MRI provided no additional information, in 17 (27%) MRI added information without changing the management and in three (5%) MRI provided additional information which changed the management. All these three cases had oligohydramnios. In all six cases of diaphragmatic hernia MRI provided additional information. Conclusions. Fetal MRI of non-CNS anomalies in the second trimester seems to be a valuable adjunct to ultrasound diagnosis of non-CNS anomalies, especially in cases of oligohydramnios and diaphragmatic hernia.

  • 186.
    Amini, Hashem
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    The Clinical Impact of Fetal Magnetic Resonance Imaging on Management of Non-CNS Anomalies in the Second Trimester of PregnancyManuscript (preprint) (Other academic)
    Abstract [en]

    Objectives: To evaluate the additional information of second trimester MRI compared to ultrasound in fetuses with identified or suspected non-CNS anomalies and to study the clinical impact of the MRI information on pregnancy management.

    Methods: Sixty-three women were included, where the second trimester ultrasound identified or raised suspicion of fetal anomalies. Ultrasound was compared to MRI in relation to the final diagnosis, fetal autopsy if performed or postnatal diagnosis. The additional information of MRI and effect on pregnancy management was estimated in consensus.

    Results: The mean gestational age at the last ultrasound before MRI was 18+1 weeks (range 13+0-21+5). The mean interval between ultrasound and MRI was 2.6 days (range 0-15). In 42 (67 %) cases MRI was performed within three days. All MRI examinations were assessable. In 43 (68 %) fetuses MRI provided no additional information, in 17 (27 %) MRI added information without changing the management and in three (5 %) MRI provided additional information which changed the management. These three cases had all oligohydramnios. In all six cases of diaphragmatic hernia MRI provided additional information.

    Conclusions: Fetal MRI of non-CNS anomalies is feasible in the second trimester and gives additional information in nearly a third of cases. It may provide a clinically valuable adjunct to ultrasound especially in cases of diaphragmatic hernia or oligohydramnios.

  • 187.
    Amiot, Ikraam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Coping strategies of men who have been sexually abused in childhood: A qualitative metasynthesis2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Estimates on the prevalence of childhood sexual abuse on boys vary from 8% to 35% globally. These figures are known to be well below the actual numbers that are believed to be much higher than those found in official data. Most cases of childhood sexual abuse are never reported, boys are less likely to report sexual abuse and if they ever do, they do so up to 10-20 years later than girls with similar experiences. This metasynthesis adds to the scarce qualitative literature on coping of male victims. It brings together the types of coping strategies men with histories of childhood sexual abuse use and allows for deeper understanding on how men cope with childhood sexual abuse.

    Aim: To explore coping strategies used by men who have been affected by childhood sexual abuse 

    Method: A qualitative metasynthesis

    Findings: Men affected by childhood sexual abuse reported the use of several coping strategies throughout their lives. These coping strategies were adapted to changes in their social environment. Meaningful inter-personal relationships were found to influence which coping strategies victims would resort to. Not all men felt affected by their experiences of childhood sexual abuse and some reject to be labelled as victims, while others felt empowered by the recognition of their victimhood.

    Conclusion: Men reported using similar coping strategies in different settings, but with different outcomes. Social support and social awareness about male victimisation were found to affect coping strategies used by men who have been affected by childhood sexual abuse.

  • 188.
    Anandavadivelan, P.
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Surg Care Sci, 2nd Floor,Norra Stationsgatan 67, S-17176 Stockholm, Sweden..
    Wikman, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Johar, A.
    Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Surg Care Sci, 2nd Floor,Norra Stationsgatan 67, S-17176 Stockholm, Sweden..
    Lagergren, P.
    Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Surg Care Sci, 2nd Floor,Norra Stationsgatan 67, S-17176 Stockholm, Sweden..
    Impact of weight loss and eating difficulties on health-related quality of life up to 10 years after oesophagectomy for cancer2018In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 105, no 4, p. 410-418Article in journal (Refereed)
    Abstract [en]

    Background: Severe weight loss is experienced by patients with eating difficulties after surgery for oesophageal cancer. The aim of this prospective cohort study was to asssess the influence of eating difficulties and severe weight loss on health-related quality of life (HRQoL) up to 10years after oesophagectomy.

    Methods: Data on bodyweight and HRQoL were collected at 6months, 3, 5 and 10years in patients who underwent surgery for oesophageal cancer in Sweden between 2001 and 2005. Exposures were percentage weight loss, and eating difficulties defined by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-OES18 questionnaire. Outcomes were HRQoL scores from the EORTC QLQ-C30 questionnaire. Repeated-measures ANOVA, adjusting for potential confounders, was used to assess the association between eating difficulties and weight loss (4 exposure groups) and HRQoL scores at each time point. Mean score differences (MDs) between time points or exposure groups were defined as clinically relevant in accordance with evidence-based interpretation guidelines.

    Results: In total, 92 of 104 10-year survivors (885 per cent) responded to the questionnaires. Weight loss was greatest within 6months of surgery. Patients with eating difficulties with or without weight loss reported clinically and statistically significantly worsened HRQoL in almost all aspects. The largest MD was seen between 5 and 10years after surgery for global quality of life, physical, role and social function (MD -22 to -30), as well for fatigue, nausea, dyspnoea, insomnia, appetite loss and diarrhoea (MD 24-36).

    Conclusion: Eating difficulties are associated with deterioration in several aspects of HRQoL up to 10years after surgery for oesophageal cancer.

  • 189.
    Anandavadivelan, Poorna
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Surg Care Sci, Stockholm, Sweden.
    Wikman, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Johar, Asif
    Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Surg Care Sci, Stockholm, Sweden.
    Lagergren, Pernilla
    Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Surg Care Sci, Stockholm, Sweden.
    Profiles of patient and tumour characteristics in relation to health-related quality of life after oesophageal cancer surgery2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 4, article id e0196187Article in journal (Refereed)
    Abstract [en]

    Strong deterioration in health-related quality of life (HRQOL) is a major concern in a sub-group of long-term oesophageal cancer survivors. This study aimed to identify potential clustering of patients and tumour variables that predicts such deterioration. Patient and tumour variables were collected in a prospective cohort of patients who underwent surgery for oesophageal cancer in Sweden 2001–2005. Latent cluster analysis identified statistically significant clustering of these variables. Multivariable logistic regression adjusted for age, BMI, tumour stage and marital status was used to determine odds ratios (ORs) with 95% confidence intervals (CIs) between patient profiles and HRQOL at 3 and 5 years from surgery. Among 155 included patients at 3 years, three patient profiles were identified: 1) ‘reference profile’ (males, younger age, employed, upper secondary education, co-habitating, urban dwellers, adenocarcinoma and advanced tumour stage) (n = 47;30%), 2) ‘adenocarcinoma profile’ (middle age, unemployed/retired, males, low education, co-habitating, adenocarcinoma, advanced tumour stage, tumour in lower oesophagus/cardia, and co-morbidities (n = 79;51%), and 3) ‘squamous-cell carcinoma profile’ (unemployed/retired, middle-age, males, low BMI, urban dwellers, squamous-cell carcinoma, tumour in upper/middle oesophagus (n = 29;19%). These profiles did not differ regarding most HRQOL measures. Exceptions were the squamous-cell carcinoma profile, reporting more constipation (OR = 5.69; 95%CI: 1.34–24.28) and trouble swallowing saliva (OR = 4.87; 95%CI: 1.04–22.78) and the adenocarcinoma profile reporting more dyspnoea (OR = 2.60; 95%CI: 1.00–6.77) and constipation (OR = 3.31; 95%CI: 1.00–10.97) compared to the reference profile. Three distinct patient profiles were identified but these could not explain the substantial deterioration in HRQOL observed in the sub-sample of survivors.

  • 190.
    Anandavadivelan, Poorna
    et al.
    Karolinska Inst, Stockholm, Sweden.
    Wikman, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Martin, Lena
    Dept Biosci & Nutr, Stockholm, Sweden.
    Rueb, Claudia
    Imperial Coll Healthcare NHS Trust, St Marys Hosp, London, England.
    Johar, Asif
    Karolinska Inst, Dept Mol Med & Surg, Surg Care Sci, Stockholm, Sweden.
    Malberg, Kalle
    Karolinska Inst, Dept Mol Med & Surg, Surg Care Sci, Stockholm, Sweden.
    Lagergren, Pernilla
    Karolinska Inst, Dept Mol Med & Surg, Surg Care Sci, Stockholm, Sweden.
    Extent of dumping symptoms and its association with malnutrition following surgery for oesophageal cancer2018In: Quality of Life Research, ISSN 0962-9343, E-ISSN 1573-2649, Vol. 27, no Supplement 1, p. S76-S76Article in journal (Other academic)
  • 191.
    Anastasopoulou, Stavroula
    et al.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Eriksson, Mats A.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Heyman, Mats
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Wang, Chen
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Niinimäki, Riitta
    Oulu Univ Hosp, Dept Children & Adolescents, Oulu, Finland;Univ Oulu, PEDEGO Res Unit, Oulu, Finland.
    Mikkel, Sirje
    Univ Tartu, Dept Hematol & Oncol, Tartu, Estonia.
    Vaitkeviciene, Goda E.
    Vilnius Univ Hosp Santaros Klin, Childrens Hosp, Vilnius, Lithuania;Vilnius Univ, Vilnius, Lithuania.
    Johannsdottir, Inga Maria
    Oslo Univ Hosp, Dept Pediat Hematol Oncol, Oslo, Norway.
    Myrberg, Ida Hed
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Jonsson, Olafur Gisli
    Univ Iceland, Dept Pediat, Reykjavik, Iceland.
    Als-Nielsen, Bodil
    Rigshosp, Univ Hosp, Dept Pediat & Adolescent Med, Copenhagen, Denmark;Univ Copenhagen, Fac Med, Inst Clin Med, Copenhagen, Denmark.
    Schmiegelow, Kjeld
    Rigshosp, Univ Hosp, Dept Pediat & Adolescent Med, Copenhagen, Denmark;Univ Copenhagen, Fac Med, Inst Clin Med, Copenhagen, Denmark.
    Banerjee, Joanna
    Univ Helsinki, Childrens Hosp, Dept Pediat Hematol Oncol & Stem Cell Transplanta, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland.
    Harila-Saari, Arja H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.
    Ranta, Susanna
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Posterior reversible encephalopathy syndrome in children with acute lymphoblastic leukemia: Clinical characteristics, risk factors, course, and outcome of disease2019In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 66, no 5, article id e27594Article in journal (Refereed)
    Abstract [en]

    Background: Posterior reversible encephalopathy syndrome (PRES) is a distinct entity with incompletely known predisposing factors. The aim of this study is to describe the incidence, risk factors, clinical course, and outcome of PRES in childhood acute lymphoblastic leukemia (ALL).

    Procedure: Patients aged 1.0 to 17.9 years diagnosed with ALL from July 2008 to December 2015 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol were included. Patients with PRES were identified in the prospective NOPHO leukemia toxicity registry, and clinical data were collected from the medical records.

    Results: The study group included 1378 patients, of whom 52 met the criteria for PRES. The cumulative incidence of PRES at one month was 1.7% (95% CI, 1.1-2.5) and at one year 3.7% (95% CI, 2.9-4.9). Older age (hazard ratios [HR] for each one-year increase in age 1.1; 95% CI, 1.0-1.2, P = 0.001) and T-cell immunophenotype (HR, 2.9; 95% CI, 1.6-5.3, P = 0.0005) were associated with PRES. Central nervous system (CNS) involvement (odds ratios [OR] = 2.8; 95% CI, 1.2-6.5, P = 0.015) was associated with early PRES and high-risk block treatment (HR = 2.63; 95% CI, 1.1-6.4, P = 0.033) with late PRES. At follow-up of the PRES patients, seven patients had epilepsy and seven had neurocognitive difficulties.

    Conclusion: PRES is a neurotoxicity in the treatment of childhood ALL with both acute and long-term morbidity. Older age, T-cell leukemia, CNS involvement and high-risk block treatment are risk factors for PRES.

  • 192.
    Ander, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Cancer during adolescence: Psychological consequences and development of psychological treatment2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The overall aim of the present thesis was to examine long-term psychological distress following cancer during adolescence and to develop a tailored psychological intervention to reduce cancer-related distress experienced by young survivors of adolescent cancer that was feasible and acceptable.

    Study I adopted a longitudinal design, assessing health-related quality of life (HRQOL) and symptoms of anxiety and depression among adolescents diagnosed with cancer from shortly after diagnosis (n=61) up to 10 years after diagnosis (n=28). Findings suggest that development of HRQOL and anxiety and depression is not linear and whilst the majority adjust well, a subgroup report long-term elevated distress. In Study II, experiences of cancer-related psychological distress were explored using unstructured interviews. Participants described cancer treatment as a mental challenge, felt marked and hindered by the cancer experience, and struggled with feelings of inadequacy and insecurity, existential issues, and difficulties handling emotions. Study III was a preliminary investigation of individualised cognitive behavioural therapy (CBT), alongside the identification and conceptualisation of cancer-related concerns using cognitive-behavioural theory. Significant difficulties with recruitment were encountered. Participants reported cancer-related concerns conceptualised as social avoidance, fear and avoidance of emotions and bodily symptoms, imbalance in activity, and worry and rumination. In Study IV, the acceptability and feasibility of an internet-administered CBT based self-help intervention (ICBT) for young persons diagnosed with cancer during adolescence was examined using an uncontrolled design and embedded process evaluation. The study protocol for Study IV was included in this thesis along with preliminary findings demonstrating significant difficulties with recruitment.

    Overall, findings suggest that whilst the majority of survivors of adolescent cancer adjust well over time a subgroup report elevated levels of distress and a range of distressing cancer-related experiences. A number of cancer-related difficulties were identified in Study II and III, which may be used to inform the development of future psychological treatments for the population. Preliminary investigation of the psychological interventions examined within this thesis further highlights the need for future development work to enhance the feasibility and acceptability of psychological support for the population. 

  • 193.
    Ander, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Grönqvist, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Cernvall, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Engvall, Gunn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hedström, Mariann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Ljungman, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Lyhagen, Johan
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    Mattsson, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    von Essen, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Development of health-related quality of life and symptoms of anxiety and depression among persons diagnosed with cancer during adolescence: a 10-year follow-up study2016In: Psycho-Oncology, ISSN 1057-9249, E-ISSN 1099-1611, Vol. 25, no 5, p. 582-589Article in journal (Refereed)
    Abstract [en]

    Objective: The main aim was to investigate the development of health-related quality of life (HRQOL) and symptoms of anxiety and depression in a cohort diagnosed with cancer during adolescence from shortly after up to 10 years after diagnosis.

    Methods: Participants (n = 61) completed the SF-36 and the HADS shortly; six, 12, and 18 months; and two, three, four, and 10 years (n = 28) after diagnosis. Polynomial change trajectories were used to model development.

    Results: Polynomial change trajectories showed an initial increase which abated over time into a decrease which abated over time for the SF-36 subscales Mental Health and Vitality; an initial decline which abated over time into an increase for HADS anxiety; and an initial decline which abated over time into an increase which abated over time for HADS depression. The SF-36 mental component summary showed no change from two to 10 years after diagnosis whereas the SF-36 physical component summary showed an increase from two years after diagnosis which declined over time. Ten years after diagnosis 29% reported possible anxiety.

    Conclusions: Development of HRQOL and symptoms of anxiety and depression appears to be nonlinear among persons diagnosed with cancer during adolescence. Well into permanent survivorship an increase in symptoms of anxiety is shown and approximately a third of the participants report possible anxiety. The findings indicate the need for: studies designed to pinpoint the times of highest psychological risk, clinical follow-up focusing on psychological problems, and development of effective psychological interventions for survivors of adolescent cancer

  • 194.
    Ander, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Psychology in Healthcare.
    Lindahl Norberg, Annika
    von Essen, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Psychology in Healthcare.
    Ljungman, Gustaf (Contributor)
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ljótsson, Brjánn (Contributor)
    Institutionen för klinisk neurovetenskap, Karolinska institutet.
    Ljungman, Lisa (Contributor)
    Cernvall, Martin (Contributor)
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Psychology in Healthcare.
    Olsson, Erik (Contributor)
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Psychology in Healthcare.
    Alfonsson, Sven (Contributor)
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Psychology in Healthcare.
    Norlund, Fredrika (Contributor)
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Psychology in Healthcare.
    Toft, Teolinda (Contributor)
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Psychology in Healthcare.
    Arlinger Karlsson, Cecilia (Contributor)
    Grönqvist, Helena (Contributor)
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Psychology in Healthcare.
    Stjernqvist, Claes (Contributor)
    Nordenstam, Lisa (Contributor)
    Boger, Marike
    Skogseid, Ellen (Contributor)
    U-CARE: UngaKan: Ett internet-administrerat guidat självhjälsprogram för unga som diagnosticerats med cancer under tonåren2017Other (Other (popular science, discussion, etc.))
  • 195.
    Ander, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Norberg, Annika Lindahl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Ljungman, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ljotsson, Brjann
    von Essen, Louise
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Identification of Cancer-related Psychological Suffering Experienced by Young People Diagnosed with Cancer During Adolescence and Development of a Psychological Treatment to Reduce This Suffering2015Conference paper (Refereed)
  • 196.
    Ander, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Thorsell Cederberg, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Lindahl Norberg, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    von Essen, Louise
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Losing your context - Exploration of emotional suffering after cancer during adolescence2016Conference paper (Refereed)
  • 197.
    Ander, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Thorsell Cederberg, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    von Essen, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Hovén, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare. Karolinska institutet.
    Exploration of psychological distress experienced by survivors of adolescent cancer reporting a need for psychological support2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 4, article id e0195899Article in journal (Refereed)
    Abstract [en]

    Objective

    In this qualitative study, we aimed to provide an in-depth exploration of cancer-related psychological distress experienced by young survivors of cancer during adolescence reporting a need for psychological support.

    Methods

    Two individual interviews were held with ten young survivors of cancer diagnosed in adolescence. The interviews were audio-recorded and transcribed verbatim. Analysis followed the guidelines for inductive qualitative manifest content analysis.

    Results

    The survivors described distress experienced during and after the end of treatment. Five categories comprising 14 subcategories were generated. The categories included: A tough treatment, Marked and hindered, Not feeling good enough, Struggling with the fragility of life, and finally, An ongoing battle with emotions.

    Conclusion

    Young survivors of adolescent cancer reporting a need for psychological support described feeling physically, socially, and mentally marked by the cancer experience. They struggled with powerlessness, insecurity, social disconnection, loneliness, and feelings of being unimportant and a failure, and had difficulties understanding and managing their experiences. These concerns should be addressed in psychological treatments for the population irrespective of which approach or model is used to understand survivors’ difficulties. A transdiagnostic approach targeting processes that underpin different manifestations of distress may be effective.

  • 198.
    Ander, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    von Essen, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Ljungman, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Mattsson, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Toft, Teolinda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Norberg, Annika Lindahl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    U-CARE: YoungCan-Development of an Internet-Based Self-Help Program of Psychosocial Support and Psychological Treatment2013Conference paper (Refereed)
  • 199.
    Ander, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Wikman, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Ljótsson, Brjánn
    Karolinska Inst, Div Psychol, Dept Clin Neurosci, Stockholm, Sweden.
    Grönqvist, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Ljungman, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Woodford, Joanne
    Univ Exeter, Coll Life & Environm Sci, CEDAR, Psychol, Exeter, Devon, England.
    Lindahl Norberg, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    von Essen, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Guided Internet-Administered Self-Help to Reduce Symptoms Of Anxiety and Depression Among Adolescents and Young Adults Diagnosed With Cancer During Adolescence (U-CARE: YoungCan): study protocol for a feasibility trial2017In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, no 1, article id e013906Article in journal (Refereed)
    Abstract [en]

    Introduction A subgroup of adolescents and young adults diagnosed with cancer during adolescence reports elevated levels of anxiety and depressive symptoms and unmet needs for psychological support. Evidence-based psychological treatments tailored for this population are lacking. This protocol describes a feasibility study of a guided-internet-administered self-help programme (YoungCan) primarily targeting symptoms of anxiety and depression among young persons diagnosed with cancer during adolescence and of the planned study procedures for a future controlled trial. Methods/analysis The study is an uncontrolled feasibility trial with a pre-post and 3-month follow-up design. Potential participants aged 15-25years, diagnosed with cancer during adolescence, will be identified via the Swedish Childhood Cancer Registry. 30 participants will be included. Participants will receive YoungCan, a 12-week therapist-guided, internet-administered self-help programme consisting primarily of cognitive-behavioural therapy organised into individually assigned modules targeting depressive symptoms, worry and anxiety, body dissatisfaction and post-traumatic stress. Interactive peer support and psychoeducative functions are also available. Feasibility outcomes include: recruitment and eligibility criteria; data collection; attrition; resources needed to complete the study and programme; safety procedures; participants' and therapists' adherence to the programme; and participants' acceptability of the programme and study methodology. Additionally, mechanisms of impact will be explored and data regarding symptoms of anxiety, depression, post-traumatic stress, body dissatisfaction, reactions to social interactions, quality of life, axis I diagnoses according to the Mini International Neuropsychiatric Interview and healthcare service use will be collected. Exploratory analyses of changes in targeted outcomes will be conducted. Ethics/dissemination This feasibility protocol was approved by the Regional Ethical Review Board in Uppsala, Sweden (ref: 2016/210). Findings will be disseminated to relevant research, clinical, health service and patient communities through publications in peer-reviewed and popular science journals and presentations at scientific and clinical conferences.

  • 200.
    Ander, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Woodford, Joanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Cernvall, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    von Essen, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Ljótsson, Brjánn
    Karolinska institutet.
    A preliminary open trial of individualised cognitive behavioural therapy for young survivors of cancer during adolescence: initial findings and conceptualisation of distressManuscript (preprint) (Other academic)
    Abstract [en]

    Objective: A subgroup of adolescent and young adult (AYA) survivors of cancer in adolescence report high levels of psychological distress. Empirically-supported treatments tailored to the concerns experienced by this population are lacking. The aims of this study were to (1) conduct a preliminary evaluation of an individualised cognitive behavioural therapy (CBT) intervention for adolescent and young adult (AYA) survivors of cancer during adolescence and (2) identify and conceptualise cancer-related psychological concerns using cognitive-behavioural theory.

    Methods: A single-arm trial in which ten AYA (17-25 years) survivors of cancer during adolescence were offered up to 15 sessions of individualised CBT guided by behavioural case formulations was undertaken. Clinical outcomes were assessed at baseline, post-treatment, and three months follow-up. Before commencing treatment, two individual qualitative interviews were conducted with each participant. Analysis of cancer-related concerns was guided by qualitative framework analysis and theoretical thematic analysis, and cognitive-behavioural theory was used to inform identification of themes.

    Results: Ten of 201 potential participants invited to participate were included resulting in an overall participation rate of 5%. Nine participants completed treatment and eight completed the follow-up assessment. The majority of concerns reported were cancer-related and conceptualised as social avoidance, fear and avoidance of emotions and bodily symptoms, low mood and unbalance in activity, and worry and rumination.

    Conclusions: Given significant difficulties with recruitment, further research is needed to examine barriers and the impact of mental health literacy and stigma on help seeking in the AYA cancer survivor population. Internet-administered CBT self-help tailored towards the main presenting concerns of AYA cancer survivors may be a promising solution.

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