1. |
- Carlsson, Per, 1951-, et al.
(författare)
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National Model for Transparent Vertical Prioritisation in Swedish Health Care
- 2007
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The proposed national model described in this report has been developed by a working group comprised of staff from the National Board of Health and Welfare, the National Centre for Priority Setting in Health Care, and other organisations involved in vertical prioritisation – including the Östergötland County Council, Stockholm County Council, Västra Götaland, the Health Services Region of Southern Sweden, the Swedish Society of Medicine, the Swedish Society of Nursing, and the Swedish Association of Health Professionals. Throughout the process of designing the model, the Swedish Federation of Occupational Therapists and the Swedish Association of Registered Physiotherapists were regularly informed and given opportunities to review and comment on the proposal. Furthermore, the report was reviewed and discussed at a meeting with invited representatives from the other county councils, the Pharmaceutical Benefits Board, and several professional interest groups. Viewpoints were also obtained at a seminar arranged by PrioNet, a network of individuals interested in prioritisation.Potentially, the working model described in Chapter 4 could be used in any context where vertical prioritisation takes place, e.g. activities arranged by the state, county councils, municipalities, hospital departments, and professional groups.This report is designed to be a useful tool for those working on development projects in priority setting. We believe that the contents must be adapted, with the help of relevant examples and some simplifications; to fit the specific needs of different projects or groups. The text must also be adapted to a target group’s knowledge and previous experience in dealing with transparent priority setting. It must be the responsibility of each provider and other affected organisation to adapt the material to the given situation and project. The National Centre for Priority Setting in Health Care, the National Board of Health and Welfare, and others who have participated actively in this effort can be helpful to various target groups in adapting this report.When and how to engage in practically implementing vertical prioritisation are questions that need to be answered at the local level. Primarily, it is the duty of the local authorities/providers to take responsibility for implementation. Professional organisations also play an important role. Public agencies, universities, and knowledge centres should be sources of support for the local authorities/providers.The Riksdag’s resolution on prioritisation served as the foundation for developing the model.Where there are areas of uncertainty in how to translate these guidelines in practice, or where practical implementation might conflict with the principles, we have pointed this out.Our conclusions and proposals are the following:When facing a choice – regardless of whether it involves allocating new resources for different purposes, or to implement cutbacks – it can be advantageous to rank the possible choices in order of priority. In our model, only the relevant options can be ranked by priority. The consequences of this ranking are not obvious at the outset, but can serve as a basis either to allocate more resources or ration by some means.In vertical prioritisation, it is advantageous to organise the prioritization process starting from a general categorisation of health problems/disease groups. As a rule, these categories cover many organisational units/clinical departments, specialties, or professional groups, thus providing a more multidimensional view of the problem. Furthermore, this allows the process to start from a patient/population perspective, which appears to be more goal-oriented than an organisational/staff perspective.That which is ranked, i.e. one of the choices, we refer to as a prioritization object. We suggest that prioritisation objects consist of different combinations of health conditions and interventions.1 When deciding on the appropriate level of detail, the decision must be based on the context in which prioritisation is carried out. A starting point would be to focus on typical cases, large-volumes services, and controversial care.All forms of vertical prioritisation should be based on the ethical principles that the Riksdag decided should apply in prioritising health services. However, these ethical principles must be made known, clarified, and perhaps complemented before they can be applied to practical priority setting. Furthermore, we believe that the Riksdag’s four so-called priority groups should not be part of the model.The human dignity principle, i.e. that all people should have equal value and equal rights to care irrespective of their personal characteristics and function in society, is the undisputed cornerstone in priority setting. When personal characteristics such as age, gender, lifestyle, or function of a group are expressions of the presence of special needs, so that benefits of the interventions are different, these personal characteristics could be addressed in a priority at the group level. Further discussion is needed regarding the question of how external effects (i.e. the effects of an intervention on families and groups other than the individual directly affected by the intervention) should be valued in priority setting.The concept of need in health care includes both the severity level of the condition and the expected benefits of intervention. As a patient, one needs only those interventions that can be expected to yield benefits. Based on this definition of need, a person does not need an intervention that does not improve health and quality of life, i.e. an intervention with no benefit. In such cases, health services have a responsibility to refer people who seek care for some type of problem, to other appropriate services.The Riksdag’s guidelines regarding the cost-effectiveness principle (applied to individual patients) are too limited to provide guidance for vertical prioritisation at the group level. From the outset, the Government’s bill (Priority Setting in Health Care) highlighted the importance of differentiating a cost-effectiveness principle that applied to choices among various interventions for the individual patient (where the principle can be applied as the Commission of Inquiry proposed) and the aim of health services to achieve high cost-effectiveness in health care generally. Here we also refer to the Riksdag’s directive to the Pharmaceutical Benefits Board. In its decisions on subsidising (prioritising) a drug, the Board should determine, e.g. whether the drug is cost effective from a societal perspective, which requires comparing the patient benefits of the drug to its cost. In such decisions, the cost effectiveness should be considered along with the needs and solidarity principle and the human dignity principle.The proposed working model essentially concurs with the working model used by the National Board of Health and Welfare in developing national guidelines. In describing a national working model, it is not possible to include every aspect that might be considered. Hence, one must start from the model and decide which other relevant aspects should be included. For instance, the International Classification on Functioning, Disability, and Health (ICF) can be used as guidance to describe the severity of health conditions.Due to the wealth of variety in outcome measures for different activities, and the limited experience in working with explicit threshold values, we believe would be premature to recommend standardised categories, e.g. risk levels. However, it is important that those working with prioritization describe their reasoning. Primarily, the categories applied by the Swedish Council on Technology Assessment in Health Care (SBU) to grade the scientific evidence of an intervention’s effects should be used. Local prioritisation projects with limited resources at their disposal should describe (text) their appraisal of the scientific evidence and reference the scientific sources used. The strength of evidence should be expressed in numbers only when supporting a conclusion of a systematic review by SBU, or other literature reviews of good quality.Prioritisation projects having access to health economic evaluation should, until further notice, adhere to the approach used by the National Board of Health and Welfare and present cost-effectiveness on a scale from low to very high cost per life-year gained or cost per quality-adjusted life-year. Economic evidence should be presented according to the principles applied by the National Board of Health and Welfare. In local projects with limited resources, or problems in consistently acquiring information on cost effectiveness, we recommend that the authors at least discuss cost effectiveness in cases where the priority ranking would be decisively affected when costs are weighed in.A 10-level ranking list should be used. The ranking list should be complemented by a “don’t do” list for methods that should not be used at all, or not used routinely, and a research and development (R&D) list for methods where the evidence still insufficient to motivate their use in standard practice. In the absence of an objective quantitative/mathematical method, a qualitative method should be used in the appraisal. Here too, we believe that it is not yet possible to establish standard criteria to determine within which ranking level a prioritisation object should fall.Results should be presented as a ranking list. The parameters used as a basis for prioritisation should also be presented in a uniform manner in ranking lists that are shared with other parties. For pedagogic reasons, details concerning language and format need to be adapted to the respective target groups.Thresholds for what constitutes an acceptable coverage of need (care quality, volume, and percentage of the patient group with access to services) a
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2. |
- Carlsson, Per, 1951-, et al.
(författare)
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Nationell modell för öppna vertikala prioriteringar inom svensk hälso- och sjukvård
- 2007
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- En arbetsgrupp med personer från Socialstyrelsen och PrioriteringsCentrum, andra organisationer som arbetat med vertikala prioriteringar såsom Landstinget i Östergötland, Stockholms läns landsting, Västra Götaland, Södra sjukvårdsregionen, Svenska Läkaresällskapet, Svensk sjuksköterskeförening och Vårdförbundet har tagit fram detta förslag. Förslaget har fortlöpande förankrats hos Förbundet Sveriges Arbetsterapeuter och Legitimerade Sjukgymnasters Riksförbund som kunnat lämna synpunkter på utformningen av odellen.Dessutom har rapporten varit föremål för granskning och diskussion vid ett möte med inbjudna representanter från övriga landsting, Läkemedelsförmånsnämnden och flera yrkesorganisationer. Synpunkter har också inkommit från ett seminarium som arrangerades av PrioNet, ett nätverk av personer med intresse för prioriteringar.Den arbetsmodell som beskrivs i kapitel 4 ska kunna användas i alla sammanhang där vertikala prioriteringar sker såsom aktiviteter som arrangeras av staten, landsting, kommuner, kliniker, professionella grupper eller motsvarande.Rapporten är skriven på ett sådant sätt att den ska kunna användas i första hand som ett stöd till dem som bedriver utvecklingsarbete rörande prioriteringar. Vi tror att innehållet måste anpassas till olika verksamheter eller personalgruppers specifika behov med hjälp av kompletterande exempel och vissa förenklingar. Texten måste givetvis också anpassas till de kunskaper och tidigare erfarenheter som den aktuella målgruppen har när det gäller arbete med öppna prioriteringar. Sådana situations- och verksamhetsanpassade versioner måste det åligga varje sjukvårdshuvudman och andra berörda organisationer att utarbeta. PrioriteringsCentrum, Socialstyrelsen och andra parter som deltagit aktivt i detta arbete kan givetvis vara behjälpliga i arbetet med att bearbeta denna rapport för olika målgrupper.Frågan om när och hur arbetet med vertikala prioriteringar ska bedrivas i praktiken kan också endast besvaras lokalt. Det är i första hand ett nsvar för huvudmännen att ta ansvar för implementeringen. Professionella organisationer har också en viktig roll. Myndigheter, universitet och kunskapscentra ska vara ett stöd till huvudmännen.Utgångspunkten i modellutvecklingen är Riksdagens beslut om prioriteringar. När det finns oklarheter om hur dessa riktlinjer ska omsättas i praktiken eller att praktiken kan förefalla i konflikt med principerna har vi påpekat detta.När man står inför ett val - oavsett om det handlar om att fördela nya resurser till olika ändamål eller att genomföra besparingar - kan det vara en fördel att kunna rangordna tänkbara valmöjligheter i enprioriteringsordning. I vår modell innebär prioritering enbart att de relevanta alternativen rangordnas. Konsekvenserna av denna rangordning är inte på förhand given utan kan ligga till grund såväl för tillskott av resurser som för ransonering av något slag.Vid en vertikal prioritering är det en fördel att organisera prioriteringsarbetet så att det utgår från en grov uppdelning i hälsoproblem/sjukdomsgrupper. En sådan uppdelning innebär i regel att flera organisationsenheter/kliniker, specialiteter eller yrkesgrupper berörs och man får en mer allsidig belysning av problemet. Dessutom utgår man från ett patient/befolkningsperspektiv vilket förefaller mer ändamålsenligt än ett organisatoriskt/personalperspektiv.Det som rangordnas och som någon väljer mellan benämner vi prioriteringsobjekt. Vi föreslår att prioriteringsobjektet utgörs av olika kombinationer av hälsotillstånd och åtgärder1. När det gäller att bestämma en lämplig detaljeringsgrad måste det avgöras utifrån sammanhanget prioriteringar ska göras i. En utgångspunkt är att fokusera på typfall, vård som representerar stor volym och kontroversiell vård.Alla former av vertikala prioriteringar ska baseras på de etiska principer som riksdagen beslutat ska gälla vid prioriteringar inom hälso- och sjukvården. De etiska principerna behöver dock göras kända, förtydligas och eventuellt kompletteras för att kunna omsättas i praktiska prioriteringar. Vidare anser vi att riksdagens fyra så kallade prioriteringsgrupper inte ska ingå i modellen.Människovärdesprincipen, som innebär att alla människor bör ha lika värde och samma rätt till vård oberoende av personliga egenskaper och funktioner i samhället, är den självklara utgångspunkten vid prioriteringar. När personliga egenskaper såsom ålder, kön, livsstil eller funktion hos en grupp är ett uttryck för att speciella behov föreligger så att nytta med insatserna blir olika ska de personliga egenskaperna kunna beaktas i en prioritering på gruppnivå. Frågan om hur externa effekter, d v s effekten av en insats för närstående och andra grupper än den individ som är direkt berörd av insatsen, ska värderas vid en prioritering behöver diskuteras ytterligare.Med behov av hälso- och sjukvård menas både tillståndets svårighetsgrad och den förväntade nyttan av en åtgärd. Som patient har man endast behov av sådana vårdåtgärder som man förväntas ha nytta av. Motsatt gäller att en människa enligt detta sätt att definiera behov inte behöver åtgärder som inte förbättrar hälsan och livskvaliteten, sådana som hon inte har nytta av. Här har givetvis hälso- och sjukvården ett ansvar att lotsa människor de kommer i kontakt med, och som far illa på något sätt, till andra lämpliga aktörer.Riksdagens riktlinjer, när det gäller kostnadseffektivitetsprincipen (tillämpad för enskilda patienter), är för begränsad för att vägleda vid vertikala prioriteringar som gäller prioritering på gruppnivå. Regeringen konstaterade redan i prioriteringspropositionen att det är angeläget att skilja på en kostnadseffektivitetsprincip som gäller val mellan olika åtgärder för den enskilde patienten (där principen kan tillämpas som utredningen föreslår) och på hälso- och sjukvårdens strävan efter en hög kostnadseffektivitet när det gäller vårdens verksamhet i allmänhet. Här stödjer vi oss på Riksdagens direktiv till Läkemedelsförmånsnämnden. Nämnden ska vid beslut om subvention (prioriteringar) av ett läkemedel bl a bedöma om det är kostnadseffektivt i ett samhälleligt perspektiv, vilket innebär att man ställer patientnyttan av läkemedlet mot kostnaden. I bedömningen ska kostnadseffektiviteten vägas samman med behovs- och solidaritetsprincipen och människovärdesprincipen.Den föreslagna arbetsmodellen överensstämmer i allt väsentligt med den arbetsmodell som används av Socialstyrelsens vid framtagning av nationella riktlinjer. Det är inte möjligt att rymma alla aspekter som kan vara aktuella att beakta vid beskrivning av en nationell arbetsmodell. Man måste därför utgå från modellen och fundera på vilka andra relevanta aspekter som dessutom bör vägas in. T ex kan den internationella klassifikationen för funktionsförmåga (ICF) användas som vägledning.På grund av den stora variationsrikedomen av effektmått i olika verksamheter och de begränsade erfarenheter som finns att arbeta med sådana explicita gränsvärden anser vi att det är för tidigt att rekommendera en enhetlig indelning i t ex risknivåer. Det är dock viktigt att de som arbetar med prioriteringar redovisar hur de har resonerat.SBU:s klassifikation för att gradera den vetenskapliga evidensen för en åtgärds effekt bör användas i första hand. Lokala prioriteringsprojekt med begränsade resurser till sitt förfogande föreslås redovisa bedömningen av det vetenskapliga underlaget med ord och referera till det kunskapsunderlag som använts. Evidensstyrkan bör endast uttryckas med siffror då man stöder en slutsats på en systematisk kunskapsöversikt från SBU eller en annan översikt av god kvalitet.Prioriteringsarbeten där hälsoekonomiska data finns tillgängliga bör tills vidare ansluta till Socialstyrelsens arbetssätt och ange kostnadseffektivitet i en skala från låg till mycket hög kostnad per vunnet levnadsår eller kostnad per kvalitetsjusterat levnadsår. Den hälsoekonomiska evidensen bör redovisas i enlighet med de principer som Socialstyrelsen tillämpar. I lokala projekt med små resurser eller svårigheter att konsekvent få fram uppgifter om kostnadseffektivitet rekommenderar vi att man åtminstone resonerar om kostnadseffektivitet i de fall prioriteringsordningen på ett avgörande sätt påverkas när kostnaderna vägs in.Tio nivåer bör användas för rangordning samt att rangordningslistan kompletteras med en ”icke-göra-lista” för metoder som inte bör utföras alls eller rutinmässigt samt en FoU-lista för metoder där det fortfarande saknas tillräcklig evidens för att kunna motivera ett införande i rutinsjukvården. Sammanvägningen sker företrädesvis med en kvalitativ metod i avsaknad av en invändningsfri kvantitativ/matematisk metod. Likaså tror vi att det för närvarade inte är möjligt att fastställa entydiga kriterier som avgör inom vilken rangordningsnivå ett prioriteringsobjekt ska hamna.Resultatet bör presenteras i form av en rangordningslista. De parametrar som ligger till grund för prioriteringen bör också på ett enhetligt sätt redovisas i sådana rangordningslistor som visas för andra. I detalj kan språket och utseendet av pedagogiska skäl behöva anpassas för respektive målgrupp.Gränser för vad som är acceptabel behovstäckning (vårdkvalitet, mängd liksom andel av de i patientgrupp som får tillgång till insatsen) är en regional och lokal fråga och ingår därför inte i den nationella modellen.
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4. |
- Bergek, Anna, 1973, et al.
(författare)
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Analysing the Dynamics and Fucntionality of Sectoral Innovation Systems - a manual
- 2005
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Ingår i: DRUID Tenth Anniversary Summer Conference 2005, Copenhagen Business School, Copenhagen, Denmark, June 27-29, 2005.
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Konferensbidrag (refereegranskat)abstract
- Various researchers and policy analysts have experimented with empirical studies of sectoral innovation systems (SIS), in which attempts have been made to understand the current structure of various innovation systems and trace their dynamics. We have captured the dynamics in terms of not only the structural components of a SIS but also pioneered such an analysis in terms of functional patterns (as well as functionality). In a collaborative work with VINNOVA (the Swedish Agency for Innovation Systems), we have taken the analysis one step further and made explicit a scheme of analysis, or a manual for policy makers. The manual is based on the received literature, our prior experience in developing and applying functional thinking and three experimental case studies, conducted in collaboration with VINNOVA. The manual can be used by policy makers to identify not only the key policy issues but also to set policy goals and to assess the usefulness of various policy instruments.
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6. |
- Bergquist, Magnus, 1960, et al.
(författare)
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The effects of PACS on radiographer’s work practice
- 2007
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Ingår i: Radiography. - London : W.B. Saunders Co. Ltd.. ; 13:3, s. 235-240
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Tidskriftsartikel (refereegranskat)abstract
- This paper identifies and analyses the effects of picture archiving and communica- tion systems (PACS) on radiographers’ work practice. It shows that the introduction of PACS did not simply entail the transfer of data and information from the analogue world to the digital world, but it also led to the introduction of new ways of communicating, and new activities and responsibilities on the part of radiography staff. Radiographers are called upon to work increasingly independently, and individual practitioners require higher levels of professional expertise. In all, this paper demonstrates that new technical solutions sometimes lead to sub- stantial changes in responsibilities in work. In this example, the radiographers’ work practice has become more highly scientific and they are enjoying a higher level of prestige.
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7. |
- Claesson, Kristina, 1965, et al.
(författare)
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Relative biological effectiveness of the alpha-particle emitter (211)At for double-strand break induction in human fibroblasts.
- 2007
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Ingår i: Radiation research. - 0033-7587 .- 1938-5404. ; 167:3, s. 312-8
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to quantify and to determine the distribution of DNA double-strand breaks (DSBs) in human cells irradiated in vitro and to evaluate the relative biological effectiveness (RBE) of the alpha-particle emitter (211)At for DSB induction. The influence of the irradiation temperature on the induction of DSBs was also investigated. Human fibroblasts were irradiated as intact cells with alpha particles from (211)At, (60)Co gamma rays and X rays. The numbers and distributions of DSBs were determined by pulsed-field gel electrophoresis with fragment analysis for separation of DNA fragments in sizes 10 kbp-5.7 Mbp. A non-random distribution was found for DSB induction after irradiation with alpha particles from (211)At, while irradiation with low-LET radiation led to more random distributions. The RBEs for DSB induction were 2.1 and 3.1 for (60)Co gamma rays and X rays as the reference radiation, respectively. In the experiments studying temperature effects, nuclear monolayers were irradiated with (211)At alpha particles or (60)Co gamma rays at 2 degrees C or 37 degrees C and intact cells were irradiated with (211)At alpha particles at the same temperatures. The dose-modifying factor (DMF(temp)) for irradiation of nuclear monolayers at 37 degrees C compared with 2 degrees C was 1.7 for (211)At alpha particles and 1.6 for (60)Co gamma rays. No temperature effect was observed for intact cells irradiated with (211)At. In conclusion, irradiation with alpha particles from (211)At induced two to three times more DSB than gamma rays and X rays.
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9. |
- Hagberg, Henrik, 1955, et al.
(författare)
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Brain injury in preterm infants--what can the obstetrician do?
- 2005
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Ingår i: Early human development. - : Elsevier BV. - 0378-3782. ; 81:3, s. 231-5
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Forskningsöversikt (refereegranskat)abstract
- Mothers at increased risk of preterm birth often receive glucocorticoids (GC), antibiotics and tocolytics by the obstetrician but the question is whether such interventions affect the risk of brain injury and neurological outcome. We suggest that one single course of antenatal GC is the most important treatment that can be offered to patients at risk of preterm birth at 24-34 weeks of gestation to prevent brain injury. Betamethasone seems advantageous to dexamethasone and repeated courses of GC should probably be avoided. Antibiotics given to patients with preterm premature rupture of membranes reduce neonatal morbidity and decrease the risk of sonographic cerebral abnormalities even though the effect on long-term neurological outcome is uncertain. From the perspective of the immature CNS, there is no evidence for treatment with tocolytics even though it allows transfer of the patient to a tertiary center and increases the likelihood of administration of a complete course of corticosteroids which may affect outcome.
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10. |
- Hagberg, Henrik, 1955, et al.
(författare)
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Förtidsbörd
- 2008
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Ingår i: Lärobok i obstetrik. Redaktörer: Marsal, Karel, Hagberg, Henrik, Westgren, Magnus. - : Studentlitteratur. - 9789144007311 ; , s. 439-448
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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12. |
- Hagberg, Henrik, 1955, et al.
(författare)
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Role of cytokines in preterm labour and brain injury.
- 2005
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Ingår i: BJOG : an international journal of obstetrics and gynaecology. - : Wiley. - 1470-0328. ; 112 Suppl 1, s. 16-8
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Forskningsöversikt (refereegranskat)abstract
- Intrauterine infection induces an intra-amniotic inflammatory response involving the activation of a number of cytokines and chemokines which, in turn, may trigger preterm contractions, cervical ripening and rupture of the membranes. Infection and cytokine-mediated inflammation appear to play a prominent role in preterm birth at early gestations (<30 weeks). The role of infection/inflammation in preterm birth in Europe has been incompletely characterised. The rate of preterm birth in Sweden is lower, and the rate of chorioamnionitis, bacterial vaginosis (BV), neonatal sepsis, and urinary tract infections during pregnancy is lower compared with the USA. In a Swedish population of women with preterm labour or preterm premature rupture of the membranes (PPROM) <34 weeks of gestation, microorganisms were detected in the amniotic fluid in 25% of women with PPROM and in 16% of those in preterm labour. Nearly half of these women had intra-amniotic inflammation defined as elevated interleukin-6 (IL-6) and IL-8, and there was a high degree of correlation between cytokine levels and preterm birth or the presence of microbial colonisation. These data do not support the hypothesis that infection-related preterm birth is less frequent in northern Europe than elsewhere. The intra-amniotic inflammatory response has also been associated with white matter injury and cerebral palsy. We find that in experimental models, induction of a systemic inflammatory response using lipopolysaccharide activates toll-like receptors (TLRs), which produce either white matter lesions or increase brain susceptibility to secondary insults. Recently, IL-18 in umbilical blood was shown to correlate with brain injury in preterm infants and IL-18 deficiency in mice decreases CNS vulnerability.
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13. |
- Holst, Rose-Marie, 1946, et al.
(författare)
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Cervical length in women in preterm labor with intact membranes: relationship to intra-amniotic inflammation/microbial invasion, cervical inflammation and preterm delivery
- 2006
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Ingår i: Ultrasound Obstet Gynecol. - : Wiley. - 0960-7692. ; 28:6, s. 768-74
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Intra-amniotic infection, diagnosed by microbial invasion of the amniotic cavity (MIAC) and/or the presence of intra-amniotic inflammation (IAI), is related to adverse perinatal outcome in women with preterm labor. Due to the subclinical nature of IAI, a correct diagnosis depends on amniocentesis, which is an invasive method not performed as a clinical routine. The aim of this study was to evaluate if cervical length measured by transvaginal sonography could assist in the identification of women at high risk for IAI. METHODS: Cervical length was assessed by transvaginal sonography in 87 women with singleton pregnancies in preterm labor (<34 weeks of gestation). Cervical (n=87) and amniotic (n=55) fluids were collected. Polymerase chain reactions for Ureaplasma urealyticum and Mycoplasma hominis, and culture for aerobic and anaerobic bacteria, were performed. Interleukin (IL)-6 and IL-8 were analyzed by enzyme-linked immunosorbent assay. RESULTS: IAI was present in 25/55 (45%) of the patients presenting with preterm labor who underwent amniocentesis. Women with IAI had a significantly shorter cervical length (median, 10 (range, 0-34) mm) than had those without IAI (median, 21 (range, 11-43) mm) (P<0.0001). Receiver-operating characteristics curve analysis showed that a cervical length (cut-off of 15 mm) predicted IAI (relative risk, 3.6; CI, 1.9-10.0) with a sensitivity of 72%, specificity of 83%, positive predictive value of 78% and negative predictive value of 78%. Cervical length was also significantly associated with preterm birth up to 7 days from sampling and at
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14. |
- Holst, Rose-Marie, 1946, et al.
(författare)
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Expression of cytokines and chemokines in cervical and amniotic fluid: Relationship to histological chorioamnionitis
- 2007
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Ingår i: J Matern Fetal Neonatal Med. - : Informa UK Limited. ; 20:12, s. 885-893
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To correlate cervical and amniotic fluid cytokines and macrophage-related chemokines to the development of histological chorioamnionitis (HCA) in patients with preterm labor (PTL) and preterm prelabor rupture of the membranes (PPROM). Study design. Cervical and amniotic fluid interleukin (IL)-6, IL-8, IL-18, monocyte chemotactic protein (MCP)-1, MCP-2, and MCP-3 from pregnant women (at
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15. |
- Holst, Rose-Marie, 1946, et al.
(författare)
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Interleukin-6 and interleukin-8 in cervical fluid in a population of Swedish women in preterm labor: relationship to microbial invasion of the amniotic fluid, intra-amniotic inflammation, and preterm delivery.
- 2005
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Ingår i: Acta obstetricia et gynecologica Scandinavica. - : Wiley. - 0001-6349. ; 84:6, s. 551-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Intrauterine infection and inflammation in women with preterm labor are related to adverse perinatal outcome. Due to its subclinical nature, a correct diagnosis depends on retrieval of amniotic fluid. Amniocentesis is, however, not performed as a clinical routine because of its invasiveness. Hypothetically, cytokines in the cervical fluid may represent an alternative diagnostic approach. The aim was to examine cervical interleukin (IL)-6 and IL-8 in relation to microbial invasion of the amniotic fluid, intra-amniotic inflammation, and preterm birth in women in preterm labor. METHODS: Women with singleton pregnancies in preterm labor (<34 weeks of gestation) and intact membranes were included. Cervical (n = 91) and amniotic fluids (n = 56) were collected. Polymerase chain reaction for Ureaplasma urealyticum and Mycoplasma hominis and culture for aerobic and anaerobic bacteria were performed. IL-6 and IL-8 were analyzed with enzyme-linked immunosorbent assay. RESULTS: Non-lactobacillus-dominated biota was detected in cervical secretion in 25% (22/89) and the presence of micro-organisms in the amniotic fluid in 16% (9/56) of the patients. The presence of U. urealyticum in the cervical fluid (21/46) was associated with significantly higher levels of IL-6 in the secretion. IL-6 and IL-8 were significantly higher in cervical fluid of women with intra-amniotic infection and inflammation and in women who delivered < or =7 days and/or before 34 weeks of gestation. Cervical IL-6 > or = 1.7 ng/ml was related to intra-amniotic inflammation (relative risk: 2.67; range: 1.50-4.74) and had a sensitivity, specificity, positive predictive value, and negative predictive value of 58, 83, 75, and 69%, respectively, in the identification of intra-amniotic inflammation. Similar data were obtained for IL-8 > or = 6.7 ng/ml. CONCLUSIONS: High levels of cervical IL-6 and IL-8 are moderately predictive of intrauterine infection/inflammation and preterm delivery.
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16. |
- Holst, Rose-Marie, 1946, et al.
(författare)
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Prediction of spontaneous preterm delivery in women with preterm labor: analysis of multiple proteins in amniotic and cervical fluids
- 2009
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Ingår i: Obstet Gynecol. ; 114:2 Pt 1, s. 268-77
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To analyze whether specific proteins in amniotic and cervical fluids, alone or in combination with risk factors, can identify women in preterm labor with intact membranes who will deliver spontaneously within 7 days of sampling. METHODS: In a cohort of 89 women in preterm labor, amniotic and cervical fluids were collected between 22 and 33 weeks of gestation. Twenty-seven proteins were analyzed simultaneously using multiplex technology. Individual levels of each protein were compared and calculations performed to find associations among different proteins, background variables, and spontaneous preterm delivery within 7 days of sampling. The area under the curve (AUC) was calculated using receiver operating characteristic curve analysis, and prediction models were created based on stepwise logistic regression. RESULTS: We found two multivariable models that predicted spontaneous preterm delivery better than any single variable. One combined multivariable prediction model was based on amniotic macrophage inflammatory protein-1beta, cervical interferon-gamma, and monocyte chemotactic protein-1. This model predicted outcome with 91% sensitivity, 84% specificity, 78% positive predictive value, and 94% negative predictive value, with a likelihood ratio of 5.6 and AUC of 0.91. An alternative, noninvasive model based on cervical length, cervical interferon-gamma, interleukin-6, and monocyte chemotactic protein-1 predicted delivery within 7 days with 85% sensitivity, 82% specificity, 74% positive predictive value, and 90% negative predictive value, with a likelihood ratio of 4.7 and AUC of 0.91. CONCLUSION: A combination of proteins from amniotic fluid and cervical fluid or cervical length can help determine which women will deliver preterm. LEVEL OF EVIDENCE: II.
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17. |
- Hvidtjorn, D., et al.
(författare)
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Cerebral palsy, autism spectrum disorders, and developmental delay in children born after assisted conception: a systematic review and meta-analysis
- 2009
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Ingår i: Arch Pediatr Adolesc Med. ; 163:1, s. 72-83
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the existing evidence of associations between assisted conception and cerebral palsy (CP), autism spectrum disorders (ASD), and developmental delay. DATA SOURCES: Forty-one studies identified in a systematical PubMed and Excerpta Medica Database (EMBASE) search for articles published from January 1, 1996, to April 1, 2008. STUDY SELECTION: Studies written in English comparing children born after assisted conception with children born after natural conception assessing CP, ASD, and developmental delay, based on original data with a follow-up of 1 year or more. Main Exposures In vitro fertilization (IVF) with or without intracytoplasmic sperm injection or ovulation induction with or without subsequent intrauterine insemination. MAIN OUTCOME MEASURES: Cerebral palsy, ASD, and developmental delay. RESULTS: Nine CP studies showed that children born after IVF had an increased risk of CP associated with preterm delivery. In our meta-analysis including 19 462 children exposed to IVF, we estimated a crude odds ratio of 2.18 (95% confidence interval, 1.71-2.77). Eight ASD studies and 30 studies on developmental delay showed inconsistent results. No studies assessed the risk of CP, ASD, or developmental delay in children born after ovulation induction exclusively. CONCLUSIONS: Methodological problems were revealed in the identified studies, and the gaps in our knowledge about the long-term outcomes of children born after assisted conception are considerable, including a lack of information on the long-term consequences of ovulation induction. Possible associations with ASD and developmental delay need assessment in larger studies. Studies on assisted conception and CP from countries outside of Scandinavia are needed, including detailed information on time to pregnancy, underlying cause of infertility, and type of IVF treatment.
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18. |
- Håkansson, Stellan, et al.
(författare)
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Group B streptococcal carriage in Sweden : a national study on risk factors for mother and infant colonisation
- 2008
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - Stockholm : Wiley. - 0001-6349 .- 1600-0412. ; 87:1, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- Background. To study group B streptococcus (GBS) colonisation in parturients and infants in relation to obstetric outcome and to define serotypes and antibiotic resistance in GBS isolates acquired. Methods. A population-based, national cohort of parturients and their infants was investigated. During 1 calendar week in 2005 all women giving birth (n=1,754) were requested to participate in the study. Results. A total of 1,569 mother/infant pairs with obstetric and bacteriological data were obtained. Maternal carriage rate was 25.4% (95% confidence interval (CI): 23.3-27.6). In GBS-positive mothers with vaginal delivery and no intrapartum antibiotics, the infant colonisation rate was 68%. Some 30% of infants were colonised after acute caesarean section, and 0% were colonised after an elective procedure. Duration of transport of maternal recto/vaginal swabs of more than 1 day impeded culture sensitivity. Infant mMales were more frequently colonised than females (76.9 versus 59.8%, odds ratio (OR): 2.16; 95% CI: 1.27-3.70), as were infants born after rupture of membranes ≥24 h (p =0.039). Gestational age, birth weight and duration of labor did not significantly influence infant colonisation. Some 30% of parturients with at least one risk factor for neonatal disease received intrapartum antibiotics. The most common GBS serotypes were type III and V. Some 5% of the isolates were resistant to clindamycin and erythromycin, respectively. Conclusions. Maternal GBS prevalence and infant transfer rate were high in Sweden. Males were more frequently colonised than females. The sensitivity of maternal cultures decreased with the duration of sample transport. Clindamycin resistance was scarce. The use of intrapartum antibiotics was limited in parturients with obstetric risk factors for early onset group B streptococcal disease.
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19. |
- Jacobsson, Benny, 1954-
(författare)
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Den sjunde världsdelen : Västgötar och Västergötland 1646-1771. En identitetshistoria
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis considers regional identity in early-modern Sweden, taking its case from the province (landskap) of Västergötland 1646–1771. The aim is to investigate verbal expressions of regional identity. A theory on the construction of regional identity is suggested from the research results, and typological categories of regional identity are established. Contrary to popular concepts of identity being constructed in relation to an outer “other”, it is argued that identity is formed from self-images. Identity is expressed in the first person (I, we), and includes an insider’s perspective of the place occupied. As the thesis shows, the theory of regional identity is substantiated by the duality of the patria-concept. Patria, Fatherland, was employed for the smaller home province as well as for the greater realm. The realm however, always could claim priority to amor patria, Love of the Fatherland. Thus, any construction of regional identity using the neighbouring provinces as a contrasting “other” would have been counter-productive to the construction of the overarching national identity. This manifold patria-concept is of Roman origin, and made its influence through the Latin language well into early-modern time. A great variety of sources in Latin and Swedish have been consulted, including orations and dissertations, minutes of the academic senate and West Geat student nation (Västgöta nation) at Uppsala University, topography, manuscripts and letters. An in-depth study has been made of the writing processes leading up to dissertations and topographical descriptions.
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20. |
- Jacobsson, Bo, 1960, et al.
(författare)
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Interleukin-6 and interleukin-8 in cervical and amniotic fluid: relationship to microbial invasion of the chorioamniotic membranes.
- 2005
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Ingår i: BJOG : an international journal of obstetrics and gynaecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 112:6, s. 719-24
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the levels of interleukin (IL)-6 and IL-8 in cervical and amniotic fluid in relation to the presence of bacteria in the membranes in women in preterm labour (PTL). DESIGN: A prospective follow up study. SETTING: Sahlgrenska University Hospital, Göteborg, Sweden. Sample Women with singleton pregnancies (<34 weeks) presenting with PTL (n = 30). METHODS: Amniotic fluid was retrieved transabdominally and cervical fluid was sampled from the uterine cervix at admission and analysed for IL-6 and IL-8 with enzyme-linked immunosorbent assay (ELISA). At birth, the chorioamniotic membranes were separated and samples for polymerase chain reaction (PCR) for Ureaplasma urealyticum and Mycoplasma hominis and general culture were obtained. MAIN OUTCOME MEASURE: IL-6 and IL-8 in relation to microbial invasion of the chorioamniotic membranes. RESULTS: Bacteria were found in the membranes in 8 of 21 patients in PTL for whom chorioamnion as well as amniotic fluid PCR and cultures were available. Cervical IL-6 was associated with detectable bacteria in the chorioamniotic membranes in women in PTL (median 8.2 ng/mL vs 0.73 ng/mL; P = 0.01). The IL-6 (median 13 ng/mL vs 1.7 ng/mL; P = 0.004) and IL-8 (median 7.2 ng/mL vs 0.28 ng/mL; P = 0.01) levels in amniotic fluid were higher in PTL cases in which bacteria were found in the chorioamniotic membranes. CONCLUSION: IL-6 in cervical fluid and IL-6 and IL-8 in amniotic fluid were higher in those PTL cases in which bacteria were found in the chorioamniotic membranes.
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21. |
- Jacobsson, Bo, 1960, et al.
(författare)
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Monocyte chemotactic protein-2 and -3 in amniotic fluid: relationship to microbial invasion of the amniotic cavity, intra-amniotic inflammation and preterm delivery
- 2005
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Ingår i: Acta Obstet Gynecol Scand. ; 84:6, s. 566-71
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the presence of monocyte chemotactic protein (MCP)-2 and MCP-3 in cervical and amniotic fluid in women in preterm labor. STUDY DESIGN: Cervical and amniotic fluid was sampled from women with singleton pregnancies (< or =34 weeks) in preterm labor (n = 58). RESULTS: Monocyte chemotactic protein-2 (range: 80-583 pg/ml) and MCP-3 (range: 36-649 pg/ml) were detectable in 7/58 women in preterm labor. Monocyte chemotactic protein-3 was found significantly more often in amniotic fluid of women delivered within 7 days (P < 0.001), <34 weeks (P = 0.002), or with intra-amniotic inflammation (P < 0.001) and microbial invasion of the amniotic fluid (P = 0.003). Women in preterm labor had detectable levels of MCP-2 significantly more often if they gave birth before 34 weeks of gestation (P = 0.038) or had intra-amniotic inflammation (P = 0.042). CONCLUSIONS: The presence of MCPs in amniotic fluid of women in preterm labor was associated with preterm birth before 34 weeks of gestation (MCP-2 and MCP-3), microbial invasion (MCP-3), and inflammation (MCP-2 and MCP-3) of the amniotic cavity.
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22. |
- Jacobsson, Bo, 1960, et al.
(författare)
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Quantification of Ureaplasma urealyticum DNA in the amniotic fluid from patients in PTL and pPROM and its relation to inflammatory cytokine levels
- 2008
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Ingår i: Acta Obstet Gynecol Scand. - 1600-0412. ; , s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To study the effect of the amniotic fluid quantity of Ureaplasma urealyticum DNA on inflammatory response levels in women with preterm labor (PTL) and preterm prelabor rupture of membranes (pPROM). Design. A prospective multi-center follow up study. Setting. Sahlgrenska University Hospital, Goteborg, Sweden and Turku University Hospital, Turku, Finland. Sample. Eleven U. urealyticum positive samples obtained after transabdominal amniocenteses in 197 women presenting with PTL and pPROM. Methods. The U. urealyticum positive samples were analyzed with real-time polymerase chain reaction, using the Lightcycler instrument with primers specific for U. urealyticum 16 S rDNA. The amniotic fluid samples were analyzed for tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-1beta and IL-10 with enzyme-linked immunosorbent assays. Main outcome measures. Correlation between U. urealyticum DNA concentrations in the amniotic fluid and inflammatory cytokine levels. Results. The concentrations of U. urealyticum DNA varied between 0.024 and 934microg/mL. A significant correlation between U. urealyticum DNA and TNF-alpha level was observed. No correlation with the other cytokines was found. Women with PTLhad higher levels of U. urealyticum DNA and a different cytokine pattern than women with pPROM. Conclusions. U. urealyticum in the amniotic fluid induces an inflammatory reaction in a dose dependent manner and the quantity of U. urealyticum DNA is well correlated with the level of the inflammatory cytokine TNF-alpha.
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23. |
- Jacobsson, Bo, 1960, et al.
(författare)
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Quantification of Ureaplasma urealyticum DNA in the amniotic fluid from patients in PTL and pPROM and its relation to inflammatory cytokine levels
- 2009
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Ingår i: Acta Obstet Gynecol Scand. ; 88:1, s. 63-70
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the effect of the amniotic fluid quantity of Ureaplasma urealyticum DNA on inflammatory response levels in women with preterm labor (PTL) and preterm prelabor rupture of membranes (pPROM). DESIGN: A prospective multi-center follow up study. SETTING: Sahlgrenska University Hospital, Goteborg, Sweden and Turku University Hospital, Turku, Finland. SAMPLE: Eleven U. urealyticum positive samples obtained after transabdominal amniocenteses in 197 women presenting with PTL and pPROM. METHODS: The U. urealyticum positive samples were analyzed with real-time polymerase chain reaction, using the Lightcycler instrument with primers specific for U. urealyticum 16 S rDNA. The amniotic fluid samples were analyzed for tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-1beta and IL-10 with enzyme-linked immunosorbent assays. MAIN OUTCOME MEASURES: Correlation between U. urealyticum DNA concentrations in the amniotic fluid and inflammatory cytokine levels. RESULTS: The concentrations of U. urealyticum DNA varied between 0.024 and 934 microg/mL. A significant correlation between U. urealyticum DNA and TNF-alpha level was observed. No correlation with the other cytokines was found. Women with PTLhad higher levels of U. urealyticum DNA and a different cytokine pattern than women with pPROM. CONCLUSIONS: U. urealyticum in the amniotic fluid induces an inflammatory reaction in a dose dependent manner and the quantity of U. urealyticum DNA is well correlated with the level of the inflammatory cytokine TNF-alpha.
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24. |
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25. |
- Johanzon, M., et al.
(författare)
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Extreme preterm birth: onset of delivery and its effect on infant survival and morbidity
- 2008
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Ingår i: Obstetrics & Gynecology. - 0029-7844. ; 111:1, s. 42-50
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate whether correlations could be found between the onset of preterm delivery and infant outcome, that is, survival and major morbidity. METHODS: The study was a retrospective, hospital-based cohort study. All women with a live fetus on admission, giving birth at 22(+0) to 27(+6) weeks of gestation between 1998 and 2003 were included. The deliveries were subdivided into those that began with either preterm labor, preterm premature rupture of membranes (PROM), or iatrogenic preterm delivery. These groups were compared for survival and survival without major morbidity (intraventricular hemorrhage grade 3-4, periventricular leukomalacia, retinopathy of prematurity grade 3-4, bronchopulmonary dysplasia, or necrotizing enterocolitis) at discharge. RESULTS: The cause of the preterm birth was preterm labor in 154 of 288 (53%), preterm PROM 83 of 288 (29%), and iatrogenic preterm delivery 51 of 288 (18%). There were 83% liveborn children, and 67% survived until discharge. Survival was lower for preterm PROM (54%) than for preterm labor (75%) and iatrogenic preterm delivery (67%). Multivariable analyses showed that survival was positively associated with gestational age and antenatal steroid treatment. Negative associations concerning survival were found for preterm PROM and being small for gestational age. Survival without major morbidity did not differ significantly between the groups and was positively associated with gestational age and negatively associated with being small for gestational age. CONCLUSION: Infant survival was significantly lower when the onset of preterm delivery was preterm PROM as compared with preterm labor and iatrogenic delivery. For surviving infants there was no significant difference in major morbidity between the groups. LEVEL OF EVIDENCE: III.
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26. |
- Kvarnstrand, L., et al.
(författare)
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Maternal fatalities, fetal and neonatal deaths related to motor vehicle crashes during pregnancy: a national population-based study
- 2008
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 87:9, s. 946-52
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Firstly, determine the mortality rate for: pregnant women; fetuses and neonates, due to motor vehicle crashes (MVCs) during pregnancy; and secondly, the rate of major injuries among pregnant women and the rate of involvement of pregnant women in crashes. DESIGN: A national population-based, retrospective descriptive study. SETTING: Sweden, 1991-2001. Population. All pregnant and non-pregnant women age 15-44. METHODS: Linkage of national traffic, medical and autopsy registers. MAIN OUTCOME MEASURES: Maternal death or injury and corresponding fetal death. Results. MVCs during pregnancy caused 1.4 maternal fatalities per 100,000 pregnancies and a fetus/neonate mortality rate of least 3.7 per 100,000 pregnancies. The incidence of maternal major injury was 23/100,000 pregnancies and crash involvement was 207/100,000 pregnancies. CONCLUSIONS: MVCs during pregnancy were a significant cause of maternal fatalities, fetal and neonatal deaths, responsible for almost 1/3 of all maternal deaths and fatalities, and caused nearly three times more fetal plus neonatal deaths than maternal fatalities.
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27. |
- Kölhed, Malin, 1977-
(författare)
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Novel on-line mid infrared detection strategies in capillary electrophoretic systems
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Infrared absorption spectra can provide analytically useful information on a large variety of compounds, ranging from small ions to large biological molecules. In fact, all analytes that possess a dipole moment that changes during vibration are infrared-active. The infrared (IR) spectrum can be subdivided into far-, mid- and near- regions. The focus of attention in this thesis is the mid-IR region, in which the fundamental vibrations of most organic compounds are located, thus providing scope for positive structural identification. However, while such near-ubiquitous signals can be very useful for monitoring simple molecules in simple systems, they can be increasingly disadvantageous as the number of analytes and/or the complexity of the sample matrix increases. Thus, hyphenation to a separation system prior to detection is desirable. Paper I appended to this thesis presents (for the first time) the on-line hyphenation between Fourier transform infrared spectroscopy, FTIR, and capillary zone electrophoresis, CZE. CZE is a highly efficient separation technique that separates ionic analytes with respect to their charge-to-size ratio. It is most commonly performed in aqueous buffers in fused silica capillaries. Since these capillaries absorb virtually all infrared light an IR-transparent flow cell had to be developed. In further studies (Paper II) the applicability of CZE is expanded to include neutral analytes by the addition of micelles to the buffer, and micellar electrokinetic chromatography, MEKC, was successfully hyphenated to FTIR for the first time. Paper III describes an application of the on-line CZE-FTIR technique in which non-UV-absorbing analytes in a complex matrix were separated, identified and quantified in one run.Measuring aqueous solutions in the mid-IR region is not straightforward since water absorbs intensely in this region, sometimes completely, leaving no transmitted, detectable light. For this reason, quantum cascade lasers are interesting. These lasers represent a new type of mid-IR semiconducting lasers with high output power due to their ingenious design. The laser action lies within one conduction band (intersubband) and can be tailored to emit light in the entire mid-IR region using the same semiconducting material. To investigate their potential to increase the optical path length in aqueous solutions, these lasers were used with an aqueous flow system (Paper IV), and the experience gained in these experiments enabled hyphenation of such lasers to a CZE system (Paper V).
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28. |
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29. |
- Lindberg, Bo, et al.
(författare)
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Modeling of Cherenkov light emission from BWR nuclear fuel with missing or substituted rods
- 2006
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Ingår i: IAEA Symposium on International Safeguards: Addressing Verification Challenges.
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Konferensbidrag (populärvet., debatt m.m.)abstract
- Computer simulations of Cherenkov glow from spent nuclear fuel were carried out. Spent nuclear fuel in storage ponds are verified with the help of the Cherenkov viewing device (CVD) and the Digital Cherenkov viewing device (DCVD). The instruments image the Cherenkov glow generated by gamma ray emissions from spent fuel into the water. An attempt to build a realistic digital model of the DCVD image containing partial-length, missing, and substituted rods was made to see if the effects of the deviations from normal can be predicted. It was concluded that partial-length or missing rods in the model was in good agreement with measured data, but replaced rods in the model showed a weaker attenuation of the Cherenkov glow than the observed DCVD images.
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30. |
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31. |
- Magnusson-Olsson, AnneLiese, et al.
(författare)
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Effect of maternal triglycerides and free fatty acids on placental LPL in cultured primary trophoblast cells and in a case of maternal LPL deficiency.
- 2007
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Ingår i: Am J Physiol Endocrinol Metab. ; 293:1
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Tidskriftsartikel (refereegranskat)abstract
- Maternal hypertriglyceridemia is a normal condition in late gestation and is an adaptation to ensure an adequate nutrient supply to the fetus. Placental lipoprotein lipase (LPL) is involved in the initial step in transplacental fatty acid transport as it hydrolyzes maternal triglycerides (TG) to release free fatty acids (FFA). We investigated LPL activity and protein (Western blot) and mRNA expression (real-time RT-PCR) in the placenta of an LPL-deficient mother with marked hypertriglyceridemia. The LPL activity was fourfold lower, LPL protein expression 50% lower, and mRNA expression threefold higher than that of normal, healthy placentas at term (n = 4-7). To further investigate the role of maternal lipids in placental LPL regulation, we isolated placental cytotrophoblasts from term placentas and studied LPL activity and protein and mRNA expression after incubation in Intralipid (as a source of TG) and oleic, linoleic, and a combination of oleic, linoleic, and arachidonic acids as well as insulin. Intralipid (40 and 400 mg/dl) decreased LPL activity by approximately 30% (n = 10-14, P < 0.05) and 400 microM linoleic and linoleic-oleic-arachidonic acid (n = 10) decreased LPL activity by 37 and 34%, respectively. No major changes were observed in LPL protein or mRNA expression. We found no effect of insulin on LPL activity or protein expression in the cultured trophoblasts. To conclude, the activity of placental LPL is reduced by high levels of maternal TG and/or FFA. This regulatory mechanism may serve to counteract an excessive delivery of FFA to the fetus in conditions where maternal TG levels are markedly increased.
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32. |
- Menon, Ramkumar, et al.
(författare)
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Ethnic differences in key candidate genes for spontaneous preterm birth: TNF-alpha and its receptors
- 2006
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Ingår i: HUMAN HEREDITY. - : S. Karger AG. - 0001-5652 .- 1423-0062. ; 62:2, s. 107-118
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Tidskriftsartikel (refereegranskat)abstract
- <i>Objectives:</i> Spontaneous preterm birth (PTB) has a significant ethnic disparity with people of African descent having an almost 2-fold higher incidence than those of European descent in the United States. This disparity may be caused by differences in the distribution of genetic risk factors. The objective of this study is to examine genetic differences between African-Americans and European Americans for single nucleotide polymorphisms (SNPs) in candidate genes for PTB. <i>Methods:</i> We examined patterns of variation in 19 SNPs in 3 candidate genes for preterm birth: TNF-α, TNF-receptor 1 and TNF-receptor 2. Allele, genotype and haplotype frequencies were compared between African-Americans (AA) and European-Americans (EA) in cases and controls separately. Both maternal and fetal genotypes were studied, as it is unclear whether one or both of these are important in the etiology of PTB. <i>Results:</i> The vast majority of the SNPs differed significantly between ethnic groups, although there are only a few suggestive results comparing cases and controls within an ethnic group. For TNF-α, four of six SNPs; for TNF-R1, 5/6; and for TNF-R2, 6/7 showed significant differences between ethnic groups in either allele and/or genotype frequency. <i>Conclusions:</i> Our data demonstrate highly significant genetic differences between ethnic groups in genes that may play a role in the risk of PTB.
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33. |
- Menon, Ramkumar, 1967, et al.
(författare)
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Increased Bioavailability of TNF-alpha in African Americans During In Vitro Infection: Predisposing Evidence for Immune Imbalance.
- 2007
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Ingår i: Placenta. ; 28:8-9, s. 946-50
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The objective of this study is to examine TNF-alpha and its soluble and membrane bound receptors in fetal membranes derived from blacks and whites in response to in vitro infectious stimulus, and the balance between TNF-alpha and the receptors. Fetal membranes collected from black and white women at term were maintained in an organ explant system and stimulated with lipopolysaccharide (LPS). TNF-alpha, soluble TNF receptors (sTNFR1 and sTNFR2) in culture media and membrane bound TNF receptors (TNFR1 and TNFR2) in tissue homogenates were measured. Molar ratio (TNF/sTNFR) was calculated between LPS stimulated and unstimulated (controls) cultures in both races. TNF-alpha was increased in both races after LPS stimulation and showed no difference between races (p=0.7). LPS decreased sTNFR1 in blacks, but increased in whites, showing a significant difference between races (p=0.001). In blacks sTNFR2 also decreased and increased in whites, but the results were not significant between races (p=0.4). Both TNFR1 and TNFR2 were increased in blacks after LPS stimulation whereas no such changes were seen in whites compared to controls that were also significant between races. After LPS stimulation TNF-alpha bioavailability was increased in blacks with a drop in soluble receptors and with an increase in membrane receptors. This was not evident in whites because in whites soluble receptors were increased with no change in membrane receptors. Our data demonstrated that LPS stimulation results in a molar ratio switch favoring TNF-alpha biofunction in blacks, but not in whites.
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34. |
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35. |
- Morken, Nils-Halvdan, 1969, et al.
(författare)
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Outcomes of preterm children according to type of delivery onset: a nationwide population-based study
- 2007
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Ingår i: Paediatric and Perinatal Epidemiology. - : Wiley. - 0269-5022 .- 1365-3016. ; 21:5, s. 458-464
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Tidskriftsartikel (refereegranskat)abstract
- The objective of the study was to investigate whether spontaneous and iatrogenic preterm births are associated with different paediatric outcomes. A nationwide population-based study comprising 1 010 487 singletons used data from 1991 to 2001 from the Swedish Medical Birth Register and the Swedish Hospital Discharge Register. Intrauterine fetal deaths, unknown type of delivery onset and congenital malformations were excluded. Neonatal, perinatal and long-term neurological outcomes were studied. Spontaneous preterm births were compared with iatrogenic preterm births. Odds ratios (OR) and hazard ratios (HR) for outcome variables were obtained using the Mantel-Haenszel technique and Cox analyses respectively. Adjustments were made for gestational age at birth, maternal age, parity and smoking. The preterm population consisted of 34 215 (73.2%) spontaneous preterm infants and 12 511 (26.8%) iatrogenic preterm infants. Spontaneous preterm infants were at increased risk of cerebral palsy at gestational age 28-31 weeks (HR: 1.86 [95% CI: 1.12, 3.10]), and of sepsis at gestational age 32-33 weeks (HR: 1.58 [95% CI: 1.28, 1.96]). Other outcome variables were associated with iatrogenic preterm birth, especially respiratory and gastrointestinal diagnoses. In conclusion, spontaneous preterm birth and iatrogenic preterm birth are associated with different paediatric outcomes.
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36. |
- Morken, Nils-Halvdan, 1969, et al.
(författare)
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Preterm birth in Sweden 1973-2001: rate, subgroups, and effect of changing patterns in multiple births, maternal age, and smoking
- 2005
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Ingår i: Acta Obstet Gynecol Scand. - : Wiley. ; 84:6, s. 558-565
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The objectives of this report are to evaluate changes in the preterm birth rate in Sweden 1973-2001. Furthermore, describe the proportion of spontaneous and indicated preterm births and assess risk factors for the subgroups of preterm birth during the period from 1991 to 2001. METHODS: A population-based register study of all births occurring in Sweden from 1973 to 2001 registered in the Swedish Medical Birth Register was designed. The analysis of subgroups was restricted to the period 1991-2001. Gestational age was calculated using last menstrual period and best estimate. Odds ratio for preterm birth related to risk factors was calculated for the subgroups' spontaneous and indicated preterm birth. RESULTS: After an increase in the beginning of the 1980s, the preterm birth rate has decreased from 6.3% in 1984 to 5.6% in 2001 (P < 0.0001). The proportion of multiple births born preterm of the total birth rate increased from 0.34% in 1973 to 0.71% in 2001 (P < 0.0001). Spontaneous preterm births account for 55.2% and iatrogenic preterm births for 20.2% of all preterm births. The strongest association with maternal smoking in early pregnancy was found at gestational age <28 weeks and spontaneous preterm birth [odds ratio (OR) smoking versus no smoking: 1.55, 95% confidence intervals (CI): 1.42-1.69]. The strongest association for maternal age was found between gestational age <28 weeks and indicated preterm birth (OR 5-year increase: 1.34, 95% CI: 1.21-1.47). CONCLUSIONS: The preterm birth rate in Sweden has decreased since the mid 1980s. The composition of different subtypes of preterm birth in a Scandinavian low-risk population seems to be similar to populations with higher incidence of preterm birth and perinatal infections.
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37. |
- Morken, Nils-Halvdan, 1969, et al.
(författare)
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Reference population for international comparisons and time trend surveillance of preterm delivery proportions in three countries
- 2008
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Ingår i: BMC Womens Health. - : Springer Science and Business Media LLC. - 1472-6874. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: International comparison and time trend surveillance of preterm delivery rates is complex. New techniques that could facilitate interpretation of such rates are needed. METHODS: We studied all live births and stillbirths (>or= 28 weeks gestation) registered in the medical birth registers in Sweden, Denmark and Norway from 1995 through 2004. Gestational age was determined by best estimate. A reference population of pregnant women was designed using the following criteria: 1) maternal age 20-35, 2) primiparity, 3) spontaneously conceived pregnancy, 4) singleton pregnancy and 5) mother born in the respective country. National preterm delivery rate, preterm delivery rate in the reference population and rate of spontaneous preterm delivery in the reference population were calculated for each country. RESULTS: The total national preterm delivery rate (< 37 completed gestational weeks), increased in both Denmark (5.3% to 6.1%, p < 0.001) and Norway (6.0% to 6.4%, p = 0.006), but remained unchanged in Sweden, during 1995-2004. In Denmark, the preterm delivery rate in the reference population (5.3% to 6.3%, p < 0.001) and the spontaneous preterm delivery rate in the reference population (4.4% to 6.8%, p < 0.001) increased significantly. No similar increase was evident in Norway. In Sweden, rates in the reference population remained stable. CONCLUSION: Reference populations can facilitate overview and thereby explanations for changing preterm delivery rates. The model also permits comparisons over time. This model may in its simplicity prove to be a valuable supplement to assessments of national preterm delivery rates for public health surveillance.
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38. |
- Morken, Nils-Halvdan, 1969, et al.
(författare)
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Subgroups of preterm delivery in the Norwegian Mother and Child Cohort Study
- 2008
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 87:12, s. 1374-7
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Tidskriftsartikel (refereegranskat)abstract
- The preterm deliveries in the Norwegian Mother and Child Cohort (MoBa) study were divided into subgroups: spontaneous preterm delivery, iatrogenic preterm delivery, multiple pregnancies, congenital malformations and intrauterine fetal deaths (IUFD). Records were linked with the Medical Birth Registry of Norway in order to permit identification of the different subgroups. The first 53,711 included pregnancies in the MoBa study were analyzed. Spontaneous preterm delivery accounted for 42% and iatrogenic preterm delivery for 28% of all preterm deliveries. Other important contributors to preterm delivery were multiple pregnancies (16%), congenital malformations (8.6%) and IUFD (5.2%). In conclusion, the subgroup composition of the preterm population in the MoBa study is similar to previously published data regarding both different and similar populations and is well suited for future studies of this complex obstetric entity.
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39. |
- Müller, Lennart, 1959, et al.
(författare)
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Ultrasonography as predictor of permanent renal damage in infants with urinary tract infection.
- 2009
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 1651-2227 .- 0803-5253. ; 98:7, s. 1156-61
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To evaluate the ability of ultrasound (US) in infants (<1 year) with acute urinary tract infection (UTI), to identify those with permanent renal damage (PRD) at scintigraphy 1 year later. METHODS: US, dimercaptosuccinic acid scintigraphy and voiding cystourethrography were performed in 191 infants. RESULTS: US was abnormal in 46 infants (24%). PRD was found in 46 infants (24%); 19 of these had abnormal US (sensitivity 41%). In 145 infants without PRD, 27 had abnormal US (specificity 81%). Dilating reflux or verified obstruction occurred in 21 (11%) infants, of whom 18 (86%) had PRD while 28 of 170 (16%) without such diagnoses had PRD. Of 16 infants with dilating reflux, 9 (sensitivity 56%) had abnormal US and 14 (88%) PRD. Dilatation at US was seen in 27 children; 7 of these had dilating reflux and 5 verified obstruction. CONCLUSION: US performed in association with acute UTI had limited ability to identify children with PRD at (99m)Tc-dimercaptosuccinic acid (DMSA) 1 year later, although abnormal renal size was a strong indicator of renal damage. The ability of US to identify children with dilating reflux was also limited. However, once detected at US, dilatation of the urinary tract was associated with dilating reflux or obstruction in half of the cases. Our study confirms that dilating reflux and obstruction are strong indicators of PRD but only half of those who developed PRD had such diagnoses.
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40. |
- Müller, Lennart, 1959, et al.
(författare)
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Ultrasound assessment of detrusor thickness in children and young adults with myelomeningocele
- 2006
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Ingår i: J Urol. - 0022-5347. ; 175:2
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We determine by ultrasonography the range of dT in carefully treated and followed children with myelomeningocele, and evaluate the role of such measurements for the understanding of bladder abnormalities in these patients. MATERIALS AND METHODS: We studied 66 children and young adults with MMC (34 males and 32 females, median age 8.1 years, range 1.1 to 20.1). Detrusor thickness was measured with a previously established ultrasonographic technique and the results were compared to those in normal children. The variation in detrusor thickness with degree of bladder dysfunction as well as with bladder wall trabeculation, kidney function and anticholinergic treatment was studied. RESULTS: The detrusor of the ventral wall was slightly thinner in children with MMC compared to normal. No significant variation in dT was found for different degrees of bladder dysfunction, bladder wall trabeculation, kidney function or anticholinergic treatment. Boys had thicker detrusor of the ventral wall than girls. CONCLUSIONS: Children with MMC, followed closely and treated according to international standards, do not acquire detrusor thickening as measured by ultrasonography. The detrusor thickness did not correlate with the degree of bladder dysfunction or renal function, or with anticholinergic treatment. Bladder wall trabeculation at VCU was not associated with bladder wall thickening on ultrasonography. We postulate that in a closely monitored and actively treated population of patients with MMC muscular hypertrophy and the development of connective tissue in the bladder wall is kept to a minimum.
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41. |
- Nielsen, L. F., et al.
(författare)
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Asphyxia-related risk factors and their timing in spastic cerebral palsy
- 2008
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Ingår i: BJOG. - : Wiley. - 1471-0528. ; 115:12, s. 1518-28
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the association of asphyxia-related conditions (reducing blood flow or blood oxygen levels in the fetus) with spastic cerebral palsy (CP) considering different gestational age groups and the timing of risk. DESIGN: Population-based case-control study. SETTING: Danish Cerebral Palsy Register in eastern Denmark and Danish Medical Birth Register. POPULATION OR SAMPLE: 271 singletons with spastic CP and 217 singleton controls, frequency matched by gestational age group, born 1982-1990 in eastern Denmark. METHODS: Data were abstracted from medical records, and a priori asphyxia-related conditions and other risk factors were selected for analysis. Each factor was classified according to the time at which it was likely to first be present. MAIN OUTCOME MEASURES: Spastic CP. RESULTS: Placental and cord complications accounted for the majority of asphyxia conditions. In multivariate analysis, placental infarction was significantly associated with a four-fold increased risk for spastic quadriplegia and cord around the neck was significantly associated with a three-fold increased risk for spastic CP overall. The combination of placental infarction and being small for gestational age (SGA) afforded an especially high risk for spastic quadriplegia. Placental and cord complications were present in 21% of cases and 12% of controls. CONCLUSIONS: The risk for spastic quadriplegia from placental infarction may be linked in some cases with abnormal fetal growth (17% of all children with spastic quadriplegia and 3% of control children both had an infarction and were SGA) -- suggesting an aetiologic pathway that encompasses both factors. The risk for spastic CP from cord around the neck is not accounted for by other prepartum or intrapartum factors we examined. Considering the relative timing of risk factors provides a useful framework for studies of CP aetiology.
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42. |
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43. |
- Pennell, C. E., et al.
(författare)
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Genetic epidemiologic studies of preterm birth: guidelines for research
- 2007
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Ingår i: Am J Obstet Gynecol. - 1097-6868. ; 196:2, s. 107-18
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Tidskriftsartikel (refereegranskat)abstract
- Over the last decade, it has become increasingly apparent that the cause of preterm birth is multifactorial, involving both genetic and environmental factors. With the development of new technologies capable of probing the genome, exciting possibilities now present themselves to gain new insight into the mechanisms leading to preterm birth. This review aims to develop research guidelines for the conduct of genetic epidemiology studies of preterm birth with the expectation that this will ultimately facilitate the comparison of data sets between study cohorts, both nationally and internationally. Specifically, the 4 areas addressed in this review includes: (1) phenotypic criteria, (2) study design, (3) considerations in the selection of control populations, and (4) candidate gene selection. This article is the product of discussions initiated by the authors at the 3rd International Workshop on Biomarkers and Preterm Birth held at the University of California, Los Angeles, Los Angeles, CA, in March 2005.
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44. |
- Rosenbaum, P., et al.
(författare)
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A report: the definition and classification of cerebral palsy April 2006
- 2007
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Ingår i: Dev Med Child Neurol Suppl. - 0419-0238. ; 109, s. 8-14
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Tidskriftsartikel (refereegranskat)abstract
- For a variety of reasons, the definition and the classification of cerebral palsy (CP) need to be reconsidered. Modern brain imaging techniques have shed new light on the nature of the underlying brain injury and studies on the neurobiology of and pathology associated with brain development have further explored etiologic mechanisms. It is now recognized that assessing the extent of activity restriction is part of CP evaluation and that people without activity restriction should not be included in the CP rubric. Also, previous definitions have not given sufficient prominence to the non-motor neurodevelopmental disabilities of performance and behaviour that commonly accompany CP, nor to the progression of musculoskeletal difficulties that often occurs with advancing age. In order to explore this information, pertinent material was reviewed on July 11-13, 2004 at an international workshop in Bethesda, MD (USA) organized by an Executive Committee and participated in by selected leaders in the preclinical and clinical sciences. At the workshop, it was agreed that the concept 'cerebral palsy' should be retained. Suggestions were made about the content of a revised definition and classification of CP that would meet the needs of clinicians, investigators, health officials, families and the public and would provide a common language for improved communication. Panels organized by the Executive Committee used this information and additional comments from the international community to generate a report on the Definition and Classification of Cerebral Palsy, April 2006. The Executive Committee presents this report with the intent of providing a common conceptualization of CP for use by a broad international audience.
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45. |
- Rüetschi, Ulla, 1962, et al.
(författare)
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Proteomic analysis using protein chips to detect biomarkers in cervical and amniotic fluid in women with intra-amniotic inflammation
- 2005
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Ingår i: J Proteome Res. ; 4:6, s. 2236-42
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Tidskriftsartikel (refereegranskat)abstract
- Intra-amniotic inflammation (IAI) may cause preterm birth with poor neonatal out-come. To identify novel biomarkers for IAI, we analyzed amniotic and cervical fluid samples from 27 patients with signs of threatening preterm birth with or without IAI by surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Seventeen proteins were significantly overexpressed in amniotic fluid from IAI cases and more often in women with preterm labor than those with rupture of membranes. Five of these were identified as human neutrophil protein 1-3, calgranulin A and B.
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46. |
- Skogstrand, K., et al.
(författare)
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Effects of blood sample handling procedures on measurable inflammatory markers in plasma, serum and dried blood spot samples
- 2008
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Ingår i: Journal of Immunological Methods. - : Elsevier BV. - 0022-1759. ; 336:1, s. 78-84
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Tidskriftsartikel (refereegranskat)abstract
- The interests in monitoring inflammation by immunoassay determination of blood inflammatory markers call for information on the stability of these markers in relation to the handling of blood samples. The increasing use of stored biobank samples for such ventures that may have been collected and stored for other purposes, justifies the study hereof. Blood samples were stored for 0, 4, 24, and 48 h at 4 degrees C, room temperature (RT), and at 35 degrees C, respectively, before they were separated into serum or plasma and frozen. Dried blood spot samples (DBSS) were stored for 0, 1, 2, 3, 7, and 30 days at the same temperatures. 27 inflammatory markers in serum and plasma and 25 markers in DBSS were measured by a previously validated multiplex sandwich immunoassay using Luminex xMAP technology. The measurable concentrations of several cytokines in serum and plasma were significantly increased when blood samples were stored for a period of time before the centrifugation, for certain cytokines more than 1000 fold compared to serum and plasma isolated and frozen immediately after venepuncture. The concentrations in serum generally increased more than in plasma. The measurable concentrations of inflammatory markers also changed in DBSS stored under various conditions compared to controls frozen immediately after preparation, but to a much lesser degree than in plasma or serum. The study demonstrates that trustworthy measurement of several inflammatory markers relies on handling of whole blood samples at low temperatures and rapid isolation of plasma and serum. Effects of different handling procedures for all markers studied are given. DBSS proved to be a robust and convenient way to handle samples for immunoassay analysis of inflammatory markers in whole blood.
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47. |
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48. |
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49. |
- Vogel, Ida, et al.
(författare)
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Acquisition and Elimination of Bacterial Vaginosis During Pregnancy: A Danish Population-Based Study
- 2006
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Ingår i: Infectious Diseases in Obstetrics and Gynecology.
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: the aim was to examine factors associated with acquisition and elimination of bacterial vaginosis in pregnancy. Methods: a group of 229 pregnant women were randomly selected from a population-based prospective cohort study of 2927. They were examined at enrollment (mean gestational weeks 16w+0d) and again in mid-third trimester (mean gestational age 32w+3d). Measures: BV (Amsel's clinical criteria), microbiological cultures of the genital tract and questionnaire data. Results: BV prevalence decreased from 17% in early second trimester to 14% in mid-third trimester due to a tenfold higher elimination rate (39%) than incidence rate (4%). Heavy smokers (>10/d) in early pregnancy were at increased risk (5.3[1.1−25]) for the acquisition of BV during pregnancy, as were women receiving public benefits (4.8[1.0−22]), having a vaginal pH above 4.5(6.3[1.4−29]) or vaginal anaerobe bacteria (18[2.7−122]) at enrollment. A previous use of combined oral contraceptives was preventive for the acquisition of BV (0.2[0.03−0.96]). Elimination of BV in pregnancy tended to be associated with a heavy growth of Lactobacillus (3.2[0.8−13]) at enrollment. Conclusions: acquisition of BV during pregnancy is rare and is associated with smoking, while the presence of anaerobe bacteria and a vaginal pH >4.5 are interpreted as steps on a gradual change towards BV. In the same way heavy growth of Lactobacillus spp in early pregnancy may be an indicator of women on the way to eliminate BV.
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50. |
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