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Sökning: WFRF:(Norman Elisabeth)

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1.
  • Horikoshi, Momoko, et al. (författare)
  • New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
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2.
  • Stoltz Sjöström, Elisabeth, et al. (författare)
  • Micronutrient Intakes Affect Early Growth in Extremely Preterm Infants : Preliminary Results from a Swedish Cohort
  • 2011
  • Ingår i: Pediatric Research. - : Nature Publishing Group. - 1530-0447 .- 0031-3998.
  • Konferensbidrag (refereegranskat)abstract
    • Background: Extremely preterm infants generally experience postnatal growth failure. It is still unclear if this is related to micronutrient intakes.Aim: To investigate the effect of micronutrient intakes (calcium, zinc, iron, phosphorus, sodium, potassium, chloride, magnesium, vitamin A, vitamin D, vitamin E, folate and vitamin B12) on growth during the first 28 days of life in extremely preterm infants.Method: From the EXPRESS cohort (all infants born < 27 gestational weeks between 2004-2007 in Sweden), those who survived the first 28 days were included (n=524). Daily parenteral and enteral intakes and anthropometric measurements were retrieved from hospital records.Results: Preliminary analyses of data from 333 infants (mean±SD gestational age 25.2±1.0 weeks, birth weight 753±168g) showed that macronutrient intakes were lower than recommended (energy 98±13kcal/kg/day, protein 2.9±0.4g/kg/day). Infants showed postnatal growth failure: mean standard deviation scores decreased by 2.2 for weight, 2.3 for length and 1.4 for head circumference. Intakes of micronutrients were generally low, e.g. adjusted enteral intakes of calcium were 66.6±21.4 mg/kg/day. The exception was iron, with a high parenteral intake of 2.7±1.6 mg/kg/day, mainly from blood transfusions. Adjusting for protein intake and other confounders, calcium intakes were positively correlated with head growth (r=+0.19, p=0.006) and iron intakes were negatively correlated with length gain (r=-0.18, p=0.009).Conclusions: Low calcium intakes and high iron intakes were associated with poor growth with regard to head circumference and length, respectively. If these results are confirmed, optimized micronutrient intakes may improve early growth in extremely preterm infants.
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3.
  • Stoltz Sjöström, Elisabeth, et al. (författare)
  • Nutrient intakes independently affect growth in extremely preterm infants: results from a population-based study
  • 2013
  • Ingår i: Acta Paediatrica. - : Wiley-Blackwell. - 0803-5253 .- 1651-2227. ; 102:11, s. 1067-1074
  • Tidskriftsartikel (refereegranskat)abstract
    • AimTo explore associations between energy and macronutrient intakes and early growth in extremely low gestational age (ELGA) infants. less thanbrgreater than less thanbrgreater thanMethodsRetrospective population-based study of all ELGA infants (andlt;27weeks) born in Sweden during 2004-2007. Detailed data on nutrition and anthropometric measurements from birth to 70days of postnatal age were retrieved from hospital records. less thanbrgreater than less thanbrgreater thanResultsStudy infants (n=531) had a meanSD gestational age of 25.3 +/- 1.1weeks and a birth weight of 765 +/- 170g. Between 0 and 70days, average daily energy and protein intakes were 120 +/- 11kcal/kg and 3.2 +/- 0.4g/kg, respectively. During this period, standard deviation scores for weight, length and head circumference decreased by 1.4, 2.3 and 0.7, respectively. Taking gestational age, baseline anthropometrics and severity of illness into account, lower energy intake correlated with lower gain in weight (r=+0.315, pandlt;0.001), length (r=+0.215, pandlt;0.001) and head circumference (r=+0.218, pandlt;0.001). Protein intake predicted growth in all anthropometric outcomes, and fat intake was positively associated with head circumference growth. less thanbrgreater than less thanbrgreater thanConclusionExtremely low gestational age infants received considerably less energy and protein than recommended and showed postnatal growth failure. Nutrient intakes were independent predictors of growth even after adjusting for severity of illness. These findings suggest that optimized energy and macronutrient intakes may prevent early growth failure in these infants.
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4.
  • Taal, H. Rob, et al. (författare)
  • Common variants at 12q15 and 12q24 are associated with infant head circumference
  • 2012
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 532-538
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
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6.
  • Abel, I, et al. (författare)
  • Overview of the JET results with the ITER-like wall
  • 2013
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
  • Tidskriftsartikel (refereegranskat)abstract
    • Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
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8.
  • Austeng, Dordi, et al. (författare)
  • Incidence of and risk factors for neonatal morbidity after active perinatal care : extremely preterm infants study in Sweden (EXPRESS)
  • 2010
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 99:7, s. 978-992
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: The aim of this study was to determine the incidence of neonatal morbidity in extremely preterm infants and to identify associated risk factors. Methods: Population based study of infants born before 27 gestational weeks and admitted for neonatal intensive care in Sweden during 2004-2007. Results: Of 638 admitted infants, 141 died. Among these, life support was withdrawn in 55 infants because of anticipation of poor long-term outcome. Of 497 surviving infants, 10% developed severe intraventricular haemorrhage (IVH), 5.7% cystic periventricular leucomalacia (cPVL), 41% septicaemia and 5.8% necrotizing enterocolitis (NEC); 61% had patent ductus arteriosus (PDA) and 34% developed retinopathy of prematurity (ROP) stage >= 3. Eighty-five per cent needed mechanical ventilation and 25% developed severe bronchopulmonary dysplasia (BPD). Forty-seven per cent survived to one year of age without any severe IVH, cPVL, severe ROP, severe BPD or NEC. Tocolysis increased and prolonged mechanical ventilation decreased the chances of survival without these morbidities. Maternal smoking and higher gestational duration were associated with lower risk of severe ROP, whereas PDA and poor growth increased this risk. Conclusion: Half of the infants surviving extremely preterm birth suffered from severe neonatal morbidities. Studies on how to reduce these morbidities and on the long-term health of survivors are warranted.
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9.
  • Backman, Sofia, et al. (författare)
  • Swedish consensus reached on recording, interpretation and reporting of neonatal continuous simplified electroencephalography that is supported by amplitude-integrated trend analysis
  • 2018
  • Ingår i: Acta Paediatrica. - : WILEY. - 0803-5253 .- 1651-2227. ; 107:10, s. 1702-1709
  • Tidskriftsartikel (refereegranskat)abstract
    • Continuous monitoring of electroencephalography (EEG), with a focus on amplitude-integrated EEG (aEEG), has been used in neonatal intensive care for decades. A number of systems have been suggested for describing and quantifying aEEG patterns. Extensive full-montage EEG monitoring is used in specialised intensive care units. The American Clinical Neurophysiology Society published recommendations for defining and reporting EEG findings in critically ill adults and infants. Swedish neonatologists and clinical neurophysiologists collaborated to optimise simplified neonatal continuous aEEG and EEG recordings based on these American documents. Conclusion: This paper describes the Swedish consensus document produced by those meetings.
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10.
  • Björk Brämberg, Elisabeth, et al. (författare)
  • Access to primary and specialized somatic health care for persons with severe mental illness: a qualitative study of perceived barriers and facilitators in Swedish health care
  • 2018
  • Ingår i: BMC Family Practice. - : Springer Science and Business Media LLC. - 1471-2296. ; 19
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Persons with severe mental illness (e.g. schizophrenia, bipolar disorder) have a high prevalence of somatic conditions compared to the general population. Mortality data in the Nordic countries reveal that these persons die 15-20 years earlier than the general population. Some factors explaining this high prevalence may be related to the individuals in question; others arise from the health care system's difficulty in offering somatic health care to these patient groups. The aim of the present study was therefore to explore the experiences and views of patients, relatives and clinicians regarding individual and organizational factors which facilitate or hinder access to somatic health care for persons with severe mental illness. Methods: Flexible qualitative design. Data was collected by means of semi-structured individual interviews with patients with severe mental illness, relatives and clinicians representing primary and specialized health care. In all, 50 participants participated. Results: The main barrier to accessing somatic care is the gap between the organization of the health care system and the patients' individual health care needs. This is observed at both individual and organizational level. The health care system seems unable to support patients with severe mental illness and their psychiatric-somatic comorbidity. The main facilitators are the links between severe mental illness patients and medical departments. These links take the form of functions (i.e. systems which ensure that patients receive regular reminders), or persons (i.e. professional contacts who facilitate patients' access the health care). Conclusions: Health care services for patients with severe mental illness need reorganization. Organizational structures and systems that facilitate cooperation between different departments must be put in place, along with training for health care professionals about somatic disease among psychiatric patients. The links between individual and organizational levels could be strengthened by introducing professional contacts, such as liaison physicians and case managers. This is also important to reduce stress and responsibility among relatives.
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12.
  • Elens, Laure, et al. (författare)
  • Genetic Predisposition to Poor Opioid Response in Preterm Infants : Impact of KCNJ6 and COMT Polymorphisms on Pain Relief after Endotracheal Intubation
  • 2016
  • Ingår i: Therapeutic Drug Monitoring. - 0163-4356 .- 1536-3694. ; 38:4, s. 525-533
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Single-nucleotide polymorphisms in genes involved in pain control might predispose to exaggerated sensitivity or difference in opioid analgesic effect. The relevance of the KCNJ6 -1250G>A (rs6517442, c.-1787G>A) and the catecholamine-O-methyltransferase (COMT) c.472G>A (rs4680, Val 158 Met) single-nucleotide polymorphisms were studied in preterm infants needing intubation and randomized to a premedication strategy including remifentanil (n 17) or morphine (n 17). Methods: Pain was scored with Astrid Lindgren and Lund Children's Hospital Pain Assessment Scale every 30 minutes for 6 hours. The pain relief provided by the opioids was compared between the different KCNJ6 and COMT genotypes. Results: Infants homozygous for the KCNJ6 -1250A allele had an increased duration after intubation to achieve a score indicating no pain compared with infants with the A/G or G/G genotypes (182 ± 30, 109 ± 29, and 60 ± 21 minutes, respectively; Logrank 7.5, P 0.006). Similarly, the duration was increased in individuals with the COMT Val/Val alleles compared with Val/Met and Met/Met (285 ± 37, 137 ± 25, and 63 ± 15 minutes, respectively; Logrank 14.4, P 0.0021). Cox proportional hazards analysis confirmed that the variation in both genes was independently associated with susceptibility to respond to therapy. Conclusion: We conclude that the KCNJ6 -1250A and COMT 158 Val alleles are predisposing preterm newborns to diminished opioid-induced pain relief.
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14.
  • Eriksson, Mats, Professor, 1959-, et al. (författare)
  • Pain scales in clinical trials in newborn infants : a mapping of the evidence
  • 2019
  • Konferensbidrag (refereegranskat)abstract
    • Background: Numerous clinical studies have aimed at finding a strategy to reduce the pain newborn infants are subjected to by their medical conditions and also by medical and caring procedures. Little is however known about whether the outcome measures in these trials are valid for the specific type of pain or group of infants included in the studies. There are today over 40 published scales, consisting of behavioral or physiological signals or a combination of both. The aim of this study was to evaluate the reporting of pain scales assessments that were most commonly used in all the published trials examining interventions related to neonatal pain.Methods: A systematic and broad search up to January 2019 was performed in Embase, PubMed, PsycInfo, Cinahl, Cochrane Library, Scopus and Luxid. Randomized and quasi-randomized clinical trials on neonatal pain were included. Title and abstract screening followed by full text screening were performed by two independent researchers using an online tool for the preparation of systematic reviews (Covidence). Disagreements were resolved by a third researcher or in discussions within the group, as recommended in the Cochrane handbook. Data extraction and quality assessment were also performed by two researchers independently. Results: The systematic search retrieved 3715 scientific articles. Following screening, 342 studies with a total of 16210 infants were included, reporting data from the use of at least one neonatal pain assessment scale. Ninety per cent of the studies concerned procedural pain where the most frequently used pain scales were PIPP or PIPP-R (43%), followed by NIPS (17%). For ongoing or post-operative pain there was a more unclear pattern with COMFORT (24%) and NFCS (10%) as the most reported. We observed a wide variation of pain scales (Fig 1) and found numerous studies where pain scales were used that were not validated for the studied population or type of pain. In 11 papers self-constructed study-specific scales were used. The most frequent sources of procedural pain were heel lance (28% of the studies) followed by venipuncture (10%) and ROP-screening (5%).Conclusion: This is the first scoping review reporting systematically how neonatal pain scales are used in clinical trials. There are a few validated pain assessment scales used in most clinical studies. It is crucial to choose an appropriate scale, validated for the type of pain and population of infants included in the study. The inappropriate use of pain scales raises serious concerns on ethical conduct of research and waste of resources. 
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15.
  • Eriksson, Mats, Professor, 1959-, et al. (författare)
  • Pain scales in clinical trials in newborn infants : a mapping of the evidence
  • 2019
  • Konferensbidrag (refereegranskat)abstract
    • Background: Numerous clinical studies have aimed at reducing pain in newborn infants. Little is known about whether the outcome measures are valid for the specific type of pain or group of infants included. Aim: To evaluate the reporting of pain assessments used in published trials.Methods: A systematic search up to January 2019 was performed in Embase, PubMed, PsycInfo, Cinahl, Cochrane Library, Scopus and Luxid. Randomized and quasi-randomized clinical trials were included. Title and abstract screening followed by full text screening were performed by two independent researchers. Data extraction and quality assessment were also performed by two researchers independently.Results: The search retrieved 3715 articles. 342 studies with a total of 16210 infants were included. 90% of the studies concerned procedural pain where the most frequently used pain scales were PIPP or PIPP-R followed by NIPS For ongoing or post-operative pain COMFORT and NFCS were mostly used. We observed a wide variation of pain scales and found numerous studies where pain scales were used that were not validated for the studied population or type of pain. Conclusion: This is the first scoping review reporting systematically how neonatal pain scales are used in clinical trials. There are a few validated pain assessment scales used in most clinical studies. It is crucial to choose an appropriate scale, validated for the type of pain and population of infants included in the study. The inappropriate use of pain scales raises serious concerns on ethical conduct of research and waste of resources.
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16.
  • Fellman, Vineta, et al. (författare)
  • One-year survival of extremely preterm infants after active perinatal care in Sweden.
  • 2009
  • Ingår i: JAMA : the journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 301:21, s. 2225-33
  • Tidskriftsartikel (refereegranskat)abstract
    • Up-to-date information on infant survival after extremely preterm birth is needed for assessing perinatal care services, clinical guidelines, and parental counseling.
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17.
  • Forouzanfar, Mohammad H, et al. (författare)
  • Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
  • 2015
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
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18.
  • Fransson, Per, et al. (författare)
  • Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC) : patient-reported quality-of-life outcomes of a randomised, controlled, non-inferiority, phase 3 trial
  • 2021
  • Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 22:2, s. 235-245
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The HYPO-RT-PC trial compared conventionally fractionated radiotherapy with ultra-hypofractionated radiotherapy in patients with localised prostate cancer. Ultra-hypofractionation was non-inferior to conventional fractionation regarding 5-year failure-free survival and toxicity. We aimed to assess whether patient-reported quality of life (QOL) differs between conventional fractionation and ultra-hypofractionation up to 6 years after treatment in the HYPO-RT-PC trial.METHODS: HYPO-RT-PC is a multicentre, open-label, randomised, controlled, non-inferiority, phase 3 trial done in 12 centres (seven university hospitals and five county hospitals) in Sweden and Denmark. Inclusion criteria were histologically verified intermediate-to-high-risk prostate cancer (defined as T1c-T3a with one or two of the following risk factors: stage T3a; Gleason score ≥7; and prostate-specific antigen 10-20 ng/mL with no evidence of lymph node involvement or distant metastases), age up to 75 years, and WHO performance status 0-2. Participants were randomly assigned (1:1) to conventional fractionation (78·0 Gy in 39 fractions, 5 days per week for 8 weeks) or ultra-hypofractionation (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) via a minimisation algorithm with stratification by trial centre, T-stage, Gleason score, and prostate-specific antigen. QOL was measured using the validated Prostate Cancer Symptom Scale (PCSS) and European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) at baseline, the end of radiotherapy, months 3, 6, 12, and 24 after radiotherapy, every other year thereafter up to 10 years, and at 15 years. The primary endpoint (failure-free survival) has been reported elsewhere. Here we report QOL, a secondary endpoint analysed in the per-protocol population, up to 6 years after radiotherapy. The HYPO-RT-PC trial is registered with the ISRCTN registry, ISRCTN45905321.FINDINGS: Between July 1, 2005, and Nov 4, 2015, 1200 patients were enrolled and 1180 were randomly assigned (conventional fractionation n=591, ultra-hypofractionation n=589); 1165 patients (conventional fractionation n=582, ultra-hypofractionation n=583) were included in this QOL analysis. 158 (71%) of 223 patients in the conventional fractionation group and 146 (66%) of 220 in the ultra-hypofractionation group completed questionnaires at 6 years. The median follow-up was 48 months (IQR 25-72). In seven of ten bowel symptoms or problems the proportion of patients with clinically relevant deteriorations at the end of radiotherapy was significantly higher in the ultra-hypofractionation group than in the conventional fractionation group (stool frequency [p<0·0001], rush to toilet [p=0·0013], flatulence [p=0·0013], bowel cramp [p<0·0001], mucus [p=0·0014], blood in stool [p<0·0001], and limitation in daily activity [p=0·0014]). There were no statistically significant differences in the proportions of patients with clinically relevant acute urinary symptoms or problems (total 14 items) and sexual functioning between the two treatment groups at end of radiotherapy. Thereafter, there were no clinically relevant differences in urinary, bowel, or sexual functioning between the groups. At the 6-year follow-up there was no difference in the incidence of clinically relevant deterioration between the groups for overall urinary bother (43 [33%] of 132 for conventional fractionation vs 33 [28%] of 120 for ultra-hypofractionation; mean difference 5·1% [95% CI -4·4 to 14·6]; p=0·38), overall bowel bother (43 [33%] of 129 vs 34 [28%] of 123; 5·7% [-3·8 to 15·2]; p=0·33), overall sexual bother (75 [60%] of 126 vs 59 [50%] of 117; 9·1% [-1·4 to 19·6]; p=0·15), or global health/QOL (56 [42%] of 134 vs 46 [37%] of 125; 5·0% [-5·0 to 15·0]; p=0·41).INTERPRETATION: Although acute toxicity was higher for ultra-hypofractionation than conventional fractionation, this long-term patient-reported QOL analysis shows that ultra-hypofractionation was as well tolerated as conventional fractionation up to 6 years after completion of treatment. These findings support the use of ultra-hypofractionation radiotherapy for intermediate-to-high-risk prostate cancer.
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19.
  • Gaulton, Kyle J, et al. (författare)
  • Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
  • 2015
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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20.
  • Hamayun, Jawwad, et al. (författare)
  • Association between neonatal intakes and hyperglycemia, and left heart and aortic dimensions at 6.5 years of age in children born extremely preterm
  • 2021
  • Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 10:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Survivors of extremely preterm birth (gestational age < 27 weeks) have been reported to exhibit an altered cardiovascular phenotype in childhood. The mechanisms are unknown. We investigated associations between postnatal nutritional intakes and hyperglycemia, and left heart and aortic dimensions in children born extremely preterm. Postnatal nutritional data and echocardiographic dimensions at 6.5 years of age were extracted from a sub-cohort of the Extremely Preterm Infants in Sweden Study (EXPRESS; children born extremely preterm between 2004–2007, n = 171, mean (SD) birth weight = 784 (165) grams). Associations between macronutrient intakes or number of days with hyperglycemia (blood glucose > 8 mmol/L) in the neonatal period (exposure) and left heart and aortic dimensions at follow-up (outcome) were investigated. Neonatal protein intake was not associated with the outcomes, whereas higher lipid intake was significantly associated with larger aortic root diameter (B = 0.040, p = 0.009). Higher neonatal carbohydrate intake was associated with smaller aorta annulus diameter (B = −0.016, p = 0.008). Longer exposure to neonatal hyperglycemia was associated with increased thickness of the left ventricular posterior wall (B = 0.004, p = 0.008) and interventricular septum (B = 0.004, p = 0.010). The findings in this study indicate that postnatal nutrition and hyperglycemia may play a role in some but not all long-lasting developmental adaptations of the cardiovascular system in children born extremely preterm.
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21.
  • Hansen, Thor Willy Ruud, et al. (författare)
  • Reversibility of acute intermediate phase bilirubin encephalopathy
  • 2009
  • Ingår i: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 98:10, s. 1689-1694
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To show the potential for reversing acute intermediate to advanced phase bilirubin encephalopathy. Methods: Case studies. Results: Six extremely jaundiced infants had symptoms of intermediate to advanced phase acute bilirubin encephalopathy. The infants were treated aggressively. Two patients had brain magnetic resonance imaging showing increased signals in the globus pallidus. On follow-up, all infants are neurologically normal. Conclusions: Intermediate-to-advanced stage acute bilirubin encephalopathy may occasionally be reversible. These cases provide a strong argument in favour of rapid and aggressive intervention in infants presenting with extreme jaundice and neurological symptoms.
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22.
  • Hardisty, Alex R., et al. (författare)
  • BioVeL: A virtual laboratory for data analysis and modelling in biodiversity science and ecology
  • 2016
  • Ingår i: BMC Ecology. - : Springer Science and Business Media LLC. - 1472-6785. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2016 The Author(s).Background: Making forecasts about biodiversity and giving support to policy relies increasingly on large collections of data held electronically, and on substantial computational capability and capacity to analyse, model, simulate and predict using such data. However, the physically distributed nature of data resources and of expertise in advanced analytical tools creates many challenges for the modern scientist. Across the wider biological sciences, presenting such capabilities on the Internet (as "Web services") and using scientific workflow systems to compose them for particular tasks is a practical way to carry out robust "in silico" science. However, use of this approach in biodiversity science and ecology has thus far been quite limited. Results: BioVeL is a virtual laboratory for data analysis and modelling in biodiversity science and ecology, freely accessible via the Internet. BioVeL includes functions for accessing and analysing data through curated Web services; for performing complex in silico analysis through exposure of R programs, workflows, and batch processing functions; for on-line collaboration through sharing of workflows and workflow runs; for experiment documentation through reproducibility and repeatability; and for computational support via seamless connections to supporting computing infrastructures. We developed and improved more than 60 Web services with significant potential in many different kinds of data analysis and modelling tasks. We composed reusable workflows using these Web services, also incorporating R programs. Deploying these tools into an easy-to-use and accessible 'virtual laboratory', free via the Internet, we applied the workflows in several diverse case studies. We opened the virtual laboratory for public use and through a programme of external engagement we actively encouraged scientists and third party application and tool developers to try out the services and contribute to the activity. Conclusions: Our work shows we can deliver an operational, scalable and flexible Internet-based virtual laboratory to meet new demands for data processing and analysis in biodiversity science and ecology. In particular, we have successfully integrated existing and popular tools and practices from different scientific disciplines to be used in biodiversity and ecological research.
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23.
  • Jansen, Willemijn J, et al. (författare)
  • Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
  • 2018
  • Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 84-95
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P=.16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P<.001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P<.001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
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24.
  • Jansen, Willemijn J, et al. (författare)
  • Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
  • 2022
  • Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
  • Tidskriftsartikel (refereegranskat)abstract
    • One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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25.
  • Jansen, Willemijn J, et al. (författare)
  • Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
  • 2015
  • Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
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26.
  • Kattge, Jens, et al. (författare)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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27.
  • Kehoe, Laura, et al. (författare)
  • Make EU trade with Brazil sustainable
  • 2019
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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28.
  • Kinoshita, Mari, et al. (författare)
  • Opioids and alpha-2-agonists for analgesia and sedation in newborn infants : protocol of a systematic review
  • 2020
  • Ingår i: Systematic Reviews. - : Springer Science and Business Media LLC. - 2046-4053. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Hospitalized newborn infants may require analgesia and sedation either for the management of procedural pain, during or after surgery, and other painful conditions. The benefits and harms of opioids administered at different doses and routes of administration have been reported in numerous trials and systematic reviews. The use of alpha-2-agonists such as clonidine and dexmedetomidine in newborn infants is more recent, and they might be prescribed to reduce the total amount of opioids which are thought to have more side effects. Moreover, alpha-2-agonists might play an important role in the management of agitation and discomfort. METHODS: We will conduct a systematic review and meta-analysis on the use of opioids, alpha-2-agonists, or the combination of both drugs. We will include randomized controlled trials to assess benefits and harms and observational studies to assess adverse events and pharmacokinetics; preterm and term infants; studies on any opioids or alpha-2-agonists administered for any indication and by any route except spinal, intraosseous, or administration for nerve blocks and wound infusions. The use of opioids or alpha-2-agonists will be compared to no intervention; placebo with normal saline or other non-sedative, non-analgesic drug; control with oral sugar solution or non-pharmacological intervention; same drug of different dose or route; or a different drug (not limiting to opioids and alpha-2-agonists) or combinations of such drugs. The primary outcomes for this review will be all-cause mortality during initial hospitalization and hypotension requiring medical therapy. We will conduct a search in the following databases: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, Embase, and CINAHL. Two review authors will independently screen records for inclusion, undertake data abstraction using a data extraction form and assess the risk of bias of all included trials using the Cochrane "Risk of bias" tool. DISCUSSION: This systematic review will summarize and update our knowledge about neonatal analgesia and sedation including pharmacokinetics/pharmacodynamics, and provide a platform for developing evidence-based guidelines that we can immediately apply to our clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2020 CRD42020170852.
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29.
  • Kleberg, Agneta, et al. (författare)
  • Lower stress responses after newborn individualized developmental care and assessment program care during eye screening examinations for retinopathy of prematurity : A randomized study
  • 2008
  • Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 121:5, s. E1267-E1278
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE. Screening examination for retinopathy of prematurity is distressing and painful. The aim of the present study was to investigate whether a Newborn Individualized Developmental Care and Assessment Program intervention during a retinopathy of prematurity examination results in less adverse behavioral, pain, and stress responses as compared with standard care. METHODS. The first 2 eye examinations in 36 preterm infants were evaluated. The infants were randomly assigned at the first eye examination to receive either Newborn Individualized Developmental Care and Assessment Program care or standard care. At the second examination, crossover of subject assignment was performed. The assessments included behavioral responses, recordings of heart rate, respiration, and oxygenation, pain scores (premature infant pain profile), and salivary cortisol at defined time points up to 4 hours after the eye examination. The nursing support given during the eye examinations (intervention score) were scored using predefined criteria. RESULTS. Altogether, 68 examinations were evaluated. Newborn Individualized Developmental Care and Assessment Program care was associated with better behavioral scores during the examination but there was no difference in heart rate, respiratory rate, oxygenation, or premature infant pain profile score between the 2 care strategies before or after the eye examination. Salivary cortisol increased from baseline to 30 minutes after the eye examination independent of care strategy and decreased significantly between 30 and 60 minutes when infants were subjected to Newborn Individualized Developmental Care and Assessment Program care but not after standard care. During the study period the intervention score for standard care increased and approached the score for Newborn Individualized Developmental Care and Assessment Program care at the later eye examinations. CONCLUSION. A Newborn Individualized Developmental Care and Assessment Program-based intervention during eye examination does not decrease pain responses but results in faster recovery, as measured by lower salivary cortisol 60 minutes after the examination. The differences were seen despite the influence from the Newborn Individualized Developmental Care and Assessment Program intervention on the standard care treatment that occurred during the study period.
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30.
  • Klevebro, Susanna, et al. (författare)
  • Early energy and protein intakes and associations with growth, BPD and ROP in extremely preterm infants
  • 2019
  • Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 38:3, s. 1289-1295
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & aim: Extremely preterm infants face substantial neonatal morbidity. Nutrition is important to promote optimal growth and organ development in order to reduce late neonatal complications. The aim of this study was to examine the associations of early nutritional intakes on growth and risks of bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) in a high-risk population.Methods: This population-based cohort study includes infants born before 27 0/7 weeks of gestational age without severe malformations and surviving ≥10 days. Intake of energy and protein on postnatal days 4–6 and association with weight standard deviation score (WSDS) from birth to day 7, as well as intakes of energy and protein on postnatal days 4–6 and 7 to 27, respectively, and association with composite outcome of death and BPD and separate outcomes of BPD and ROP were examined, and adjusted for potential confounders.Results: The cohort comprised 296 infants with a median gestational age of 25 3/7 weeks. Expressed as daily intakes, every additional 10 kcal/kg/d of energy during days 4–6 was associated with 0.08 higher WSDS on day 7 (95% CI 0.06–0.11; p < 0.001). Between days 7 and 27, every 10 kcal/kg/d increase in energy intake was associated with a reduced risk of BPD of 9% (95% CI 1–16; p = 0.029) and any grade of ROP with a reduced risk of 6% (95% CI 2–9; p = 0.005) in multivariable models. This association was statistically significant in infants with ≤10 days of mechanical ventilation. In infants with >10 days of mechanical ventilation, a combined higher intake of energy and protein was associated with a reduced risk of BPD.Conclusion: Early provision of energy and protein may reduce postnatal weight loss and risk of morbidity in extremely preterm infants.
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31.
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32.
  • Larsson, P, et al. (författare)
  • Thiopentone elimination in newborn infants: exploring Michaelis-Menten kinetics.
  • 2011
  • Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 55, s. 444-451
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Thiopentone elimination has been described using Michaelis-Menten pharmacokinetics in adults after prolonged infusion or overdose, but there are few reports of elimination in neonates. Methods: Time-concentration profiles for neonates (n=37) given single-dose thiopentone were examined using both first-order (constant clearance) and mixed-order (Michaelis-Menten) elimination processes using nonlinear mixed effects models. These profiles included a 33-week post-menstrual age (PMA) neonate given an overdose. A two-compartment mamillary model was used to fit data. Parameter estimates were standardized to a 70 kg person using allometric models. Results: There were 197 observations available for analysis from neonates with a mean post-menstrual age of 35 (SD 4.5) weeks and a mean weight of 2.5 (SD 0.9) kg. They were given a mean thiopentone dose of 3 (SD 0.4) mg/kg as a rapid bolus. Clearance at 26 weeks PMA was 0.015 l/min/70 kg and increased to 0.119 l/min/70 kg by 42 weeks PMA. The maximum rate of elimination (V(max) ) at 26 weeks PMA was 0.22 mg/min/70 kg and increased to 4.13 mg/min/70 kg by 42 weeks PMA. These parameter estimates are approximately 40% adult values at term gestation. The Michaelis constant (K(m) ) was 28.3 [between subject variability (BSV) 46.4%, 95% confidence interval (CI) 4.49-99.2] mg/l; intercompartment clearance was 0.44 (BSV 97.5%, 95% CI 0.27-0.63) l/min/70 kg; central volume of distribution was 46.4 (BSV 29.2%, 95% CI 41.7-59.8) l/70 kg; peripheral volume of distribution was 95.7 (BSV 70.3%, 95% CI 61.3-128) l/70 kg. Conclusions: Both first-order and mixed-order processes satisfactorily described elimination. First-order elimination adequately described the time-concentration profile in the premature neonate given an overdose. Clearance is immature in the pre-term neonate although there is rapid maturation around 40 weeks PMA, irrespective of post-natal age.
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33.
  • Lindholm, Elisabeth S, et al. (författare)
  • Health Care Consumption during Pregnancy in relation to Maternal Body Mass Index : A Swedish Population Based Observational Study
  • 2015
  • Ingår i: Journal of Obesity. - : Hindawi Limited. - 2090-0708 .- 2090-0716. ; 2015, s. 7-
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To assess whether antenatal health care consumption is associated with maternal body mass index (BMI). Design. A register based observational study. Methods. The Swedish Medical Birth Register, the Maternal Health Care Register, and the Inpatient Register were used to determine antenatal health care consumption according to BMI categories for primiparous women with singleton pregnancies, from 2006 to 2008, . Pairwise comparisons among BMI groups are obtained post hoc by Tukey HSD test. Result. Obese women were more often admitted for in-patient care (), had longer antenatal hospital stays (), and were more often sick-listed by an obstetrician () during their pregnancy, compared to women with normal weight women. Preeclampsia was more than four times as common, hypertension five times as common, and gestational diabetes 11 times as common when comparing in-patient care, obese to normal weight women ( for all comparisons). Underweight mothers had longer stay in hospitals () and hydronephrosis and hyperemesis gravidarum were more than twice as common (both ). Conclusion. Obese and underweight mothers consumed significantly more health care resources and obese women were significantly more often sick-listed during their pregnancy when compared to pregnant women of normal weight.
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34.
  • Lucisano, Marco, et al. (författare)
  • Stratified forming as a tool for resource efficient papermaking
  • 2015
  • Ingår i: Paper Conference and Trade Show (PaperCon 2015). - : TAPPI Press. - 9781510818873 ; , s. 767-785
  • Konferensbidrag (refereegranskat)abstract
    • Pilot-scale demonstration of stratified forming with innovative design of vane technology. Stratified dosage of fillers tested for: •SC-paper •Fine paper Dosage of filler and retention aid through the liquid layers gives a wider window of operation (retention-formation). Filler content can be increased with no adverse effects on strength and structure.
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35.
  • Lundqvist, Pia, et al. (författare)
  • Development and psychometric properties of the Swedish ALPS-Neo pain and stress assessment scale for newborn infants
  • 2014
  • Ingår i: Acta Paediatrica. - : Wiley-Blackwell. - 0803-5253 .- 1651-2227. ; 103:8, s. 833-839
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: To validate and evaluate the psychometric properties of the ALPS-Neo, a new pain assessment scale created for the continuous evaluation of pain and stress in preterm and sick term infants.METHODS: A unidimensional scale for continuous pain, Astrid Lindgren Children's Hospital Pain Scale (ALPS 1), was developed further to assess continuous pain and stress in infants treated in the neonatal intensive care unit (NICU). The pain scale includes observations of five behaviours. A manual was created, clarifying the scoring criteria. An internal and an external panel assessed face validity. Psychometric properties were evaluated in three different steps. Inter-rater reliability was estimated from video-based assessments (n = 625) using weighted kappa statistics (test I). Inter-rater reliability was further evaluated in test II (n = 125) and test III (n = 96) by real-time assessments using the intraclass correlation coefficient (ICC) and Cronbach's alpha.RESULTS: The final inter-rater reliability (test III) was assessed as good with ICC 0.91 for the total score and 0.62-0.81 for the five items. Cronbach's alpha showed 0.95 for the total score.CONCLUSION: ALPS-Neo is a new assessment tool for optimising the management of pain and stress in newborn infants in the NICU. It has proved easy to implement and user-friendly, permitting fast, reliable observations with high inter-rater reliability.
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36.
  • Lundqvist, Pia, et al. (författare)
  • Development and psychometric properties of the Swedish ALPS-Neo pain and stress assessment scale for newborn infants
  • 2014
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 103:8, s. 833-839
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To validate and evaluate the psychometric properties of the ALPS-Neo, a new pain assessment scale created for the continuous evaluation of pain and stress in preterm and sick term infants. Methods: A unidimensional scale for continuous pain, Astrid Lindgren Children's Hospital Pain Scale (ALPS 1), was developed further to assess continuous pain and stress in infants treated in the neonatal intensive care unit (NICU). The pain scale includes observations of five behaviours. A manual was created, clarifying the scoring criteria. An internal and an external panel assessed face validity. Psychometric properties were evaluated in three different steps. Inter-rater reliability was estimated from video-based assessments (n = 625) using weighted kappa statistics (test I). Inter-rater reliability was further evaluated in test II (n = 125) and test III (n = 96) by real-time assessments using the intraclass correlation coefficient (ICC) and Cronbach's alpha. Results: The final inter-rater reliability (test III) was assessed as good with ICC 0.91 for the total score and 0.62-0.81 for the five items. Cronbach's alpha showed 0.95 for the total score. Conclusion: ALPS-Neo is a new assessment tool for optimising the management of pain and stress in newborn infants in the NICU. It has proved easy to implement and user-friendly, permitting fast, reliable observations with high inter-rater reliability.
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37.
  • Matic, Maja, et al. (författare)
  • Effect of UGT2B7-900G > A (-842G > A; rs7438135) on morphine glucuronidation in preterm newborns: results from a pilot cohort
  • 2014
  • Ingår i: Pharmacogenomics. - 1462-2416 .- 1744-8042. ; 15:12, s. 1589-1597
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: Assess association between UGT2B7 polymorphism -900G>A (rs7438135, also known as -842G>A) with morphine kinetics in preterm newborns undergoing mechanical ventilation. Materials & methods: Thirty-four infants were enrolled in a randomized clinical trial and allocated to rapid sequence intubation with remifentanil (1 mu g/kg) or morphine (0.3 mg/kg). The latter group was included in our study. Results: Morphine plasma concentrations at 20 min post intubation were associated with postnatal age (p = 0.017) and UGT2B7 -900G>A (p = 0.036). UGT2B7 -900A allele carriers (n = 13) had lower morphine levels compared with UGT2B7 -900G/G patients (n = 2). Morphine-3-glucuronide and morphine-6-glucuronide plasma concentrations were only found to be associated with gestational and postnatal age. However, -900A allele carriers had a higher morphine-3-glucuronide: morphine metabolic ratio compared with patients genotyped as -900G/G (p = 0.005), as determined by linear regression. Conclusion: Our small pilot study illustrates that in addition to gestational and postnatal age, the UGT2B7 -900G>A polymorphism significantly alters morphine pharmacokinetics in preterm infants.
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38.
  • Mattsson, H., et al. (författare)
  • Improved infrastructure and support needed for paediatric clinical trials in Sweden
  • 2020
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 109:12, s. 2740-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim There is a lack of authorised medicines for paediatric patients and improved drug development is necessary. The aim of this study was to evaluate the need for infrastructure and support for paediatric clinical trials in Sweden. Methods A web-based survey was sent to doctors and nurses involved in the care of neonates, children and adolescents assessing the current situation and future needs for paediatric clinical trials in Sweden. Questions regarding premises, competence, organisation, support for paediatric clinical trials and Good Clinical Practice Training were addressed. Results In total, 137 individuals responded to the survey (109 doctors and 28 nurses). Overall, 61% of the respondents had previous experience of paediatric clinical trials. Some respondents had access to trial units, but only 34% had used the trial unit for support. Half of the responders were interested in recurrent paediatric Good Clinical Practice training. Doctors responded that clinical work often had to be prioritised and emphasised the need for research time. Conclusion This study clearly shows the commitment for clinical trials among doctors and nurses involved in paediatric care in Sweden, but also that administrative, logistic and economic support in a sustainable setting and an expanded national collaboration are needed.
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39.
  • Mörelius, Evalotte, et al. (författare)
  • Is a nappy change stressful to neonates?
  • 2006
  • Ingår i: Early Human Development. - : Elsevier BV. - 1872-6232 .- 0378-3782. ; 82:10, s. 669-676
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Infants in neonatal intensive care (NICU infants) are often cared for in a stressful environment that includes potentially painful or stressful interventions. The aim was to investigate whether NICU infants have different pattern of stress and pain responses than healthy newborns when challenged by a non-painful everyday care routine. Methods: NICU infants born at 23-38 weeks gestation (n=39) were compared to healthy fullterm newborns (n=30). Cortisol concentrations in saliva were determined before and 30 min after a standardised nappy change. The premature infant pain profile (PIPP) and the neonatal infant pain scale (NIPS) were evaluated before, during, directly after, 3 min after, and 30 min after the nappy change. The investigation was performed on two different occasions, first between postnatal days 2-7 and then between postnatal days 10-18. Results: NICU infants had higher median baseline salivary cortisol levels compared to full-term newborns on both occasions (17.1 nmol/L vs. 6.2 nmol/L p < 0.01 and 8.5 nmoL/L vs. 2.4 nmoL/L p < 0.01, respectively). Salivary cortisol decreased-in response to the second nappy change in NICU infants (p=0.01). NICU infants had higher PIPP scores during both nappy changes (p < 0.001 for both occasions) and more sustained increases in PIPP and NIPS up to 30 min after the nappy changes compared to full-term newborns. Conclusions: NICU infants have higher baseline salivary cortisol than healthy full-term newborns. There is a change in baseline cortisol. by age in both groups. Full.-term infants as well as NICU infants show an increased pain response to a standardised nappy change.
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40.
  • Nilsson, Sofie, et al. (författare)
  • A Bedside Method for Measuring Effects of a Sedative Drug on Cerebral Function in Newborn Infants
  • 2023
  • Ingår i: Sensors. - : MDPI AG. - 1424-8220. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Data on the cerebral effects of analgesic and sedative drugs are needed for the development of safe and effective treatments during neonatal intensive care. Electroencephalography (EEG) is an objective, but interpreter-dependent method for monitoring cortical activity. Quantitative computerized analyses might reveal EEG changes otherwise not detectable. Methods: EEG registrations were retrospectively collected from 21 infants (mean 38.7 gestational weeks; range 27–42) who received dexmedetomidine during neonatal care. The registrations were transformed into computational features and analyzed visually, and with two computational measures quantifying relative and absolute changes in power (range EEG; rEEG) and cortico-cortical synchrony (activation synchrony index; ASI), respectively. Results: The visual assessment did not reveal any drug effects. In rEEG analyses, a negative correlation was found between the baseline and the referential frontal (rho = 0.612, p = 0.006) and parietal (rho = −0.489, p = 0.035) derivations. The change in ASI was negatively correlated to baseline values in the interhemispheric (rho = −0.753; p = 0.001) and frontal comparisons (rho = −0.496; p = 0.038). Conclusion: Cerebral effects of dexmedetomidine as determined by EEG in newborn infants are related to cortical activity prior to DEX administration, indicating that higher brain activity levels (higher rEEG) during baseline links to a more pronounced reduction by DEX. The computational measurements indicate drug effects on both overall cortical activity and cortico-cortical communication. These effects were not evident in visual analysis.
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41.
  • Norman, Elisabeth, et al. (författare)
  • Electroencephalographic response to procedural pain in healthy term newborn infants
  • 2008
  • Ingår i: Pediatric Research. - 0031-3998 .- 1530-0447. ; 64:4, s. 429-34
  • Tidskriftsartikel (refereegranskat)abstract
    • The current study aimed to characterize changes in EEG-related measures after noxious stimuli in neonates, and to assess their potential utility as measures of pain and/or discomfort during neonatal intensive care.Seventy-two healthy term infants were investigated: Twenty-eight had a non skin-breaking pin-prick on the heel, randomized to receive either oral glucose (n=16) or water (n=12) before the stimulus. 21 infants were studied during a venous blood sample from the dorsum of the hand, 23 infants during a capillary heel stick. Behavioral pain responses were assessed with the Premature Infant Pain Profile (PIPP) scale. The stimulus evoked a significant increase in higher frequency components (10-30Hz) which also correlated to behavioral measures. The frontotemporal localization of the increased activity with frequency bands similar to electromuscular artifacts and the relation to behavioral measures confirmed that this activity corresponds to an increase in muscle tone. There was no change in frontal EEG asymmetry in any of the groups. The present results indicate that responses in cortical activity recorded by EEG are not useful for clinical assessment of infants' responses to noxious stimuli.
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42.
  • Norman, Elisabeth, et al. (författare)
  • Individual variations in fentanyl pharmacokinetics and pharmacodynamics in preterm infants
  • 2019
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 108:8, s. 1441-1446
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim Fentanyl pharmacokinetics and pharmacodynamics are lacking in preterm infants. Our aim was to study these and their relation with a new formulation of fentanyl 5 mu g/mL for procedural pain. Methods Preterm infants were given 0.5 (n = 20, median gestational age 26.5; range 23.3-34.1 weeks) and 2 mu g/kg (n = 8, 27.4; 25.3-30.7 weeks) fentanyl, respectively, before skin-breaking procedures or tracheal intubation. Blood samples were collected after ten minutes, two, four, eight and 24 hours. Physiologic parameters were monitored and pain scores assessed. Results The median fentanyl concentrations were 0.18, 0.15, 0.15 and 0.57, 0.37, 0.35 ng/mL at 15-31 minutes, two and four hours and the half-lives were 1.6 to 20.5 or 4.1 to 32.6 hours for the low- and high-dose groups, respectively. A significant correlation was seen between weight at study inclusion and half-life (Spearman ' s r = -0.9, p < 0.001), volume of distribution (r = -0.8, p < 0.01) and clearance (r = -0.9, p < 0.01) in the low-dose group (n = 9). Pain assessment results were not correlated to pharmacokinetic variables. Fentanyl was well tolerated. Conclusion The inter-individual variation of fentanyl pharmacokinetics is large in preterm infants, and the dose of 0.5 mu g/kg seems not effective for skin-breaking procedures.
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43.
  • Norman, Elisabeth, et al. (författare)
  • Nyfödda barns smärta
  • 2016
  • Ingår i: Smärta och smärtbehandling hos barn och ungdomar. - Lund : Studentlitteratur AB. - 9789144092447 ; , s. 205-226
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
  •  
44.
  • Norman, Elisabeth, et al. (författare)
  • Placental transfer and pharmacokinetics of thiopentone in newborn infants.
  • 2010
  • Ingår i: Archives of disease in childhood. Fetal and neonatal edition. - : BMJ. - 1468-2052 .- 1359-2998. ; 95, s. 277-282
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Objectives Thiopentone, a short-acting barbiturate, has been introduced as premedication for intubation in newborn infants. The objectives of this study were to assess the pharmacokinetics of thiopentone in newborn infants, and to unravel whether placental transfer of the drug should be taken into account if administered to infants exposed to it during delivery. Methods Plasma concentrations were assessed with high-pressure liquid chromatography in samples from delivering mothers (n=27) receiving a median dose of 5.5 mg/kg (range 3.8-7.7) thiopentone for Caesarean section in gestational week 37.6 (range 25.7-41.4) and from corresponding umbilical cord blood (n=28). In infants (n=30) born at 35.4 weeks gestation (range 27.9-42.0) undergoing surgery at a median postnatal age of 24.5 h (range 4-521), repeated blood levels were assessed after administering a dose of 3 mg/kg thiopentone on clinical indication before intubation (seven samples per infant from 5 min to 48 h after administration). Results The umbilical/maternal concentration ratio was 0.7, the mean concentration of thiopentone was 55.7 micromol/l (SD+/-15.3) in mothers and 39.3 micromol/l (SD+/-12.5) in venous cord blood. In newborn infants undergoing surgery, the terminal half-life of thiopentone was 8 h (interquartile range (IQR) 2.5-10.8), and clearance 0.092 l/min per kg/postnatal age in days (IQR 0.02-0.1). Conclusions Thiopentone might be used as premedication for short-lasting intubation after birth, for example, for surfactant administration. During the first 4 h after birth the dose needs to be adjusted for maternal dosage as well as for the weight of the infant.
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45.
  • Norman, Elisabeth (författare)
  • Premedication for intubation in newborn infants; pain assessment, pharmacokinetics and pharmacodynamics
  • 2011
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Preterm infants undergo intensive care during a vulnerable period with hemodynamic instability and a rapidly developing and immature CNS. Adequate pain management is essential, since pain experience might lead to acute physiological reactions as well as neurological and neuropsychological sequels. There is no “golden standard” for objective pain assessment, and no evidence-based recommendations for premedication before endotracheal intubation in newborn infants. The aims of the research project were to investigate the possibilities to objectively assess pain with amplitude-integrated EEG (aEEG), to develop a safe and effective strategy for premedication before tracheal intubation, and to study pharmacokinetics and pharmacodynamics of the chosen drugs in the preterm infant population. The responses to three different types of noxious stimuli in healthy term infants were measured with aEEG/EEG and pain scales. Thiopental pharmacokinetics was assessed in maternal and cord blood after caesarean section in thiopental anesthesia, and in newborn infants receiving thiopental before neonatal surgery. Preterm infants needing semi-urgent intubation were enrolled to receive either Rapid Sequence Induction (RSI) with glycopyrrolate, thiopental, suxamethonium and remifentanil or atropine and morphine in a blinded randomized controlled trial (RCT). The main outcome measure was good intubation conditions, secondary were procedural duration, as well as changes in physiological and biochemical parameters, aEEG and pain scales that were monitored during and after the intubation. There were no changes in frontal EEG asymmetry to the different noxious stimuli. Thiopental placental transfer ratio was 0.7, and the median terminal half-life of thiopental in the infants was 8 hours depending on weight and postnatal age. The RCT demonstrated superior intubation conditions and shorter duration in the RSI group. Compared to RSI, the morphine group had prolonged heart rate decrease and mean arterial blood pressure (MABP) increase during intubation, and a progressive MABP decrease concomitant with neurophysiologic depression for 6 h afterwards. Neurophysiologic parameters were significantly depressed for 24 h. The results of these studies indicate that responses in cortical activity, registered as EEG frontal asymmetry, are not useful for clinical assessment of pain responses in newborn infants. Further, thiopental can be used as premedication for intubation in preterm and term infants, with dose adjustments for maternal dosage and infant weight when administered during the first four hours after birth. The RSI used in the trial can be implemented in clinical practice. Morphine should be avoided because of circulatory and neurophysiologic depression during and after the intubation.
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46.
  • Norman, Elisabeth, et al. (författare)
  • Premedication for intubation with morphine causes prolonged depression of electrocortical background activity in preterm infants
  • 2013
  • Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 73:1, s. 87-94
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Sedative and analgesic medications are used in critically ill newborns, but little is known about their effects on electrocortical activity in preterm infants. We hypothesized that morphine might induce prolonged neurodepression, independent of blood pressure, as compared with rapid sequence induction/intubation (RSI). METHODS: Of 34 infants enrolled in a randomized controlled trial (RCT) comparing RSI (including thiopental 2-3 mg/kg and remifentantil 1 mcg/kg) with morphine (0.3 mg/kg) as premedication for intubation, 28 infants (n = 14 + 14; median gestational age 26.1 wk and postnatal age 138 h) had continuous two-channel amplitude-integrated electroencephalogram (aEEG/EEG) and blood pressure monitoring during 24h after the intubation. Thirteen infants not receiving any additional medication constituted the primary study group. Visual and quantitative analyses of aEEG/EEG and blood pressure were performed in 3-h epochs. RESULTS: RSI was associated with aEEG/EEG depression lasting <3 h. Morphine premedication resulted in aEEG/EEG depression with more discontinuous background and less developed cyclicity for 24h, and during the first 9h, interburst intervals (IBI) were significantly increased as compared with those of RSI treatment. The difference was not related to blood pressure. CONCLUSION: Premedication with morphine is associated with prolonged aEEG/EEG depression independent of blood pressure changes and may not be optimal for short procedures.
  •  
47.
  • Norman, Elisabeth, et al. (författare)
  • Rapid Sequence Induction is Superior to Morphine for Intubation of Preterm Infants : A Randomized Controlled Trial
  • 2011
  • Ingår i: Journal of Pediatrics. - : Elsevier BV. - 0022-3476 .- 1097-6833. ; 159:6, s. 893-899
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To compare rapid sequence intubation (RSI) premedication with morphine for intubation of preterm infants. Study design: Preterminfants needing semi-urgent intubation were enrolled to either RSI (glycopyrrolate, thiopental, suxamethonium, and remifentanil, n=17) or atropine andmorphine (n=17) in a randomized trial. The main outcome was "good intubation conditions'' (score <= 10 assessed with intubation scoring), and secondary outcomes were procedural duration, physiological and biochemical variables, amplitude-integrated electroencephalogram, and pain scores. Results: Infants receiving RSI had superior intubation conditions (16/17 versus 1/17, P < .001), the median (IQR) intubation score was 5 (5-6) compared with 12 (10.0-13.5, P < .001), and a shorter procedure duration of 45 seconds (35-154) compared with 97 seconds (49-365, P = .031). The morphine group had prolonged heart rate decrease (area under the curve, P < .009) and mean arterial blood pressure increase (area under the curve, P < .005 and %change: mean +/- SD 21% +/- 23% versus -2% +/- 22%, P < .007) during the intubation, and a subsequent lower mean arterial blood pressure 3 hours after the intubation compared with baseline (P = .033), concomitant with neurophysiologic depression (P < .001) for 6 hours after. Plasma cortisol and stress/pain scores were similar. Conclusion: RSI with the drugs used can be implemented as medication for semi-urgent intubation in preterm infants. Because of circulatory changes and neurophysiological depression found during and after the intubation in infants given morphine, premedication with morphine should be avoided.
  •  
48.
  • Norman, Elisabeth, et al. (författare)
  • Smärta i nyföddhetsperioden
  • 2023. - 2
  • Ingår i: Smärta och smärtbehandling hos barn och ungdomar. - Lund : Studentlitteratur AB. - 9789144166506 ; , s. 215-240
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
  •  
49.
  • Norman, Elisabeth, et al. (författare)
  • Thiopental pharmacokinetics in newborn infants: a case report of overdose.
  • 2009
  • Ingår i: Acta paediatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 98, s. 1680-1682
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract Thiopental may be used for sedation before intubation in newborn infants. A boy, born at 33 weeks of gestation (gw); birth weight 2435 g, was prescribed thiopental 3 mg/kg before intubation. He developed temporary hypotension and oxygen desaturation, and remained unconscious for longer than expected with a suppressed electroencephalography for 48 h. Serum thiopental concentration was 82, 59, 42 and 32 mumol/L after 20 min and 6, 24 and 68 h respectively. Serum concentrations from five newborn infants at the same time points after intubation with the same thiopental dose were used as reference values, and indicated a 10-fold overdose in the index case. The cause of the overdose could not be identified. The infant recovered; cerebral magnetic resonance imaging at the age of 42 gw and psychomotor development at 2 years were normal. These results show that thiopental concentrations are variable in neonates and there is a high risk of dosage error as no specific paediatric formulation is available. Conclusion: Well-designed procedures and continuous education are required to prevent errors and adverse events during drug delivery to newborn infants. To develop a safe method of administration for thiopental, an extended pharmacokinetic and pharmacodynamic study in neonates is warranted.
  •  
50.
  • Norman, M., et al. (författare)
  • Urinary fluoride excretion in preschool children after intake of fluoridated milk and use of fluoride-containing toothpaste
  • 2017
  • Ingår i: Community Dental Health. - Suffolk : FDI World Dental Press Ltd.. - 0265-539X. ; 34:1, s. 27-31
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To assess the urinary fluoride excretion in preschool children after drinking fluoridated milk with 0.185 mg F and 0.375 mg F and to study the impact of use of fluoride toothpaste.Basic research design: Double-blind cross-over study.Participants: Nine healthy children, 2.5-4.5 years of age.Intervention: In a randomized order, participants drank 1.5 dl milk once daily for 7 days with no fluoride added (control), 0.185 mg fluoride added and 0.375 mg fluoride added. The experiment was performed twice with (Part I) and without (Part II) parental tooth brushing with 1,000 ppm fluoride toothpaste. The fluoride content in the piped drinking water was 0.5 mg F/L.Main outcome measure: Urinary fluoride excretion.Results: The 24-hour urinary fl uoride excretion/kg body weight varied from 0.014 mg F for the placebo intervention and non-fluoride toothpaste to 0.027 mg F for the 0.375 mg intervention with use of 1,000 ppm fluoride toothpaste. The difference compared with the placebo intervention was not statistically significant for any of the interventions when fluoride toothpaste was used (p⟩0.05) while it was statistically significantly different when non-fluoride toothpaste was used (p⟨0.05).Conclusions: All sources of fluoride must be considered when designing community programs. With 0.5 mg F/L in the drinking water and daily use of fluoride toothpaste, most children had a fluoride intake optimal for dental health. In this setting, additional intake of fluoride milk was within safe limits up to 0.185 mg/day while conclusions about the safety of 0.375 mg/day were uncertain.
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