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| 3. |
- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 7. |
- Anand, Kanwlajeet J. S., et al.
(författare)
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Assessment of continuous pain in newborns admitted to NICUs in 18 European countries
- 2017
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Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 106:8, s. 1248-1259
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Continuous pain occurs routinely, even after invasive procedures, or inflammation and surgery, but clinical practices associated with assessments of continuous pain remain unknown.Methods: A prospective cohort study in 243 Neonatal Intensive Care Units (NICUs) from 18 European countries recorded frequency of pain assessments, use of mechanical ventilation, sedation, analgesia, or neuromuscular blockade for each neonate upto 28 days after NICU admission.Results: Only 2113/6648 (31·8%) of neonates received assessments of continuous pain, occurring variably among tracheal ventilation (TrV, 46·0%), noninvasive ventilation (NiV, 35·0%), and no ventilation (NoV, 20·1%) groups (p<0·001). Daily assessments for continuous pain occurred in only 10·4% of all neonates (TrV: 14·0%, NiV: 10·7%, NoV: 7·6%; p<0·001). More frequent assessments of continuous pain occurred in NICUs with pain guidelines, nursing champions, and surgical admissions prompted (all p<0·01), and for newborns <32 weeks gestational age, those requiring ventilation, or opioids, sedatives-hypnotics, general anesthetics (O-SH-GA) (all p<0·001), or surgery (p=0·028). Use of O-SH-GA drugs increased the odds for pain assessment in the TrV (OR:1·60, p<0·001) and NiV groups (OR:1·40, p<0·001).Conclusion: Assessments of continuous pain occurred in less than one-third of NICU admissions, and daily in only 10% of neonates. NICU clinical practices should consider including routine assessments of continuous pain in newborns.
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| 8. |
- Andersen, Camilla Eline, et al.
(författare)
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Lyssnandets pedagogik i Sverige och Norge i dag. Kartbilder över olika sätt att förstå och praktisera fenomenet
- 2022
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Ingår i: Nordisk Barnehageforskning. - : Cappelen Damm AS - Cappelen Damm Akademisk. - 1890-9167. ; 19:4, s. 1-9
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Vad är det som efter många år fortfarande lockar förskollärare, pedagoger och forskare inom förskolefältet att inspireras av lyssnandets pedagogik i sina praktiker i Sverige och Norge? Vad är lyssnandets pedagogik för dem i dag, i praktiken och i teorin? Hur ska vi förstå vad som hände då och vad som händer nu i olika kontexter som kan utgöras också av två grannationer? Vad har lyssnande pedagogik betytt för förskolans framväxt och med särskilt fokus på Sverige och Norge där Ann Åbergs texter fått ett stort genomslag? Detta är frågor vi ställde oss och ville få svar på när vi efterlyste bidrag till detta specialnummer av tidskriften Nordisk Barnehageforskning på temat Lyssnandets pedagogik. Ett tjugotal forskare svarade och efter en, på grund av pandemin, utdragen och rigorös review-process publiceras nu elva artiklar i detta temanummer. Tillsammans avspeglar de en angelägen bredd i intresset för vad lyssnandets pedagogik är i dag och kan bli i framtiden.
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| 9. |
- Andersen-Hoppe, Annemette, et al.
(författare)
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Deltagarkultur : i teori och praktik
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Texterna i denna digitala antologi är författade av studenterna och lärarna på kursen ”Deltagarkultur”, som är en del av Interreg-projektet Öresundsregionen som kreativ metapol. Texterna är författade av tjänstemän på kulturförvaltningar i Skåne och Danmark, samt av lärare från Malmö högskola. En gemensam nämnare är att de alla ringar in olika både möjligheter och problem med deltagarkultur i praktiken. Vad händer när idealen möter verkligheten? Hur uppfattar deltagarna själva sin roll i de olika kulturella eller pedagogiska projekt de mer eller mindre frivilligt söker sig till eller blir indragna i? Texterna spänner över ett brett spektrum av praktiker, erfarenheter och problemställningar. De använder olika begrepp och angreppsätt för att närma sig alltifrån deltagarstyrda musikfestivaler och konstprojekt till litteraturläsning och projektarbeten på lärarutbildningen. Nya former för kulturstöd som utmanar traditionella bidragssystem undersöks i en av texterna. Läsaren introduceras för fenomen som crowd funding, crowd sourcing, mikrofinansiering och viral spridning. Filosofins hantering av lek och begär konfronteras med kulturpolitiska visioner och policydokument i en annan text. Sist men inte minst ägnar sig texterna åt intensiv självreflexion – vilket inte skall förväxlas med självupptagenhet.
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| 10. |
- Andersen, Lisa M. J., et al.
(författare)
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The Swedish Version of the Ritvo Autism and Asperger Diagnostic Scale: Revised (RAADS-R) : A Validation Study of a Rating Scale for Adults
- 2011
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Ingår i: Journal of autism and developmental disorders. - New, York, USA : Springer. - 0162-3257 .- 1573-3432. ; 41:12, s. 1635-1645
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Tidskriftsartikel (refereegranskat)abstract
- There is a paucity of diagnostic instruments for adults with autism spectrum disorder (ASD). This study evaluates the psychometric properties of the Swedish version of the Ritvo Autism and Asperger Diagnostic Scale-Revised (RAADS-R), an 80-item self-rating scale designed to assist clinicians diagnosing ASD in adults. It was administered to 75 adults with ASD and 197 comparison cases. Also, a subset completed the Autism Spectrum Quotient (AQ). Three out of four subscales had high internal consistency. Sensitivity was 91% and specificity was 93%. The ASD subjects had significantly higher mean scores on all subscales. ASD females had higher scores than ASD males on the sensory motor subscale, a dimension not included in the AQ. RAADS-R showed promising test re-test reliability.
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| 11. |
- Andersen, Maria Goul, et al.
(författare)
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Population Pharmacokinetics of Piperacillin in Sepsis Patients : Should Alternative Dosing Strategies Be Considered?
- 2018
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 62:5
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Tidskriftsartikel (refereegranskat)abstract
- Sufficient antibiotic dosing in septic patients is essential for reducing mortality. Piperacillin-tazobactam is often used for empirical treatment, but due to the pharmacokinetic (PK) variability seen in septic patients, optimal dosing may be a challenge. We determined the PK profile for piperacillin given at 4 g every 8 h in 22 septic patients admitted to a medical ward. Piperacillin concentrations were compared to the clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/liter), and the following PK/pharmacodynamic (PD) targets were evaluated: the percentage of the dosing interval that the free drug concentration is maintained above the MIC (fTMIC) of 50% and 100%. A two-compartment population PK model described the data well, with clearance being divided into renal and nonrenal components. The renal component was proportional to the estimated creatinine clearance (eCLCR) and constituted 74% of the total clearance in a typical individual (eCLCR, 83.9 ml/min). Patients with a high eCLCR (>130 ml/min) were at risk of subtherapeutic concentrations for the current regimen, with a 90% probability of target attainment being reached at MICs of 2.0 (50% fTMIC) and 0.125 mg/liter (100% fTMIC). Simulations of alternative dosing regimens and modes of administration showed that dose increment and prolonged infusion increased the chance of achieving predefined PK/PD targets. Alternative dosing strategies may therefore be needed to optimize piperacillin exposure in septic patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02569086.)
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| 12. |
- Andersén, Mikael, 1985-, et al.
(författare)
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“It’s about how you take in things with your brain” - young people’s perspectives on mental health and help seeking : an interview study
- 2024
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Ingår i: BMC Public Health. - : BioMed Central (BMC). - 1471-2458. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Poor mental health in young people has become a growing problem globally over the past decades. However, young people have also been shown to underutilize available healthcare resources. The World Health Organisation (WHO) has formulated guidelines for youth-friendly health services (YFHSs) to increase youth participation in healthcare. Still, little is known about how young people using these services perceive mental health, indicating a knowledge gap concerning the subjective evaluation of their mental health.Aim: To investigate how young people visiting youth health clinics (YHC) perceive the concept of mental health and factors they view as central to maintaining mental health.Methods: In total 21 interviews were carried out, 16 in 2018, and 5 in 2023 to assure no changes in findings after the COVID-19 pandemic. Subjects were recruited during visits to youth health clinics (YHCs) in mid-Sweden and were aged 15–23 years. Recruitment strived to achieve heterogeneity in the sample concerning gender, sexual orientation, gender identity and age. Interviews were transcribed and analysed using qualitative content analysis.Findings: Findings of the analysis revealed two themes, “Mental health is helped and hindered by the surroundings” and “Mental health is difficult to understand and difficult to achieve”. The participants described their health as highly dependent on their social surroundings, and that these are important to maintaining health but may also affect health negatively. They described mixed experiences of the health care services and mentioned prerequisites for seeking care for mental health problems such as accessibility and respect for their integrity, including the right to turn down offered treatment. The informants also viewed mental health as an ongoing undertaking that one must work for, and that it is sometimes difficult to know what constitutes mental health. They also expressed a need from healthcare services to enquire about their health, and to show an active interest in how they are doing.Conclusions: Findings underline the need of young people’s individual needs to be met in the healthcare system and their vulnerability to their social surroundings. Health status assessments in young people should consider social and individual factors to fully capture mental health.
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| 13. |
- Andersen, Pia, et al.
(författare)
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Factors associated with increased physical activity among patients prescribed physical activity in Swedish routine health care including an offer of counselor support : a 1-year follow-up
- 2022
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Ingår i: BMC Public Health. - : BioMed Central (BMC). - 1471-2458. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The study addresses knowledge gaps in research regarding influences of routine health care delivery of physical activity on prescription (PAP). The aim was to investigate if patient and health care characteristics are associated with increased physical activity 1 year after prescription among patients offered counselor support in addition to health care professionals' prescription. The study was conducted in primary and secondary care in a Swedish health care region. Methods All PAP recipients during 1 year were invited (N = 1503) to participate in this observational prospective study. Data were collected from medical records and questionnaires (baseline and follow-up). Descriptive statistics and multiple logistic regression analysis were used. The outcome variable was increased physical activity after 1 year. Study variables were patient and health care characteristics. Results Three hundred and fifty-five patients with complete follow-up data were included. The mean age was 62 years (SD = 14; range, 18-90) and 68% were females. Almost half (47%) had increased physical activity 1 year after PAP. Multiple logistic regression analysis showed that increased physical activity at follow-up was positively associated with lower baseline activity, counselor use, and positive perception of support. Counselor users with low baseline activity had higher odds ratio for increased physical activity at follow-up than non-users (OR = 7.2, 95% CI = 2.2-23.5 vs. OR = 3.2, 95% CI = 1.4-7.5). Positive perception of support was associated with increased physical activity among counselor users but not among non-users. Conclusions An increase in physical activity after PAP was related to low baseline activity, positive perception of support, and use of counselor support after PAP. Qualified counseling support linked to PAP seems to be important for achieving increased physical activity among patients with lower baseline activity.
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| 14. |
- Andersen, Pia, et al.
(författare)
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Patients' experiences of physical activity on prescription with access to counsellors in routine care : a qualitative study in Sweden
- 2019
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Ingår i: BMC Public Health. - : BioMed Central. - 1471-2458. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPhysical activity on prescription (PAP) has been implemented in several countries, including Sweden, to support patients who might benefit from increased physical activity. This study explores the experiences of recipients of PAP in routine health care in Sweden that offers the recipients support from physical activity counsellors. The aim was to explore influences on engagement in physical activity by PAP recipients' from a long-term perspective.MethodsWe conducted individual semi-structured interviews using a topic guide with a purposively selected sample of 13 adult PAP recipients 1.5 to 2.5years after PAP. Interviews were recorded, transcribed verbatim and analysed through inductive and deductive content analysis. The questions were informed by Capability-Opportunity-Motivation-Behaviour (COM-B), which was also used as a framework to analyse the data by means of categorizing the factors (influences on the behaviour).ResultsTen factors (i.e. sub-categories) that influenced the participants' engagement in physical activity were identified. PAP recipients' capability to engage in physical activity was associated with adapting the PAP to the individual's physical capacity and taking into account the individual's previous experiences of physical activity. PAP recipients' opportunity to engage in physical activity was related to receiving a prescription, receiving professional counselling and follow-up from a physical activity counsellor, collaboration between prescriber and counsellor, having access to appropriate activities, having a balanced life situation and having support from someone who encouraged continued physical activity. PAP recipients' motivation to engage in physical activity was associated with the desire to improve his or her health condition and finding activities that encouraged continuation.ConclusionsPAP recipients' engagement in physical activity was influenced by their capability, opportunity and motivation to undertake this behaviour. Numerous extraneous factors influence capability and motivation. Physical activity counsellors were found to be important for sustained activity because they use an individual approach to counselling and flexible follow-up adapted to each individual's need of support.
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| 15. |
- Andersen, Pia, et al.
(författare)
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Physical Activity on Prescription in Routine Health Care : 1-Year Follow-Up of Patients with and without Counsellor Support
- 2020
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 17:16, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of counsellor support in addition to physical activity on prescription (PAP) from health care professionals has rarely been evaluated. This observational follow-up study investigated differences in physical activity levels and health-related quality of life (HRQoL) one year after PAP regarding patients' use of counsellor support in addition to PAP in routine care. The study was conducted in a Swedish health care region in which all patients receiving PAP from health care professionals were offered counsellor support. Data were collected from medical records and questionnaires (baseline and follow-up). Of the 400 study participants, 37% used counsellor support. The group of counsellor users attained a higher level of physical activity one year after receiving PAP compared to the group of non-users (p< 0.001). The level of physical activity was measured by a validated index (score 3-19) calculated from weekly everyday activity and exercise training. Comparison of the change in scores between baseline and follow-up showed a significant difference between the two groups, (p< 0.001). The median difference in the PAP + C group was 2.0 (interquartile range, 7.0) and 0.0. among non-users (interquartile range, 4.0). Significant differences in HRQoL were due to positive improvements among counsellor users, with the main improvement in general health. The conclusion is that patients using counsellor support after receiving PAP from health care professionals had higher physical activity and better HRQoL one year after compared with patients who did not use this support.
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| 16. |
- Andersen, Pia, 1958-
(författare)
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Physical activity on prescription with access to counsellor support implemented in routine care : Healthcare and patient perspectives
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The Swedish PAP (physical activity on prescription) programme FaR®, introduced in 2001, has been adopted by all Swedish regions, which are responsible for provision of healthcare in Sweden. Several studies have shown positive outcomes of the Swedish PAP on patients’ physical activity and other health-related outcomes. There are no guidelines for best practises of the Swedish PAP, which has led to the development of different organizational structures for its delivery. This thesis project was developed with the ambition of providing knowledge for further development of PAP in clinical practise.Aim: The overall aim was to investigate and generate improved understanding of a structure for physical activity on prescription with access to physical activity counsellors, implemented in routine healthcare.Methods: To address the overall aim, four real-world studies with different design and analysis methods were carried out. The study population consisted of patients 18 years or older prescribed PAP in primary and secondary care in Region Kronoberg’s healthcare organization. Study I investigated characteristics of healthcare delivery of PAP over a four-year period, including all patients prescribed PAP in these years. Study II explored factors that influenced patient’s long-term engagement in physical activity after prescription. Study III investigated differences in physical activity and health-related quality of life (HRQoL) at one-year follow-up between patients who used versus patients who did not use counsellor support after prescription. Study IV investigated factors associated with patients increase in physical activity at one-year follow-up. Data sources for the studies were electronic medical records (Studies I, II, III and IV), individual interviews (Study II) and a baseline and a follow-up questionnaire (Studies III and IV). Different statistical analyses were performed in Studies I, III and IV. Study II used qualitative content analysis based on an approach including both inductive and deductive analysis. The final study samples of PAP recipients were N = 4,879 (Study I), n = 13 (Study II), n = 400 (Study = III) and n = 355 (Study IV).Results: Study I: 4,879 PAP recipients were identified, one-third had used the offer of counsellor support. PAP recipients had a high frequency of diagnosis and healthcare consumption prior to PAP. Counsellor users had higher frequency of multiple diagnoses and healthcare visits than non-counsellor users. The main prescriber of PAP was physicians and the main prescribing setting was primary care. Study II: PAP recipients’ long-term engagement with physical activity was influenced by the determinants of capability, opportunity, and motivation. Receiving a prescription of physical activity, and professional counselling and follow up from a physical activity counsellor, and adaption of PAP to the individual’s capacity were important for patients change of physical activity. Study III: Counsellor users had better outcomes in both physical activity and HRQoL than non-users of this support. Study IV: Nearly half of the PAP recipients had increased physical activity one year after prescription. Increased physical activity was positively associated with lower baseline activity, counsellor use, and positive perception of given support after PAP.Conclusions: Patients who were prescribed PAP had a high frequency of diagnoses and high healthcare consumption in the year prior to the prescription. Due to the positive findings regarding patient outcomes on physical activity, and patient experiences of counsellor support, it could be suggested that individualized counselling and follow up by a physical activity counsellor is of importance for patients’ engagement in physical activity, especially for patients with lower baseline activity. Since increased activity was also seen among nonusers of counsellor support, a general recommendation for physical activity counsellor support for all PAP recipients could not be suggested.
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| 17. |
- Andersen, Pia, et al.
(författare)
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Physical Activity on Prescription with Counsellor Support : A 4-Year Registry-Based Study in Routine Health Care in Sweden
- 2018
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Ingår i: Healthcare. - : MDPI. - 2227-9032. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Public health gains from physical activity on prescription (PAP) depend on uptake in routine care. We performed an evaluation of the implementation, in a Swedish county council, of counsellors who give personalized support to PAP recipients aimed at facilitating PAP delivery. The aim was to compare characteristics between PAP recipients and the health care population as well as between PAP recipients who used and did not use counsellor support. We also investigated professional belonging and health care setting of health care professionals who prescribed PAP. Methods: All patients' >= 18 years who received PAP during 2009-2012 in primary and secondary care in the County Council of Kronoberg were included (n = 4879). Data were retrieved from electronic medical records. Main outcome measures were patient and professional characteristics. Results: A third of the PAP recipients had diseases in >= 5 diagnostic groups and more than half had >= 11 office visits the year before receiving PAP. Counsellor support was used by one-third and PAP recipients who used counsellor support had more multiple diagnoses and office visits compared with non-users. Physicians issued 44% of prescriptions and primary care was the predominant setting. The amount of PAP did not change over time, but the proportion of physicians' prescriptions decreased while the proportion of nurses' prescriptions increased. Conclusions: PAP recipients had high morbidity and were frequent health care attenders, indicating that PAP was predominantly used for secondary or tertiary prevention. PAP rates did not increase as intended after the implementation of counsellor support.
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| 18. |
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| 19. |
- Ask, Katrina, et al.
(författare)
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Performance of four equine pain scales and their association to movement asymmetry in horses with induced orthopedic pain
- 2022
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Ingår i: Frontiers in Veterinary Science. - : Frontiers Media SA. - 2297-1769. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study investigated the relationship between orthopedic pain experienced at rest, and degree of movement asymmetry during trot in horses with induced reversible acute arthritis. Orthopedic pain was assessed with the Horse Grimace Scale (HGS), the Equine Utrecht University Scale of Facial Assessment of Pain (EQUUS-FAP), the Equine Pain Scale (EPS), and the Composite Orthopedic Pain Scale (CPS). Reliability and diagnostic accuracy were evaluated with intraclass correlation coefficients (ICC) and area under the curve (AUC).Study design and animals: Eight healthy horses were included in this experimental study, with each horse acting as its own control.Methods: Orthopedic pain was induced by intra-articular lipopolysaccharide (LPS) administration. Serial pain assessments were performed before induction and during pain progression and regression, where three observers independently and simultaneously assessed pain at rest with the four scales. Movement asymmetry was measured once before induction and a minimum of four times after induction, using objective gait analysis.Results: On average 6.6 (standard deviation 1.2) objective gait analyses and 12.1 (2.4) pain assessments were performed per horse. The ICC for each scale was 0.75 (CPS), 0.65 (EPS), 0.52 (HGS), and 0.43 (EQUUS-FAP). Total pain scores of all scales were significantly associated with an increase in movement asymmetry (R2 values ranging from −0.0649 to 0.493); with CPS pain scores being most closely associated with movement asymmetry. AUC varied between scales and observers, and CPS was the only scale where all observers had a good diagnostic accuracy (AUC > 0.72).Conclusions and clinical relevance: This study identified significant associations between pain experienced at rest and degree of movement asymmetry for all scales. Pain scores obtained using CPS were most closely associated with movement asymmetry. CPS was also the most accurate and reliable pain scale. All scales had varying linear and non-linear relations between total pain scores and movement asymmetry, illustrating challenges with orthopedic pain assessment during rest in subtly lame horses since movement asymmetry needs to be rather high before total pain score increase.
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| 20. |
- Benzinou, Michael, et al.
(författare)
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Common nonsynonymous variants in PCSK1 confer risk of obesity.
- 2008
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:8, s. 943-5
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in PCSK1 cause monogenic obesity. To assess the contribution of PCSK1 to polygenic obesity risk, we genotyped tag SNPs in a total of 13,659 individuals of European ancestry from eight independent case-control or family-based cohorts. The nonsynonymous variants rs6232, encoding N221D, and rs6234-rs6235, encoding the Q665E-S690T pair, were consistently associated with obesity in adults and children (P = 7.27 x 10(-8) and P = 2.31 x 10(-12), respectively). Functional analysis showed a significant impairment of the N221D-mutant PC1/3 protein catalytic activity.
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| 21. |
- Berge, Tone, et al.
(författare)
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T cell specific adapter protein (TSAd) interacts with Tec kinase ITK to promote CXCL12 induced migration of human and murine T cells
- 2010
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 5:3, s. e9761-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The chemokine CXCL12/SDF-1alpha interacts with its G-protein coupled receptor CXCR4 to induce migration of lymphoid and endothelial cells. T cell specific adapter protein (TSAd) has been found to promote migration of Jurkat T cells through interaction with the G protein beta subunit. However, the molecular mechanisms for how TSAd influences cellular migration have not been characterized in detail. PRINCIPAL FINDINGS: We show that TSAd is required for tyrosine phosphorylation of the Lck substrate IL2-inducible T cell kinase (Itk). Presence of Itk Y511 was necessary to boost TSAd's effect on CXCL12 induced migration of Jurkat T cells. In addition, TSAd's ability to promote CXCL12-induced actin polymerization and migration of Jurkat T lymphocytes was dependent on the Itk-interaction site in the proline-rich region of TSAd. Furthermore, TSAd-deficient murine thymocytes failed to respond to CXCL12 with increased Itk phosphorylation, and displayed reduced actin polymerization and cell migration responses. CONCLUSION: We propose that TSAd, through its interaction with both Itk and Lck, primes Itk for Lck mediated phosphorylation and thereby regulates CXCL12 induced T cell migration and actin cytoskeleton rearrangements.
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| 22. |
- Bergmann, T K, et al.
(författare)
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Impact of CYP2C8*3 on paclitaxel clearance: a population pharmacokinetic and pharmacogenomic study in 93 patients with ovarian cancer
- 2011
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Ingår i: PHARMACOGENOMICS JOURNAL. - : Nature Publishing Group. - 1470-269X .- 1473-1150. ; 11:2, s. 113-120
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Tidskriftsartikel (refereegranskat)abstract
- The primary purpose of this study was to evaluate the effect of CYP2C8*3 and three genetic ABCB1 variants on the elimination of paclitaxel. We studied 93 Caucasian women with ovarian cancer treated with paclitaxel and carboplatin. Using sparse sampling and nonlinear mixed effects modeling, the individual clearance of unbound paclitaxel was estimated from total plasma paclitaxel and Cremophor EL. The geometric mean of clearance was 385 l h(-1) (range 176-726 l h(-1)). Carriers of CYP2C8*3 had 11% lower clearance than non-carriers, P = 0.03. This has not been shown before in similar studies; the explanation is probably the advantage of using both unbound paclitaxel clearance and a population of patients of same gender. No significant association was found for the ABCB1 variants C1236T, G2677T/A and C3435T. Secondarily, other candidate single-nucleotide polymorphisms were explored with possible associations found for CYP2C8*4 (P = 0.04) and ABCC1 g.7356253C andgt; G (P = 0.04).
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| 23. |
- Blauhut, Veit, et al.
(författare)
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Lessons from the 2018-2019 European droughts : a collective need for unifying drought risk management
- 2022
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Ingår i: Natural hazards and earth system sciences. - : Copernicus Publications. - 1561-8633 .- 1684-9981. ; 22:6, s. 2201-2217
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Tidskriftsartikel (refereegranskat)abstract
- Drought events and their impacts vary spatially and temporally due to diverse pedo-climatic and hydrologic conditions, as well as variations in exposure and vulnerability, such as demographics and response actions. While hazard severity and frequency of past drought events have been studied in detail, little is known about the effect of drought management strategies on the actual impacts and how the hazard is perceived by relevant stakeholders. In a continental study, we characterised and assessed the impacts and the perceptions of two recent drought events (2018 and 2019) in Europe and examined the relationship between management strategies and drought perception, hazard, and impact. The study was based on a pan-European survey involving national representatives from 28 countries and relevant stakeholders responding to a standard questionnaire. The survey focused on collecting information on stakeholders' perceptions of drought, impacts on water resources and beyond, water availability, and current drought management strategies on national and regional scales. The survey results were compared with the actual drought hazard information registered by the European Drought Observatory (EDO) for 2018 and 2019. The results highlighted high diversity in drought perception across different countries and in values of the implemented drought management strategies to alleviate impacts by increasing national and sub-national awareness and resilience. The study identifies an urgent need to further reduce drought impacts by constructing and implementing a European macro-level drought governance approach, such as a directive, which would strengthen national drought management and mitigate damage to human and natural assets.
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| 24. |
- Blauhut, Veit, et al.
(författare)
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Lessons from the 2018–2019 European droughts: A collective need for unifying drought risk management
- 2021
-
Ingår i: Natural hazards and earth system sciences. - : Copernicus Publications. - 1561-8633 .- 1684-9981.
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Drought events and their impacts vary spatially and temporally due to diverse pedo-climatic and hydrologic conditions, as well as variations in exposure and vulnerability, such as demographics and response actions. While hazardous severity and frequency of past drought events have been studied in detail, little is known about the effect of drought management strategies on the actual impacts, and how the hazard is perceived by relevant stakeholders for inducing action. In a continental study, we characterised and assessed the impacts and the perceptions of two recent drought events (2018 and 2019) in Europe and examined the relationship between management strategies and drought perception, hazard and impacts. The study was based on a pan-European survey involving national representatives from 28 countries and relevant stakeholders responding to a standard questionnaire. The survey focused on collecting information on stakeholders’ perceptions of drought, impacts on water resources and beyond, water availability and current drought management strategies at national and regional scales. The survey results were compared with the actual drought hazard information registered by the European Drought Observatory (EDO) for 2018 and 2019. The results highlighted high diversity in drought perceptions across different countries and in values of implemented drought management strategies to alleviate impacts by increasing national and sub-national awareness and resilience. The study concludes with an urgent need to further reduce drought impacts by constructing and implementing a European macro-level drought governance approach, such as a directive, which would strengthen national drought management and lessen harm to human and natural potentials.
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| 25. |
- Blum, Nadine Schäffer, et al.
(författare)
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Patients’ experience of a novel interdisciplinary nurse-led self-management intervention (INSELMA)—a qualitative evaluation
- 2024
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Ingår i: BMC Rheumatology. - 2520-1026. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite continuous improvements in anti-rheumatic pharmacological treatment, people with chronic inflammatory arthritis still report substantial disease impact. Based on the framework for complex interventions, we thus developed INSELMA, a novel nurse-coordinated multidisciplinary self-management intervention for patients with rheumatoid arthritis, psoriatic arthritis or axial spondyloarthritis. Based on individual biopsychosocial assessments, a rheumatology nurse facilitated goal setting and coordinated interdisciplinary support. The aim of this study was to explore the patients’ experience of participating in the six-months INSELMA intervention. Methods: Individual semi-structured interviews were conducted with 15 of the participants after their final follow-up. Thematic analysis was applied. Results: The analysis derived four overall themes. (1) A new opportunity at the right time. The participants’ disease impacted all areas of daily life. Participation in INSELMA was experienced as an opportunity to improve symptoms and together reduce long-held challenges they had fought alone, until now. (2) The importance of person-centred goals. The participants found it meaningful to work with their individual goals, which encompassed physical, psychological, and social factors. Having time between consultations to work with goals at home was important. (3) Empathy, partnership and a little nudging from health professionals are essential. The empathic nurses’ continuous support and coaching helped participants become aware of their own resources. The participants highlighted having access to support from a physiotherapist and occupational therapist with rheumatology experience as important. (4) I got more than I could have hoped for. Most of the participants experienced decreased symptom load and improvement in physical strength, mobility, sleep, and mood as well as increased energy, knowledge, and self-management ability. The participants expressed new hope for the future with an improved ability to manage their symptoms and work towards new goals. Conclusion: The participants found the INSELMA intervention meaningful and feasible. They experienced decreased disease impact and increased activity levels, facilitated by empathy and self-management support from health professionals.
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| 26. |
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| 27. |
- Boden, Robert, et al.
(författare)
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Early non-adherence to medication and other risk factors for rehospitalization in schizophrenia and schizoaffective disorder
- 2011
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Ingår i: Schizophrenia Research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 133:1-3, s. 36-41
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Tidskriftsartikel (refereegranskat)abstract
- Non-adherence to antipsychotic medication and hospitalization in psychotic disorders are common and costly problems. Our aim was to identify risk factors for rehospitalization of patients with recent onset schizophrenia or schizoaffective disorder in a population-based cohort study. All patients with a first hospitalization for schizophrenia or schizoaffective disorder between 2006 and 2007 were included (n = 861). Patients were identified through and data retrieved from national Swedish health and population registers. We investigated how socio-demographic variables, duration of first hospitalization and prescription fills of antipsychotics were associated with rehospitalization in Cox regression models. A higher risk for rehospitalization within 28 days was observed in patients with a first hospitalization that was shorter than two weeks compared with patients who were hospitalized for more than four weeks: hazard ratio (HR) 2.30,95% confidence interval (CI) 1.42 to 3.74. Further, patients who did not fill a prescription of antipsychotics within the first week after discharge had a higher risk of early rehospitalization than patients who were given antipsychotics (HR 1.75, 95% CI 1.13 to 2.72). More than 12 years of education was associated with a lower risk of early rehospitalization (HR 0.44,95% CI 0.26 to 0.77). Sex, age, being born in Sweden, urban area residence and prescription fills of antipsychotics prior to first admission did not significantly affect the risk of early rehospitalization. In conclusion, we identified two potentially modifiable risk factors for rehospitalization: short duration of initial hospitalization and early non-adherence to medication.
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| 28. |
- Boden, Robert, et al.
(författare)
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Risks of adverse pregnancy and birth outcomes in women treated or not treated with mood stabilisers for bipolar disorder : population based cohort study
- 2012
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Ingår i: The BMJ. - : BMJ. - 1756-1833. ; 345, s. e7085-
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the risks of adverse pregnancy and birth outcomes for treated and untreated bipolar disorder during pregnancy. Design Population based cohort study using data from national health registers. Setting Sweden. Participants 332 137 women with a last menstrual period anytime after 1 July 2005 and giving birth anytime before the end of 31 December 2009. Women with a record of at least two bipolar diagnoses were identified and grouped as treated (n=320)-those who had filled a prescription for mood stabilisers (lithium, antipsychotics, or anticonvulsants) during pregnancy-or untreated (n=554). Both groups were compared with all other women giving birth (n=331 263). Main outcome measures Preterm birth, mode of labour initiation, gestational diabetes, infants born small or large for gestational age, neonatal morbidity, and congenital malformations. Results Of the untreated women, 30.9% (n=171) were induced or had a planned caesarean delivery compared with 20.7% (n=68 533) without bipolar disorder (odds ratio 1.57, 95% confidence interval 1.30 to 1.90). The corresponding values for the treated women were 37.5% (n=120) (2.12, 1.68 to 2.67). The risks of preterm birth in both treated and untreated women were increased by 50%. Of the untreated women, 3.9% (n=542) had a microcephalic infant compared with 2.3% (324 844) of the women without bipolar disorder (1.68, 1.07 to 2.62). The corresponding values for the treated women were 3.3% (n=311) (1.26, 0.67 to 2.37). Similar trends were observed for risks of infants being small for gestational age infants for weight and length. Among infants of untreated women, 4.3% (n=24) had neonatal hypoglycaemia compared with 2.5% (n=8302) among infants of women without bipolar disorder (1.51, 1.04 to 2.43), and 3.4% (n=11) of the treated women (1.18, 0.64 to 2.16). The analyses of variation in outcomes did not support any significant differences between treated and untreated women. Conclusions Bipolar disorder in women during pregnancy, whether treated or not, was associated with increased risks of adverse pregnancy outcomes.
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| 29. |
- Carbajal, Ricardo, et al.
(författare)
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Pain Assessment in Ventilated and Non-Ventilated Neonates in NICUs across Europe : EUROpean Pain Audit in Neonates (EUROPAIN Survey)
- 2014
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Konferensbidrag (refereegranskat)abstract
- Background: Neonates undergo many painful procedures during their NICU stay. These may include tracheal intubation/ventilation, skin-breaking procedures, drainage/suctioning of body orifices or cavities. Inherent subjectivity and difficulties of neonatal pain assessment contribute to a wide variety of assessment tools and clinical practices. To date, these practices have been not studied at a large scale. OBJECTIVE: To determine current clinical practices for neonatal pain assessment in NICUs across Europe. DESIGN/METHODS: An epidemiological observational study on bedside pain assessment practices collected data for all neonates in participating NICUs until infants left the unit (discharge, death, transfer to another hospital) or for 28 days. Data collection occurred via an online database for 1 month at each NICU. All neonates up to a gestational age of 44 weeks were included. RESULTS: From October 2012 to June 2013, 243 NICUs from 18 European countries collected pain assessment data in 6680 neonates. Of these, 2142 received tracheal ventilation (ventilated) and 4538 had spontaneous breathing or non- invasive ventilation (non-ventilated). The median (IQR) gestational age of ventilated neonates [32.1 (28.1-37.4)] was less than non-ventilated neonates [36.6 (33.6-39.1), p<0.001]. Overall, 58.5% of ventilated neonates and 35.2%% of non-ventilated neonates received bedside pain assessments (p<0.001). CONCLUSIONS: Over half (58.5%) of ventilated neonates and about one third (35.2%) of non-ventilated neonates had pain assessments performed in European NICUs. Wide variations in the methods used and rates of pain assessment exist among countries
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| 30. |
- Carbajal, Ricardo, et al.
(författare)
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Pain Assessment in Ventilated and Non-Ventilated Neonates in NICUS across Europe : Results from the EUROPAIN Study
- 2016
-
Konferensbidrag (refereegranskat)abstract
- Aim of Investigation: Pain from invasive or noninvasive procedures, mechanical ventilation, or painful medical and surgical conditions is commonplace in neonatal intensive care units (NICUs). While prevention and treatment of neonatal pain seem essential, an adequate analgesic approach cannot be implemented without relevant and timely pain assessments. Data on neonatal pain assessment practices are scarce, with undefined best practices or clinical benefits. We aimed to describe pain assessment practices in 243 NICUs from 18 European countries and to examine the NICU and patient characteristics influencing pain assessments at the bedside.Methods: Demographic data, modes of respiration, use of sedation, analgesia, or neuromuscular blockers, frequency and types of pain assessments were recorded for all newborns during the first 28 days of NICU admission. Multivariable models tested the associations between the performance of pain assessments and center and neonatal factors.Results: Among 6648 neonates enrolled, highest level of ventilation during the study period classified patients into tracheal ventilation (TV, n=2138 [32%]), non-invasive ventilation (NIV, n=1493 [23%]), and spontaneous ventilation groups (SV, n=3017 [45%]). Pain assessments were performed in 1250 (58%), 672 (45%), and 916 (30%) of these groups respectively (p<0.001). Using data from 78,742 patient-days, we found that 2,838 (43%) neonates received 4.3 (5.2) pain assessments per neonate and per day (median (IQR): 2.4 (1-5)), whereas 3810 (57%) neonates did not receive any pain assessments. Pain assessments occurred on every day of the NICU stay in 461/2138 (22%) TV patients, 236/1493 (16%) NIV patients, and 393/3016 (13%) SV patients (p<0.001).Many different pain assessment methods were used; the EDIN scale was used most frequently (42.3% among those who had at least one pain assessment). We analysed 33,625 patient-days in the TV group to test for associations between pain assessment and the use of opioids, sedatives-hypnotics, or general anaesthetics (O-SH-GA). The rates of pain assessments on patient-days with and without O-SH-GA use were, respectively, 57% vs. 43% while receiving mechanical ventilation, and 60% vs. 34% while not receiving mechanical ventilation (both p<0.001). Multivariable analyses showed that NICU-based guidelines, nursing leadership, and increased surgical admissions promoted the use of routine pain assessments (p<0.001). More pain assessments were performed in newborns below 32-weeks gestational age, those with decreased severity of illness, those already intubated at admission, those requiring mechanical or non-invasive ventilation, or surgery, or use of O-SH-GA.Conclusion: Even though pain is considered the 5th vital sign, only 43% of NICU neonates received bedside pain assessments. Clinical practice variability and low rates of pain assessments in NICUS may reflect weaknesses in the current paradigm used for neonatal pain assessments, their subjectivity, lack of inter-rater reliability, and other long-standing concerns. Results suggest that training to improve the rate of pain assessment in NICUs will enhance pain management in NICUs.Trial Registration: ClinicalTrials.gov #NCT01694745
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| 31. |
- Carbajal, Ricardo, et al.
(författare)
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Pain Assessment In Ventilated And Non-ventilated Neonates In Nicus Across Europe : European Pain Audit In Neonates (europain Survey)
- 2014
-
Ingår i: Archives of Disease in Childhood. - London, United Kingdom : BMJ Publishing Group Ltd. - 0003-9888 .- 1468-2044. ; 99, s. A68-A68
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Neonates undergo many painful procedures during their NICU stay. These may include tracheal intubation/ventilation, skin-breaking procedures, drainage/suctioning of body orifices or cavities. Inherent subjectivity and difficulties of neonatal pain assessment contribute to a wide variety of assessment tools and clinical practices. To date, these practices have been not studied at a large scale.Objective: To determine current clinical practices for neonatal pain assessment in NICUs across Europe.Methods: An epidemiological observational study on bedside pain assessment practices collected data for all neonates in participating NICUs until infants left the unit (discharge, death, transfer to another hospital) or for 28 days. Data collection occurred via an online database for 1 month at each NICU. All neonates up to a gestational age of 44 weeks were included.Results: From October 2012 to June 2013, 243 NICUs from 18 European countries collected pain assessment data in 6680 neonates. Of these, 2142 received tracheal ventilation (TV), 1496 non-invasive ventilation (NIV) and 3042 only spontaneous ventilation (SV). The median (IQR) gestational age of TV, NIV and SV neonates were 32.1 (28.1–37.4), 33.6 (31.0–36.6) and 37.9 (35.0–39.9), respectively (p < 0.001). Overall, 58.5% of TV neonates, 45.0% of NIV neonates and 30.4% of SV neonates received bedside pain assessments (p < 0.001). Fig. shows pain assessments by country.Conclusions: Over half (58.5%) of TV neonates and less than half (45.0%) of NIV neonates had pain assessments performed in European NICUs. Wide variations in the rates of pain assessment exist among countries and an important improvement seems necessary.
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| 32. |
- Carbajal, Ricardo, et al.
(författare)
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Sedation And Analgesia For Neonates In Nicus Across Europe : The Europain Survey
- 2014
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Ingår i: Archives of Disease in Childhood. - London, United Kingdom : BMJ Publishing Group Ltd. - 0003-9888 .- 1468-2044. ; 99, s. A64-A64
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pain and stress induced by mechanical ventilation, invasive procedures, or painful diseases supports the use of sedation/analgesia (S/A) in newborns admitted to Neonatal Intensive Care Units (NICUs). To date, these practices have not been studied at a large scale.Objective: To determine current clinical practices regarding the use of S/A drugs in NICUs across Europe.Methods: This epidemiological observational study on bedside clinical practices regarding S/A collected data for all neonates in participating NICUs until the infant left the unit (discharge, death, transfer) or for up to 28 days. Data collection occurred via an online database for 1 month at each NICU. All neonates up to 44 weeks gestation were included.Results: From October 2012 to June 2013, 243 NICUs from 18 European countries collected data on 6680 eligible neonates. Of these, 2142 received tracheal ventilation (TV), 1496 non-invasive ventilation (NIV) and 3042 only spontaneous ventilation (SV). The median (IQR) gestational age of TV, NIV and SV neonates were 32.1 (28.1–37.4), 33.6 (31.0–36.6) and 37.9 (35.0–39.9), respectively (p < 0.001). Overall, more TV neonates [81.5% (n = 1746)] received S/A drugs than NIV neonates [17.8% (n = 266)] and SV neonates [9.3% (n = 282)]; p < 0.001. Fig. shows the rate of S/A use by country; table shows S/A drugs used.Conclusions: Most ventilated but few non-ventilated neonates (NIV and SV) receive S/A therapy in European NICUs. Wide variations in S/A use, drugs used, and mode of administration (continuous, bolus, or both) exist among countries.
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| 33. |
- Carbajal, Ricardo, et al.
(författare)
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Sedation and analgesia practices in neonatal intensive care units (EUROPAIN) : results from a prospective cohort study
- 2015
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Ingår i: The Lancet Respiratory Medicine. - : Elsevier. - 2213-2600 .- 2213-2619. ; 3:10, s. 796-812
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neonates who are in pain or are stressed during care in the intensive care unit (ICU) are often given sedation or analgesia. We investigated the current use of sedation or analgesia in neonatal ICUs (NICUs) in European countries. Methods: EUROPAIN (EUROpean Pain Audit In Neonates) was a prospective cohort study of the management of sedation and analgesia in patients in NICUs. All neonates admitted to NICUs during 1 month were included in this study. Data on demographics, methods of respiration, use of continuous or intermittent sedation, analgesia, or neuromuscular blockers, pain assessments, and drug withdrawal syndromes were gathered during the first 28 days of admission to NICUs. Multivariable linear regression models and propensity scores were used to assess the association between duration of tracheal ventilation (TV) and exposure to opioids, sedatives-hypnotics, or general anaesthetics in neonates (O-SH-GA). This study is registered with ClinicalTrials.gov, number NCT01694745. Findings: From Oct 1, 2012, to June 30, 2013, 6680 neonates were enrolled in 243 NICUs in 18 European countries. Mean gestational age of these neonates was 35∙0 weeks (SD 4∙6) and birthweight was 2384 g (1007). 2142 (32%) neonates were given TV, 1496 (22%) non-invasive ventilation (NIV), and 3042 (46%) were kept on spontaneous ventilation (SV). 1746 (82%), 266 (18%), and 282 (9%) neonates in the TV, NIV, and SV groups, respectively, were given sedation or analgesia as a continuous infusion, intermittent doses, or both (p<0∙0001). In the participating NICUs, the median use of sedation or analgesia was 89∙3% (70∙0–100) for neonates in the TV group. Opioids were given to 1764 (26%) of 6680 neonates and to 1589 (74%) of 2142 neonates in the TV group. Midazolam was given to 576 (9%) of 6680 neonates and 536 (25%) neonates of 2142 neonates in the TV group. 542 (25%) neonates in the TV group were given neuromuscular blockers, which were administered as continuous infusions to 146 (7%) of these neonates. Pain assessments were recorded in 1250 (58%) of 2138, 672 (45%) of 1493, and 916 (30%) of 3017 neonates in the TV, NIV, and SV groups, respectively (p<0∙0001). In the univariate analysis, neonates given O-SH-GA in the TV group needed a longer duration of TV than did those who were not given O-SH-GA (mean 136∙2 h [SD 173∙1] vs 39∙8 h [94∙7] h; p<0∙0001). Multivariable and propensity score analyses confirmed this association (p<0∙0001). Interpretation: Wide variations in sedation and analgesia practices occur between NICUs and countries. Widespread use of O-SH-GA in intubated neonates might prolong their need for mechanical ventilation, but further research is needed to investigate the therapeutic and adverse effects of O-SH-GA in neonates, and to develop new and safe approaches for sedation and analgesia.
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| 34. |
- Dinasquet, Julie, et al.
(författare)
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Cascading effects of the ctenophore Mnemiopsis leidyi on the planktonic food web in a nutrient-limited estuarine system
- 2012
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Ingår i: Marine Ecology Progress Serie. - : Inter-Research Science Center. - 0171-8630 .- 1616-1599. ; 460, s. 49-61
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Tidskriftsartikel (refereegranskat)abstract
- Increasing biomasses of gelatinous zooplankton presumably have major implications for the structure and function of marine food webs at large; however, current data on lower trophic levels are scarce, as most studies have focused on the immediate effects on zooplankton and fish larvae only. We examined the short-term impact of larvae and adults of the invasive ctenophore Mnemiopsis leidyi on a summer planktonic food web in the estuarine southern Baltic Sea, with special emphasis on the microbial loop. Grazing by M. leidyi reduced the mesozooplankton biomass, followed by increased dinoflagellate biomass in treatments with M. leidyi. While chlorophyll a increased most in the treatments with M. leidyi, small phytoplankton and ciliates decreased in all treatments. M. leidyi had a slight effect on bacterial abundance, but not on bacterial production, ectoenzymatic activities, or community composition. Undetectable levels of phosphate and a gradual accumulation of dissolved organic carbon during the experiment suggested a malfunctioning microbial loop scenario. The experiment shows that direct and indirect short-term effects of M. leidyi on the estuarine food web are limited to higher trophic levels and indicates that top-down and bottom-up consequences of M. leidyi expansions on the microbial loop will likely depend on local nutrient conditions.
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| 35. |
- Ek, Weronica E., et al.
(författare)
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Tea and coffee consumption in relation to DNA methylation in four European cohorts
- 2017
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 26:16, s. 3221-3231
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Tidskriftsartikel (refereegranskat)abstract
- Lifestyle factors, such as food choices and exposure to chemicals, can alter DNA methylation and lead to changes in gene activity. Two such exposures with pharmacologically active components are coffee and tea consumption. Both coffee and tea has been suggested to play an important role in modulating disease-risk in humans by suppressing tumour progression, decreasing inflammation and influencing estrogen metabolism. These mechanisms may be mediated by changes in DNA methylation.To investigate if DNA methylation in blood is associated with coffee and tea consumption we performed a genome-wide DNA methylation study for coffee and tea consumption in four European cohorts (N = 3,096). DNA methylation was measured from whole blood at 421,695 CpG sites distributed throughout the genome and analysed in men and women both separately and together in each cohort. Meta-analyses of the results and additional regional-level analyses were performed.After adjusting for multiple testing, the meta-analysis revealed that two individual CpG-sites, mapping to DNAJC16 and TTC17, were differentially methylated in relation to tea consumption in women. No individual sites were associated in men or in the sex-combined analysis for tea or coffee. The regional analysis revealed that 28 regions were differentially methylated in relation to tea consumption in women. These regions contained genes known to interact with estradiol metabolism and cancer. No significant regions were found in the sex-combined and male-only analysis for either tea or coffee consumption.
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| 36. |
- Godoy, Patricio, et al.
(författare)
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Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME
- 2013
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 87:8, s. 1315-1530
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Forskningsöversikt (refereegranskat)abstract
- This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4 alpha, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4 alpha), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell-derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun.
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| 37. |
- Grübler, Arnulf, et al.
(författare)
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Policies for the Energy Technology Innovation System (ETIS)
- 2012
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Ingår i: Global Energy Assessment: Toward a Sustainable Future. - 9780521182935 ; , s. 1665-1744
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Bokkapitel (refereegranskat)abstract
- The development and introduction of heat pumps provides an interesting illustration of policy influence and effectiveness in relation to energy technology innovation. Heat pumps have been supported by several countries since the 1970s as a strategy to improve energy efficiency, support energy security, reduce environmental degradation, and combat climate change. Sweden and Switzerland have been essential to the development and commercialization of heat pumps in Europe. In both countries, numerous policy incentives have lined the path of technology and market development. Early policy initiatives were poorly coordinated but supported technology development, entrepreneurial experimentation, knowledge development, and the involvement of important actors in networks and organisations. The market collapse in the mid 1980s could have resulted in a total failure ‐ but did not. The research programmes continued in the 1980s, and a new set of stakeholders formed ‐ both publicly and privately funded researchers, authorities, and institutions ‐ and provided an important platform for further development. In the 1990s and 2000s, Sweden and Switzerland introduced more coordinated and strategic policy incentives for the development of heat pumps. The approaches were flexible and adjusted over time. The policy interventions in both countries supported learning, successful development and diffusion processes, and cost reductions. This assessment of innovation and diffusion policies for heat pump systems can be used to generalise some insights for energy technology innovation policy.
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| 38. |
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| 39. |
- Higelin, Julia, et al.
(författare)
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NEK1 loss-of-function mutation induces DNA damage accumulation in ALS patient-derived motoneurons
- 2018
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Ingår i: Stem Cell Research. - : Elsevier. - 1873-5061 .- 1876-7753. ; 30, s. 150-162
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in genes coding for proteins involved in DNA damage response (DDR) and repair, such as C9orf72 and FUS (Fused in Sarcoma), are associated with neurodegenerative diseases and lead to amyotrophic lateral sclerosis (ALS). Heterozygous loss-of-function mutations in NEK1 (NIMA-related kinase 1) have also been recently found to cause ALS. NEK1 codes for a multifunctional protein, crucially involved in mitotic checkpoint control and DDR. To resolve pathological alterations associated with NEK1 mutation, we compared hiPSC-derived motoneurons carrying a NEK1 mutation with mutant C9orf72 and wild type neurons at basal level and after DNA damage induction. Motoneurons carrying a C9orf72 mutation exhibited cell specific signs of increased DNA damage. This phenotype was even more severe in NEK1c.2434A>T neurons that showed significantly increased DNA damage at basal level and impaired DDR after induction of DNA damage in an maturation-dependent manner. Our results provide first mechanistic insight in pathophysiological alterations induced by NEK1 mutations and point to a converging pathomechanism of different gene mutations causative for ALS. Therefore, our study contributes to the development of novel therapeutic strategies to reduce DNA damage accumulation in neurodegenerative diseases and ALS.
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| 40. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 41. |
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| 42. |
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| 43. |
- Lehmann, Manuela, et al.
(författare)
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Aggregate-selective antibody attenuates seeded aggregation but not spontaneously evolving disease in SOD1 ALS model mice
- 2020
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Ingår i: Acta neuropathologica communications. - : BMC. - 2051-5960. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence suggests that propagation of the motor neuron disease amyotrophic lateral sclerosis (ALS) involves the pathogenic aggregation of disease-associated proteins that spread in a prion-like manner. We have identified two aggregate strains of human superoxide dismutase 1 (hSOD1) that arise in the CNS of transgenic mouse models of SOD1-mediated ALS. Both strains transmit template-directed aggregation and premature fatal paralysis when inoculated into the spinal cord of adult hSOD1 transgenic mice. This spread of pathogenic aggregation could be a potential target for immunotherapeutic intervention. Here we generated mouse monoclonal antibodies (mAbs) directed to exposed epitopes in hSOD1 aggregate strains and identified an aggregate selective mAb that targets the aa 143–153 C-terminal extremity of hSOD1 (αSOD1143–153). Both pre-incubation of seeds with αSOD1143–153 prior to inoculation, and weekly intraperitoneal (i.p.) administration attenuated transmission of pathogenic aggregation and prolonged the survival of seed-inoculated hSOD1G85R Tg mice. In contrast, administration of a mAb targeting aa 65–72 (αSOD165–72), which exhibits high affinity towards monomeric disordered hSOD1, had an adverse effect and aggravated seed induced premature ALS-like disease. Although the mAbs reached similar concentrations in CSF, only αSOD1143–153 was found in association with aggregated hSOD1 in spinal cord homogenates. Our results suggest that an aggregate-selective immunotherapeutic approach may suppress seeded transmission of pathogenic aggregation in ALS. However, long-term administration of αSOD1143–153 was unable to prolong the lifespan of non-inoculated hSOD1G85R Tg mice. Thus, spontaneously initiated hSOD1 aggregation in spinal motor neurons may be poorly accessible to therapeutic antibodies.
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| 44. |
- Lejding, Tina, et al.
(författare)
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Analysis of Hexavalent Chromium in Cement Samples From Countries Within and Outside the EU : A Study From the International Contact Dermatitis Research Group
- 2023
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Ingår i: Dermatitis : contact, atopic, occupational, drug. - : Mary Ann Liebert Inc. - 1710-3568. ; 34:4, s. 323-328
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allergic contact dermatitis (ACD) caused by hexavalent chromium (Cr(VI)) is often severe and difficult to treat. The content of Cr(VI) in cement can be reduced by, for example, addition of iron(II) sulfate. Since 2005 the content of Cr(VI) in cement is regulated in the EU Directive 2003/53/EC and must not exceed 2 ppm. Since this regulation came into force, ACD caused by cement has markedly been reduced. Objective: To investigate Cr(VI) and total chromium content in samples of cement from countries within and outside the EU. Methods: The members of the International Contact Dermatitis Research Group (ICDRG) were invited to participate in the study with the aim to collect cement samples from geographically different areas. The content of Cr(VI) in the samples was estimated by the diphenyl carbazide spot test, atomic absorption spectroscopy was used to assess the total chromium content. Results: Forty-five cement samples were analyzed, containing amounts of Cr(VI) from <0.1 to >70 ppm. Twenty-one samples contained >2 ppm Cr(VI), 24 contained less. Four of 17 samples from within the EU contained >2 ppm Cr(VI), that is, higher amounts than stipulated in the EU directive, as compared with 17 samples from countries outside the EU. Conclusion: In countries outside the EU, significantly more cement samples contained >2 ppm Cr(VI).
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| 45. |
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| 46. |
- Malmeström, Clas, 1965, et al.
(författare)
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Relapses in multiple sclerosis are associated with increased CD8+ T-cell mediated cytotoxicity in CSF.
- 2008
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Ingår i: Journal of neuroimmunology. - : Elsevier BV. - 0165-5728. ; 196:1-2, s. 159-65
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Tidskriftsartikel (refereegranskat)abstract
- MS is thought to be mediated by CD4(+) T-helper cells. To investigate the importance of CD8(+) cytotoxic T-cells in MS we analyzed peripheral blood T-cells by DNA microarray, and plasma and CSF levels of granzymes from MS patients and controls. Cytotoxic gene expression was decreased in peripheral T-cells from RRMS patients whereas plasma levels of granzymes were unchanged. However, granzyme levels were elevated in the CSF of RRMS patients at relapse compared with controls and remission. Thus, CD8+ T-cell-mediated cytotoxicity is confined to the CSF/CNS compartment in RRMS patients and may be involved in the immunopathogenesis of clinical relapses.
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| 47. |
- Moll, Guido, et al.
(författare)
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Are Therapeutic Human Mesenchymal Stromal Cells Compatible with Human Blood?
- 2012
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Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1066-5099 .- 1549-4918. ; 30:7, s. 1565-1574
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Tidskriftsartikel (refereegranskat)abstract
- Multipotent mesenchymal stromal cells (MSCs) are tested in numerous clinical trials. Questions have been raised concerning fate and function of these therapeutic cells after systemic infusion. We therefore asked whether culture-expanded human MSCs elicit an innate immune attack, termed instant blood-mediated inflammatory reaction (IBMIR), which has previously been shown to compromise the survival and function of systemically infused islet cells and hepatocytes. We found that MSCs expressed hemostatic regulators similar to those produced by endothelial cells but displayed higher amounts of prothrombotic tissue/stromal factors on their surface, which triggered the IBMIR after blood exposure, as characterized by formation of blood activation markers. This process was dependent on the cell dose, the choice of MSC donor, and particularly the cell-passage number. Short-term expanded MSCs triggered only weak blood responses in vitro, whereas extended culture and coculture with activated lymphocytes increased their prothrombotic properties. After systemic infusion to patients, we found increased formation of blood activation markers, but no formation of hyperfibrinolysis marker D-dimer or acute-phase reactants with the currently applied dose of 1.0-3.0 x 10(6) cells per kilogram. Culture-expanded MSCs trigger the IBMIR in vitro and in vivo. Induction of IBMIR is dose-dependent and increases after prolonged ex vivo expansion. Currently applied doses of low-passage clinical-grade MSCs elicit only minor systemic effects, but higher cell doses and particularly higher passage cells should be handled with care. This deleterious reaction can compromise the survival, engraftment, and function of these therapeutic cells.
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| 48. |
- Mölelr, Hanne, et al.
(författare)
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Food waste and date labelling - Issues affecting the durability
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of the project has been to identify how date labelling legislation on food is practised in Denmark, Finland, Norway and Sweden and how the durability can be affected in the food supply chain. The project recommends enhanced guidance for manufacturers, retailers and consumers.
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| 49. |
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| 50. |
- Neij, Lena, et al.
(författare)
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Experience Curves for Wind Power
- 2004
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Ingår i: International Journal of Energy Technology and Policy. - 1472-8923. ; 2:1-2, s. 15-32
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to improve the understanding of the use of different experience curves in energy analysis. The study was based on the application of experience curves to wind power systems, but the approach is generic and can be used in other energy technologies. In the study, experience curves for wind power were developed, and it has been demonstrated that different types of experience curves can be developed for one and the same technology. Depending on the system boundaries used, the market perspective used, the time frame, the manufacturers included and the size of the turbines included, the progress ratios of the curves ranged from 83% to 117%, indicating a cost reduction of 0–17% per doubling of produced or installed capacity. We discuss the interpretation of these curves and the most appropriate experience curve for use in energy analysis.
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