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Grindarbotnseinkenni eftir fæðingu og snemmíhlutun með sjúkraþjálfun
Get PDFMarkmið: Meginmarkmið þessa doktorsverkefnis var að kanna tíðni
grindarbotnseinkenna og vanlíðunar sem þau valda frumbyrjum á fyrstu
mánuðum eftir fæðingu, ásamt því að rannsaka hvort tengsl findust milli
grindarbotnseinkennanna og fæðingartengdra þátta. Annað meginmarkmið
var að kanna áhrif snemmbærrar grindarbotnsþjálfunar, sem stýrt var af
sjúkraþjálfara, í hópi frumbyrja með einkenni frá grindarbotni. Þriðja markmið
var að kanna áhrif íþróttaiðkunar fyrir fæðingu hjá afreksíþróttakonum á
fæðingarútkomu fyrstu fæðingar. Þrjár vísindagreinar sem byggðar voru á
þremur rannsóknum eru hluti af þessari ritgerð. Sértæk markmið voru:
Rannsókn I: Að kanna tíðni grindarbotnseinkenna og vanlíðunar sem
tengdist einkennunum hjá norður-evrópskum frumbyrjum 6-10 vikum eftir
fæðingu og bera saman fæðingu um fæðingarveg og með keisaraskurði.
Rannsókn II: Að kanna áhrif einstaklingsmiðaðrar grindarbotnsþjálfunar,
sem sjúkraþjálfari leiðir á fyrstu mánuðum eftir fæðingu, á þvag- og
endaþarmsleka og þá vanlíðan sem slík einkenni valda hjá frumbyrjum. Áhrif
slíkrar þjálfunar á styrk og vöðvaúthald í grindarbotni var einnig metin.
Rannsókn III: Að kanna fæðingarútkomu, þar á meðal tíðni
bráðakeisaraskurða, lengdar fyrsta og annars stigs fæðingar og alvarlegra
spangarrifa hjá frumbyrjum sem voru annaðhvort afreksíþróttakonur eða
konur sem ekki æfðu íþróttir.
Aðferðir: Rannsókn I var þversniðsrannsókn með 721 manns úrtaki
frumbyrja sem fæddu einbura á höfuðborgarsvæðinu Reykjavík. Frá apríl
2015 til mars 2017 svöruðu þátttakendur rafrænum spurningalista heima 6-10
vikum eftir fæðingu. Upplýsingum um þvag- og endaþarmsleka, sig
grindarholslíffæra og vandkvæðum tengd kynlífi ásamt tengdri vanlíðan var
safnað og borið saman við gögn frá íslensku fæðingarskráningunni.
Meginútkomubreytur voru framangreind grindarbotnseinkenni eftir fæðingu og
tengd vanlíðan. Rannsókn II var slembi-samanburðarrannsókn til að kanna
áhrif grindarbotnsþjálfunar, sem leidd var af sjúkraþjálfara, á tíðni þvag- og
endaþarmsleka (aðal-útkomubreytur). Mæliaðilinn var blindaður á
rannsóknahópana. Vanlíðan tengd raunverulegum einkennum, ásamt mati á
styrk og úthaldi vöðva í grindarbotni voru flokkaðar sem aðrar útkomubreytur.
Frá árinu 2016 til 2017 voru svör kvenna sem tóku þátt í Rannsókn I athuguð
til að finna konur sem uppfylltu skilyrði til þátttöku. Þetta var gert um leið og
konur skiluðu svörunum 6-10 vikum eftir fyrstu fæðingu. Níutíu og fimm
konum sem töldust vera með þvagleka samkvæmt svörun spurningalistans
var boðið að taka þátt. Af þeim þáðu 84 boðið. Samtals var 41 konu
slembiraðað í íhlutunarhóp og 43 í samanburðarhóp. Þrjár og ein kona hættu
þátttöku úr þessum tveim hópum. Íhlutunin, sem hófst um 9 vikum eftir
fæðingu, samanstóð af 12 vikulegum tímum með sjúkraþjálfara. Eftir það
voru útkomubreytur metnar ( 6 mánuðum eftir fæðingu). Viðbótar-eftirfylgni
var framkvæmd um 12 mánuðum eftir fæðingu. Samanburðarhópurinn fékk
engar sértækar leiðbeiningar eftir upphaflegu skoðunina. Rannsókn III var
afturskyggn tilfella-viðmiðuð rannsókn þar sem fæðingarútkoma fyrstu
fæðingar afreksíþróttakvenna var borin saman við útkomu kvenna sem ekki
æfðu íþróttir. Íþróttakonurnar voru flokkaðar samkvæmt há-þungaberandi og
lág-þungaberandi íþróttagreinum. Íþróttakonurnar höfði fyrir fyrstu fæðingu
keppt með landsliðum eða tekið þátt í keppnum á alþjóðlegum vettvangi eða
verið í sambærilegri stöðu í sinni íþróttagrein. Samtals tóku 248 konur þátt,
89 voru í há-þungaberandi og 41 í lág-þungaberandi íþróttum og 118 konur í
samanburðahópi. Einennum kvenna sem skiptu máli fyrir rannsóknina ásamt
svörum um tíðni íþróttaiðkunar í að minnsta kosti þrjú ár fyrir fyrstu
meðgöngu og upplýsingum um almenna hreyfingu þeirra var safnað með
spurningalista sem sendur var með tölvupósti. Upplýsingar fengust frá
íslensku fæðingarskráningunni um tiltekin atriði varðandi fyrstu fæðingu allra
þeirra kvenna sem tóku þátt í rannsóknunum.
Niðurstöður: Í Rannsókn I var tíðni þvagleka 48% og tíðni endaþarmsleka
60%, auk þess sem 27% og 56% þátttakenda þjáðust af vanlíðan sökum
þessa í viðkomandi hópum. Sigeinkenni grindarholslíffæra fundust hjá 29%
kvenna og af öllum þátttakendum sögðust 13% glíma við vanlíðan vegna
þess. Fimmtíu og fimm prósent kvennanna sögðust vera kynferðislega virkar,
af þeim greindu 66% frá sársauka við samfarir. Af öllum þátttakendum
sögðust 48% upplifa vanlíðan vegna kynlífstengdra atriða. Þvagleki með
undirflokkum og sig á líffærum grindarhols var algengari hjá konum sem
fæddu um fæðingarveg borið saman við keisaraskurð, en ekki fannst
marktækur munur þegar um endaþarmsleka og sársauka við samfarir var að
ræða. Að vera í offituflokki, borið saman við eðlilega þyngd (LÞS<25kg/m2)
var tengt aukinni hættu á þvagleka hjá konum sem fæddu um fæðingarveg
(LH 1.94; 95% ÖB 1.20-3.14). Fyrir konur sem fæddu um fæðingarveg var
fæðingarþyngd yfir 50. hlutfallsmarki einnig áhættuþáttur fyrir bráðaþvagleka
(LH 1.53; 95% ÖB; 1.05-2.21). Auk þess var spangarskurður tengdur auknum
líkum á endaþarmsleka fyrir sama hóp kvenna (LH 2.19; 95% ÖB; 1.30-3.67).
Engin tengsl fundust milli einkenna móður eða einstakra fæðingarbreyta við
grindarbotnseinkenni hjá konum sem fæddu með keisaraskurði. Í Rannsókn II
var þvagleki marktækt minni í lok meðferðar hjá íhlutunarhóp, með 21 konu
(57%) enn með einkenni borið saman við 31 (82%) í samanburðarhópi
(p=0,33). Einnig var þvagleka-tengd vanlíðan minni í íhlutunarhópnum, með
10 konur (27%) sem enn fundu fyrir slíku borið saman við 23 (60%) í
samanburðarhópnum (p=0,005). Endaþarmsleki minnkaði ekki við
grindarbotnsþjálfunina og var ekki marktækur munur á hópunum við lok
meðferðar (p=0,33). Ekki fannst heldur munur á vanlíðan sem tengdist
endaþarmsleka við lok meðferðar (p=0,82). Meðaltalsmunur hópanna á
styrkbreytingum grindarbotnsvöðva var 5 hPa4 (95% ÖB 2-8; p=0,003), og
varðandi úthaldsbreytingar var munurinn 50 hPa/sek (95% ÖB 23-77;
p=0,001), hvort tveggja íhlutunarhópnum í vil. Meðaltalsmunur hópanna á
styrkbreytingum hringvöðva endaþarms var 10 hPa (95% ÖB 2-18; p=0,01).
Úthaldsbreytingin var 95 hPa/sek (95% ÖB 16-173; p=0,02), hvor tveggja
íhlutunarhópnum í vil. Við eftirfylgni 12 mánuðum eftir fæðingu var ekki
munur milli hópa á tíðni þvag- eða endaþarmsleka né tengdri vanlíðan. Styrkog
úthaldsmunur bæði grindarbotnsvöðva og hringvöðva endaþarms
íhlutunarhópnum í vil, var enn til staðar. Í Rannsókn III fannst enginn munur
milli hópa á tíðni bráðakeisaraskurðar né lengdar á fyrsta og öðru stigi
fæðingar. Tíðni þriðju og fjórðu gráðu spangarrifa var marktækt hærri (23,7%)
hjá konum sem æfðu lág-þungaberandi íþróttir borið saman við háþungaberandi
(5,1%, p=0,01). Enginn munur fannst þegar hvor
íþróttahópurinn um sig var borinn saman við samanburðarhóp (12%, p=0,09
fyrir lág-þungaberandi og p=0,12 fyrir há-þungaberandi íþróttahópinn). Tíðni
íþóttaiðkunar fyrir- og á meðgöngu, aldur móður eða LÞS fyrir fæðingu hafði
ekki áhrif á útkomu og gang fæðingar.
Ályktanir: Einkenni frá grindarbotni og vanlíðan sem tengdist þeim var
algeng hjá frumbyrjum á fyrstu vikum eftir fæðingu. Ekki ætti að líta fram hjá
þessu né þeim áhrifum sem grindarbotnsveikleiki hefur á konur. Hjá hópi
kvenna með einkenni frá grindarbotni dró grindarbotnsþjálfun úr þvagleka og
tengdri vanlíðan 6 mánuðum eftir fæðingu auk þess að bæta styrk og
úthaldsgetu vöðva í grindarbotni. Endaþarmsleki minnkaði hins vegar ekki við
íhlutunina. Þegar skoðaður var hópur kvenna með tilliti til líkamsþjálfunar fyrir
fyrstu fæðingu, fannst ekkert samband mikillar íþróttaiðkunar á afreksstigi og
verri útkomu fæðingar þegar metin var lengd fyrsta og annars stigs fæðingar,
tíðni bráðakeisaraskurða og alvarlegar spangarrifur. Margar konur glíma við
tiltölulega mild einkenni frá grindarbotni eftir fæðingu, einkenni sem eru líkleg
til að minnka á fyrsta árinu eftir barnsburð. Bera þarf kennsl á þann hóp
kvenna sem á við alvarleg grindarbotnseinkenni og vanlíðan að stríða þar
sem þær eru líklegar til að hafa gagn af sérmiðaðri sjúkraþjálfun.University of Iceland Research Fund
The Icelandic Physiotherapy Association Research Fund
The Landspitali University Hospital Research Fund
The Public Health Fund, Icelandic Directorate of Healt
Feasibility of ActivABLES to promote home-based exercise and physical activity of community-dwelling stroke survivors with support from caregivers: A mixed methods study
Get PDFPublisher's version (útgefin grein)Background: Technical applications can promote home-based exercise and physical activity of community-dwelling stroke survivors. Caregivers are often able and willing to assist with home-based exercise and physical activity but lack the knowledge and resources to do so. ActivABLES was established to promote home-based exercise and physical activity among community-dwelling stroke survivors, with support from their caregivers. The aim of our study is to investigate the feasibility of ActivABLES in terms of acceptability, demand, implementation and practicality. Methods: A convergent design of mixed methods research in which quantitative results were combined with personal experiences of a four-week use of ActivABLES by community-dwelling stroke survivors with support from their caregivers. Data collection before, during and after the four-week period included the Berg Balance Scale (BBS), Activities-Specific Balance Confidence Scale (ABC), Timed-Up-and-Go (TUG) and Five Times Sit to Stand Test (5xSST) and data from motion detectors. Semi-structured interviews were conducted with stroke survivors and caregivers after the four-week period. Descriptive statistics were used for quantitative data. Qualitative data was analysed with direct content analysis. Themes were identified related to the domains of feasibility: acceptability, demand, implementation and practicality. Data was integrated by examining any (dis)congruence in the quantitative and qualitative findings. Results: Ten stroke survivors aged 55–79 years participated with their informal caregivers. Functional improvements were shown in BBS (+ 2.5), ABC (+ 0.9), TUG (− 4.2) and 5xSST (− 2.7). More physical activity was detected with motion detectors (stand up/sit down + 2, number of steps + 227, standing + 0.3 h, hours sitting/lying − 0.3 h). The qualitative interviews identified themes for each feasibility domain: (i) acceptability: appreciation, functional improvements, self-initiated activities and expressed potential for future stroke survivors; (2) demand: reported use, interest in further use and need for follow-up; (3) implementation: importance of feedback, variety of exercises and progression of exercises and (4) practicality: need for support and technical problems. The quantitative and qualitative findings converged well with each other and supported the feasibility of ActivABLES. Conclusions: ActivABLES is feasible and can be a good asset for stroke survivors with slight or moderate disability to use in their homes. Further studies are needed with larger samples.The reported work was mainly funded by the NordForsk ActivABLES project. We also received smaller grants from the Icelandic Physiotherapy Association and the Icelandic Ministry of Welfare. This funding financed the design of the study, the development of the prototypes, the collection, analysis and interpretation of data, and the writing of the manuscript. In addition, the funding financed traveling cost for researchers and the cost of the final publication.Peer Reviewe
Dampness and mold at home and at work and onset of insomnia symptoms, snoring and excessive daytime sleepiness
Get PDFPublisher's version (útgefin grein)Aim: To investigate whether exposure to dampness and mold at home and at work induce sleep disturbances and daytime sleepiness among adults. Materials and methods: Associations between onset of sleep disturbances and dampness, mold and mold odor at home and at work were investigated in a cohort of 11,318 adults from the population in Iceland, Norway, Sweden, Denmark and Estonia. The participants answered a questionnaire at baseline and 10 years later, with questions on sleep disturbances, including difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), early morning awakening (EMA), insomnia symptoms, snoring and excessive daytime sleepiness (EDS). Multiple logistic regression models were applied to estimate associations adjusting for potential confounders including gender, age, smoking habit at baseline, change of smoking habit from baseline to follow up, BMI at baseline, change of BMI from baseline to follow up, education level at follow up, allergic rhinitis at baseline, doctor diagnosed asthma at baseline and chronic bronchitis at baseline. Results: Baseline floor dampness, visible mold and mold odor at home increased onset of DIS, DMS, EMA, insomnia symptoms and snoring during follow up (OR 1.29–1.87). Any sign of dampness at baseline increased onset of DIS (OR 1.28, 95%CI 1.06–1.55), DMS (OR 1.17, 95%CI 1.02–1.34) and insomnia symptoms (OR 1.18, 95%CI 1.03–1.36). Dampness at home during follow up increased onset of DIS, DMS, EMA, insomnia symptoms and EDS (OR 1.17–1.36). Dampness at work during follow up increased onset of DIS, EMA, insomnia symptoms and EDS (OR 1.16–1.34). Combined dampness at home and at work during follow up increased the risk of onset of DIS, DMS, EMA, insomnia symptoms and EDS (OR 1.29–1.74). Conclusions: Dampness and mold at home and at work can increase the development of insomnia symptoms, snoring and EDS among adults.The study was funded by the Icelandic Research Council, Landspitali University, Reykjavik, the Swedish Heart and Lung Foundation, the Vårdal Foundation for Health Care and Allergic Research, the Swedish Association Against Asthma and Allergy, the Swedish Council for Work Live and Social Research, the Swedish AFA Insurance (No. 467801100), the Bror Hjerpstedt Foundation, the Norwegian Research Council, the Norwegian Asthma and Allergy Association, the Danish Lung Association and the Estonian Science Foundation.Peer Reviewe
Serum 25-hydroxyvitamin D concentrations in 16-year-old Icelandic adolescent and its association with bone mineral density
Get PDFPublisher's version (útgefin grein)Objective: The aim of the study was to assess the potential association between serum 25-hydroxyvitamin D (25(OH)D) and whole-body bone mineral density (BMD) among 16-year-old adolescents and to study the prevalence of 25(OH)D insufficiency, defined as concentration under 50 nmol/l.Design: A cross-sectional study.Setting: Reykjavik, Iceland, latitude 64°08′N. Measurements took place in the Icelandic Heart Association's research lab during April-June 2015.Participants: In total, 411 students in Reykjavik, Iceland, were invited to participate, 315 accepted the invitation (76·6 %) and 289 had valid data (mainly Caucasian).Results: 25(OH)D < 50 nmol/l was observed in 70 % of girls and 66·7 % of boys. 25(OH)D ≥ 50 nmol/l was significantly associated with higher whole-body BMD after adjusting for the influence of sex, height, fat mass and lean mass. A linear relationship between 25(OH)D and whole-body BMD was significant for 25(OH)D < 50 nmol/l (n 199, P < 0·05) but NS for 25(OH)D ≥ 50 nmol/l (n 86, P = 0·48).Conclusions: Our results are in line with some but not all previous studies on the relationship between BMD and 25(OH)D in adolescents. The observed difference in BMD between those with above v. below a 25(OH)D concentration of 50 nmol/l was of about a fifth of one SD, which may have a clinical relevance as one SD decrease in volumetric BMD has been associated with a 89 % increase in 2 years risk of fracture. Icelandic adolescents should be encouraged to increase their vitamin D intake as it is possible that their current intake is insufficient to achieve optimal peak bone mass.The authors would like to thank the participants of the study, the staff at the Icelandic Heart Association. They also thank The Icelandic Centre for Research (RANNIS) and the Research Fund of the Icelandic College of Family Physicians for financial support. Financial support : The study was funded by the Icelandic Centre for research (RANNIS) (grant number 152509-051). Conflict of interest : The authors certify that they have NO affiliations with or involvement in any organisation or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. Authorship : S.L.G. and H.H. wrote the manuscript with input from all authors. H.H. and S.L.G. designed the statistical models and H.H. performed the data analyses. E.L.S. and E.J. conceived the study and managed the overall direction of the project. Disclosure: The Icelandic Centre for Research had no role in the design, analysis or writing of this article. Ethics of human subject participation : The current study was conducted according to the guidelines laid down in the Declaration of Helsinki, and all procedures involving research study participants were approved by The National Bioethics Committee in Iceland. Written informed consent was obtained from all subjects and their guardians.Peer Reviewe
Electron-photonic topological states on the surface of a bulk semiconductor driven by a high-frequency field
Get PDFPublisher's version (útgefin grein)It is shown theoretically that the strong coupling of electrons in a bulk gapless semiconductor (HgTe) to a circularly polarized high-frequency electromagnetic field induces topological states on the surface of the semiconductor. Their branches lie near the center of the Brillouin zone and have the Dirac dispersion. Thus, the light-induced topological phase transition in the semiconductor appears. The structure of the found surface states is studied both analytically and numerically in the broad range of their parameters.The work was partially supported by Russian Foundation for Basic Research (project 17-02-00053), Rannis project 163082-051, Ministry of Science and High Education of Russian Federation (projects 3.4573.2017/6.7, 3.8051.2017/8.9, 14.Y26.31.0015), and the Government of the Russian Federation through the ITMO Fellowship and Professorship Program.Peer Reviewe
An evaluation of the cost-competitiveness of maritime fuels – a comparison of heavy fuel oil and methanol (renewable and natural gas) in Iceland
Get PDFPublisher's version (útgefin grein)Alternative fuels have been proposed to ensure compliance with the increasingly more stringent emission standards proposed by the International Maritime Organization. In addition, the Icelandic government aims to introduce 10% renewable energy into the maritime sector before 2030, as well as eventually phasing out the use of heavy fuel oil (HFO). This paper conducts an extended cost-competitiveness comparison concerning three fuels: conventional methanol (NG), renewable methanol (RN) and HFO in the context of the Icelandic maritime sector. NG, RN and HFO are compared and evaluated under three scenarios (low, medium and high) for fuel prices between 2018 and 2050, and three scenarios (low, medium and high) for the external costs of fuel consumption. The methodology for estimating external costs involved Impact Pathway Analysis for emissions of sulphur dioxide, nitrous oxide, particulate matter and non-methane volatile organic compounds, and increasing shadow prices for the costs of greenhouse gas emissions. The application of this methodology provides new information about the economic and environmental trade-offs between the three fuel types. In our findings, excluding external costs, HFO emerges as the most cost-competitive option. However, when the externalities of fuel consumption are monetised and added to the fuel price, NG is the most cost-competitive option when high values are assumed for external costs. RN is the most expensive option according to all trajectories for fuel prices and external costs, not becoming more cost-competitive than HFO under any scenario until the 2040s. Therefore, on cost criteria alone, it is improbable that the fuel will contribute to Iceland's 10% renewable energy goal in the maritime sector before 2030 without subsidies or renewable marine fuel quotas.This paper has been funded by NordForsk (grant number 76654) via their financial support to the Nordic Centre of Excellence ARCPATH (Arctic Climate Predictions – Pathways to Resilient, Sustainable Communities), and the Icelandic Research Council (RANNIS) through grant number 163464-051Peer Reviewe
Melflufen, a peptide‐conjugated alkylator, is an efficient anti‐neo‐plastic drug in breast cancer cell lines
Get PDFPublisher's version (útgefin grein)Melphalan flufenamide (hereinafter referred to as “melflufen”) is a peptide-conjugated drug currently in phase 3 trials for the treatment of relapsed or refractory multiple myeloma. Due to its lipophilic nature, it readily enters cells, where it is converted to the known alkylator melphalan leading to enrichment of hydrophilic alkylator payloads. Here, we have analysed in vitro and in vivo the efficacy of melflufen on normal and cancerous breast epithelial lines. D492 is a normal-derived nontumorigenic epithelial progenitor cell line whereas D492HER2 is a tumorigenic version of D492, overexpressing the HER2 oncogene. In addition we used triple negative breast cancer cell line MDA-MB231. The tumorigenic D492HER2 and MDA-MB231 cells were more sensitive than normal-derived D492 cells when treated with melflufen. Compared to the commonly used anti-cancer drug doxorubicin, melflufen was significantly more effective in reducing cell viability in vitro while it showed comparable effects in vivo. However, melflufen was more efficient in inhibiting metastasis of MDA-MB231 cells. Melflufen induced DNA damage was confirmed by the expression of the DNA damage proteins ƴH2Ax and 53BP1. The effect of melflufen on D492HER2 was attenuated if cells were pretreated with the aminopeptidase inhibitor bestatin, which is consistent with previous reports demonstrating the importance of aminopeptidase CD13 in facilitating melflufen cleavage. Moreover, analysis of CD13high and CD13low subpopulations of D492HER2 cells and knockdown of CD13 showed that melflufen efficacy is mediated at least in part by CD13. Knockdown of LAP3 and DPP7 aminopeptidases led to similar efficacy reduction, suggesting that also other aminopeptidases may facilitate melflufen conversion. In summary, we have shown that melflufen is a highly efficient anti-neoplastic agent in breast cancer cell lines and its efficacy is facilitated by aminopeptidases.We thank Inovotion for their work and support in the CAM assays.Peer Reviewe
Drug Tolerant Anti-drug Antibody Assay for Infliximab Treatment in Clinical Practice Identifies Positive Cases Earlier
Get PDFPublisher's version (útgefin grein)A subgroup of patients treated with infliximab lose response to the treatment and one reason for this is the development of anti-drug antibodies (ADA). If used optimally, measuring drug and ADA level could lead to a more personalized and efficient treatment regime, and enable identification of ADA-positive patients before the underlying disease flares or allergic reactions occur. With the use of a drug-tolerant ADA assay which can detect ADA irrespective of drug levels in the sample, we determined the impact of ADA on treatment failure to infliximab. The aims of this study were to estimate the real-life optimal serum infliximab (sIFX) level and set a clinical threshold value for a drug-tolerant ADA assay. Trough levels of sIFX were measured with ELISA. Free ADA was measured with two drug-sensitive methods (ELISA and a bioassay) and one drug-tolerant method (PandA). Two real-life cohorts treated with infliximab were included; a cross-sectional cohort including patients with inflammatory rheumatic diseases (n = 270) and a prospective cohort of rheumatoid arthritis (RA) patients (n = 73) followed for 1 year. Normal range of sIFX was estimated from the prospective cohort and an arbitrary optimal drug level was set to be between 1 and 6 μg/mL. Using this range, optimal sIFX was found in only 60% (163/270) of the patients in the cross-sectional cohort. These patients had significantly better treatment response than those with a drug level under 1 μg/mL, who had an ADA frequency of 34% (19/56) using the drug-tolerant method. In the prospective cohort, the drug-tolerant assay could identify 34% (53/155 samples) as ADA positive in samples with sIFX level >0.2 μg/mL. ADA were seldom detected in patients with >1 μg/mL sIFX, with three interesting exceptions. A clinically relevant ADA threshold was determined to be >3 RECL as measured with the drug-tolerant assay. In a real-life setting, there was a substantial number of patients with suboptimal drug levels and a proportion of these had ADA. Both too low and too high drug levels correlated with worse disease, but for different reasons. Adding a drug-tolerant assay enabled detection of ADA earlier and regardless of drug level at time of sampling.We would like to thank all patients for their participation in this study. We would also like to thank Consuelo Gomez, Pascual Gonzalez, Anna G. Mattsson, Arne St?hl, and Yousra Rehouma for excellent technical assistance. Funding. The research leading to these results has received support from Swelife, Stockholm County Council (ALF project) #20140333 and the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115303, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kind contribution. This work was also supported by the grants from Aina (Ann) Wallstr?ms och Mary-Ann Sj?bloms Foundation for Medical Research, Professor Nanna Svartz Foundation, the Gothenburg Medical Society (GLS-889421 to RP), the Swedish Rheumatism Association (R-862061 and R-663511 to RP), Adlerbertska research Foundation and the Regional agreement on medical training and clinical research between the Western G?taland county council and the University of Gothenburg (ALFGBG-926621).Peer Reviewe
Variations in use of childbirth interventions in 13 high-income countries: A multinational cross-sectional study
Get PDFPublisher's version (útgefin grein)Background:
Variations in intervention rates, without subsequent reductions in adverse outcomes, can indicate overuse. We studied variations in and associations between commonly used childbirth interventions and adverse outcomes, adjusted for population characteristics.
Methods and findings:
In this multinational cross-sectional study, existing data on 4,729,307 singleton births at ≥37 weeks in 2013 from Finland, Sweden, Norway, Denmark, Iceland, Ireland, England, the Netherlands, Belgium, Germany (Hesse), Malta, the United States, and Chile were used to describe variations in childbirth interventions and outcomes. Numbers of births ranged from 3,987 for Iceland to 3,500,397 for the USA. Crude data were analysed in the Netherlands, or analysed data were shared with the principal investigator. Strict variable definitions were used and information on data quality was collected. Intervention rates were described for each country and stratified by parity. Uni- and multivariable analyses were performed, adjusted for population characteristics, and associations between rates of interventions, population characteristics, and outcomes were assessed using Spearman’s rank correlation coefficients. Considerable intercountry variations were found for all interventions, despite adjustments for population characteristics. Adjustments for ethnicity and body mass index changed odds ratios for augmentation of labour and episiotomy. Largest variations were found for augmentation of labour, pain relief, episiotomy, instrumental birth, and cesarean section (CS). Percentages of births at ≥42 weeks varied from 0.1% to 6.7%. Rates among nulliparous versus multiparous women varied from 56% to 80% versus 51% to 82% for spontaneous onset of labour; 14% to 36% versus 8% to 28% for induction of labour; 3% to 13% versus 7% to 26% for prelabour CS; 16% to 48% versus 12% to 50% for overall CS; 22% to 71% versus 7% to 38% for augmentation of labour; 50% to 93% versus 25% to 86% for any intrapartum pain relief, 19% to 83% versus 10% to 64% for epidural anaesthesia; 6% to 68% versus 2% to 30% for episiotomy in vaginal births; 3% to 30% versus 1% to 7% for instrumental vaginal births; and 42% to 70% versus 50% to 84% for spontaneous vaginal births. Countries with higher rates of births at ≥42 weeks had higher rates of births with a spontaneous onset (rho = 0.82 for nulliparous/rho = 0.83 for multiparous women) and instrumental (rho = 0.67) and spontaneous (rho = 0.66) vaginal births among multiparous women and lower rates of induction of labour (rho = −0.71/−0.66), prelabour CS (rho = −0.61/−0.65), overall CS (rho = −0.61/−0.67), and episiotomy (multiparous: rho = −0.67). Variation in CS rates was mainly due to prelabour CS (rho = 0.96). Countries with higher rates of births with a spontaneous onset had lower rates of emergency CS (nulliparous: rho = −0.62) and higher rates of spontaneous vaginal births (multiparous: rho = 0.70). Prelabour and emergency CS were positively correlated (nulliparous: rho = 0.74). Higher rates of obstetric anal sphincter injury following vaginal birth were found in countries with higher rates of spontaneous birth (nulliparous: rho = 0.65). In countries with higher rates of epidural anaesthesia (nulliparous) and spontaneous births (multiparous), higher rates of Apgar score < 7 were found (rhos = 0.64). No statistically significant variation was found for perinatal mortality. Main limitations were varying quality of data and missing information.
Conclusions:
Considerable intercountry variations were found for all interventions, even after adjusting for population characteristics, indicating overuse of interventions in some countries. Multivariable analyses are essential when comparing intercountry rates. Implementation of evidence-based guidelines is crucial in optimising intervention use and improving quality of maternity care worldwide.This study was developed during meetings with COST members (European Cooperation in Science and Technology). These meetings were funded by the COST Action IS1405 ‘BIRTH’ (European Cooperation in Science and Technology). To collect the data for England, a support grant from the University of Liverpool was received of £2,000 (LF; https://www.liverpool.ac.uk/), and the Western Norway University of Applied Sciences paid NOK 12,600 for the data provided from the Medical Birth Registry of Norway (ABVN; https://www.hvl.no/en/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer Reviewe
Public Perception of Wilderness in Iceland
Get PDFPublisher's version (útgefin grein)In recent years, there has been a gradually growing emphasis on the protection of wilderness in Iceland. This is highlighted in the current preparation of a new national park in the Icelandic central highlands, which will become Europe's largest national parks. However, in order to protect the wilderness, a mutual understanding, both on what it is and where it is, is needed. This paper seeks to evaluate Icelanders' perception and understanding of wilderness. Furthermore, to assess the value of wilderness for the Icelandic public and determine what lies behind the valuation, an online survey aided by maps from Google Earth and photographic scenarios of different landscapes was sent out to a nationally representative sample of Icelanders. The survey respondents mapped their perceived scope of Icelandic wilderness and furthermore chose between several landscape scenarios they thought most and least suited to their perception of wilderness. The results show that nearly all land located above the 300 m elevation line is perceived as wilderness, reflecting the country's uninhabited highlands areas. The results also show that for the general public in Iceland it is chiefly an open and vast landscape, uninhabited areas, and the absence of anthropogenic features that bestow an area with the status of wilderness. The results demonstrate that any sign of anthropogenic interference, aside from archaeological remains, decrease Icelanders' perception of wilderness. Moreover, despite being mostly categorized as urbanists or neutralists according to the purism scale, the majority of Icelanders still consider services, such as petrol stations, hotels, shops, restaurants, and diverse leisure services, along with energy production, to negatively impact the value of wilderness. Most Icelanders thus seem to regard wilderness as a valuable asset from the economic, cultural, and environmental perspectives, which underscores its uniqueness.This research was funded by the Ministry for the Environment and Natural Resources and the steering committee for the Icelandic Master Plan for Nature Protection and Energy Utilization.Peer Reviewe