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  • Falorni, Alberto, et al. (författare)
  • Determination of 21-hydroxylase autoantibodies: inter-laboratory concordance in the Euradrenal International Serum Exchange Program
  • 2015
  • Ingår i: Clinical Chemistry and Laboratory Medicine. - De Gruyter. - 1434-6621. ; 53:11, s. 1761-1770
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: 21-Hydroxylase autoantibodies (21OHAb) are markers of an adrenal autoimmune process that identifies individuals with autoimmune Addison's disease (AAD). Quality and inter-laboratory agreement of various 21OHAb tests are incompletely known. The objective of the study was to determine inter-laboratory concordance for 21OHAb determinations. Methods: Sixty-nine sera from 51 patients with AAD and 51 sera from 51 healthy subjects were blindly coded by a randomization center and distributed to 14 laboratories that determined 21OHAb, either by an "in-house" assay (n=9) using in vitro-translated S-35-21OH or luciferase-labeled 21OH or a commercial kit with I-125-21OH (n=5). Main outcome measures were diagnostic accuracy of each participating laboratory and inter-laboratory agreement of 21OHAb assays. Results: Intra-assay coefficient of variation ranged from 2.6% to 5.3% for laboratories using the commercial kit and from 5.1% to 23% for laboratories using "in-house" assays. Diagnostic accuracy, expressed as area under ROC curve (AUC), varied from 0.625 to 0.947 with the commercial kit and from 0.562 to 0.978 with "in-house" methods. Cohen's. of inter-rater agreement was 0.603 among all 14 laboratories, 0.691 among "in-house" laboratories, and 0.502 among commercial kit users. Optimized cutoff levels, calculated on the basis of AUCs, increased the diagnostic accuracy of every laboratory (AUC >0.9 for 11/14 laboratories) and increased the Cohen's. of inter-rater agreement. Discrepancies in quantitation of 21OHAb levels among different laboratories increased with increasing autoantibody levels. Conclusions: The quality of 21OHAb analytical procedures is mainly influenced by selection of cutoff value and correct handling of assay materials. A standardization program is needed to identify common standard sera and common measuring units.
  • Gore, C., et al. (författare)
  • Treatment and secondary prevention effects of the probiotics Lactobacillus paracasei or Bifidobacterium lactis on early infant eczema : randomized controlled trial with follow-up until age 3 years
  • 2012
  • Ingår i: Clinical and Experimental Allergy. - 0954-7894 .- 1365-2222. ; 42:1, s. 112-122
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background Allergic disease has been associated with altered intestinal microbiota. Therefore, probiotics have been suggested as a potential treatment for eczema.</p> <p>Objective We investigated whether dietary supplementation of infants with eczema at age 3-6 months with Lactobacillus paracasei CNCM I-2116 or Bifidobacterium lactis CNCM I3446 had a treatment effect or altered allergic disease progression.</p> <p>Methods Primary outcome included eczema severity (SCORing Atopic Dermatitis, SCORAD) 3 months post-randomization. Secondary: SCORAD (other visits); infant dermatitis quality of life (IDQoL); gastrointestinal permeability; urinary eosinophilic protein X; allergen- sensitization; allergic symptoms (age 12, 18, 36 months). A total of 208 infants aged 3-6 months with physician-diagnosed eczema were recruited; 137/208 (SCORAD &gt;= 10, consuming &gt;= 200 mL standard formula/day) were randomized to daily supplements containing L. paracasei or B. lactis or placebo for a 3-month period, while receiving extensively hydrolysed whey-formula (dairy-free diet). There were two open observational groups, one group exclusively breastfed (n = 22) and the other, standard formula-fed (n = 49). Trial number: ISRCTN41490500.</p> <p>Results Eczema severity decreased significantly over time in all groups. No significant difference was observed between randomized groups after 12-week treatment-period (SCORAD-score pre-/post-intervention: B. lactis 25.9 [95% CI: 22.8-29.2] to 12.8 [9.416.6]; L. paracasei 25.4 [22.1-29] to 12.5 [9.2-16.4]; placebo 26.9 [23.4-30.6] to 11.8 [9.6-14.3]; P = 0.7). Results were similar when analysis was controlled for allergen-sensitization, or when only sensitized infants were analysed. No differences were found for secondary outcomes. No difference was observed in SCORAD-score between randomized and observational groups.</p> <p>Conclusion and Clinical Relevance We found no benefit from supplementation with B. lactis or L. paracasei in the treatment of eczema, when given as an adjunct to basic topical treatment, and no effect on the progression of allergic disease from age 1 to 3 years.</p>
  • Green, Richard E., et al. (författare)
  • Three crocodilian genomes reveal ancestral patterns of evolution among archosaurs
  • 2014
  • Ingår i: Science. - 0036-8075 .- 1095-9203. ; 346:6215, s. 1335-
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>To provide context for the diversification of archosaurs-the group that includes crocodilians, dinosaurs, and birds-we generated draft genomes of three crocodilians: Alligator mississippiensis (the American alligator), Crocodylus porosus (the saltwater crocodile), and Gavialis gangeticus (the Indian gharial). We observed an exceptionally slow rate of genome evolution within crocodilians at all levels, including nucleotide substitutions, indels, transposable element content and movement, gene family evolution, and chromosomal synteny. When placed within the context of related taxa including birds and turtles, this suggests that the common ancestor of all of these taxa also exhibited slow genome evolution and that the comparatively rapid evolution is derived in birds. The data also provided the opportunity to analyze heterozygosity in crocodilians, which indicates a likely reduction in population size for all three taxa through the Pleistocene. Finally, these data combined with newly published bird genomes allowed us to reconstruct the partial genome of the common ancestor of archosaurs, thereby providing a tool to investigate the genetic starting material of crocodilians, birds, and dinosaurs.</p>
  • Guérin, C, et al. (författare)
  • A prospective international observational prevalence study on prone positioning of ARDS patients : the APRONET (ARDS Prone Position Network) study
  • 2018
  • Ingår i: Intensive Care Medicine. - 0342-4642 .- 1432-1238. ; 44:1, s. 22-37
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>INTRODUCTION:</strong> While prone positioning (PP) has been shown to improve patient survival in moderate to severe acute respiratory distress syndrome (ARDS) patients, the rate of application of PP in clinical practice still appears low.</p><p><strong>AIM:</strong> This study aimed to determine the prevalence of use of PP in ARDS patients (primary endpoint), the physiological effects of PP, and the reasons for not using it (secondary endpoints).</p><p><strong>METHODS:</strong> The APRONET study was a prospective international 1-day prevalence study performed four times in April, July, and October 2016 and January 2017. On each study day, investigators in each ICU had to screen every patient. For patients with ARDS, use of PP, gas exchange, ventilator settings and plateau pressure (Pplat) were recorded before and at the end of the PP session. Complications of PP and reasons for not using PP were also documented. Values are presented as median (1st-3rd quartiles).</p><p><strong>RESULTS:</strong> Over the study period, 6723 patients were screened in 141 ICUs from 20 countries (77% of the ICUs were European), of whom 735 had ARDS and were analyzed. Overall 101 ARDS patients had at least one session of PP (13.7%), with no differences among the 4 study days. The rate of PP use was 5.9% (11/187), 10.3% (41/399) and 32.9% (49/149) in mild, moderate and severe ARDS, respectively (P = 0.0001). The duration of the first PP session was 18 (16-23) hours. Measured with the patient in the supine position before and at the end of the first PP session, PaO2/FIO2 increased from 101 (76-136) to 171 (118-220) mmHg (P = 0.0001) driving pressure decreased from 14 [11-17] to 13 [10-16] cmH2O (P = 0.001), and Pplat decreased from 26 [23-29] to 25 [23-28] cmH2O (P = 0.04). The most prevalent reason for not using PP (64.3%) was that hypoxemia was not considered sufficiently severe. Complications were reported in 12 patients (11.9%) in whom PP was used (pressure sores in five, hypoxemia in two, endotracheal tube-related in two ocular in two, and a transient increase in intracranial pressure in one).</p><p><strong>CONCLUSIONS:</strong> In conclusion, this prospective international prevalence study found that PP was used in 32.9% of patients with severe ARDS, and was associated with low complication rates, significant increase in oxygenation and a significant decrease in driving pressure.</p>
  • Hildenwall, H, et al. (författare)
  • Care-seeking in the development of severe community acquired pneumonia in Ugandan children
  • 2009
  • Ingår i: Annals of Tropical Paediatrics. - 0272-4936 .- 1465-3281. ; 29:4, s. 281-289
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background: Improved case management of paediatric pneumonia is recognised as a key strategy for pneumonia control. Since symptoms of pneumonia and malaria often overlap, there are concerns that children with pneumonia are treated with antimalarial drugs. There is a need to describe how children with severe pneumonia have been managed prior to their arrival at hospital, including possible risks of developing more severe disease. Methods: A case-series study of 140 children, aged 2-59 months, with severe radiologically verified pneumonia at Mulago Hospital, Kampala was undertaken. Caretakers were interviewed about initial symptoms, treatment given and care sought. Using WHO definitions, children were clinically classified as having severe or very severe pneumonia. Results: The children had been ill for a median of 7 days before arrival at hospital, 90/140 (64%) had received treatment at home, and 72/140 (51%) had seen another health-care provider prior to presentation at hospital. Altogether, 32/140 (23%) children had reportedly received antibiotics only prior to admission, 18/140 (13%) had received anti-malarials only and 35/140 (25%) had received both. Being classified as very severe pneumonia was more common among children who had received anti-malarials only ( OR 5.5, 1.8-16.4). Conclusions: Although the majority of caretakers were able to recognise the key symptoms of pneumonia, they did not respond with any immediate care-giving action. Since progression from first recognition of pneumonia symptoms to severe disease is rapid, management guidelines regarding timing of care-seeking need to be clearly defined. The reason why children who sought health facility care failed to improve should be investigated. Meanwhile, there is a need to increase caretakers' and health workers' awareness of the urgency to act promptly when key pneumonia symptoms are observed.</p>
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