Corn-Soy-Blend Fortified with Phosphorus to Prevent Refeeding Hypophosphatemia in Undernourished Piglets

<div><p>Background</p><p>Phosphorus (P) levels in refeeding diets are very important as undernourished children are at risk of hypophosphatemia during refeeding. For this reason, conventional corn-soy-blends (CSB) have been reformulated by the World Food Programme to obtain a mono-calcium-phosphate fortified product (CSB+) and a product further fortified with skim milk powder (CBS++).</p><p>Methods</p><p>Using a piglet model of undernourished children, we hypothesized that feeding of CSB+, CSB++ or CSB+ with added whey permeate (CSB+/wp) would help to prevent refeeding hypophosphatemia. Pigs were weaned at 4 weeks of age and undernutrition was induced with a nutritionally inadequate pure maize diet for 7 weeks, after which they were refed for 3 weeks with either CSB+ (n = 10), CSB++ (n = 10) or CSB+/wp (n = 10). For reference, a fourth group continued on the maize diet (REF, n = 10).</p><p>Results</p><p>Following induction of undernutrition, body weight and length were 29±5% and 67±4% (means±SD) of values in age-matched pigs fed a nutritionally adequate diet, and the mean serum P level was 1.77±0.34 mmol/l. During the first week of refeeding, P levels in the CSB+ pigs decreased to 55% of values before refeeding (P < 0.05) while values in the CSB++ and CSB+/wp pigs were able to maintain their plasma phosphate at a similar level as before refeeding.</p><p>Conclusion</p><p>We conclude that fortification of CSB with only monocalcium-phosphate does not prevent hypophosphatemia. Dairy products like skim milk powder or whey permeate may represent relevant sources of phosphorus during refeeding. The content and form of phosphorus in such diets need to be carefully evaluated, and the undernourished piglet may be used to test the efficacy of such diets.</p></div

Agents intervening against delirium in the intensive care unit trial-Protocol for a secondary Bayesian analysis

Background Delirium is highly prevalent in the intensive care unit (ICU) and is associated with high morbidity and mortality. The antipsychotic haloperidol is the most frequently used agent to treat delirium although this is not supported by solid evidence. The agents intervening against delirium in the intensive care unit (AID-ICU) trial investigates the effects of haloperidol versus placebo for the treatment of delirium in adult ICU patients. Methods This protocol describes the secondary, pre-planned Bayesian analyses of the primary and secondary outcomes up to day 90 of the AID-ICU trial. We will use Bayesian linear regression models for all count outcomes and Bayesian logistic regression models for all dichotomous outcomes. We will adjust for stratification variables (site and delirium subtype) and use weakly informative priors supplemented with sensitivity analyses using sceptical priors. We will present results as absolute differences (mean differences and risk differences) and relative differences (ratios of means and relative risks). Posteriors will be summarised using median values as point estimates and percentile-based 95% credibility intervals. Probabilities of any benefit/harm, clinically important benefit/harm and clinically unimportant differences will be presented for all outcomes. Discussion The results of this secondary, pre-planned Bayesian analysis will complement the primary frequentist analysis of the AID-ICU trial and facilitate a nuanced and probabilistic interpretation of the trial results.Peer reviewe

Population genomics of the Viking world.

The maritime expansion of Scandinavian populations during the Viking Age (about AD 750-1050) was a far-flung transformation in world history1,2. Here we sequenced the genomes of 442 humans from archaeological sites across Europe and Greenland (to a median depth of about 1×) to understand the global influence of this expansion. We find the Viking period involved gene flow into Scandinavia from the south and east. We observe genetic structure within Scandinavia, with diversity hotspots in the south and restricted gene flow within Scandinavia. We find evidence for a major influx of Danish ancestry into England; a Swedish influx into the Baltic; and Norwegian influx into Ireland, Iceland and Greenland. Additionally, we see substantial ancestry from elsewhere in Europe entering Scandinavia during the Viking Age. Our ancient DNA analysis also revealed that a Viking expedition included close family members. By comparing with modern populations, we find that pigmentation-associated loci have undergone strong population differentiation during the past millennium, and trace positively selected loci-including the lactase-persistence allele of LCT and alleles of ANKA that are associated with the immune response-in detail. We conclude that the Viking diaspora was characterized by substantial transregional engagement: distinct populations influenced the genomic makeup of different regions of Europe, and Scandinavia experienced increased contact with the rest of the continent

Furosemide versus placebo for fluid overload in intensive care patients—The randomised GODIF trial second version : Statistical analysis plan

Publisher Copyright: © 2023 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.Background: Fluid overload is associated with increased mortality in intensive care unit (ICU) patients. The GODIF trial aims to assess the benefits and harms of fluid removal with furosemide versus placebo in stable adult patients with moderate to severe fluid overload in the ICU. This article describes the detailed statistical analysis plan for the primary results of the second version of the GODIF trial. Methods: The GODIF trial is an international, multi-centre, randomised, stratified, blinded, parallel-group, pragmatic clinical trial, allocating 1000 adult ICU patients with moderate to severe fluid overload 1:1 to furosemide versus placebo. The primary outcome is days alive and out of hospital within 90 days post-randomisation. With a power of 90% and an alpha level of 5%, we may reject or detect an improvement of 8%. The primary analyses of all outcomes will be performed in the intention-to-treat population. For the primary outcome, the Kryger Jensen and Lange method will be used to compare the two treatment groups adjusted for stratification variables supplemented with sensitivity analyses in the per-protocol population and with further adjustments for prognostic variables. Secondary outcomes will be analysed with multiple linear regressions, logistic regressions or the Kryger Jensen and Lange method as suitable with adjustment for stratification variables. Conclusion: The GODIF trial data will increase the certainty about the effects of fluid removal using furosemide in adult ICU patients with fluid overload. Trial Registrations: EudraCT identifier: 2019-004292-40 and ClinicalTrials.org: NCT04180397.Peer reviewe

Prematurity and Prescription Asthma Medication from Childhood to Young Adulthood: A Danish National Cohort Study

<div><p>Introduction</p><p>Preterm birth is associated with increased risk of asthma-like symptoms and purchase of prescription asthma medication in childhood. We investigated whether this association persists into adulthood and whether it is affected by accounting for neonatal respiratory morbidity (acute respiratory disease and bronchopulmonary dysplasia).</p><p>Methods</p><p>A national cohort of all infants born in Denmark in the period 1980–2009 was included in this register study. Data on purchase of asthma medication (combination of inhaled β-2 agonists and other drugs for obstructive airway disease) in 2010–2011 were obtained from the Danish National Prescription Registry. Associations between gestational age (GA), neonatal respiratory morbidity and a cross-sectional evaluation of asthma medication purchase were explored by multivariate logistic regressions.</p><p>Results</p><p>A full dataset was obtained on 1,790,241 individuals, 84.6% of all infants born in the period. Odds-ratios (95% CI) for the association between GA and purchase of asthma medication during infancy were: 3.86 (2.46–6.04) in GA 23–27 weeks, 2.37 (1.84–3.04) in GA 28–31 weeks and 1.59 (1.43–1.77) in GA 32–36 weeks compared to term infants with GA 37–42 weeks. Associations weakened in older age groups and became insignificant in young adults born extremely and very preterm with odds-ratios: 1.41 (0.63–3.19) and 1.15 (0.83–1.60) in GA 23–27 and 28–31 respectively. When adjusting for neonatal respiratory morbidity, the associations weakened but persisted both in childhood and adolescence.</p><p>Conclusion</p><p>There was a strong dose-response association between gestational age and the purchase of prescription asthma medication in infancy and childhood. This association weakened during adolescence and was mostly non-significant in young adulthood. The increased risk of prescription asthma medication purchase in ex-preterm children could only partly be explained by neonatal respiratory morbidity.</p></div