Hospital-acquired anemia among patients in a university hospital and the affiliated general practices in the capital region of Denmark, 2019.

INTRODUCTION: Approximately 25% of the patients with hospital acquired anemia (HAA) develop moderate to severe HAA during hospitalization. This is related to an increased risk of prolonged stay, readmission and mortality. The primary aim was during one year to characterize a population with very frequent phlebotomies based on a university hospital in the Capital Region of Denmark and the related general practitioners. MATERIAL AND METHODS: We conducted a retrospective cohort study using administrative data on phlebotomies from 1 January 2019 to 31 December 2019 analyzed at a university hospital. RESULTS: A total of 203,811 patients had 10,083,207 requisitions and 1,373,013 tubes. One percent, 1985 patients, had an extreme of frequent phlebotomies >60 tubes and formed the basis for the study population. The study population was significantly older as compared to the excluded patients (<60 tubes) (mean 65.7 vs. 51.6 years, p < .001).The likelihood of hemoglobin decrease per 100 mL blood drawn were calculated at four levels of decreases: Hemoglobin decrease of 2 mmol/L (adjusted OR; 95%; 2.03, CI 1.79-2.31), hemoglobin decrease of 3 mmol/L (adjusted OR; 95%, 1.36, CI 1.28-1.45), hemoglobin decrease of 4 mmol/L, (adjusted OR; 95%, 1.27, CI 1.19-1.35) and hemoglobin decrease of 5 mmol/L, (adjusted OR; 95% 1.22, CI 1.13-1.31). CONCLUSIONS: Moderate to severe HAA occurred in a limited group with excessive many phlebotomies. It was a worrisome trend that the frailest patients had the highest risk of developing HAA.

Rational design of alpha-helical antimicrobial peptides: do's and don'ts.

Antimicrobial peptides (AMPs) are promising candidates for battling multiresistant bacteria. Despite extensive research, structure-activity relationships of AMPs are not fully understood, and there is a lack of structural data relating to AMPs in lipids. Here we present the NMR structure of anoplin (GLLKRIKTLL-NH2 ) in a micellar environment. A vast library of substitutions was designed and tested for antimicrobial and hemolytic activity, as well as for changes in structure and lipid interactions. This showed that improvement of antimicrobial activity without concomitant introduction of strong hemolytic activity can be achieved through subtle increases in the hydrophobicity of the hydrophobic face or through subtle increases in the polarity of the hydrophilic face of the helix, or-most efficiently-a combination of both. A set of guidelines based on the results is given, for assistance in how to modify cationic α-helical AMPs in order to control activity and selectivity. The guidelines are finally tested on a different peptide.

Low-dose azathioprine and allopurinol versus azathioprine monotherapy in patients with ulcerative colitis (AAUC): An investigator-initiated, open, multicenter, parallel-arm, randomised controlled trial.

Background: Retrospective studies suggest that for patients with ulcerative colitis (UC) combination therapy with low-dose azathioprine and allopurinol (L-AZA/ALLO) may result in higher remission rates than monotherapy with azathioprine (AZA). We prospectively investigated the effects of these drugs for remission in patients with moderate-to-severe UC. Methods: Open-label, unblinded, randomised, controlled, investigator-initiated, multicentre study conducted at eight hospital sites in Denmark. Adult patients with established UC, who were steroid dependent/refractory, thiopurine naïve, had a normal thiopurine methyltransferase, and achieved remission with steroids or infliximab were eligible for inclusion. Patients were randomly assigned by the investigators (1:1) to 52 weeks of treatment with once daily oral AZA (median dose 50 mg) combined with ALLO 100 mg versus AZA monotherapy (median dose 200 mg), using a computer-generated randomisation list with blocks of six. The trial was open without masking. All randomised patients who received at least one dose of study drug were included in primary and safety analyses (intention to treat population). The primary outcome was steroid and infliximab free remission after 52 weeks, defined as a Mayo Score of ≤1 and no rectal bleeding. The trial is completed and is registered in ClinicalTrials.gov (ClinicalTrials.gov NCT03101800). Findings: Between January 9, 2017 and February 10, 2021, 47 patients were randomised to l-AZA/ALLO and 42 to AZA and received at least one dose of the study drug. After 52 weeks, 20 of 47 (43%) patients in the l-AZA/ALLO group and nine of 42 (21%) patients in the AZA group achieved remission (odds ratio 2·54 [95% CI 1·00 to 6.78, p < 0·048]). Fourteen patients (30%) in the l-AZA/ALLO group and 16 (38%) in the AZA group were withdrawn from the study due to adverse events. Interpretation: This study suggests that after one year l-AZA/ALLO therapy may be associated with a beneficial effect on steroid- and infliximab-free clinical remission in patients with moderate-to-severe UC and should be considered as first line therapy. Funding: Funding for AAUC was provided by The Capital Region of Denmark (Regionernes Medicinpulje (6062/16)).

[Therapeutic drug monitoring of ß-lactam antibiotics].

Traditional ß-lactam antibiotic dosing does not consider physiological changes in medical conditions such as sepsis. Optimal antibiotic exposure could be achieved by therapeutic drug monitoring (TDM). This review gives a brief summary. Current studies are sparse, but suggestive of a potential beneficial role of TDM to patients with reduced renal function, obese patients and the critically ill. TDM can potentially reduce adverse effects and optimise antibiotic exposure. However, standardised TDM methods are lacking and randomised clinical studies are warranted in order to prove clinical benefit.

The Effects of Two Intervention Strategies to Reduce the Intake of Salt and the Sodium-To-Potassium Ratio on Cardiovascular Risk Factors. A 4-Month Randomised Controlled Study among Healthy Families.

The aim was to examine the effects of two different salt reduction strategies on selected cardiovascular risk factors. The study was a four-month cluster randomised controlled study. Eighty-nine healthy Danish families (309 individuals) were randomly assigned to either (A) gradually salt-reduced bread, (B) gradually salt-reduced bread and dietary counselling to further reduce salt intake and increase potassium intake or (C) standard bread (control). The effect was assessed using linear mixed models. Intention to treat analyses comparing changes in the three groups showed a significant reduction in body fat percent (-1.31% (-2.40; -0.23)) and a borderline significant reduction in total plasma cholesterol (-0.25 mmol/L (-0.51; 0.01) and plasma renin (-0.19 pmol/L (-0.39; 0.00) in group A compared to the control group. Adjusted complete case analyses showed a significant reduction in total plasma cholesterol (-0.29 mmol/L (-0.50; -0.08), plasma LDL cholesterol (-0.08 mmol/L (-0.15; -0.00)), plasma renin (-0.23 pmol/L (-0.41; -0.05)), plasma adrenaline (-0.03 nmol/L (-0.06; -0.01)) and body fat percent (-1.53% (-2.51; -0.54)) in group A compared to the control group. No significant changes were found in group B compared to the control group. In conclusion, receiving sodium reduce bread was associated with beneficial changes in cardiovascular risk factors. No adverse effects were observed.

Salt Reduction Intervention in Families Investigating Metabolic, Behavioral and Health Effects of Targeted Intake Reductions: Study Protocol for a Four Months Three-Armed, Randomized, Controlled "Real-Life" Trial.

Reductions in salt intake have the potential to markedly improve population health at low cost. Real life interventions that explore the feasibility and health effects of a gradual salt reduction lasting at least four weeks are required. The randomized controlled SalT Reduction InterVEntion (STRIVE) trial was developed to investigate the metabolic, behavioral and health effects of four months of consuming gradually salt reduced bread alone or in combination with dietary counselling. This paper describes the rationale and methods of STRIVE. Aiming at 120 healthy families, participants were recruited in February 2018 from the Danish Capital Region and randomly allocated into: (A) Salt reduced bread; (B) Salt reduced bread and dietary counseling; (C) Standard bread. Participants were examined before the intervention and at four months follow-up. Primary outcome is change in salt intake measured by 24 h urine. Secondary outcomes are change in urine measures of potassium and sodium/ potassium ratio, blood pressure, plasma lipids, the renin-angiotensin system, the sympathetic nervous response, dietary intake as well as salt taste sensitivity and preferences. The results will qualify mechanisms affected during a gradual reduction in salt intake in compliance with the current public health recommendations.