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.

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)).

FluoroMatch 2.0-making automated and comprehensive non-targeted PFAS annotation a reality.

Because of the pervasiveness, persistence, and toxicity of per- and polyfluoroalkyl substances (PFAS), there is growing concern over PFAS contamination, exposures, and health effects. The diversity of potential PFAS is astounding, with nearly 10,000 PFAS catalogued in databases to date (and growing). The ability to detect the thousands of known PFAS, and discover previously uncatalogued PFAS, is necessary to understand the scope of PFAS contamination and to identify appropriate remediation and regulatory solutions. Current non-targeted methods for PFAS analysis require manual curation and are time-consuming, prone to error, and not comprehensive. FluoroMatch Flow 2.0 is the first software to cover all steps of data processing for PFAS discovery in liquid chromatography-high-resolution tandem mass spectrometry samples. These steps include feature detection, feature blank filtering, exact mass matching to catalogued PFAS, mass defect filtering, homologous series detection, retention time pattern analysis, class-based MS/MS screening, fragment screening, and predicted MS/MS from SMILES structures. In addition, a comprehensive confidence level criterion is implemented to help users understand annotation certainty and integrate various layers of evidence to reduce overreporting. Applying the software to aqueous film forming foam analysis, we discovered over one thousand likely PFAS including previously unreported species. Furthermore, we were able to filter out 96% of features which were likely not PFAS. FluoroMatch Flow 2 increased coverage of likely PFAS by over tenfold compared to the previous release. This software will enable researchers to better characterize PFAS in the environment and in biological systems.

The 10 most frequently requested blood tests in the Capital Region of Denmark, 2010-2019 and simulated effect of minimal retesting intervals.

As healthcare costs continue to rise throughout the world, critical assessment of the appropriateness of expenses gain focus. OBJECTIVES: We aimed to describe the developments in test numbers of the 10 most frequently requested tests, and to simulate the effect of introducing minimal retesting intervals. DESIGN & METHODS: Data from the blood tests - albumin, alanine transaminase, cholesterol, creatinine, C-reactive protein, hemoglobin, hemoglobin A1c, potassium, sodium, and thyrotropin - from 2,687,589 patients handled by the Capital Region of Denmark from 2010 to 2019 was used. Tallies of each test per year were graphed. A simulation of the effect of minimal retesting intervals on test count and blood sampling volume was performed by virtually removing requests made prior to a set of possible minimal retesting intervals. RESULTS: Increases in requests were observed both from hospitals and general practitioners. The number of requests for hemoglobin A1c increased more than the other tests. The increases could not be accounted for by an increase in population size and aging of the population, and therefore suggests possible inappropriate increase in monitoring of patients. The simulated effect of applying minimal retesting intervals showed large reductions in tests and blood sampled. CONCLUSIONS: For hospitals, the simulation suggested that applying minimal retesting intervals could lead to significant reductions in both the number of blood tests performed and in the amount of blood drawn for testing. For general practitioners, the simulation showed only minimal reductions in number of tests and blood volume drawn.

Fractionated free fatty acids and their relation to diabetes status after Roux-en-Y gastric bypass: A cohort study.

Bariatric surgery is associated with near-immediate remission of type 2 diabetes and recently suggested as a treatment for type 2 diabetes. Specifically, Roux-en-Y gastric bypass has been a focus of much research, but still, the mechanisms of action are only partly elucidated. We aim to investigate whether some mechanisms might be mediated by free fatty acids (FFAs). We measured eight fractionated FFAs before and up to 2 years after Roux-en-Y gastric bypass surgery in 207 patients, divided into three groups. One non-diabetic group, one diabetic group with post-operative remission and one diabetic group with persistent diabetes after surgery. Pre- and postoperative levels of fractionated FFAs were compared within and between groups. The sum of the measured FFAs were lower in the group with persistent diabetes, compared to the other groups. The pre-surgery level of linoleic acid in the group with persistent diabetes was significantly lower compared to the other two groups. The levels of fractionated FFAs decreased from pre-surgery to three months after surgery, except for oleic acid and arachidonic acid and for Docosahexaenoic acid (DHA) in the non-diabetic group. The FFAs with decreasing levels from pre-surgery to three months post-surgery are all precursors to oleic acid, arachidonic acid, and DHA, respectively, which may imply a drift, indicating that they need to be sustained at an acceptable level for optimal metabolic function. The fact that the sum of the measured FFAs is lower in the group with persistent diabetes may suggest that this group and the group with diabetes remission represent two distinct types of type 2 diabetes. It is proposed that linoleic acid could be used as a biomarker to determine the plausibility for type 2 diabetes remission after Roux-en-Y gastric bypass surgery.

[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.

A compulsory pop-up form reduces the number of vitamin D requests from general practitioners by 25 percent.

OBJECTIVE: Healthcare costs, including costs for laboratory tests, are increasing worldwide. One example is the measurement of vitamin D. General practitioners in the Capital Region of Denmark include a vitamin D status in approximately 20% of all laboratory requisitions. This study intended to examine the effect of a compulsory pop-up form in the electronic request system on the number of vitamin D tests and to monitor the indications. DESIGN: From 1 January 2017, we introduced a compulsory pop-up form in which the general practitioners had to state the indication for measuring vitamin D, choosing from a predefined set of indications. Intervention practitioners were compared with control practitioners before and after the intervention. SETTING: General practices in the Capital Region of Denmark. SUBJECTS: In total, 572 general practitioners and 383,964 patients were included in the period from 1 January 2016 to 31 December 2018. MAIN OUTCOME MEASURES: Number of vitamin D tests and distribution of indications. RESULTS: We observed a drop in number of vitamin D requisitions to 70% (in 2017) and 75% (in 2018) relative to 2016. During the same period, the number of requisitions increased by 33% in a non-intervention group of practitioners. The indication 'Monitoring of treatment with vitamin D' was the most frequently used indication, recorded in 121,475 patients. CONCLUSION: A compulsory pop-up form reduces the number of vitamin D requests from general practitioners by 25%. The implication is that pop-up forms can be used to decrease healthcare costs.

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.

Change in HbA1c concentration as decision parameter for frequency of HbA1c measurement.

Hemoglobin A1c (HbA1c) is a long-term measure for glucose concentration in plasma. Since its introduction as a diabetes monitoring tool, and its more recent application as a diagnostic tool, the number of measurements of HbA1c have risen dramatically. However, HbA1c change is slow, so repeating measurements should not be done too often. We use a large, unfiltered dataset from 52,017 patients to determine the possible rate of change in HbA1c concentration. In our laboratory, the critical difference between HbA1c measurements is 8.5%. Our data show that a 1-unit HbA1c rise takes 4 weeks to occur, hence, at a HbA1c concentration around 50 mmol/mol Hgb, a critically increased HbA1c concentration cannot be determined until after 16 weeks. Conversely a critically lower HbA1c can manifest itself after 2 weeks, but after 7 weeks the dropping tendency stops. The amount of measurements that can be cancelled because they were taken sooner than 16 weeks is 23 percent.

Field note: comparative efficacy of a woody evapotranspiration landfill cover following the removal of aboveground biomass.

Woody vegetation cultivated for moisture management on evapotranspiration (ET) landfill covers could potentially serve a secondary function as a biomass crop. However, research is required to evaluate the extent to which trees could be harvested from ET covers without significantly impacting their moisture management function. This study investigated the drainage through a six-year-old, primarily poplar/cottonwood ET test cover for a period of one year following the harvest of all woody biomass exceeding a height of 30 cm above ground surface. Results were compared to previously reported drainage observed during the years leading up to the coppice event. In the first year following coppice, the ET cover was found to be 93% effective at redirecting moisture during the spring/summer season, and 95% effective during the subsequent fall/winter season. This was slightly lower than the 95% and 100% efficacy observed in the spring/summer and fall/winter seasons, respectively, during the final measured year prior to coppice. However, the post-coppice efficacy was higher than the efficacy observed during the first three years following establishment of the cover. While additional longer-term studies are recommended, this project demonstrated that woody ET covers could potentially produce harvestable biomass while still effectively managing aerial moisture.

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.

Structural features of peptoid-peptide hybrids in lipid-water interfaces.

The inclusion of peptoid monomers into antimicrobial peptides (AMPs) increases their proteolytic resistance, but introduces conformational flexibility (reduced hydrogen bonding ability and cis/trans isomerism). We here use NMR spectroscopy to answer how the insertion of a peptoid monomer influences the structure of a regular α-helical AMP upon interaction with a dodecyl phosphocholine (DPC) micelle. Insertion of [(2-methylpropyl)amino]acetic acid in maculatin-G15 shows that the structural change and conformational flexibility depends on the site of insertion. This is governed by the micelle interaction of the amphipathic helices flanking the peptoid monomer and the side chain properties of the peptoid and its preceding residue.

Synthetic analogs of anoplin show improved antimicrobial activities.

We present the antimicrobial and hemolytic activities of the decapeptide anoplin and 19 analogs thereof tested against methicillin-resistant Staphylococcus aureus ATCC 33591 (MRSA), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), vancomycin-resistant Enterococcus faecium (ATCC 700221) (VRE), and Candida albicans (ATCC 200955). The anoplin analogs contain substitutions in amino acid positions 2, 3, 5, 6, 8, 9, and 10. We use these peptides to study the effect of altering the charge and hydrophobicity of anoplin on activity against red blood cells and microorganisms. We find that increasing the charge and/or hydrophobicity improves antimicrobial activity and increases hemolytic activity. For each strain tested, we identify at least six anoplin analogs with an improved therapeutic index compared with anoplin, the only exception being Enterococcus faecium, against which only few compounds are more specific than anoplin. Both 2Nal(6) and Cha(6) show improved therapeutic index against all strains tested.

Synthesis of antimicrobial peptoids.

Peptoids (N-substituted glycines) are mimics of α-peptides in which the side chains are attached to the backbone N (α) -amide nitrogen instead of the C (α) -atom. Peptoids hold promise as therapeutics since they often retain the biological activity of the parent peptide and are stable to proteases. In recent years, peptoids have attracted attention as new potential antibiotics against multiresistant bacteria. Here we describe the submonomer solid-phase synthesis of an antimicrobial peptoid, H-Nmbn-Nlys-Nlys-Nnap-Nbut-Nmbn-Nlys-NH2.

Assessing the performance of a cold region evapotranspiration landfill cover using lysimetry and electrical resistivity tomography.

In order to test the efficacy ofa cold-region evapotranspiration (ET) landfill cover against a conventional compacted clay (CCL) landfill cover, two pilot scale covers were constructed in side-by-side basin lysimeters (20m x 10m x 2m) at a site in Anchorage, Alaska. The primary basis of comparison between the two lysimeters was the percolation of moisture from the bottom of each lysimeter. Between 30 April 2005 and 16 May 2006, 51.5 mm of water percolated from the ET lysimeter, compared to 50.6 mm for the the CCL lysimeter. This difference was not found to be significant at the 95% confidence level. As part of the project, electrical resistivity tomography (ERT) was utilized to measure and map soil moisture in ET lysimeter cross sections. The ERT-generated cross sections were found to accurately predict the onset and duration of lysimeter percolation. Moreover, ERT-generated soil moisture values demonstrated a strong linear relationship to lysimeter percolation rates (R-Squared = 0.92). Consequently, ERT is proposed as a reliable tool for assessing the function of field scale ET covers in the absence of drainage measurement devices.