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2. The Feasibility of C-Reactive Protein Point-of-Care Testing to Reduce Overuse of Antibiotics in Children with Acute Respiratory Tract Infections in Rural Kyrgyzstan: A Pilot Study

Author

Isaeva E, Akylbekov A, Bloch J, Poulsen A, Kurtzhals J, Siersma V, Sooronbaev T, Aabenhus RM, and Kjærgaard J

Subjects
paediatrics, family medicine, respiratory medicine, c-reactive protein, feasibility, Pediatrics, RJ1-570
Abstract

Elvira Isaeva,1 Azamat Akylbekov,2 Joakim Bloch,3 Anja Poulsen,3 Jørgen Kurtzhals,4,5 Volkert Siersma,6 Talant Sooronbaev,2 Rune Munck Aabenhus,6 Jesper Kjærgaard3 1Allergology Department, National Centre of Maternity and Childhood Care (NCMCC), Bishkek, Kyrgyzstan; 2Pulmonology Department, National Centre of Cardiology and Internal Medicine Named After Academician M. Mirrakhimov, Bishkek, Kyrgyzstan; 3Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 4Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 5Centre for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark; 6Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen, DenmarkCorrespondence: Elvira Isaeva, Allergology Department, National Centre of Maternity and Childhood Care (NCMCC), Postal Address: 720038, 190, Akhunbaev St, Bishkek, Kyrgyzstan, Tel +996 (709) 795 979, Email rhc358@sund.ku.dkBackground: In Kyrgyzstan, the morbidity prevalence of and morbidity from acute respiratory tract infections (ARTI) in children is high. Local healthcare workers (HCW) often prescribe antibiotics that are not indicative due to a mix of professional and societal factors. It is suggested to precede with a decision on antibiotics by a point-of-care test (POCT) on the appropriateness of the treatment, eg, a measurement of C-reactive protein (CRP). CRP-guided antibiotic stewardship in children with ARTI has not previously been studied in Central Asia.Purpose: This pilot study was conducted to examine the feasibility of the methods and procedures to be used in the upcoming randomised controlled COORDINATE clinical trial (NCT05195866) and in daily clinical practice in primary care.Patients and methods: HCWs from three selected rural healthcare facilities were trained in the CRP POCT and in interpretation of results. Children aged 6 months to 12 years attending the primary healthcare facilities with respiratory symptoms were randomly assigned to CRP-guided management or standard care, guided by clinical findings only. Children were followed up for 14 days by scheduled telephone calls to caregivers.Results: Eighty-one children participated in this pilot study. The CRP POCT and the trial procedures were acceptable to the target group as well as to the HCWs. Children from both groups recovered equally well, with an observed significant lower use of antibiotics in the CRP group. HCWs generally adhered to the CRP guidelines, and only once was an antibiotic prescribed despite low CRP results. No safety concerns were observed. Four parents provided wrong phone numbers impeding follow-up. We will collect all mobile phone numbers in the household for the main trial.Conclusion: The pilot provided satisfactory results, suggesting that the COORDINATE trial of CRP POCT is effective, feasible with minor adjustments and without apparent safety concerns for the participants.Keywords: paediatrics, family medicine, respiratory medicine, C-reactive protein, feasibility

Published
2024

8. Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock

Author

Møller, J. E., Engstrøm, T., Jensen, L. O., Eiskjær, H., Mangner, N., Polzin, A., Schulze, P. C., Skurk, C., Nordbeck, P., Clemmensen, P., Panoulas, V., Zimmer, S., Schäfer, A., Werner, N., Frydland, M., Holmvang, L., Kjærgaard, J., Sørensen, R., Lønborg, J., Lindholm, M. G., Udesen, N. L.J., Junker, A., Schmidt, H., Terkelsen, C. J., Christensen, S., Christiansen, E. H., Linke, A., Woitek, F. J., Westenfeld, R., Möbius-Winkler, S., Wachtell, K., Ravn, H. B., Lassen, J. F., Boesgaard, S., Gerke, O., Hassager, C., Møller, J. E., Engstrøm, T., Jensen, L. O., Eiskjær, H., Mangner, N., Polzin, A., Schulze, P. C., Skurk, C., Nordbeck, P., Clemmensen, P., Panoulas, V., Zimmer, S., Schäfer, A., Werner, N., Frydland, M., Holmvang, L., Kjærgaard, J., Sørensen, R., Lønborg, J., Lindholm, M. G., Udesen, N. L.J., Junker, A., Schmidt, H., Terkelsen, C. J., Christensen, S., Christiansen, E. H., Linke, A., Woitek, F. J., Westenfeld, R., Möbius-Winkler, S., Wachtell, K., Ravn, H. B., Lassen, J. F., Boesgaard, S., Gerke, O., and Hassager, C.

Abstract

BACKGROUND The effects of temporary mechanical circulatory support with a microaxial flow pump on mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock remains unclear. METHODS In an international, multicenter, randomized trial, we assigned patients with STEMI and cardiogenic shock to receive a microaxial flow pump (Impella CP) plus standard care or standard care alone. The primary end point was death from any cause at 180 days. A composite safety end point was severe bleeding, limb ischemia, hemolysis, device failure, or worsening aortic regurgitation. RESULTS A total of 360 patients underwent randomization, of whom 355 were included in the final analysis (179 in the microaxial-flow-pump group and 176 in the standard-care group). The median age of the patients was 67 years, and 79.2% were men. Death from any cause occurred in 82 of 179 patients (45.8%) in the microaxial-flow-pump group and in 103 of 176 patients (58.5%) in the standard-care group (hazard ratio, 0.74; 95% confidence interval [CI], 0.55 to 0.99; P=0.04). A composite safety end-point event occurred in 43 patients (24.0%) in the microaxial-flow-pump group and in 11 (6.2%) in the standard-care group (relative risk, 4.74; 95% CI, 2.36 to 9.55). Renal-replacement therapy was administered to 75 patients (41.9%) in the microaxial-flow-pump group and to 47 patients (26.7%) in the standard-care group (relative risk, 1.98; 95% CI, 1.27 to 3.09). CONCLUSIONS The routine use of a microaxial flow pump with standard care in the treatment of patients with STEMI-related cardiogenic shock led to a lower risk of death from any cause at 180 days than standard care alone. The incidence of a composite of adverse events was higher with the use of the microaxial flow pump. (Funded by the Danish Heart Foundation and Abiomed; DanGer Shock ClinicalTrials.gov number, NCT01633502.), background The effects of temporary mechanical circulatory support with a microaxial flow pump on mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock remains unclear. METHODS In an international, multicenter, randomized trial, we assigned patients with STEMI and cardiogenic shock to receive a microaxial flow pump (Impella CP) plus standard care or standard care alone. The primary end point was death from any cause at 180 days. A composite safety end point was severe bleeding, limb ischemia, hemolysis, device failure, or worsening aortic regurgitation. RESULTS A total of 360 patients underwent randomization, of whom 355 were included in the final analysis (179 in the microaxial-flow-pump group and 176 in the standard-care group). The median age of the patients was 67 years, and 79.2% were men. Death from any cause occurred in 82 of 179 patients (45.8%) in the microaxial-flow-pump group and in 103 of 176 patients (58.5%) in the standard-care group (hazard ratio, 0.74; 95% confidence interval [CI], 0.55 to 0.99; P=0.04). A composite safety end-point event occurred in 43 patients (24.0%) in the microaxial-flow-pump group and in 11 (6.2%) in the standard-care group (relative risk, 4.74; 95% CI, 2.36 to 9.55). Renal-replacement therapy was administered to 75 patients (41.9%) in the microaxial-flow-pump group and to 47 patients (26.7%) in the standard-care group (relative risk, 1.98; 95% CI, 1.27 to 3.09). CONCLUSIONS The routine use of a microaxial flow pump with standard care in the treatment of patients with STEMI-related cardiogenic shock led to a lower risk of death from any cause at 180 days than standard care alone. The incidence of a composite of adverse events was higher with the use of the microaxial flow pump. (Funded by the Danish Heart Foundation and Abiomed; DanGer Shock ClinicalTrials.gov number, NCT01633502.)

Published
2024

12. Long-term survival and return to work after refractory out-of-hospital cardiac arrest managed with extracorporeal cardiopul-monary resuscitation; a nationwide follow-up study

Author

Gregers, E, Kragholm, K, Moerk, S R, Linde, L, Boending, J A, Terkelsen, C J, Lassen, J F, Moeller, J E, Laugesen, H, Smerup, M, Kjaergaard, J, Moeller-soerensen, P H, Holmvang, L, Hassager, C, Soeholm, H, Gregers, E, Kragholm, K, Moerk, S R, Linde, L, Boending, J A, Terkelsen, C J, Lassen, J F, Moeller, J E, Laugesen, H, Smerup, M, Kjaergaard, J, Moeller-soerensen, P H, Holmvang, L, Hassager, C, and Soeholm, H

Abstract

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Rigshospitalets and Odense Universitetshospitals common foundation Background Survival after refractory out-of-hospital cardiac arrest (OHCA) is low. Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used for selected patients aiming to increase survival after refractory OHCA. However, ECPR is resource heavy and carries risk of poor functional status. Previous studies have shown favorable neurological outcome in the majority of survivors of OHCA managed with ECPR; yet the share of patients able to return to work has not previously been explored. Purpose The purpose of this study is to investigate the fraction of patients returning to work after OHCA managed with ECPR in a national cohort of refractory OHCA-patients. Methods Of about 44,000 OHCAs during the period of 2011-2020, this nationwide registry-based study included 812 refractory OHCA-patients in the working age between 18 years and 65 years (as 65 was the current age of retirement) who were in employment prior to the event. We excluded 113 ECPR-patients and 3,536 refractory OHCA-patients managed with standard advanced cardiac life support (sACLS) due to age or unemployment. We defined refractory OHCA as patients with OHCA brought to hospital with on-going CPR. Information on demographics, OHCA circumstances, status at hospital arrival, and survival were retrieved through the Danish Cardiac Arrest Register. Employment status were retrieved through the Danish Research Institute for Economic Analysis and Modelling database. Maintenance of work was defined as return to work without any sick leave relapse (>4 weeks) during six months of employment. Results Of 812 included refractory OHCA-patients, 137 patients received ECPR while 675 were managed with sACLS. ECPR-patients were slightly younger than sACLS-patients (median 51 vs. 53 years), a higher perce

Published
2023

15. Long-term survival and return to work after refractory out-of-hospital cardiac arrest managed with extracorporeal cardiopul-monary resuscitation; a nationwide follow-up study

Author

Gregers, E, primary, Kragholm, K, additional, Moerk, S R, additional, Linde, L, additional, Boending, J A, additional, Terkelsen, C J, additional, Lassen, J F, additional, Moeller, J E, additional, Laugesen, H, additional, Smerup, M, additional, Kjaergaard, J, additional, Moeller-Soerensen, P H, additional, Holmvang, L, additional, Hassager, C, additional, and Soeholm, H, additional

Published
2023
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16. Low-dose dobutamine infusion and single-dose tocilizumab in acute myocardial infarction patients with high risk of cardiogenic shock development - rationale and design of the DOBERMANN trial

Author

Bo Kunkel, J, primary, Frydland, M, additional, Duus Holle, S, additional, Kjaergaard, J, additional, Pecini, R, additional, Evi Bang, L, additional, Palm, P, additional, Wiberg, S, additional, Holmvang, L, additional, Engstroem, T, additional, Loenborg, J, additional, Eifer Moeller, J, additional, Hartvig Thomsen, J, additional, Hassager, C, additional, and Soeholm, H, additional

Published
2023
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23. Centralisation of post-resuscitation care after out-of-hospital cardiac arrest at heart centres - a nationwide follow-up study

Author

Rasalingam Mork, S, primary, Gregers, E, additional, Kragholm, K, additional, Kjaergaard, J, additional, Folke, F, additional, Torp-Pedersen, C, additional, Kober, L, additional, Boas Soja, A M, additional, Juhl Terkelsen, C, additional, Michalik, F, additional, Eifer Moller, J, additional, Lund Henriksen, F, additional, Bundgaard Ringgren, K, additional, Hassager, C, additional, and Soholm, H, additional

Published
2023
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29. External validation of the simple NULL-PLEASE clinical score in predicting outcomes in men and women with out-of-hospital cardiac arrest

Author

Byrne, C, primary, Barcella, C, additional, Krogager, M L, additional, Pareek, M, additional, Ringgren, K B, additional, Wissenberg, M, additional, Folke, F, additional, Gislason, G, additional, Kober, L, additional, Lippert, F, additional, Kjaergaard, J, additional, Hassager, C, additional, Torp-Pedersen, C, additional, Lip, G Y H, additional, and Kragholm, K, additional

Published
2022
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30. Selection of patients for mechanical circulatory support for refractory out-of-hospital cardiac arrest: a Danish nationwide multicenter study

Author

Linde, L, primary, Moerk, S R, additional, Gregers, E, additional, Andreasen, J B, additional, Lassen, J F, additional, Ravn, H B, additional, Schmidt, H, additional, Riber, L P, additional, Laugesen, H, additional, Terkelsen, C J, additional, Moeller-Soerensen, P H, additional, Holmvang, L, additional, Kjaergaard, J, additional, Hassager, C, additional, and Moeller, J E, additional

Published
2022
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34. Extracorporeal cardiopulmonary resuscitation: a national study on the association between survival and biomarkers of hypoperfusion, inflammation, and organ failure

Author

Gregers, E, primary, Moerk, S R, additional, Linde, L, additional, Andreasen, J B, additional, Smerup, M, additional, Kjaergaard, J, additional, Moeller-Soerensen, P H, additional, Holmvang, L, additional, Christensen, S, additional, Terkelsen, C J, additional, Moeller, J E, additional, Lassen, J F, additional, Rieber, L P, additional, Laugesen, H, additional, and Soeholm, H, additional

Published
2022
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38. Untargeted toxicology in sudden cardiac arrest victims

Author

Stampe, NK, primary, Glinge, C, additional, Rasmussen, BS, additional, Bhardwaj, P, additional, Linnet, K, additional, Jabbari, R, additional, Hassager, C, additional, Kjaergaard, J, additional, Tfelt-Hansen, J, additional, and Winkel, BG, additional

Published
2022
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44. Mechanical circulatory support for refractory out-of-hospital cardiac arrest: a nationwide multicentre study

Author

Moerk, S R, primary, Stengaard, C, additional, Linde, L, additional, Moller, J E, additional, Andreasen, J B, additional, Laugesen, H, additional, Thomassen, S A, additional, Freeman, P M, additional, Christensen, S, additional, Tang, M, additional, Gregers, E, additional, Kjaergaard, J, additional, Hassager, C, additional, Eiskjaer, H, additional, and Terkelsen, C J, additional

Published
2021
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47. ASsociation of the apolipoprotein M and sphingosine-1-phosphate complex with brown adipose tissue after cold exposure in humans

Author

Borup, A., primary, Donkin, I., additional, Boon, M.R., additional, Frydland, M., additional, Martinez-Tellez, B., additional, Loft, A., additional, Keller, S.H., additional, Kjaer, A., additional, Kjaergaard, J., additional, Hassager, C., additional, Barres, R., additional, Rensen, P.C.N., additional, and Christoffersen, C., additional

Published
2021
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48. Oxygen Targets in Comatose Survivors of Cardiac Arrest.

Author

Schmidt, H., Kjaergaard, J., Hassager, C., Mølstrøm, S., Grand, J., Borregaard, B., Obling, L. E. Roelsgaard, Venø, S., Sarkisian, L., Mamaev, D., Jensen, L. O., Nyholm, B., Høfsten, D. E., Josiassen, J., Thomsen, J. H., Thune, J. J., Lindholm, M. G., Meyer, M. A. Stengaard, Winther-Jensen, M., and Sørensen, M.

Subjects
*ENZYME analysis, *RESEARCH, *RESPIRATORY insufficiency, *OXYGEN, *RESEARCH methodology, *EVALUATION research, *ARTIFICIAL respiration, *COMPARATIVE studies, *RANDOMIZED controlled trials, *RESEARCH funding, *COMA
Abstract

Background: The appropriate oxygenation target for mechanical ventilation in comatose survivors of out-of-hospital cardiac arrest is unknown.Methods: In this randomized trial with a 2-by-2 factorial design, we randomly assigned comatose adults with out-of-hospital cardiac arrest in a 1:1 ratio to either a restrictive oxygen target of a partial pressure of arterial oxygen (Pao2) of 9 to 10 kPa (68 to 75 mm Hg) or a liberal oxygen target of a Pao2 of 13 to 14 kPa (98 to 105 mm Hg); patients were also assigned to one of two blood-pressure targets (reported separately). The primary outcome was a composite of death from any cause or hospital discharge with severe disability or coma (Cerebral Performance Category [CPC] of 3 or 4; categories range from 1 to 5, with higher values indicating more severe disability), whichever occurred first within 90 days after randomization. Secondary outcomes were neuron-specific enolase levels at 48 hours, death from any cause, the score on the Montreal Cognitive Assessment (ranging from 0 to 30, with higher scores indicating better cognitive ability), the score on the modified Rankin scale (ranging from 0 to 6, with higher scores indicating greater disability), and the CPC at 90 days.Results: A total of 789 patients underwent randomization. A primary-outcome event occurred in 126 of 394 patients (32.0%) in the restrictive-target group and in 134 of 395 patients (33.9%) in the liberal-target group (hazard ratio, 0.95; 95% confidence interval, 0.75 to 1.21; P = 0.69). At 90 days, death had occurred in 113 patients (28.7%) in the restrictive-target group and in 123 (31.1%) in the liberal-target group. On the CPC, the median category was 1 in the two groups; on the modified Rankin scale, the median score was 2 in the restrictive-target group and 1 in the liberal-target group; and on the Montreal Cognitive Assessment, the median score was 27 in the two groups. At 48 hours, the median neuron-specific enolase level was 17 μg per liter in the restrictive-target group and 18 μg per liter in the liberal-target group. The incidence of adverse events was similar in the two groups.Conclusions: Targeting of a restrictive or liberal oxygenation strategy in comatose patients after resuscitation for cardiac arrest resulted in a similar incidence of death or severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.). [ABSTRACT FROM AUTHOR]

Published
2022
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49. Blood-Pressure Targets in Comatose Survivors of Cardiac Arrest.

Author

Kjaergaard, J., Møller, J. E., Schmidt, H., Grand, J., Mølstrøm, S., Borregaard, B., Venø, S., Sarkisian, L., Mamaev, D., Jensen, L. O., Nyholm, B., Høfsten, D. E., Josiassen, J., Thomsen, J. H., Thune, J. J., Obling, L. E. R., Lindholm, M. G., Frydland, M., Meyer, M. A. S., and Winther-Jensen, M.

Subjects
*ENZYME analysis, *CARDIOPULMONARY resuscitation, *RESEARCH, *OXYGEN, *RESEARCH methodology, *ARTERIAL pressure, *HEALTH status indicators, *EVALUATION research, *COMPARATIVE studies, *RANDOMIZED controlled trials, *BLIND experiment, *CRITICAL care medicine, *RESEARCH funding, *COMA
Abstract

Background: Evidence to support the choice of blood-pressure targets for the treatment of comatose survivors of out-of-hospital cardiac arrest who are receiving intensive care is limited.Methods: In a double-blind, randomized trial with a 2-by-2 factorial design, we evaluated a mean arterial blood-pressure target of 63 mm Hg as compared with 77 mm Hg in comatose adults who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause; patients were also assigned to one of two oxygen targets (reported separately). The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category (CPC) of 3 or 4 within 90 days (range, 0 to 5, with higher categories indicating more severe disability; a category of 3 or 4 indicates severe disability or coma). Secondary outcomes included neuron-specific enolase levels at 48 hours, death from any cause, scores on the Montreal Cognitive Assessment (range, 0 to 30, with higher scores indicating better cognitive ability) and the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at 3 months, and the CPC at 3 months.Results: A total of 789 patients were included in the analysis (393 in the high-target group and 396 in the low-target group). A primary-outcome event occurred in 133 patients (34%) in the high-target group and in 127 patients (32%) in the low-target group (hazard ratio, 1.08; 95% confidence interval [CI], 0.84 to 1.37; P = 0.56). At 90 days, 122 patients (31%) in the high-target group and 114 patients (29%) in the low-target group had died (hazard ratio, 1.13; 95% CI, 0.88 to 1.46). The median CPC was 1 (interquartile range, 1 to 5) in both the high-target group and the low-target group; the corresponding median modified Rankin scale scores were 1 (interquartile range, 0 to 6) and 1 (interquartile range, 0 to 6), and the corresponding median Montreal Cognitive Assessment scores were 27 (interquartile range, 24 to 29) and 26 (interquartile range, 24 to 29). The median neuron-specific enolase level at 48 hours was also similar in the two groups. The percentages of patients with adverse events did not differ significantly between the groups.Conclusions: Targeting a mean arterial blood pressure of 77 mm Hg or 63 mm Hg in patients who had been resuscitated from cardiac arrest did not result in significantly different percentages of patients dying or having severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.). [ABSTRACT FROM AUTHOR]

Published
2022
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