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Article ; Online: Thoraxfoto draagt niet bij aan besluit over antibiotica bij kinderen met een luchtweginfectie op de SEH.

Garcia Pérez, Daniella P / van de Maat, Josephine S / Oostenbrink, Rianne

2022 Volume 166

Abstract: The chest x-ray (CXR) was the gold standard in the diagnosis of pneumonia in children. However, CXR has limitations and cannot discriminate in etiology. Current guidelines recommend against routine use of CXR in children with uncomplicated lower ... ...

Title translation	Chest x-rays do not aid in antibiotic treatment decisions for children with lower respiratory infections in the Emergency Department.
Abstract	The chest x-ray (CXR) was the gold standard in the diagnosis of pneumonia in children. However, CXR has limitations and cannot discriminate in etiology. Current guidelines recommend against routine use of CXR in children with uncomplicated lower respiratory tract infections (LRTI). We used routine care data from a multicentre RCT including 597 children with LRTI symptoms, to evaluate the influence of CXR on antibiotic prescription in the emergency department (ED). CXR remains frequently performed in non-complex children suspected of LRTI in the ED (18%). Children who underwent CXR were more likely to receive antibiotics, even when adjusted for symptoms, hospital and CXR results. Our study highlights the inferior role of CXR in treatment decisions for children with LRTI as CXR, regardless of its results, is independently associated with more antibiotic prescriptions.
MeSH term(s)	Anti-Bacterial Agents/therapeutic use ; Child ; Emergency Service, Hospital ; Humans ; Pneumonia/diagnostic imaging ; Pneumonia/drug therapy ; Respiratory Tract Infections/diagnostic imaging ; Respiratory Tract Infections/drug therapy ; X-Rays
Chemical Substances	Anti-Bacterial Agents
Language	Dutch
Publishing date	2022-08-17
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	82073-8
ISSN	1876-8784 ; 0028-2162
ISSN (online)	1876-8784
ISSN	0028-2162
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Article ; Online: Corrigendum: The impact of circadian rhythm on Bacillus Calmette-Guérin vaccination effects on SARS-CoV-2 infections.

Föhse, Konstantin / Taks, Esther J M / Moorlag, Simone J C F M / Bonten, Marc J M / van Crevel, Reinout / Ten Oever, Jaap / van Werkhoven, Cornelis H / Netea, Mihai G / van de Maat, Josephine S / Hoogerwerf, Jacobien J

Frontiers in immunology

2023 Volume 14, Page(s) 1208659

Abstract: This corrects the article DOI: 10.3389/fimmu.2023.980711.]. ...

Abstract	[This corrects the article DOI: 10.3389/fimmu.2023.980711.].
Language	English
Publishing date	2023-05-24
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1208659
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Article ; Online: The impact of circadian rhythm on Bacillus Calmette-Guérin vaccination effects on SARS-CoV-2 infections.

Frontiers in immunology

2023 Volume 14, Page(s) 980711

Abstract: Background and objective: A recent study has suggested that circadian rhythm has an important impact on the immunological effects induced by Bacillus Calmette-Guérin (BCG) vaccination. The objective of this study was to evaluate whether the timing of ... ...

Abstract	Background and objective: A recent study has suggested that circadian rhythm has an important impact on the immunological effects induced by Bacillus Calmette-Guérin (BCG) vaccination. The objective of this study was to evaluate whether the timing of BCG vaccination (morning or afternoon) affects its impact on severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infections and clinically relevant respiratory tract infections (RTIs). Methods: This is a Results: The subdistribution hazard ratio of SARS-CoV-2 infection in the first six months after vaccination was 2.394 (95% confidence interval [CI], 0.856-6.696) for the morning BCG group and 0.284 (95% CI, 0.055-1.480) for the afternoon BCG group. When comparing those two groups, the interaction hazard ratio was 8.966 (95% CI, 1.366-58.836). In the period from six months until 12 months after vaccination cumulative incidences of SARS-CoV-2 infection were comparable, as well as cumulative incidences of clinically relevant RTI in both periods. Conclusion: Vaccination with BCG in the afternoon offered better protection against SARS-CoV-2 infections than BCG vaccination in the morning in the first six months after vaccination.
MeSH term(s)	Aged ; Humans ; Middle Aged ; COVID-19 ; BCG Vaccine ; SARS-CoV-2 ; Circadian Rhythm ; Mycobacterium bovis ; Respiratory Tract Infections ; Vaccination
Chemical Substances	BCG Vaccine
Language	English
Publishing date	2023-02-16
Publishing country	Switzerland
Document type	Randomized Controlled Trial ; Multicenter Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.980711
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Article ; Online: Timing and sequence of vaccination against COVID-19 and influenza - Author's reply.

Dulfer, Elisabeth A / Geckin, Büsra / Taks, Esther J M / GeurtsvanKessel, Corine H / Dijkstra, Helga / van Emst, Liesbeth / van der Gaast-de Jongh, Christa E / Koopmans, Petra C / Domínguez-Andrés, Jorge / van Crevel, Reinout / van de Maat, Josephine S / de Jonge, Marien I / Netea, Mihai G

The Lancet regional health. Europe

2023 Volume 30, Page(s) 100669

Language	English
Publishing date	2023-06-15
Publishing country	England
Document type	Journal Article
ISSN	2666-7762
ISSN (online)	2666-7762
DOI	10.1016/j.lanepe.2023.100669
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Article ; Online: Bacillus Calmette-Guérin vaccine for prevention of COVID-19 and other respiratory tract infections in older adults with comorbidities: a randomized controlled trial.

Koekenbier, Eva L / Fohse, Konstantin / van de Maat, Josephine S / Oosterheert, Jan Jelrik / van Nieuwkoop, Cees / Hoogerwerf, Jacobien J / Grobusch, Martin P / van den Bosch, Maurice A A J / van de Wijgert, Janneke H H / Netea, Mihai G / Rosendaal, Frits R / Bonten, Marc J M / Werkhoven, C H Henri van

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases

2023 Volume 29, Issue 6, Page(s) 781–788

Abstract: Objectives: To test whether Bacillus Calmette-Guérin (BCG) vaccination would reduce the incidence of COVID-19 and other respiratory tract infections (RTIs) in older adults with one or more comorbidities.: Methods: Community-dwelling adults aged 60 ... ...

Abstract	Objectives: To test whether Bacillus Calmette-Guérin (BCG) vaccination would reduce the incidence of COVID-19 and other respiratory tract infections (RTIs) in older adults with one or more comorbidities. Methods: Community-dwelling adults aged 60 years or older with one or more underlying comorbidities and no contraindications to BCG vaccination were randomized 1:1 to BCG or placebo vaccination and followed for 6 months. The primary endpoint was a self-reported, test-confirmed COVID-19 incidence. Secondary endpoints included COVID-19 hospital admissions and clinically relevant RTIs (i.e. RTIs including but not limited to COVID-19 requiring medical intervention). COVID-19 and clinically relevant RTI episodes were adjudicated. Incidences were compared using Fine-Gray regression, accounting for competing events. Results: A total of 6112 participants with a median age of 69 years (interquartile range, 65-74) and median of 2 (interquartile range, 1-3) comorbidities were randomized to BCG (n = 3058) or placebo (n = 3054) vaccination. COVID-19 infections were reported by 129 BCG recipients compared to 115 placebo recipients [hazard ratio (HR), 1.12; 95% CI, 0.87-1.44]. COVID-19-related hospitalization occurred in 18 BCG and 21 placebo recipients (HR, 0.86; 95% CI, 0.46-1.61). During the study period, 13 BCG recipients died compared with 18 placebo recipients (HR, 0.71; 95% CI, 0.35-1.43), of which 11 deaths (35%) were COVID-19-related: six in the placebo group and five in the BCG group. Clinically relevant RTI was reported by 66 BCG and 72 placebo recipients (HR, 0.92; 95% CI, 0.66-1.28). Discussion: BCG vaccination does not protect older adults with comorbidities against COVID-19, COVID-19 hospitalization, or clinically relevant RTIs.
MeSH term(s)	Humans ; Aged ; COVID-19/epidemiology ; COVID-19/prevention & control ; BCG Vaccine ; Vaccination ; Hospitalization ; Incidence
Chemical Substances	BCG Vaccine
Language	English
Publishing date	2023-02-02
Publishing country	England
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	1328418-6
ISSN	1469-0691 ; 1470-9465 ; 1198-743X
ISSN (online)	1469-0691
ISSN	1470-9465 ; 1198-743X
DOI	10.1016/j.cmi.2023.01.019
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Zs.A 4541: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Timing and sequence of vaccination against COVID-19 and influenza (TACTIC): a single-blind, placebo-controlled randomized clinical trial.

Dulfer, Elisabeth A / Geckin, Büsra / Taks, Esther J M / GeurtsvanKessel, Corine H / Dijkstra, Helga / van Emst, Liesbeth / van der Gaast-de Jongh, Christa E / van Mourik, Djenolan / Koopmans, Petra C / Domínguez-Andrés, Jorge / van Crevel, Reinout / van de Maat, Josephine S / de Jonge, Marien I / Netea, Mihai G

The Lancet regional health. Europe

2023 Volume 29, Page(s) 100628

Abstract: Background: Novel mRNA-based vaccines have been used to protect against SARS-CoV-2, especially in vulnerable populations who also receive an annual influenza vaccination. The TACTIC study investigated potential immune interference between the mRNA COVID- ...

Abstract	Background: Novel mRNA-based vaccines have been used to protect against SARS-CoV-2, especially in vulnerable populations who also receive an annual influenza vaccination. The TACTIC study investigated potential immune interference between the mRNA COVID-19 booster vaccine and the quadrivalent influenza vaccine, and determined if concurrent administration would have effects on safety or immunogenicity. Methods: TACTIC was a single-blind, placebo-controlled randomized clinical trial conducted at the Radboud University Medical Centre, the Netherlands. Individuals ≥60 years, fully vaccinated against COVID-19 were eligible for participation and randomized into one of four study groups: 1) 0.5 ml influenza vaccination Vaxigrip Tetra followed by 0.3 ml BNT162b2 COVID-19 booster vaccination 21 days later, (2) COVID-19 booster vaccination followed by influenza vaccination, (3) influenza vaccination concurrent with the COVID-19 booster vaccination, and (4) COVID-19 booster vaccination only (reference group). Primary outcome was the geometric mean concentration (GMC) of IgG against the spike (S)-protein of the SARS-CoV-2 virus, 21 days after booster vaccination. We performed a non-inferiority analysis of concurrent administration compared to booster vaccines alone with a predefined non-inferiority margin of -0.3 on the log10-scale. Findings: 154 individuals participated from October, 4, 2021, until November, 5, 2021. Anti-S IgG GMCs for the co-administration and reference group were 1684 BAU/ml and 2435 BAU/ml, respectively. Concurrent vaccination did not meet the criteria for non-inferiority (estimate -0.1791, 95% CI -0.3680 to -0.009831) and antibodies showed significantly lower neutralization capacity compared to the reference group. Reported side-effects were mild and did not differ between study groups. Interpretation: Concurrent administration of both vaccines is safe, but the quantitative and functional antibody responses were marginally lower compared to booster vaccination alone. Lower protection against COVID-19 with concurrent administration of COVID-19 and influenza vaccination cannot be excluded, although additional larger studies would be required to confirm this. Trial registration number: EudraCT: 2021-002186-17. Funding: The study was supported by the ZonMw COVID-19 Programme.
Language	English
Publishing date	2023-04-12
Publishing country	England
Document type	Journal Article
ISSN	2666-7762
ISSN (online)	2666-7762
DOI	10.1016/j.lanepe.2023.100628
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Article ; Online: The influence of chest X-ray results on antibiotic prescription for childhood pneumonia in the emergency department.

van de Maat, Josephine S / Garcia Perez, Daniella / Driessen, Gertjan J A / van Wermeskerken, Anne-Marie / Smit, Frank J / Noordzij, Jeroen G / Tramper-Stranders, Gerdien / Obihara, Charlie C / Punt, Jeanine / Moll, Henriette A / Oostenbrink, Rianne

European journal of pediatrics

2021 Volume 180, Issue 9, Page(s) 2765–2772

Abstract: The aim of this study is to evaluate the influence of chest X-ray (CXR) results on antibiotic prescription in children suspected of lower respiratory tract infections (RTI) in the emergency department (ED). We performed a secondary analysis of a stepped- ... ...

Abstract	The aim of this study is to evaluate the influence of chest X-ray (CXR) results on antibiotic prescription in children suspected of lower respiratory tract infections (RTI) in the emergency department (ED). We performed a secondary analysis of a stepped-wedge, cluster randomized trial of children aged 1 month to 5 years with fever and cough/dyspnoea in 8 EDs in the Netherlands (2016-2018), including a 1-week follow-up. We analysed the observational data of the pre-intervention period, using multivariable logistic regression to evaluate the influence of CXR result on antibiotic prescription. We included 597 children (median age 17 months [IQR 9-30, 61% male). CXR was performed in 109/597 (18%) of children (range across hospitals 9 to 50%); 52/109 (48%) showed focal infiltrates. Children who underwent CXR were more likely to receive antibiotics, also when adjusted for clinical signs and symptoms, hospital and CXR result (OR 7.25 [95% CI 2.48-21.2]). Abnormalities on CXR were not significantly associated with antibiotic prescription.Conclusion: Performance of CXR was independently associated with more antibiotic prescription, regardless of its results. The limited influence of CXR results on antibiotic prescription highlights the inferior role of CXR on treatment decisions for suspected lower RTI in the ED. What is Known: • Chest X-ray (CXR) has a high inter-observer variability and cannot distinguish between bacterial or viral pneumonia. • Current guidelines recommend against routine use of CXR in children with uncomplicated respiratory tract infections (RTIs) in the outpatient setting. What is New: • CXR is still frequently performed in non-complex children suspected of lower RTIs in the emergency department • CXR performance was independently associated with more antibiotic prescriptions, regardless of its results, highlighting the inferior role of chest X-rays in treatment decisions.
MeSH term(s)	Anti-Bacterial Agents/therapeutic use ; Child, Preschool ; Drug Prescriptions ; Emergency Service, Hospital ; Female ; Humans ; Infant ; Male ; Pneumonia/diagnostic imaging ; Pneumonia/drug therapy ; X-Rays
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2021-03-22
Publishing country	Germany
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	194196-3
ISSN	1432-1076 ; 0340-6199 ; 0943-9676
ISSN (online)	1432-1076
ISSN	0340-6199 ; 0943-9676
DOI	10.1007/s00431-021-03996-2
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Article ; Online: Few bacterial co-infections but frequent empiric antibiotic use in the early phase of hospitalized patients with COVID-19: results from a multicentre retrospective cohort study in The Netherlands.

Karami, Zara / Knoop, Bram T / Dofferhoff, Anton S M / Blaauw, Marc J T / Janssen, Nico A / van Apeldoorn, Marjan / Kerckhoffs, Angèle P M / van de Maat, Josephine S / Hoogerwerf, Jacobien J / Ten Oever, Jaap

Infectious diseases (London, England)

2020 Volume 53, Issue 2, Page(s) 102–110

Abstract: Background: Knowledge on bacterial co-infections in COVID-19 is crucial to use antibiotics appropriately. Therefore, we aimed to determine the incidence of bacterial co-infections, antibiotic use and application of antimicrobial stewardship principles ... ...

Abstract	Background: Knowledge on bacterial co-infections in COVID-19 is crucial to use antibiotics appropriately. Therefore, we aimed to determine the incidence of bacterial co-infections, antibiotic use and application of antimicrobial stewardship principles in hospitalized patients with COVID-19. Methods: We performed a retrospective observational study in four hospitals (1 university, 2 non-university teaching, 1 non-teaching hospital) in the Netherlands from March to May 2020 including consecutive patients with PCR-confirmed COVID-19. Data on first microbiological investigations obtained at the discretion of the physician and antibiotic use in the first week of hospital admission were collected. Results: Twelve (1.2%) of the 925 patients included had a documented bacterial co-infection (75.0% pneumonia) within the first week. Microbiological testing was performed in 749 (81%) patients: sputum cultures in 105 (11.4%), blood cultures in 711 (76.9%), pneumococcal urinary antigen testing in 202 (21.8%), and Conclusions: On presentation to the hospital bacterial co-infections are rare, while empiric antibiotic use is abundant. This implies that in patients with COVID-19 empiric antibiotic should be withheld. This has the potential to dramatically reduce the current overuse of antibiotics in the COVID-19 pandemic.
MeSH term(s)	Aged ; Anti-Bacterial Agents/administration & dosage ; Antimicrobial Stewardship ; Bacterial Infections/drug therapy ; Bacterial Infections/epidemiology ; Bacterial Infections/microbiology ; Blood Culture ; COVID-19/epidemiology ; COVID-19/virology ; Coinfection ; Drug Administration Routes ; Drug Administration Schedule ; Female ; Guideline Adherence/statistics & numerical data ; Hospitalization ; Humans ; Incidence ; Male ; Middle Aged ; Netherlands/epidemiology ; Pandemics ; Prescription Drug Overuse/prevention & control ; Prescription Drug Overuse/statistics & numerical data ; Retrospective Studies ; SARS-CoV-2/pathogenicity
Chemical Substances	Anti-Bacterial Agents
Keywords	covid19
Language	English
Publishing date	2020-10-24
Publishing country	England
Document type	Journal Article ; Multicenter Study ; Observational Study
ZDB-ID	2839775-7
ISSN	2374-4243 ; 2374-4235
ISSN (online)	2374-4243
ISSN	2374-4235
DOI	10.1080/23744235.2020.1839672
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Article ; Online: Risk factors for in-hospital mortality in laboratory-confirmed COVID-19 patients in the Netherlands: A competing risk survival analysis.

Nijman, Gerine / Wientjes, Maike / Ramjith, Jordache / Janssen, Nico / Hoogerwerf, Jacobien / Abbink, Evertine / Blaauw, Marc / Dofferhoff, Ton / van Apeldoorn, Marjan / Veerman, Karin / de Mast, Quirijn / Ten Oever, Jaap / Hoefsloot, Wouter / Reijers, Monique H / van Crevel, Reinout / van de Maat, Josephine S

PloS one

2021 Volume 16, Issue 3, Page(s) e0249231

Abstract: Background: To date, survival data on risk factors for COVID-19 mortality in western Europe is limited, and none of the published survival studies have used a competing risk approach. This study aims to identify risk factors for in-hospital mortality in ...

Abstract	Background: To date, survival data on risk factors for COVID-19 mortality in western Europe is limited, and none of the published survival studies have used a competing risk approach. This study aims to identify risk factors for in-hospital mortality in COVID-19 patients in the Netherlands, considering recovery as a competing risk. Methods: In this observational multicenter cohort study we included adults with PCR-confirmed SARS-CoV-2 infection that were admitted to one of five hospitals in the Netherlands (March to May 2020). We performed a competing risk survival analysis, presenting cause-specific hazard ratios (HRCS) for the effect of preselected factors on the absolute risk of death and recovery. Results: 1,006 patients were included (63.9% male; median age 69 years, IQR: 58-77). Patients were hospitalized for a median duration of 6 days (IQR: 3-13); 243 (24.6%) of them died, 689 (69.9%) recovered, and 74 (7.4%) were censored. Patients with higher age (HRCS 1.10, 95% CI 1.08-1.12), immunocompromised state (HRCS 1.46, 95% CI 1.08-1.98), who used anticoagulants or antiplatelet medication (HRCS 1.38, 95% CI 1.01-1.88), with higher modified early warning score (MEWS) (HRCS 1.09, 95% CI 1.01-1.18), and higher blood LDH at time of admission (HRCS 6.68, 95% CI 1.95-22.8) had increased risk of death, whereas fever (HRCS 0.70, 95% CI 0.52-0.95) decreased risk of death. We found no increased mortality risk in male patients, high BMI or diabetes. Conclusion: Our competing risk survival analysis confirms specific risk factors for COVID-19 mortality in a the Netherlands, which can be used for prediction research, more intense in-hospital monitoring or prioritizing particular patients for new treatments or vaccination.
MeSH term(s)	Aged ; Anticoagulants/therapeutic use ; Body Mass Index ; COVID-19/diagnosis ; COVID-19/mortality ; COVID-19/virology ; Cohort Studies ; Diabetes Complications ; Female ; Hospital Mortality ; Humans ; Immunocompromised Host ; L-Lactate Dehydrogenase/biosynthesis ; Length of Stay ; Male ; Middle Aged ; Netherlands ; Proportional Hazards Models ; RNA, Viral/analysis ; Risk Factors ; SARS-CoV-2/genetics ; SARS-CoV-2/isolation & purification ; Survival Analysis
Chemical Substances	Anticoagulants ; RNA, Viral ; L-Lactate Dehydrogenase (EC 1.1.1.27)
Language	English
Publishing date	2021-03-26
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0249231
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Article ; Online: Evaluation of a clinical decision rule to guide antibiotic prescription in children with suspected lower respiratory tract infection in The Netherlands: A stepped-wedge cluster randomised trial.

van de Maat, Josephine S / Peeters, Daphne / Nieboer, Daan / van Wermeskerken, Anne-Marie / Smit, Frank J / Noordzij, Jeroen G / Tramper-Stranders, Gerdien / Driessen, Gertjan J A / Obihara, Charlie C / Punt, Jeanine / van der Lei, Johan / Polinder, Suzanne / Moll, Henriette A / Oostenbrink, Rianne

PLoS medicine

2020 Volume 17, Issue 1, Page(s) e1003034

Abstract: Background: Optimising the use of antibiotics is a key component of antibiotic stewardship. Respiratory tract infections (RTIs) are the most common reason for antibiotic prescription in children, even though most of these infections in children under 5 ... ...

Abstract	Background: Optimising the use of antibiotics is a key component of antibiotic stewardship. Respiratory tract infections (RTIs) are the most common reason for antibiotic prescription in children, even though most of these infections in children under 5 years are viral. This study aims to safely reduce antibiotic prescriptions in children under 5 years with suspected lower RTI at the emergency department (ED), by implementing a clinical decision rule. Methods and findings: In a stepped-wedge cluster randomised trial, we included children aged 1-60 months presenting with fever and cough or dyspnoea to 8 EDs in The Netherlands. The EDs were of varying sizes, from diverse geographic and demographic regions, and of different hospital types (tertiary versus general). In the pre-intervention phase, children received usual care, according to the Dutch and NICE guidelines for febrile children. During the intervention phase, a validated clinical prediction model (Feverkidstool) including clinical characteristics and C-reactive protein (CRP) was implemented as a decision rule guiding antibiotic prescription. The intervention was that antibiotics were withheld in children with a low or intermediate predicted risk of bacterial pneumonia (≤10%, based on Feverkidstool). Co-primary outcomes were antibiotic prescription rate and strategy failure. Strategy failure was defined as secondary antibiotic prescriptions or hospitalisations, persistence of fever or oxygen dependency up to day 7, or complications. Hospitals were randomly allocated to 1 sequence of treatment each, using computer randomisation. The trial could not be blinded. We used multilevel logistic regression to estimate the effect of the intervention, clustered by hospital and adjusted for time period, age, sex, season, ill appearance, and fever duration; predicted risk was included in exploratory analysis. We included 999 children (61% male, median age 17 months [IQR 9 to 30]) between 1 January 2016 and 30 September 2018: 597 during the pre-intervention phase and 402 during the intervention phase. Most children (77%) were referred by a general practitioner, and half of children were hospitalised. Intention-to-treat analyses showed that overall antibiotic prescription was not reduced (30% to 25%, adjusted odds ratio [aOR] 1.07 [95% CI 0.57 to 2.01, p = 0.75]); strategy failure reduced from 23% to 16% (aOR 0.53 [95% CI 0.32 to 0.88, p = 0.01]). Exploratory analyses showed that the intervention influenced risk groups differently (p < 0.01), resulting in a reduction in antibiotic prescriptions in low/intermediate-risk children (17% to 6%; aOR 0.31 [95% CI 0.12 to 0.81, p = 0.02]) and a non-significant increase in the high-risk group (47% to 59%; aOR 2.28 [95% CI 0.84 to 6.17, p = 0.09]). Two complications occurred during the trial: 1 admission to the intensive care unit during follow-up and 1 pleural empyema at day 10 (both unrelated to the study intervention). Main limitations of the study were missing CRP values in the pre-intervention phase and a prolonged baseline period due to logistical issues, potentially affecting the power of our study. Conclusions: In this multicentre ED study, we observed that a clinical decision rule for childhood pneumonia did not reduce overall antibiotic prescription, but that it was non-inferior to usual care. Exploratory analyses showed fewer strategy failures and that fewer antibiotics were prescribed in low/intermediate-risk children, suggesting improved targeting of antibiotics by the decision rule. Trial registration: Netherlands Trial Register NTR5326.
MeSH term(s)	Anti-Bacterial Agents/standards ; Anti-Bacterial Agents/therapeutic use ; Antimicrobial Stewardship/methods ; Antimicrobial Stewardship/standards ; Child, Preschool ; Clinical Decision Rules ; Cluster Analysis ; Drug Prescriptions/standards ; Female ; Humans ; Infant ; Male ; Netherlands/epidemiology ; Respiratory Tract Infections/diagnosis ; Respiratory Tract Infections/drug therapy ; Respiratory Tract Infections/epidemiology
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2020-01-31
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2185925-5
ISSN	1549-1676 ; 1549-1277
ISSN (online)	1549-1676
ISSN	1549-1277
DOI	10.1371/journal.pmed.1003034
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