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Gambadauro A, Mollica S, Rosa E, Xerra F, Li Pomi A, Valenzise M, Messina MF, Vitale A, Gitto E, Wasniewska M, Zirilli G, Manti S. Bronchiolitis Severity Affects Blood Count and Inflammatory Marker Levels: A Real-Life Experience. Viruses 2025; 17:77. [PMID: 39861866 PMCID: PMC11769181 DOI: 10.3390/v17010077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 01/03/2025] [Accepted: 01/07/2025] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND Bronchiolitis is the most common cause of lower respiratory tract infection (LRTI) in the first year of life. We analyzed the association between complete blood count (CBC), c-reactive protein (CRP), and novel inflammatory indexes (NLR, PLR, MLR, ELR, LMR, NPR, LPR, LNR, PNR, SII, SIRI) in predicting bronchiolitis severity at hospital admission. METHODS We retrospectively collected data from 95 infants hospitalized for bronchiolitis in a third-level hospital during three epidemic seasons. Five outcomes of severity were analyzed: BRAS; pediatric intensive care unit (PICU) admission; ventilatory support; intravenous (IV) rehydration; and length of stay (LOS). RESULTS Lower age and weight at admission were statistically associated with four of the five severity outcomes. Prolonged LOS (≥6 days) was associated with high values of total white blood cells, lymphocytes, and eosinophils. Only three inflammatory indexes (PLR, MLR, and PNR) showed a significant association with one outcome (prolonged LOS). A new index (RBC/AiW/1000) was statistically associated with each severity outcome for a value > 350. CONCLUSIONS We proposed a comprehensive analysis of the association between CBC, CRP, and novel inflammatory indexes and bronchiolitis severity. RBC/AiW/1000 could represent a future predictive marker of disease severity at hospital admission in infants with bronchiolitis.
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Affiliation(s)
- Antonella Gambadauro
- Pediatric Unit, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy; (S.M.); (F.X.); (M.V.); (M.F.M.); (A.V.); (M.W.); (G.Z.); (S.M.)
| | - Salvatore Mollica
- Pediatric Unit, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy; (S.M.); (F.X.); (M.V.); (M.F.M.); (A.V.); (M.W.); (G.Z.); (S.M.)
| | - Emanuela Rosa
- Faculty of Medicine and Surgery, University of Messina, Piazza Pugliatti 1, 98122 Messina, Italy;
| | - Federica Xerra
- Pediatric Unit, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy; (S.M.); (F.X.); (M.V.); (M.F.M.); (A.V.); (M.W.); (G.Z.); (S.M.)
| | - Alessandra Li Pomi
- Pediatric Unit, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy; (S.M.); (F.X.); (M.V.); (M.F.M.); (A.V.); (M.W.); (G.Z.); (S.M.)
| | - Mariella Valenzise
- Pediatric Unit, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy; (S.M.); (F.X.); (M.V.); (M.F.M.); (A.V.); (M.W.); (G.Z.); (S.M.)
| | - Maria Francesca Messina
- Pediatric Unit, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy; (S.M.); (F.X.); (M.V.); (M.F.M.); (A.V.); (M.W.); (G.Z.); (S.M.)
| | - Agata Vitale
- Pediatric Unit, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy; (S.M.); (F.X.); (M.V.); (M.F.M.); (A.V.); (M.W.); (G.Z.); (S.M.)
| | - Eloisa Gitto
- Neonatal and Pediatric Intensive Care Unit, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy;
| | - Malgorzata Wasniewska
- Pediatric Unit, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy; (S.M.); (F.X.); (M.V.); (M.F.M.); (A.V.); (M.W.); (G.Z.); (S.M.)
| | - Giuseppina Zirilli
- Pediatric Unit, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy; (S.M.); (F.X.); (M.V.); (M.F.M.); (A.V.); (M.W.); (G.Z.); (S.M.)
| | - Sara Manti
- Pediatric Unit, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy; (S.M.); (F.X.); (M.V.); (M.F.M.); (A.V.); (M.W.); (G.Z.); (S.M.)
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Burrack N, Adar A, Goldbart A, Weissmann S, Cohen B, Hazan I, Horev A, Golan-Tripto I. Monocyte and neutrophil to lymphocyte ratios in hospitalized children with RSV bronchiolitis. Pediatr Pulmonol 2023; 58:3530-3541. [PMID: 37728225 DOI: 10.1002/ppul.26687] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 08/14/2023] [Accepted: 09/05/2023] [Indexed: 09/21/2023]
Abstract
OBJECTIVE Acute bronchiolitis is the most common cause of hospitalization in young children. Data on monocyte-to-lymphocyte-ratio (MLR) and neutrophil-to-lymphocyte-ratio (NLR) as biomarkers are limited. We aim to evaluate these ratios in children hospitalized with respiratory syncytial virus (RSV) bronchiolitis and their value as biomarkers for severe clinical outcomes. STUDY DESIGN A single-center retrospective cohort study of children aged <2 years hospitalized due to RSV bronchiolitis, between January 2018 and March 2022, with a complete blood count upon admission. We divided the cohort into quartiles based on MLR and NLR values. We examined associations between quartiles and four clinical severity outcomes. RESULTS A total of 2038 children (median age: 4.4 months, IQR: 1.9-9.8) were included in the study. The median MLR and NLR values for quartiles 1-4 were 0.14, 0.22, 0.30, 0.47, and 0.37, 0.70, 1.16, 2.29, respectively. Children with higher MLR had higher hospitalization rates to the pediatric intensive care unit (PICU) (Q1 2.4%, Q4 9.4%, p < .001), extended hospital stays (Q1 19.4%, Q4 32%, p < .001), and lower minimal oxygen saturation (Q1 90%, Q4 87%, p < .001). Cut-off values of 0.34 for MLR and 0.67 for NLR optimally identified PICU admissions. In a model accounting for age and sex, the fourth MLR quartile had an RR of 3.4 (95% CI: 1.76-7.22) and successfully predicted PICU admissions (area under the curve = 0.73; 95% CI: 0.681-0.789). CONCLUSIONS MLR and NLR are potential biomarkers for identifying children with RSV bronchiolitis at a higher risk for severe outcomes, specifically PICU admission.
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Affiliation(s)
- Nitzan Burrack
- Clinical Research Center, Soroka University Medical Center, Beer Sheva, Israel
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Assaf Adar
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
- Department of Pediatrics, Soroka University Medical Center, Beer-Sheva, Israel
| | - Aviv Goldbart
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
- Department of Pediatrics, Soroka University Medical Center, Beer-Sheva, Israel
- Pediatric Pulmonary Unit, Soroka University Medical Center, Beer Sheva, Israel
| | - Sarah Weissmann
- Clinical Research Center, Soroka University Medical Center, Beer Sheva, Israel
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Bracha Cohen
- Clinical Research Center, Soroka University Medical Center, Beer Sheva, Israel
| | - Itai Hazan
- Clinical Research Center, Soroka University Medical Center, Beer Sheva, Israel
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Amir Horev
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
- Pediatric Dermatology Service, Soroka University Medical Center, Beer Sheva, Israel
| | - Inbal Golan-Tripto
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
- Department of Pediatrics, Soroka University Medical Center, Beer-Sheva, Israel
- Pediatric Pulmonary Unit, Soroka University Medical Center, Beer Sheva, Israel
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Mouliou DS. C-Reactive Protein: Pathophysiology, Diagnosis, False Test Results and a Novel Diagnostic Algorithm for Clinicians. Diseases 2023; 11:132. [PMID: 37873776 PMCID: PMC10594506 DOI: 10.3390/diseases11040132] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 09/15/2023] [Accepted: 09/19/2023] [Indexed: 10/25/2023] Open
Abstract
The current literature provides a body of evidence on C-Reactive Protein (CRP) and its potential role in inflammation. However, most pieces of evidence are sparse and controversial. This critical state-of-the-art monography provides all the crucial data on the potential biochemical properties of the protein, along with further evidence on its potential pathobiology, both for its pentameric and monomeric forms, including information for its ligands as well as the possible function of autoantibodies against the protein. Furthermore, the current evidence on its potential utility as a biomarker of various diseases is presented, of all cardiovascular, respiratory, hepatobiliary, gastrointestinal, pancreatic, renal, gynecological, andrological, dental, oral, otorhinolaryngological, ophthalmological, dermatological, musculoskeletal, neurological, mental, splenic, thyroid conditions, as well as infections, autoimmune-supposed conditions and neoplasms, including other possible factors that have been linked with elevated concentrations of that protein. Moreover, data on molecular diagnostics on CRP are discussed, and possible etiologies of false test results are highlighted. Additionally, this review evaluates all current pieces of evidence on CRP and systemic inflammation, and highlights future goals. Finally, a novel diagnostic algorithm to carefully assess the CRP level for a precise diagnosis of a medical condition is illustrated.
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Dangor Z, Lala S, Verwey C, Reubenson G, White D, Moore D, Jeena P, Masekela R, Zar H. Bronchiolitis versus bronchopneumonia: navigating antibiotic use within the LRTI spectrum. S Afr Med J 2023; 113:20-23. [PMID: 37278266 DOI: 10.7196/samj.2023.v113i6.709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Accepted: 02/06/2023] [Indexed: 06/07/2023] Open
Abstract
Bronchiolitis, a common reason for infant hospitalisation in South Africa (SA), is caused by viral pathogens. Bronchiolitis is typically an illness of mild to moderate severity that occurs in well-nourished children. Hospitalised SA infants frequently have severe disease and/or coexisting medical conditions, and these cases of bronchiolitis may have bacterial co-infection that requires antibiotic therapy. However, the existence of widespread antimicrobial resistance in SA warrants the judicious use of antibiotics. This commentary describes: (i) common clinical pitfalls leading to an incorrect diagnosis of bronchopneumonia; and (ii) considerations for antibiotic therapy in hospitalised infants with bronchiolitis. If antibiotics are prescribed, the indication for their use should be clearly stated, and antibiotic therapy must be stopped promptly if investigations indicate that bacterial co-infection is unlikely. Until more robust data emerge, we recommend a pragmatic management strategy to inform antibiotic use in hospitalised SA infants with bronchiolitis in whom bacterial co-infection is suspected.
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Isa HM, Hasan AZ, Khalifa SI, Alhewaizem SS, Mahroofi AD, Alkhan FN, Al-Beltagi M. Hepatic involvement in children with acute bronchiolitis. World J Hepatol 2022; 14:1907-1919. [PMID: 36340752 PMCID: PMC9627436 DOI: 10.4254/wjh.v14.i10.1907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 08/22/2022] [Accepted: 10/10/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Respiratory syncytial virus (RSV) is a prevalent cause of lower respiratory tract infections. It may be associated with hepatocellular involvement, as indicated by increased liver enzymes aspartate aminotransferase and alanine transaminase (ALT). AIM To evaluate the rate of increased liver enzyme levels in children with acute bronchiolitis and correlate them with clinical, laboratory, and radiological variables. METHODS The study was a retrospective review of the medical records of children who presented with acute bronchiolitis when admitted to the Pediatric Department, Salmaniya Medical Complex, the Kingdom of Bahrain, between 2019 and 2020. We collected the demographic data, the clinical presentation, the laboratory and radiological findings, and the clinical outcomes. We compared the patients with elevated liver enzymes to those with normal levels at the time of presentation and at follow-up. RESULTS We included 166 (57.8%) of 287 patients with acute bronchiolitis who fulfilled the inclusion criteria. Ninety-three (56%) patients were males. The median age at presentation was 3.4 (interquartile range 1.1 to 12.4) mo. Fifty-four (28%) patients tested positive for RSV, which was confirmed in 15 of them (28%) by PCR. Laboratory findings of 161 patients tested at presentation showed high ALT levels in 14 (8.7%) patients and normal ALT in 147 (91.3%). Coagulation profiles were measured in 46 (27.7%) of 166 patients. High prothrombin time was present in 15 (32.6%), a high international normalized ratio was present in 13 (28.3%), and high activated partial thromboplastin time was present in three (6.5%). Thrombin time was elevated in nine (27.3%) of 33 patients. Five (21.7%) of 23 patients with available radiological data had hepatomegaly; one of them had findings suggestive of fatty infiltration. High ALT had a significant association with lengthy hospital stays (P < 0.05) and positive urine culture (P < 0.05). Seventy (42.2%) patients had documented follow-up with liver function tests over a median follow-up period of 10.2 (IQR, 2.4-23.3) mo. Total serum protein and serum globulin levels were normalized at the follow-up time, with a significant P value of < 0.05. CONCLUSION This study showed a low prevalence of liver function involvement in patients with acute bronchiolitis with a benign course. However, there was a rising trend in ALT during follow-up. Prolonged hospital stay and positive urine cultures were associated with elevated liver enzymes.
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Affiliation(s)
- Hasan M Isa
- Department of Pediatrics, Salmaniya Medical Complex, Manama 12, Bahrain
- Department of Pediatrics, Arabian Gulf University, Manama 26671, Bahrain
| | - Asma Z Hasan
- Department of Pediatrics, Sulwan Psychiatric Hospital, Manama 973, Bu Quwah, Bahrain
| | - Sara I Khalifa
- Department of Pediatrics, Salmaniya Medical Complex, Manama 12, Bahrain
| | - Sana S Alhewaizem
- Department of Pediatrics, Dream Reem Medical Center, Muharraq 50573, Bahrain
| | | | - Fatema N Alkhan
- Department of Pediatrics, Salmaniya Medical Complex, Manama 12, Bahrain
| | - Mohammed Al-Beltagi
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31527, Algharbia, Egypt
- Department of Pediatrics, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
- Department of Pediatrics, University Medical Center, Dr. Sulaiman Al-Habib Medical Group, Bahrain, Manama 26671, Bahrain.
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Smedemark SA, Aabenhus R, Llor C, Fournaise A, Olsen O, Jørgensen KJ. Biomarkers as point-of-care tests to guide prescription of antibiotics in people with acute respiratory infections in primary care. Cochrane Database Syst Rev 2022; 10:CD010130. [PMID: 36250577 PMCID: PMC9575154 DOI: 10.1002/14651858.cd010130.pub3] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND Acute respiratory infections (ARIs) are by far the most common reason for prescribing an antibiotic in primary care, even though the majority of ARIs are of viral or non-severe bacterial aetiology. It follows that in many cases antibiotic use will not be beneficial to a patient's recovery but may expose them to potential side effects. Furthermore, limiting unnecessary antibiotic use is a key factor in controlling antibiotic resistance. One strategy to reduce antibiotic use in primary care is point-of-care biomarkers. A point-of-care biomarker (test) of inflammation identifies part of the acute phase response to tissue injury regardless of the aetiology (infection, trauma, or inflammation) and may be used as a surrogate marker of infection, potentially assisting the physician in the clinical decision whether to use an antibiotic to treat ARIs. Biomarkers may guide antibiotic prescription by ruling out a serious bacterial infection and help identify patients in whom no benefit from antibiotic treatment can be anticipated. This is an update of a Cochrane Review first published in 2014. OBJECTIVES To assess the benefits and harms of point-of-care biomarker tests of inflammation to guide antibiotic treatment in people presenting with symptoms of acute respiratory infections in primary care settings regardless of patient age. SEARCH METHODS We searched CENTRAL (2022, Issue 6), MEDLINE (1946 to 14 June 2022), Embase (1974 to 14 June 2022), CINAHL (1981 to 14 June 2022), Web of Science (1955 to 14 June 2022), and LILACS (1982 to 14 June 2022). We also searched three trial registries (10 December 2021) for completed and ongoing trials. SELECTION CRITERIA We included randomised controlled trials (RCTs) in primary care patients with ARIs that compared the use of point-of-care biomarkers with standard care. We included trials that randomised individual participants, as well as trials that randomised clusters of patients (cluster-RCTs). DATA COLLECTION AND ANALYSIS Two review authors independently extracted data on the following primary outcomes: number of participants given an antibiotic prescription at index consultation and within 28 days follow-up; participant recovery within seven days follow-up; and total mortality within 28 days follow-up. We assessed risk of bias using the Cochrane risk of bias tool and the certainty of the evidence using GRADE. We used random-effects meta-analyses when feasible. We further analysed results with considerable heterogeneity in prespecified subgroups of individual and cluster-RCTs. MAIN RESULTS We included seven new trials in this update, for a total of 13 included trials. Twelve trials (10,218 participants in total, 2335 of which were children) evaluated a C-reactive protein point-of-care test, and one trial (317 adult participants) evaluated a procalcitonin point-of-care test. The studies were conducted in Europe, Russia, and Asia. Overall, the included trials had a low or unclear risk of bias. However all studies were open-labelled, thereby introducing high risk of bias due to lack of blinding. The use of C-reactive protein point-of-care tests to guide antibiotic prescription likely reduces the number of participants given an antibiotic prescription, from 516 prescriptions of antibiotics per 1000 participants in the control group to 397 prescriptions of antibiotics per 1000 participants in the intervention group (risk ratio (RR) 0.77, 95% confidence interval (CI) 0.69 to 0.86; 12 trials, 10,218 participants; I² = 79%; moderate-certainty evidence). Overall, use of C-reactive protein tests also reduce the number of participants given an antibiotic prescription within 28 days follow-up (664 prescriptions of antibiotics per 1000 participants in the control group versus 538 prescriptions of antibiotics per 1000 participants in the intervention group) (RR 0.81, 95% CI 0.76 to 0.86; 7 trials, 5091 participants; I² = 29; high-certainty evidence). The prescription of antibiotics as guided by C-reactive protein tests likely does not reduce the number of participants recovered, within seven or 28 days follow-up (567 participants recovered within seven days follow-up per 1000 participants in the control group versus 584 participants recovered within seven days follow-up per 1000 participants in the intervention group) (recovery within seven days follow-up: RR 1.03, 95% CI 0.96 to 1.12; I² = 0%; moderate-certainty evidence) (recovery within 28 days follow-up: RR 1.02, 95% CI 0.79 to 1.32; I² = 0%; moderate-certainty evidence). The use of C-reactive protein tests may not increase total mortality within 28 days follow-up, from 1 death per 1000 participants in the control group to 0 deaths per 1000 participants in the intervention group (RR 0.53, 95% CI 0.10 to 2.92; I² = 0%; low-certainty evidence). We are uncertain as to whether procalcitonin affects any of the primary or secondary outcomes because there were few participants, thereby limiting the certainty of evidence. We assessed the certainty of the evidence as moderate to high according to GRADE for the primary outcomes for C-reactive protein test, except for mortality, as there were very few deaths, thereby limiting the certainty of the evidence. AUTHORS' CONCLUSIONS The use of C-reactive protein point-of-care tests as an adjunct to standard care likely reduces the number of participants given an antibiotic prescription in primary care patients who present with symptoms of acute respiratory infection. The use of C-reactive protein point-of-care tests likely does not affect recovery rates. It is unlikely that further research will substantially change our conclusion regarding the reduction in number of participants given an antibiotic prescription, although the size of the estimated effect may change. The use of C-reactive protein point-of-care tests may not increase mortality within 28 days follow-up, but there were very few events. Studies that recorded deaths and hospital admissions were performed in children from low- and middle-income countries and older adults with comorbidities. Future studies should focus on children, immunocompromised individuals, and people aged 80 years and above with comorbidities. More studies evaluating procalcitonin and potential new biomarkers as point-of-care tests used in primary care to guide antibiotic prescription are needed. Furthermore, studies are needed to validate C-reactive protein decision algorithms, with a specific focus on potential age group differences.
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Affiliation(s)
- Siri Aas Smedemark
- Department of Geriatric Medicine, Odense University Hospital, Odense, Denmark
- Geriatric Research Unit, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Rune Aabenhus
- The Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Carl Llor
- University Institute in Primary Care Research Jordi Gol, Via Roma Health Centre, Barcelona, Spain
- Research Unit of General Practice, Department of Public Health, General Practice, University of Southern Denmark, Odense, Denmark
| | - Anders Fournaise
- Department of Geriatric Medicine, Odense University Hospital, Odense, Denmark
- Geriatric Research Unit, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Cross-sectoral Collaboration, Region of Southern Denmark, Vejle, Denmark
- Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark
| | - Ole Olsen
- The Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
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