Rapid viral diagnosis for acute febrile respiratory illness in children in the Emergency Department
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To determine if the use of a rapid viral detection test for children with an ARI in EDs changes patient management and resource use in the ED, compared to not using a rapid viral detection test.
Background
Description of the condition
Acute respiratory infections (ARIs) are a serious public health issue and rank among the top five causes of illness and hospitalization in children. During influenza seasons, fever and respiratory infection symptoms make up to 25% of all reasons for a visit to an emergency department (ED) (Silka 2003). Although ARIs can be caused by bacteria, they are most commonly caused by viral infections. A rapid diagnosis of a viral infection may lead to a decrease in the use of antibiotics, additional testing and possibly admissions. The most commonly implicated causal viruses are influenza (A and B), respiratory syncytial virus (RSV), human parainfluenza (1, 2 and 3), rhinovirus and adenovirus. Viral etiology for ARIs is confirmed in 35 to 87% of children with an ARI when tested for the above mentioned viruses, with nasopharyngeal aspirate or swab. The variability in the range of positive viral diagnosis may be affected by the choice of viral tests used and their scope of viral detection (Jennings 2004; Weigl 2000). There is a risk of concurrent bacterial infection in children with a confirmed viral ARI. A study of children 3 to 36 months old with recognizable viral infections showed a concurrent rate of bacteremia of 0.01 to 0.8% (Greens 1999). A prospective multicenter study of infants less than 60 days old with an ARI showed a significant difference in the rate of urinary tract infection between RSV positive (5.4%) and negative infants (10.1%), a non‐significant difference rate of bacteremia (1.1% and 2.3%) and no cases of bacterial meningitis among the 251 RSV positive infants and 8 cases out of 938 RSV negative infants (not statistically significant) (Levine 2004).
The symptoms of viral ARI, however, overlap with those of severe viral or bacterial infections. Thus, without a confirmed viral diagnosis, medical assessment and diagnostic tests are needed before a decision on patient management, parental advice, and/or hospital admission can be made. These precautionary tests lead to intense use of human health resources (nursing, laboratory and radiology staff) and hospital facilities. Furthermore, these tests are often invasive, sometimes unnecessarily prolonging a child's visit to the ED, resulting in sub‐optimal ED service provision and contributing to lengthy ED waiting times and overcrowding. ARIs impose phenomenal costs on the health system, from a high number of physician visits, ED visits, hospitalization and antibiotic prescriptions. A study comparing the costs associated with a visit to the ED versus a primary care provider, showed that the average cost for assessing a patient for an ARI in the ED (excluding antibiotics cost) is $206 to $221 and in comparison is $101 to $106 in a primary care provider's office. The physician and nursing costs only contributed to 17.5% of these amounts (Martin 2000). Studies comparing health care utilization for ARIs in children 0 to 15 years old during influenza season and the rest of the year showed significant excess in physician visits (28,000 to 51,000/100,000 age specific population annually), ED visits (˜1600/100,000 age specific population annually), hospital admission (300 to 9500/100,000 age specific population annually) and antibiotic prescription (31,000/100,000 age specific population annually). Most of this burden came from children below three years of age (Menec 2003; Neuzil 2000).
Description of the intervention
Despite the fact that most ARIs are caused by viruses, up to 60% of patients with a common cold are treated with antimicrobials, which costs $37.5 million annually (Rosenstein 1998). Advances in virology testing now allow for viral detection within 30 to 120 minutes by direct immuno‐fluorescent antibody detection. These have been reported to have high sensitivity (up to 90%) and specificity (up to 99%) (Vega 2005) Confirmation of specific diagnosis of viral respiratory infection is now accessible and reliable.
How the intervention might work
Various approaches have been used to investigate the issue of differential diagnosis of the child who presents to an ED with fever and respiratory symptoms. However, clear evidence for improvement of ED patient management during seasonal peaks is not readily available. During the SARS emergency in 2003, there was access to rapid respiratory viral diagnosis in acute care settings; that is, provision of same‐day identification of influenza virus (A and B), parainfluenza virus (1, 2 and 3), RSV and adenovirus. This enabled rapid, informed patient management decisions and helped with training. This experience suggests a role for rapid viral diagnosis in alleviating the burden on EDs and improving health service delivery and health resource allocation, in the situation of increased use of EDs for ARI symptoms. The literature suggests that a prompt single viral diagnosis improves decision‐making and reduces unnecessary hospital admittance, prescription of antibiotics, and further diagnostic investigations. Retrospective chart reviews of children admitted to hospital, with subsequent confirmed diagnosis of adenovirus infection, revealed a change in management for 36% of these children, including revision of antibiotic treatment and use of antiviral therapy (Rocholl 2004). Similarly, chart reviews of children testing positive via a rapid influenza diagnostic test were less likely to be prescribed antibiotics in the ED (20% versus 53%; P = 0.04) and when admitted were on antibiotics for fewer days (3.5 versus 5.4 days; P = 0.03) (Noyola 2000). Children with an early diagnosis of influenza also had fewer blood tests (17% versus 44%; P = 0.02) and urine tests performed (2% versus 24%; P = 0.006), compared to those children with a late diagnosis (Sharma 2002).
Why it is important to do this review
Although the literature suggests that a prompt single viral diagnosis improves decision‐making, the literature has yet to be systematically reviewed to examine the impact of a rapid viral detection test, or the impact of the timing of such a test, on management of children with an ARI in the ED.
Objectives
To determine if the use of a rapid viral detection test for children with an ARI in EDs changes patient management and resource use in the ED, compared to not using a rapid viral detection test.
Methods
Criteria for considering studies for this review
Types of studies
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Randomized controlled trials evaluating the use of rapid viral diagnosis in children admitted to the ED with an ARI.
Types of participants
We will include:
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studies of otherwise healthy children aged 0 to 17 years old; or
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studies which separately reported data on subgroups of children under 17 years of age, admitted to an ED with a clinical presentation consistent with an ARI (fever and respiratory symptoms such as cough, runny nose, sore throat, or congested nose).
We will not consider:
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studies including patients who are immuno‐compromised;
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studies including patients who have underlying chronic severe respiratory conditions (cystic fibrosis, bronchopulmonary dysplasia); or
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studies including patients with chronic heart conditions (such as uncorrected cyanotic heart lesions, and prosthetic valves).
Types of interventions
Rapid viral diagnosis from nasal pharyngeal aspirates or swabs by direct or indirect immunofluorescent antibody test (IDF, IFA), enzyme immunoassays (EIA), optical immunoassay (OIA) or molecular testing (multiplex PCR). Rapid viral diagnosis implies that results are made available during the patients stay in the ED. The intervention group will include patients who have rapid viral diagnostic testing; while patients in the control group will have had no rapid viral diagnostic test performed.
Types of outcome measures
Primary outcomes
Antimicrobial prescription rate in the ED.
Secondary outcomes
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Length of hospital (ED) stay.
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Rate of ancillary tests (any blood tests or chest imaging or urine investigations) requested.
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Hospital admission rate.
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Rate of adverse effects of the test (nasal mucosal trauma evidenced by bleeding).
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Rate of physician visit (ED or office) within two weeks after discharge from ED.
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Rate of antimicrobial prescription within two weeks after discharge from ED.
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Rate of severe bacterial infection (pneumonia, bacteremia, urinary tract infection, meningitis) within two weeks after discharge from ED.
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Rate of death.
Search methods for identification of studies
Electronic searches
We will search the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, latest issue); MEDLINE (1966 to present); and EMBASE (1990 to present).
The following search strategy will be run over MEDLINE in conjunction with the highly sensitive search strategy designed by the Cochrane Collaboration for identifying randomized controlled trials (Dickersin 1994). The same strategy will be used to search CENTRAL and adapted to search EMBASE.
MEDLINE
1. exp infant/
2. exp child/
3. Adolescent/
4. exp pediatrics/
5. (infan$ or child$ or adolescen$ or schoolchild$ or paediatric? or pediatric?).mp.
6. or/1‐5
7. exp Respiratory Tract Infections/
8. exp Influenza A virus/
9. Influenza B virus/
10. Influenza, Human/
11. respiratory syncytial virus, human/
12. *Respiratory Syncytial Virus Infections/
13. exp Respirovirus Infections/
14. exp Orthomyxoviridae/
15. exp Adenoviridae/
16. Adenovirus Infections, Human/
17. Rhinovirus/
18. exp Paramyxoviridae Infections/
19. rhinovirus$.mp.
20. RSV.mp.
21. parainfluenza$.mp.
22. (influenza adj (A or B)).mp.
23. respiratory syncytial virus.mp.
24. *Fever/
25. (febrile adj3 respiratory).mp.
26. exp Antigens, Viral/
27. or/7‐26
28. sensitiv$.ti,ab.
29. exp "sensitivity and specificity"/
30. diagnos$.ti,ab.
31. Diagnosis/
32. Diagnosis, Differential/
33. di.fs.
34. diagnostic tests, routine/
35. du.fs.
36. or/28‐35
37. rapid.ti,ab.
38. "same day".ti,ab.
39. "point of care".ti,ab.
40. or/37‐39
41. exp Fluorescent Antibody Technique/
42. Immunoenzyme Techniques/
43. Enzyme‐Linked Immunosorbent Assay/
44. Polymerase Chain Reaction/
45. Reverse Transcriptase Polymerase Chain Reaction/
46. exp Enzymes/
47. exp Immunologic Techniques/
48. exp Peroxidases/
49. Gene Amplification/
50. ((virus$ or viral) adj3 detect$).mp.
51. IFA.mp.
52. DFA.mp.
53. direct antigen detection.mp.
54. EIA.mp.
55. ((enzyme or optical) adj (immunoassay? or immuno assay?)).mp.
56. molecular test$.mp.
57. ELISA.mp.
58. (PCR or RT‐PCR).mp.
59. (immunofluorescen$ or immuno‐fluorescen$ or immuno fluorescen$ or IF).mp.
60. or/41‐59
These terms will be combined then limited to a population aged less than 17 years of age, or combined with 'paediatric' 'pediatric' and 'adolescent'. There will be no language or publication restrictions.
Searching other resources
We will contact experts in the areas of acute respiratory infections and Pediatric Emergency to locate additional studies.
Data collection and analysis
Selection of studies
Two review authors will screen titles and abstracts of identified citations to exclude trials which are clearly not relevant or do not meet the inclusion criteria of the review. For all abstracts or titles deemed relevant or potentially meeting the criteria by either review author, the full article will be retrieved for further examination. The two review authors will assess these articles to confirm that they meet inclusion criteria for the review.
Data extraction and management
Two review authors will independently extract data from the published studies using standard forms. Trial authors will be contacted to obtain unpublished information, including outcome data that was not explicitly stated in the published papers. Disagreements in data extraction will be resolved by discussion and consensus.
Assessment of risk of bias in included studies
The review authors will evaluate the methodological quality of each trial, while remaining blinded to the names of the trial authors, the institution and the journal in which the trial was published. Review authors will use the Jadad scoring system (Jadad 1996). Allocation concealment as described by Schulz will also be assessed as clearly adequate, clearly inadequate and unclear (Schulz 1995). Agreement among the review authors regarding the quality of the articles will be assessed using the kappa statistic. Disagreements will be resolved by discussion and consensus.
Unit of analysis issues
Dichotomous data such as antibiotic prescription in ED (primary objective), ancillary test performed in ED, admission to the hospital and physician visits or re‐visits to the ED within two weeks of discharge from original ED visit will be expressed as relative risk (RR). Continuous data such as mean length of stay in ED will be expressed as mean differences (MD) and we will calculate an overall MD. We will use a random‐effects method.
Assessment of heterogeneity
Heterogeneity will be tested for using the chi square statistic. We will assess possible sources of heterogeneity using sensitivity analyses. Variables used to explore heterogeneity will include low versus high quality studies and studies with small versus large sample sizes.
Assessment of reporting biases
We will assess for publication bias and small study effects by visual inspection of a funnel plot.
Subgroup analysis and investigation of heterogeneity
When possible, subgroup analyses for age groups (0 to 12 months old, 12 to 60 months old and 5 to 17 years old) will be performed.
Sensitivity analysis
We will perform a sensitivity analysis comparing studies with a Jadad score of 2 or less (low quality) to studies with a score greater than 2 (high quality). The maximum score achievable being 3, since the studied intervention in this context can not be blinded.
