Paediatric Ambulatory Care 2 EVIDENCE BASED PRACTICE PRESENTATION Produced in 2010 Lower Respiratory Tract Infection in

1. Paediatric Ambulatory Care 2EVIDENCE BASED PRACTICE PRESENTATIONProduced in 2010Lower Respiratory Tract Infection in Children Robin Hyde APNP trainee NHS Borders

2. Lower Respiratory Tract Infection (LRTI) Common Signs and Symptoms Infants Poor feeding Irritability and Lethargy Grunting/Cyanosis Fever Cough/wheeze Chest in drawing Pre-School As Above and; Vomiting Complaints of pain (chest and abdominal) School aged-Older Child As above and; A-typical presentations more common More articulate of symptoms • Lower Respiratory Tract Infection LRTI is infection below the larynx-that encompasses • Pneumonia • Bronchiolitis • Bronchitis • Laryngotracheobronchitis (croup) • Statistically • The incidence of LRTI is 30 per 1,000 children per year in the UK • Pneumonia is one the leading causes of mortality amongst children worldwide • 19% internationally in the those <5 year old Patient UK (2010)Sinaniotis (2005) White et al (2004) Qazi, S (2002)

3. Differentiation between serious viral and bacterial infection remains a challenge A tool for consistent, rapid and accurate diagnosis Rationale

4. Formulation of clinical question “In infants over 6 months of age to 12 years of age, presenting to the acute in patient unit, with lower respiratory tract infection, does serum Procalcitonin compared to C-Reactive Protein differentiate better diagnostically between viral and bacterial infection, thus improving patient management”?

5. Procalcitonin (PCT)C-Reactive Protein (CRP) • Procalcitonin PCT • Procalcitonin is infact a precursor to the hormone calcitonin • Calcitonin is produced by the C-cells in the Thyroid gland • Involved in the Calcium Homeostasis • It is morphed into calcitonin, katacalcin and protein residue • In healthy individuals PCT is almost always un detectable • In infection PCT becomes detectable in the blood, and rise dramatically • Historically PCT was really only first described in the early 1990s • C-Reactive Protein CRP • Protein found in blood • Levels of which rise in response to inflammation (acute-phase protein) • Physiologically it binds to phosphocholine which is found expressed on the surface of dead/dying cells ( and some types of bacteria) • CRP is synthesised in the liver-a response to factors released by fat cells (adipocytes) • Historically CRP was discovered in 1930 Assicot et al (1993) Lopez et al (2003) Hillard and Waites (2002)

6. SEARCH STRATEGY • Search Terms • -infant, child -paed/pediatric • -LRTI -viral/bacterial • -pneumococcal -atypical • -Diagnostic markers • -Procalcitonin -C-reactive protein • Inclusion Criteria-RCTs, Cohort Studies • Involving infants >6mo with LRTI symptoms • Full Text Articles and Available using NHS Athens Account Scotland/England • Limited 2000-2010 • Exclusion Criteria– Meta Analysis, Cochrane reviews, infants <6mo, or infants with chronic respiratory diseases, e.g. CF • Articles pre 2000, unavailable in full text • Following databases accessed via NHS Evidence • Medline hits= 16 • Cinahl hits = 1 • BNI hits = 0 • EMBASE hits = 20 • No Systematic Reviews were found in regards to PCT vs CRP in LRTI

7. Articles Chosen • Is Procalcitonin better than c-reactive protein for early diagnosis of bacterial pneumonia in children? • Khan et al (2010) • Journal of clinical laboratory analysis • Pakistan • Procalcitonin, C-Reactive protein, and leukocyte count in children with lower respiratory tract infection • Prat et al (2003) • Pediatric Infectious Diseases Journal • Spain

8. Appraisal Combination CASP tool (PHRU 2006)12 questions to help make sense of a diagnostic test study12 questions to help make sense of a cohort study • Question 1 • Was there a clear question for the study? • Did the study address a clearly focused question? • Question 2 • Was there a comparison with an appropriate reference standard? • Did the authors use an appropriate method to answer their question?

9. Appraisal Combination CASP tool (PHRU 2006)12 questions to help make sense of a diagnostic test study12 questions to help make sense of a cohort study • Question 3 • Did all the patients get the diagnostic test and the reference standard? • Was the cohort recruited in an acceptable way?

10. Appraisal Combination CASP tool (PHRU 2006)12 questions to help make sense of a diagnostic test study12 questions to help make sense of a cohort study • Question 4 • Could the results of the test of interest have been influenced by the results of the reference standard?

11. Appraisal Combination CASP tool (PHRU 2006)12 questions to help make sense of a diagnostic test study12 questions to help make sense of a cohort study • Question 5 • Is the disease status of the tested population clearly described? • Was the outcome accurately measured to minimise bias?

12. Appraisal Combination CASP tool (PHRU 2006)12 questions to help make sense of a diagnostic test study12 questions to help make sense of a cohort study • Question 6 • Were the methods for performing the test described in sufficient detail?

13. Appraisal Combination CASP tool (PHRU 2006)12 questions to help make sense of a diagnostic test study12 questions to help make sense of a cohort study • Question 7 • What are the results? • Question 8 • How sure are we about these results?

14. Appraisal Combination CASP tool (PHRU 2006)12 questions to help make sense of a diagnostic test study12 questions to help make sense of a cohort study • Question 9 • Can the results be applied to your patients/population of interest? • Question 10 • Can the test be applied to your patient or population of interest?

15. Appraisal Combination CASP tool (PHRU 2006)12 questions to help make sense of a diagnostic test study12 questions to help make sense of a cohort study • Question 11 • Were all the outcomes important to the individual or population considered? • Question 12 • What would be the impact of using this test on your patients/population? • Do the results of this study fit with other available evidence?

16. CONCLUSIONImpact on APNP practice • Did I answer my question? • Yes I believe so... • Significant association between PCT and CRP and pneumococcal pneumonia • PCT has shown example of increased specificity more so than CRP in differentiation between viral and bacterial aetiologies • PCT can also be utilised as an early marker (more so than CRP) for diagnosing bacterial pneumonia • Impact on APNP practice... • Evidence to support new improved diagnostic methods in diagnosis of serious infection • This evidence could lead to us as APNPs promoting better practice in the use of antibiotics used to treat the children within our care • Continuing to present this kind of evidence to initiate further discussion with local laboratory staff and paediatricians may help in a change in practice

17. References • Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, and • Bohuhon C (1993) High serum procalcitonin concentrations in patients • with sepsis and infection Lancet 341:515–8. • Hilliard, N and Waites, K (2002) CME: C-reactive protein and ESR: What can one tell you that the other can’t? Contemporary Pediatrics http://www.contemporarypediatrics.com/contpeds/content/print/contentpopup.jsp?id(accessed 2/2/10) • Khan, A D Rahman, A and Khan, F A (2010) Is Procalcitonin better than C-Reactive Protein for Early Diagnosis of Bacterial Pneumonia in Children? Journal of Clinical Laboratory Analysis 24 1-5 • Korczowski, B and Szybist, W (2004) Serum procalcitonin and c-reactive protein in children with diarrhoea of various aetiologies Acta Paediatrica 93 169-173 • Lopez, A F Cubells, L Garcia, J Fernandez, J and The Spanish Society for Pediatric Emergencies (2003) Procalcitonin in pediatric emergency departments for early diagnosis of invasive in infectious infants: results of a multicenter study and utility of rapid qualitative test for this marker Pediatric Infectious Diseases Journal 22 895 -903 • Patient UK (2010) • http://www.patient.co.uk/doctor/LRTI-children-.htm(accessed04/03/10) • Prat, C Dominguez, J Rodrigo, C Gimenez, M Azuara, M Jemenz, O Gali, N and Ausina V (2003) Procalcitonin, C-Reactive Protein and leukocyte count in children with lower respiratory tract infection Pediatric Infectious Disease Journal 22 963-967 • Rossum, A M C Wulkan, R W and Oudesluys-Murphy, A M (2004) Procalcitonin as an early marker of infection in neonates and children The Lancet Infectious Diseases 4 10 620-630 • Sinaniotis, C A (2005) Community-acquired pneumonia in children Current opinion in Pulmonary Medicine 11 218-225 • White, A R Kaye, C Poupard, J Pypstra, R Woodnutt, G and Wynne B (2004) Augmentin (amoxicillin/clavulnate) in the treatment of community –acquired respiratory tract infection: a review of the continuing development of an innovative antimicrobial agent Journal of Antimicrobial Chemotherapy 53, Suppl S1 3-20

18. References • White, A R Kaye, C Poupard, J Pypstra, R Woodnutt, G and Wynne B (2004) Augmentin (amoxicillin/clavulnate) in the treatment of community –acquired respiratory tract infection: a review of the continuing development of an innovative antimicrobial agent Journal of Antimicrobial Chemotherapy 53, Suppl S1 3-20 • Qazi, S (2002) Clinical efficacy of 3 days versus 5 days of oral amoxicillin for treatment of childhood pneumonia: a multicentre double-blind trial The Lancet 360 835-842

19. THANK YOU FOR LISTENINING ANY QUESTIONS?