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To Test or Not to Test – that is the question …

To Test or Not to Test – that is the question …. Kevin Chan, MD, MPH, FRCPC, FAAP Clinical Chief, Children’s Health Division Head, Pediatric Emergency, Janeway Children’s Hospital. Objectives.

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To Test or Not to Test – that is the question …

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  1. To Test or Not to Test – that is the question … Kevin Chan, MD, MPH, FRCPC, FAAP Clinical Chief, Children’s Health Division Head, Pediatric Emergency, Janeway Children’s Hospital

  2. Objectives To indicate when should investigations be conducted for fever: bloodwork, urine, chest X-rays, and LP To look at what the value of clinical and ultrasound is on predicting acute appendicitis Identify current risk factors for the need for CT in head injury Identify the various rules for ankles and knees and their requirements for X-rays

  3. Case #1 • A 6 week old baby comes in with a 1 day history of fever. Besides the temperature, his vitals signs are stable and his examination is normal? • How many of you would: • Do a full septic workup including LP? • Do a partial septic workup without a LP? • Do a urine test? • Do no testing?

  4. Case #1 • A 6 week old baby comes in with a 1 day history of fever. Besides the temperature, his vitals signs are stable and his examination is normal? • How many of you would: • Do a full septic workup including LP? • Do a partial septic workup without a LP? • Do a urine test? • Do no testing? * All of the answers may be right …

  5. In the Pre-Hib and Pre-Prevenar eras Source: Baraff LJ. “Management of fever without source in infants and children.” Annals of Emergency Medicine. 2000; 36: 602-614. Prior to Hib and Prevenar vaccines: • 20% of children had a fever with no identifiable source of infection, or a self-limited viral infection • 10% of all children with fever without focus had occult bacteremia or serious bacterial illness • 3% of well appearing children had bacteremia

  6. In the 1980s, pre-Hib and pre-Prevenar vaccines 5% Risk of bacteremia 1% 15,000 30,000 WBC

  7. Why Are We Interested? Source: Lee GM, Harper MB. “Risk of bacteremia for febrile young children in the post-Haemophilus influenzae type b era.” Archives of Pediatrics and Adolescent Medicine. 1998; 152: 624-628. After Hib: • 1.5-2% rate of occult bacteremia • 90% of bacteremia was Streptococcus pneumoniae

  8. Traditional Work-up Source: Baraff LJ, Bass JW, Fleisher GR, et al. “Practice guideline for the management of infants and children 0 to 36 months of age with fever without source. Agency for Health Care Policy and Research.” Annals of Emergency Medicine. 1993 July; 22 (7): 1198-1210. • Toxic children: Septic work-up with iv antibiotics • < 28 days: Full septic-workup until culture results are obtained, or source of fever is identified • 28-90 days: Screening blood work, and Ceftriaxone given (50 mg/kg) • 3-36 months, non-toxic, < 39°C: Observation unless other diagnoses considered • 3-36 months, non-toxic, > 39°C, and WBC > 15,000: Treat with antibiotics until culture results obtained

  9. Diagnostic Criteria

  10. Stoll and Rubin (2004) Stoll ML, Rubin LG. “Incidence of Occult Bacteremia Among Highly Febrile Young Children in the Era of the Pneumococcal Conjugate Vaccine.” Archive of Pediatrics and Adolescent Medicine. July 2004; 158: 671-675. Retrospective Chart Review over 15 months 2-36 months of age Occult Bacteremia: 0.91% (0-1.9%) PPV of WBC Count > 15,000 = 3.2% PPV of WBC Count > 20,000 = 7.1% Caveat: only 28% of infants < 6 months had 3 vaccinations; only 66% of infants < 12 months had received 3 vaccinations

  11. Herz et al. (2006) Source: Herz AM, Greenhow TL, Alcantara J, et al. “Changing Epidemiology of Outpatient Bacteremia in 3- to 36- Month-Old Children After the Introduction of Heptavalent-Conjugated Pneumococcal Vaccine.” Pediatric Infectious Disease Journal. April 2006; 25 (4): 293-300. Retrospective case series, 1998-2003 3 months to 3 years Prevenar introduced: April 2000 84% reduction in S. pneumoniaebactermia (1.3 to 0.2%) 56% reduction in overall bacteremia (1.6 to 0.7%) E.coli dominating < 1 year (2.5 time more frequent than S. pneumoniae), all 27 patient had UTIs as well

  12. Blood Cultures Obtained

  13. Important Change • WBC count > 15,000: • 74% sensitivity, 54.5% specificity in predicting bacteremia • Positive Predictive Value: 1.5% • Negative Predictive Value: 99.5% • Treating a child with WBC > 15,000 has little value in the post-Prevenar era

  14. Sard et al. (2006) Source: Sard B, Bailey MC, Vinci R. “An Analysis of Pediatric Blood Cultures in the Postpneumococcal Conjugate Vaccine Era in a Community Hospital Emergency Department.” Pediatric Emergency Care. May 2006; 22 (5): 295-300. Retrospective chart review, community setting US 1-36 months January 1997 – January 2005 Significant decline of S. pneumoniae from 1% to 0.2% in patients with blood cultures drawn If WBC < 15 x 109, time to positive culture > 24 hours, and Gram stain negative  predictive of contaminant

  15. Carstairs et al. (2007) Carstairs KL, et al. “Pneumococcal Bacteremia in Febrile Infants Presenting to the Emergency Department Before and After the Introduction of the Heptavalent Pneumococcal Vaccine.” Annals of Emergency Medicine. June 2007; 49 (6): 772-777. Noncurrent prospective observational cohort study < 36 months Compared vaccinated vs. unvaccinated children for pneumococcal bacteremia 0% vs. 2.4% positive pneumococcal blood cultures (vac. vs. unvac)

  16. Waddle and Jhaveri (2009) Source: Waddle E, Jhaveri R. “Outcomes of febrile children without localising signs after pneumococcal conjugate vaccine.” Archives of Disease in Childhood. 2009; 94: 144-147. Retrospective review: microbiology laboratory database and chart review 3-36 months Significant drop in occult bacteremia from 6.8% (3.6-12.1%) to 0.4% (0 – 2.2%) between the pre- and post- PCV7 era, fever with no focus No change in UTI rates (6.8% vs. 7.6%) However, antibiotic usage did not change

  17. Wilkinson et al. (2009) Source: Wilkinson M, Bulloch B, Smith M. “Prevalence of Occult Bacteremia in Children Aged 3 to 36 Months Presenting to the Emergency Department with Fever in the Postpneumococcal Conjugate Vaccine Era.” Academic Emergency Medicine. 2000; 16: 220-225. Retrospective chart review over 4 years 8408 children, 3-36 months Not all children got blood cultures with fever (results are therefore underreported) Occult bacteremia: 0.25% (0.16-0.37%) Streptococcal bacteremia: 0.17% (0.09-0.27%) 7.6 contaminants for every true positive blood culture

  18. Implications Need 588 cultures to detect 1 case Need 14,700 cultures to detect one S. Pneumoniae meningitis, 49,000 cultures to prevent one neurologic sequelae and 184,000 cultures to prevent 1 S. pneumoniae death Large costs associated with contaminated blood cultures

  19. Summary of Articles 3 to 36 months, well-appearing children: • 0.17 - 0.91% have pneumococcal bacteremia • 0.65 - 0.91% have occult bacteremia • UTI rates have not declined (consideration for during urinalysis) • Time to get rid of the blood culture and relying on the WBC count if the child is immunized • There is something that is useful, but expensive: pro-Calcitonin … (Enguix et al. Intensive Care Medicine, 2001: 27: 211-215)

  20. The evidence for doing bloodwork 0.2% Risk of bacteremia .025% 15,000 30,000 WBC

  21. Caveats Sources: * Singleton RJ, Hennessy TW, Bulkow LR. “Invasive Pneumococcal Disease Caused by Nonvaccine Serotypes Among Alaska Native Children With High Levels of 7-Valent Pneumococcal Conjugate Vaccine Coverage.”JAMA. April 25, 2007; 297 (16): 1784-1792. † Williams ER, Meza Ye, Salazar S, Dominici P, Fasano CJ. “Immunization Histories Given by Adult Caregivers Accompanying Children 3-36 Months to the Emergency Department: Are Their Histories Valid for the Haemophilus influenza B and Pneumococcal Vaccines?”Pediatric Emergency Care. May 2007; 23 (5): 285-288. Evidence of serotype replacement occurring (with non-vaccine specific serotypes) * Immunization accuracy is questionable when taken from parents, an ED registry, and a state immunization registry†

  22. For Children, 28-90 days old Source: Poehling KA, Talbot TR, Griffin MR et al. “Invasive Pneumococcal Disease Among infants Before and After Introduction of Pneumococcal Conjugate Vaccine.” JAMA. 2006; 295 (14): 1668-1674. • Evidence of a decline in Invasive Pneumococcal Disease (bacteremia or meningitis) secondary to herd effects • 43% reduction of population rates in the US • Studies from Ontario show 30% reduction • At this time, no studies on initial ED presentation and correlation with outcomes • Time to revisit the Boston/Rochester/ Philadelphia criteria?

  23. The need for urine • Rates of UTI generally hover about 7% (Levine et al. Pediatrics; 2004: 113: 1728-1734) • Even in RSV+ bronchiolitis patients, the UTI risk is 5.4% (3.0-8.8%) • In RSV- bronchiolitis, the UTI risk is 10.1% (8.3-12.2%) • However, urine bag specimens are not useful (Al-Orifi F, J Peds, 2000: 137: 221-226) • 63% false positivity rate leading to significant call backs, and too many children being placed on antibiotics inappropriately

  24. Do I need to do a CXR? • If there’s no symptoms, there’s no value in doing a CXR (Bramson, Pediatrics: 1993: 92 (4): 524-526) • Clinical findings • Tachypnea • Rales/rhonchi • Retractions, wheezing, coryza • Grunting, stridor, nasal flaring • Cough

  25. Previously 1 in about 12 children with fever and cough past 48 hours would have a lobar pneumonia (irrespective of the severity) In the post-Prevenar era, this is about 1 in 20-25 (Nelson et al. Vaccine. 2008; 26 : 4947-4954)

  26. What to do? • Infectious Disease Society of North America (Bradley et al. Clinical Infectious Disease; 2011 53(7): e25-e76) • Treat if looks like pneumonia • Don’t treat if it doesn’t look like pneumonia • Do CXR if you’re not sure, but not useful if done too early (at least 24 hours) • There is another argument, do CXR to prevent overprescribing antibiotics

  27. Investigations for fever • <28 days, full septic work-up • 28-60 days is controversial • Full septic • Partial septic are generally agreed upon (from PAS conference 2013)

  28. Investigations for fever For children > 60 days • Sick or not sick? • If sick, investigate • Vaccinated or unvaccinated? • If unvaccinated, consider investigating • Then, take a urine • CXR if unsure about respiratory diagnosis

  29. When do I investigate when fever persists? • There’s no clear statement in the literature • Generally, accepted at 14 days, you should test • Essentially to r/o leukemia • But investigate chronic infections/rheumatologic conditions • 5-14 days is a gray zone • Definitely, if Kawasaki’s suspected • Otherwise, no clear literature • <5 days, looking well: no need for bloodwork

  30. Case #2 A 14 year-old girl comes in with RLQ pain for 12 hours, she has a fever, anorexia, but has not vomited. The pain did not migrate, but she does have cough and percussion tenderness. She comes back and has a normal WBC and no left shift. What is the likelihood that she has appendicitis?

  31. Pediatric Appendicitis Score Cough/percussion tenderness = 2 Anorexia = 1 Pyrexia (fever) = 1 Nausea/emesis = 1 Tenderness in the RLQ = 2 Leukocytosis (> 10,000 WBC) = 1 PMN = 1 Migration of pain = 1

  32. Pediatric Appendicitis Score Score 8 and above, indicates a likely appendicitis Score 3 and below, indicates unlikely appendicitis

  33. Case #2 A 14 year-old girl comes in with RLQ pain for 12 hours, she has a fever, anorexia, but has not vomited. The pain did not migrate, but she does have cough and percussion tenderness. She comes back and has a normal WBC and no left shift. What is the likelihood that she has appendicitis? Her PAS is 6. We’re not sure … she’s equivocal.

  34. The American Algorithm Established by Barbara Garcia-Pena (at Children’s Hospital, Boston) was to do US then CT for suspected pediatric appendicitis (AJR, 2000; 175 (1): 71-74) Currently, the recommendation by the American Society of Radiology Recognition of CT abdomen and its potential cancer risks (Brenner, AJR, 2001; 176: 289-296, and Pearce, Lancet, 2012, 380: 499-505.)

  35. The Canadian Algorithm Initial U/S, with a repeat U/S for equivocal examinations Grant Thompson did a survey across the PERC sites and showed that this was the most common algorithm

  36. Combined Use of Ultrasound and Interval Pediatric Appendicitis Score in Suspected Appendicitis Suzanne Schuh, Andrea Doria, Marcela Preto-Zampreski, Jacob Langer, Carina Man, and Kevin Chan

  37. Our Research • Looked at a 4 hour PAS scores, in combination with an U/S to determine if repeated clinical examination could eliminate the need for further testing • Primary objective: To compare the proportion of children who are candidates for early disposition from the ED • US-PAS approach versus a strict (1 or 2) Ultrasound approach • Secondary objectives: • Clinical outcomes, resource use and economic costs

  38. Candidates for Early Disposition

  39. What does this mean for early discharge? The U/S approach = 72/294 (24.5%) could be discharged early The U/S – PAS approach = 179/294 (60.9%) could be discharge early (p<0.0001)

  40. Test characteristics of 2 pathways US – PAS Approach 95.2% diagnostically accurate 97.2% of appendicitis cases detected 94% of non-appendicitis cases detected Sens: 97.3%, Spec: 94%, PPV: 90.8%, NPV: 98.2% US approach • 93.2% diagnostically accurate • 97.2% of appendicitis cases detected • 90.7% of non-appendicitis cases detected • Sens: 97.3%, Spec: 90.7%, PPV: 86.4%, NPV: 98.2%

  41. Resource Usage of 2 pathways US – PAS approach 38 second ultrasounds 4 CTs 115 operations, 9 negative operations 128 hospitalizations Mean LOS = 530 minutes US approach • 43 second ultrasounds • 4 CTs • 120 surgeries, 14 negative operations • 136 hospitalizations • Mean LOS in ED = 597 minutes

  42. Cost Savings The US-PAS approach saves approximately $110 million ($82-146 million) to the health care system and $115 million ($86-156 million) to society in the US It saves $1.8 million ($1.4-2.3 million) to the health care system and $2.4 million ($1.8-3.0 million) to society in Canada Compared to the US-CT approach, the savings are approximately $170 million ($126-$245 million) in the US.

  43. Discussion First study to look at the interval PAS score to help disposition decisions in suspected appendicitis Doing this, reduces the number of CTs, and provides an indication of who can be discharged sooner in the Emergency department This approach saves resources and costs, and represents a small but sizable savings in appendicitis care.

  44. Discussion A recent study by Mittal et al. (Academic Emergency Medicine. 2013; 20: 697-702) showed that U/S have suboptimal sensitivity, and highlights the value of ultrasound with clinical re-assessment. The initial PAS by itself was not helpful in identifying appendicitis.

  45. Note • Just because an ultrasound is reported at positive, 1/3 of them with low PAS scores (2-5) did NOT have appendicitis • Suggest surgical consultation with this group • Remember that negative appendectomies do have a complication risk of about 4.6%, and cannot be ignored.

  46. Discussion • In the US, still about 35% of children (Bachur et al., J Peds; 2012; 160: 1034-1038) undergo a CT, yet only 3% of these cases required CT. • How do we avoid the CT? • Re-evaluation of the criteria of appendicitis at 6 mm may be warranted • New work on focused MRI examination of the RLQ being conducted • Longer duration of abdominal pain, increases U/S sensitivity

  47. Case #3 • A 12 year-old boy is playing soccer and is pushed into the goal post. He comes in with a headache and is dizzy. He has a severe headache and a large hematoma on his frontal-temporal region. He has a GCS of 14. His examination right now is otherwise normal (including normal vital signs, no neck stiffness and a normal neurological exam.) • What do you do? • Get a CT of the head • Get a skull X-ray • Observe for 6 hours in the ER • Admit to hospital for observation

  48. Case #3 • A 12 year-old boy is playing soccer and is pushed into the goal post. He comes in with a headache and is dizzy. He has a severe headache and a large hematoma on his frontal-temporal region. He has a GCS of 14. His examination right now is otherwise normal (including normal vital signs, no neck stiffness and a normal neurological exam) • What do you do? • Get a CT of the head • Get a skull X-ray • Observe for 4-6 hours in the ER • Admit to hospital for observation

  49. How important is mechanism? • CATCH rules (3866 patients (Osmond et al. CMAJ, 2010: 182 (4): 341-348) (for patients with GCS of 13-15) • 4 high risk factors (sensitivity of 100% (86.2-100%)) • Failure to reach GCS within 2 hours • Suspicion of open skull fracture • Worsening headache • Irritability • 3 medium risks factors (sensitivity of 98.1%) (94.6-99.4%)) • Large, boggy hematoma • Signs of basilar skull fracture • Dangerous mechanism of injury • Any of them should necessitate a CT

  50. How important is mechanism? • PECARN has tracked out 42,412 patients (Kuperman et al., Lancet 2009; 374: 1160-1170) • Severe injury mechanisms: • High-speed MVA (either occupant or pedestrian struck) • Bicycle-related injury (or similar vehicle) • High-speed projectile • Fall from a height or down stairs • Isolated severe injury mechanisms (PECARN Head Injury Predictor Rules) • No significant signs or symptoms of TBI • Altered mental status (GCS < 15, agitation, sleepiness, slow responses or repetitive questioning) • Nonfrontal scalp hematoma • LOC > 5 seconds • Palpable skull fracture • Not acting normally according to parents

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