Evidence-based paediatrics

Altruistic reasons for practising EBM

Practicing EBM improves patient care. There really should be no other incentive. Considering this in terms of the four pillars of medical ethics can be helpful:

• 1.

  Autonomy : All patients have the right to make decisions about their own care. This is central to EBM. Their values, preferences and beliefs should always be taken into account when making decisions.

• 2.

  Beneficence : When starting therapies you need the best available evidence to be certain that they have a meaningful benefit to the patient.

• 3.

  Non-maleficence : If a therapy or test has no meaningful benefit but is harming the patient (e.g. through side effects) then it should be stopped or not used in the first place.

• 4.

  Justice : Scarce resources must be fairly distributed. When rationing provisions, there must be good evidence that they are effective. If they are not, this resource could have been used elsewhere.

Personal reasons for practising EBM

There are also selfish reasons for wanting to practise EBM:

• 1.

  Personal development/examinations : EBM is included in the RCPCH Curriculum for Paediatric Training, which states that: ‘In addition to a detailed knowledge and understanding of diseases in children and young people, paediatricians must ensure they are up-to-date, conform with highest standards of practice, aim to promote evidence-based medicine where possible and audit practice (assessment standards 18–20).’

• 2.

  Self-preservation : Clinicians are presented with huge volumes of research evidence. Without the time to read all this information, skills are required to filter out the good from the bad.

• 3.

  Reduced workload: Practising EBM will hopefully help patients to be diagnosed more effectively and get better quicker, therefore reducing workload.

‘Just in case’ information

Reading this book is an example of just in case information: packing in a range of general nuggets to provide a good underlying understanding of paediatrics in order to be good clinicians. When taken to the extreme, it is the diligent, regular reading of a series of journals ‘just in case’ a particular case was to present. This is inefficient and induces guilt when you cannot manage it.

‘Just in time’ information

This is a lifelong skill – the acquisition of information ‘just’ as you need it, e.g. reading a patient's clinic notes before they arrive. In the EBM context, it is identifying information that will help us best manage our patients by seeking rapid answers to specific queries. Research has shown that a doctor in training will have two unanswered questions for every three patients they consult (Green et al 2000). An inquisitive clinician could have many more questions. As our clinical experience improves, this number is unlikely to change, but the content may become more focused.

Framing a clear question: PICO questions

A popular method for framing a clinical question is the PICO method ( Box 39.2 ):

• P – Patient, Pathology, Problem or Population : What are the key features that describe the patient or population? Be specific.

• I – Intervention or Interest : Be specific about the intervention, test or risk factor you are considering.

• C – Control or Comparison : What would be appropriate alternatives? This may be placebo or more often currently used treatments.

• O – Outcomes : Consider patient-oriented short-term and long-term outcomes; remember negative effects too. Avoid surrogate markers (e.g. improved CRP).

Choosing the right outcomes to search is incredibly important. If you have a strong opinion on a topic, it is likely to be drawn from experience, e.g. always giving inhaled salbutamol to wheezy children in A&E. But what do we actually want to know about our intervention? Will it stop the patient dying? Will it keep them out of hospital for longer? Will they feel better? These are all important questions.

Converting PICO questions into searchable terms

Once you have written a sound PICO question you must convert the question into searchable terms.

To form a search strategy:

• 1.

  Convert each arm of your PICO into search terms (including alternate spellings, synonyms, and truncations).

• 2.

  Search for the correct MeSH term (if you are using a database that does not automatically map). ‘MeSH’ is essentially the National Institute of Health (NIH) thesaurus of medical terms that guides towards the ‘correct medical term’. This means a searching clinician is able to find the relevant research, including when the papers' authors have not used the ‘preferred’ medical term). (See http://www.nlm.nih.gov/mesh/ ; Tutorial: http://www.nlm.nih.gov/bsd/viewlet/mesh/searching/mesh1.html ).

• 3.

  Combine the search terms using the correct Boolean operators ( Table 39.2 ).

  Table 39.2

  Boolean operators

  Term	Search description
  OR	(Infant OR child) will find all articles/documents containing at least one of these keywords
  NOT	(Infant NOT child) will find articles/documents containing the keyword infant but exclude those also including the keyword child
  AND	(Infant AND child) will find articles/documents containing both of these keywords
  * (Truncation)	Infant* will find articles/documents containing the keywords infant OR infants OR infantile OR infancy, etc.

Where to search

There is probably no correct answer to the question, ‘where is best to search?’ You are likely to find databases which you are more comfortable using. Trip®, the Cochrane library® or PubMed® are good databases to be familiar with ( Box 39.3 ).

Hierarchical searches

A hierarchical search aims to look for the best quality evidence first, and then work downwards if insufficient research is discovered ( Fig. 39.2 ). If you are searching in a clinical environment, a database such as Trip® will often find results quickly ( Table 39.3 ) and present them in evidence type. If this fails, the Cochrane library and DARE website should be searched ( Table 39.4 ). If this does not yield any results, then PubMed's ‘Clinical Queries’ is the next best port of call followed by a search for primary resources in PubMed.

Table 39.3

Best evidence topic (BET) – treatment

Cates CJ, et al. Holding chambers (spacers) versus nebulizers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev 2006;(2):CD000052.

Treatment – acute exacerbation of asthma

Scenario: A 6-year-old child is admitted with a moderate exacerbation of asthma. He has been given a nebulizer of salbutamol in the A&E department and needs admission for a trial of inhaler and holding chamber (spacer). You wonder if he could have been given the inhaler in the A&E and the child sent home sooner? Step 1: Asking a question (PICO): In a child with a moderate exacerbation of asthma [patient], is inhaled, spaced, salbutamol [intervention] as effective as nebulized [comparison] β 2 agonist in terms of time to resolution of symptoms, likelihood of admission and deterioration [outcomes]? Step 2: Acquiring evidence: Search terms: Asthma AND spacer AND nebulizer. Databases: Trip database – 110 results. Best result – Cochrane review. Step 3: Appraising the evidence:

Study group	Intervention	Study type	Outcomes	Key results	Comments
2295 children in 27 trials from emergency and community setting.	Any β 2 agonist given by any nebulizer versus the same β 2 agonist given by metered-dose inhaler with any spacer.	Cochrane systematic review. Only RCTs considered for review.	Primary outcomes : Admission to hospital or duration of stay. Secondary outcomes : Duration in emergency department, change in respiratory rate, blood gases, pulse rate, tremor, symptom score, lung function, use of steroids, relapse rates.	Meta-analysis of probably heterogeneous results. Spacer versus nebulizer relative risk of admission was 0.72 (95% CI: 0.47 to 1.09). In children, length of stay in the emergency department was shorter with spacer, mean difference of −0.53 hours (95% CI: −0.62 to −0.44 hours).	Clear primary and secondary outcome measures. Particular emphasis on the allocation concealment, which in general appears poor in most papers.
Commentary : Acute exacerbation of asthma is common in both hospital and primary care. The airways are narrowed due to mucosal oedema, hypersecretion and bronchospasm. β 2 agonists have been used successfully to relieve the bronchospasm. This paper included RCTs including adults and children. It can be argued that adults and children differ in their ability to use the devices being tested. Therefore, the results for adults and children were separated for each outcome. In this systematic review it was found that the method of delivery of β 2 agonist did not appear to affect hospital admission rates but did significantly reduce the duration of stay in the emergency department. Step 4: Applying the evidence (the clinical bottom line): 1. No outcomes were significantly worse with spacers, and in most cases spacers can be substituted for nebulizers to deliver β 2 agonists in acute asthma (excluding life-threatening asthma). 2. Spacers offer a significant advantage in terms of time spent in emergency department, oxygenation and side effects. 3. Spacers should be routinely used instead of nebulizers to administer β 2 agonists for acute asthma in children and young people. (Strong recommendation, high quality evidence.)

Reference:

Table 39.4

Best evidence topic (BET) – diagnosis

Thangaratinam S, et al. Pulse oximetry screening for critical congenital heart defects in asymptomatic newborn babies: a systematic review and meta-analysis. Lancet 2012;379(9835):2459–64.

Diagnosis – cyanotic heart disease

Scenario: You start at a new hospital where you undertake ‘postnatal checks’ on newborn infants. You notice that in this hospital you do not need to perform post-ductal pulse oximetry testing. You discuss this with your consultant, who asks you to find out more exact details on the benefits of this. Step 1: Asking a question (PICO): In an asymptomatic newborn infant [patient], does post-ductal pulse oximetry [intervention] increase the number of infants correctly identified with congenital heart disease or reduce mortality rates [outcomes]? Step 2: Acquiring evidence: Search terms: (Infant, newborn OR infant* OR newborn OR ‘newborn infant’ OR neonat*) AND (heart defects, congenital OR congenital heart defect* OR Defect*, congenital heart OR heart, malformation of OR heart abnormalit* OR congenital heart disease OR cyanotic heart disease OR cyanotic heart defect OR congenital heart malformation) AND (oximetry OR oximetry, pulse OR blood gas monitoring, transcutaneous OR oximetry, transcutaneous OR oximetry, transcutaneous OR saturation*, oxygen OR oxygen saturation*) Databases: Cochrane: 164 results, 4 non-Cochrane reviews including below meta-analysis. Step 3: Appraising the evidence:

Study group	Intervention	Study type	Outcomes	Key results	Comments
13 eligible studies with data for 229,421 asymptomatic newborn babies. 118 infants with critical congenital heart defects. 748 false positives. 33 false negatives.	Pulse oximetry. 60% of studies used foot alone (postductal).	Systematic review and meta-analysis of 12 cohort and 1 case-control study.	Detection of critical congenital heart defects.	Sensitivity 76.5% (95% CI 67.7–83.5), specificity was 99.9% (99.7–99.9), false positive rate 0.14 (0.06–0.33). Likelihood ratio positive 549 (238–1195), likelihood ratio negative 0.24 (0.17–0.33). Lower false positive rate if oximetry >24 hours (p=0.0017), but no effect on sensitivity.	Clear description of search strategy. No statistical description of heterogeneity. Significant publication bias was reported.
Commentary: Screening for critical congenital heart defects in newborn babies can aid early recognition, with the prospect of improved outcome. In this case, the new doctor was not interested in an individual patient but a population. As the search had the potential to lead to widespread change in the clinical assessment of all newborns, the search for evidence needed to identify the most relevant and highest quality available. The search was therefore very comprehensive. Though this systematic review found that pulse oximetry is highly specific for critical congenital heart disease, it does not look at broader outcomes. For example, do infants who have their diagnosis made earlier using screening have better long-term outcomes (e.g. mortality)? This would be an important consideration when balancing the cost (equipment, time, etc.) of implementing such a screening tool. Step 4: Applying the evidence (the clinical bottom line): 1. Pulse oximetry is a non-invasive test that is easy to perform with high accuracy and could identify other disorders such as septicaemia or symptomatic pulmonary hypertension. 2. The false-positive rate for detection of defects was significantly lower when pulse oximetry was done after 24 hours 3. ‘In view of the many babies that have now been tested with pulse oximetry, further research in this area is unlikely to produce substantially different findings’ 4. Routine pulse oximetry should be undertaken on neonates prior to discharge, ideally after 24 hours. (Strong recommendation, moderate quality evidence.)

NB: The * in the search terms is referring to search truncations to ensure optimum sensitivity of the search (see Table 39.2 ).

Reference:

If performing a more detailed search (e.g. for guideline development) then an extensive search should be undertaken, preferably with the help of an information specialist at your local library.

What is ‘current best evidence’?

A common misconception regarding EBM is that only RCTs or systematic reviews constitute the ‘evidence’ in EBM. Though double-blinded RCTs are often considered the ‘gold standard’ for establishing treatment effects, they will not be the best at answering questions about diagnosis, prognosis and/or harm. Secondly, there may not be RCTs available to answer certain treatment questions. There are barriers to research in child health and this often means that good quality information is unavailable (see Box 37.1 ). If no literature is available to answer your question, then an email/discussion with an expert may be the ‘current best evidence’ for your clinical question. Do not negate the importance of qualitative research, which significantly adds to the wealth of evidence available on particular subjects.