Predicting adverse outcome from lower
respiratory tract infection in primary care:
The 3C cohort study of LRTI in primary care
Moore, M.
Little, P., Stuart B, Smith S, Thompson MJ,
Knox K, van den Bruel A, Lown,M., Mant,D
01 June 2015
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Family Practice in Salisbury
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University of Southampton
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No financial or other
conflicts of interest
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Where?
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Overview
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LRTI- why prescribe?
Methods
Results
Clinical Implications
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Background
Lower Respiratory Tract Infection
LRTI:
• Is common
• Antibiotics often prescribed
NAPCRG 2016
6
Respiratory infection account for the
majority of outpatient prescribing
• UK database data 568 practices 2010-11
• Median prescribing rates
-48% for ‘cough and bronchitis’
-60% for ‘sore throat’
-60% for ‘otitis-media’
• Median for RTI 54% (39-69%) lowest/highest
Background
Drivers of prescribing in LRTI:
• Relief of symptoms?
• Worries about pneumonia?
• Worries about adverse outcome?
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Background- symptom relief?
• Cochrane review acute bronchitis
-17 trials 2936 participants
• No difference in clinical improvement
• Some reduction in cough and night cough
• Modest reduction in cough duration
(-0.46 days)
Cochrane library 2014
Background- symptom relief?
GRACE study whole population n=2061
0.00
0.25
0.50
0.75
1.00
Kaplan-Meier survival estimates
0
10
20
30
analysis time
groupnumber = 0
groupnumber = 1
time to resolution of moderately bad symptoms
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Background- symptom relief?
GRACE study: Missed radiological pneumonia
0.00
0.25
0.50
0.75
1.00
Kaplan-Meier survival estimates
0
10
20
30
analysis time
groupnumber = 0
groupnumber = 1
time to symptom resolution - Xray pneumonia subgroup
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Background- symptom relief?
In Summary: For symptoms:
• Overall cochrane review modest treatment
effect
• GRACE study subgroups: Only those with missed
radiological pneumonia derived significant
benefit
• Worth thinking about the diagnosis of
pneumonia
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Background- worry about adverse
outcome?
• Re-consultation with new or
worsening illness
• Admission
• Death
• Late onset pneumonia
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Methods
 Adults presenting in UK general practice with LRTI
had symptoms, signs, and antibiotic prescribing
strategies recorded.
 Re-consultation with new or non–resolving
symptoms, or hospitalisation or death, were
documented within 30 days.
NAPCRG 2016
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Methods
• Inclusion Patients aged 16 or over presenting in UK
general practice with acute LRTI. We used a pragmatic:
cough as the main symptom, judged to be infective in
origin by the GP.
 Exclusion: other cause of acute cough (e.g. heart failure,
acid reflux, fibrosing alveolitis etc); patients unable to
fill out the diary; immune compromised; previously
presented with the same episode of illness
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Results
 28867 adult patients with acute cough
were recruited with informed consent by
522 general practices in the UK General
Practice Research Network between
October 2009 and April 2013
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Baseline characteristics
 Age >60
 Female
 Co-morbidity
 Hx of fever
 Chills
 Fever >37.8
 Sats <95%
 Low BP
38%
59%
30%
38%
32%
6%
6%
8%
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Results -28867
 37 same day admission to hospital
 6484 patients re-consulted within 30 days
 258 hospitalisations in total
 720 were referred for a chest x-ray in the
first week
 30 patients died
 7349 (25%) no antibiotic
17573 (61%) immediate antibiotic
3819 (13%) delayed antibiotic prescription
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0
5
percent
10
15
Results- re-consultation
0
7
14
21
day reconsulted after initial consultation
28
23
0
5
percent
10
15
Results timing of
admission
0
7
14
21
day hospitalised after initial consultation
28
27
0
5
percent
10
15
Results timing of x-ray
diagnosis pneumonia
0
7
14
21
day xray pneumonia confirmed after initial consultation
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Results- to summarise
Risk of serious adverse outcome after
presentation with LRTI is low in this cohort of
28883
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SAPC 2016
6484 (22%) re-consultation
230 (0.8%) x-ray pneumonia
Admissions 258, 234 (0.8%) related
Deaths 30, 13 related (0.04%)
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Results- modelling
Is it possible to predict those at risk of serious
adverse outcome (admission death)
For the clinician- Well if I don’t decide to admit
you today- how can I tell who might do badly?
273 hospitalisations or deaths
Exclude those
- admitted on the day
-unrelated to index consultation
122 late diagnosis pneumonia (clinical +xray)
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Results- modelling
Risk factors at first consultation for death or
hospitalization from LRTI complications within 30
days or late-onset or unresolved pneumonia
confirmed by x-ray or re-consultation 8-30 days
after first consultation (n=325)
Analyses controlled for antibiotics at index
consultation
Prior probability of serious adverse outcome
325/28830= (1.1%)
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Results- clinical score
 Items carried forward significant at the 1% level
Nine items combined into a total score which
ranges from 0 (none of these) to 9 (all of these).
 The AUROC of this score is 0.72
(Bootstrapped 95% CI 0.69, 0.75).
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Results- clinical score
O2 sat < 95%
Age 60+ years
SBP< 90 or DBP < 60 mmHg
Temp > 37.8°C
Any co-morbidity
Chills
No coryza
Sputum: purulent
Severity assessment > 5/10
Crackles
Shortness of breath
Chest pain
Headache
Risk Ratio (95% CI)
2.37 (1.80, 3.12)
2.02 (1.59, 2.57)
p-value
<0.001
<0.001
1.65 (1.16, 2.33)
1.81 (1.29, 2.55)
1.61 (1.23, 2.11)
1.37 (1.07, 1.74)
1.49 (1.16, 1.91)
0.74 (0.58, 0.95)
1.51 (1.15, 1.97)
1.30 (0.95, 1.78)
1.32 (0.98, 1.79)
1.49 (1.16, 1.91)
0.81 (0.62, 1.06)
0.005
0.001
0.001
0.011
0.002
0.015
0.003
0.098
0.070
0.002
0.119
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Score Items
Age 60+,
Co-morbidity
No coryza
History of chills/shivering
Presence of chest pain
Severity score 6 or over (out of 10)
Low BP (systolic <90 diastolic <60)
Temp>37.8
O2 saturation <95%
,
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Predictive value of
clinical score
Cut off score
to use
1 or more
2 or more
3 or more
4 or more
5 or more
6 or more
7 or more
N (%) of
total
cohort
22,308
(94.5%)
18,237
(77.3%)
11,781
(49.9%)
5,662
(24.0%)
1,969
(8.3%)
525
(2.2%)
90
(0.4%)
Sensitivit Specificit NPV
y
y
PPV
99.2%
5.3%
99.8%
1.2%
96.2%
22.9%
99.8%
1.4%
82.4%
50.4%
99.6%
1.8%
53.4%
76.3%
99.3%
2.5%
27.1%
91.9%
99.1%
3.6%
11.8%
97.9%
99.0%
5.9%
3.8%
99.7%
98.9%
11.1%
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Applying in practice?
• A score of 3 or less
(76% of population) NPV 99.6% No treatment
 A score of 4
(16% of population) PPV 2.5% NPV 99.3%
Delayed?
 A score of 5 or more
8.3% of population PPV 3.6%
Immediate prescription
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Strengths and Limitations
• Observational data residual confounding
• Large numbers of patients in real life
practice
• Over fitting of model
• No validation sample
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Implications for Practice
• A clinical score can be used to predict the
risk of hospitalisation/death/late onset
pneumonia
• Although complex (9 item) it could be used
to direct antibiotic strategy
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Wrapping up
 Overall little symptomatic benefit from
antibiotics
 It is worth spotting ‘missed pneumonia’
 Adverse outcomes are rare after LRTI
 Use a score to identify those at low risk of
adverse outcome
 This low risk group have little or nothing to
gain from antibiotics
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Any Questions?
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