pediatric primary care infectious diseases...pediatric primary care infectious diseases corinne...
TRANSCRIPT
Pediatric Primary care
Infectious Diseases
Corinne Levy, Robert Cohen
ECPCP Autumn meeting – Lyon, France
Friday 8 November 2019 - Sunday 10 November
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The questions are:
Why we have to create ambulatory
networks?
And how ?
Activ birth 👼 Before the 1990s, in France, as in many countries, ambulatory pediatricians were
“excluded” from “research”
Nobody had clearly excluded them, but they were not included in any research project
Clinical studies were performed in hospital by "UNIVERSITIES" with "ACADEMICS ».
Compare to patients in ambulatory settings, patients « profile » seen at hospital are
different:
Severity, epidemiology, resistance, etc…
In this context, we created an non-profit research group, “ACTIV” (Pediatric Clinical
and Therapeutical Association of Val de Marne) and performed the first French clinical
study in an ambulatory setting
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Few words of our research group, ACTIV
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ACTIV is a National Non-Profit
Organization founded in 1988
2 main goals:
- Research in the field of
community acquired infections
- Post-graduate teaching
Funding (pharmaceutical industry >
university > government)
ACTIV board: 12 members
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ACTIV team: 12 members
The research platform
Built over several years
The ACTIV Network is widely represented all over France
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Investigators (pediatricians) and their
training are the cornerstone of the
research system
Investigators quickly and directly
found a real benefit from participation
Adaptation of clinical practices
Feedback to the investigators through
congress organized by and for our
network
Infectious diseases are the most frequent reasons for visits in pediatrics (> 50 à 70% of visits)
• Prevention : Immunization programs and other aspects of well baby visits – Pediatricians are good vaccinators
• Management of community acquired viral or bacterial infections – And frequently the question is: does this patient need antibiotics ?
– Why: It is estimated that antibiotics discovery had prolonged human life do 10 years (As vaccination programs and Hygiene)
– However overuse of antibiotics increase antibiotic resistance
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OR = 2,33 CI 95% 2,19-2,49
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The prescriptions of antibiotics should be guided
by several factors
Usually, medical history, interrogation and examination are sufficient
Sometimes point of care tests could be useful
However, pre-test probability determined by the first point is
always the cornerstone of the test’s accuracy
Does this patient should received antibiotics?
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No
Should I re-evaluate the patient?
Point-of-care test to improve the diagnosis
accuracy ?
Urinary dipstick
Influenza RAT
GAS RAT
Rotavirus RAT RSV rapid test
CRP rapid test?
EBV, Chlamydia, proteinomic…
Does this patient should received antibiotics?
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yes
Which ATB according to the level of resistant strains?
What are the consequences of my ATB prescriptions?
Which treatment duration ?
No Point-of-care test to improve diagnostic
accuracy?
Should I re-evaluate the
patient?
Two examples AOM and Pharyngitis
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AOM studies AOM: leading bacterial infection in childhood
McGrath LJ, PLoS One. 2013; 8(12):e81210
AOM: leading cause of ATB prescriptions
Antibiotics are recommended for young children in most countries in the world
The questions are:
• how to improve the diagnosis?
• which treatment
• which duration?
Comparison of 2 types of ATBs, doses, duration of treatment
Rigorous inclusion criteria
The interpretation of tympanic membrane findings varies by the level of pediatrician experience so…
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AOM : the same disease ?
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Congestive Abnormal color or opacity Bulging Otorrhea
< 6 months 6 months to 2 years > 2 years
Tympanic
aspect
< 38°C 38 to 38.4°C > 38.5°C
Patient
age
Fever
Otalgia
0…………3………….6…………..9……………..12… Number of epidodes
OME between AOM
episodes
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AOM studies
Training sessions to better examine ears
Good otoscopic examination: MANDATORY
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For everyone, in french: https://www.activ-france.com/e-learning/
Entérovirus Autres infections à SGA
Whooping cough, influenza, urinary infections…
The e-learning website
The environment changes (30 years)
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Which impact on
AOM?
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2019
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AOM clinical trials with a network of almost 100 primary care
pediatricians
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AOM ATB treatment depends of the involved bacteria resistance
Sp, Hi, Bc
NP samples
Easy to obtain Painless Non-traumatic Epidemiologic value for monitoring change in bacteria distribution and ATB resistance
Central lab +++
Nasopharyngeal samples
!
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Evaluation of the ecological impact of ATBs for AOMs on composition of NP flora
and ATB resistance
2 NP samples were obtained
before ATB treatment
2/6 days after the end of ATB for AOM
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Among Sp carriers, after ATB treatment, rate of
resistant strains increased after beta-lactam ATB
We had to obtain NP samples for all AOM studies
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To perform these studies we had to deal with…
High-quality standards were required For industrial trials
For European and North American drug regulators
Good Clinical Practice
Publications
And feasibility in real life Simplify as much as possible the work of investigators who enrolled patients in
the study
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One visit = one questionnaire (CRF)
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From ATB treatment to prevention with vaccines
The context: in 2000, PCV7 was soon to be implemented in our country…
The advantage of the expertise acquired
>15000 NP samples collected in 10 years
>15 publications in this field
Which allowed us to perform a pivotal study on NP carriage after PCV7 implementation in France
This study was performed as a post-licensing commitment requested by the
European Medicines Agency to determine the impact of PCV7
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Aim of the study: Determine the changes in pneumococcal serotypes and
change in ATB resistance after PCV7 implementation
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0
10
20
30
40
50
60
70
80
1 (n=663)
2 (n=573)
3(n=658)
4(n=622)
5(n=750)
6 (n=645)
7(n=530)
8(n=600)
9 (n=601)
10(n=598)
11(n=582)
12(n=591)
13(n=578)
14(n=582)
15(n=547)
16(n=539)
17(n=545)
18(n=536)
Sp PCV7 ST ST 6add+6C Non PCV13 ST
% children
Non
PCV13
6
add+6C
Sp
PCV
7
PCV13 PCV7
Sp Nasopharyngeal Carriage, AOM fever± otalgia, 10 740 children, 18 y
-7%
Study Years (Year 1: Oct 2001/June 2002, Year 18: Oct 2018/ April 2019)
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Carriage and penicillin susceptibility by vaccination status and
ATB use within the last 3 months
%
Vaccinated +
Antibiotics+
N=491
PSP
IC95%
33 [29%; 36%]
21 [18%; 24%]
31 [27%; 35%]
24 [20%; 27%]
PIP
IC95% 27
[24%; 30%]
34 [30%; 38%]
24 [20%; 27%]
23 [20%; 27%]
PRP
IC95% 10
[8%; 12%]
15 [13%; 18%]
4 [3%; 6%]
8 [6%; 11%]
Non-carriers
IC95% 30
[27%; 33%]
30 [26%; 33%]
41 [37%; 45%]
45 [41%; 50%]
Vaccinated -
Antibiotics -
N=782
Vaccinated -
Antibiotics +
N=650
Vaccinated +
Antibiotics –
N=603
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Tonsillopharyngitis diagnosis
GAS Virus
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Antibiotics are recommended in most countries
Antibiotics are not recommended
The accuracy of clinical scores are not sufficient for children
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We are able to confirm that
RADT are >>> clinical scores
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Link with the hospital network
Following the successes of our studies and network in
ambulatory settings,
The French Society of Pediatric Infectious Diseases entrusted us
with the surveillance of community acquired infections visiting
emergency room or hospitalized
It was particularly important for pneumococcal diseases : we
need multifaceted impact of PCV implementation
The ambulatory surveillance was not enough to totally evaluate
IPD
National hospital network for bacterial meningitis
A team of pediatricians (n=230) and microbiologists (n=168) in
each participating center had to report standardized clinical and
laboratory data for meningitis
Close collaboration with experts of national reference centers for
different bacterial species
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Our research line for infectious diseases: ambulatory and hospital
Example of studies Cohorts Number of International Publications
Starting
year
Number of
enrolled patients
Where?
NP carriage (AOM+ healthy
controls)
2001 18 000 Ambulatory N=20 (Clin Infect Dis, Vaccine, PIDJ, BMC inf Dis, J Antim
Chem, Emerg Inf Dis, Plos one)
Bacterial meningitis 2001 7200 Hospital N=35 (Lancet Inf Dis, Clin Infect Dis, Vaccine, PIDJ, BMC
inf Dis, Clin Micr, Infect, An Emerg Med, Acta Ped, EJCMID,
J Ped)
Pneumonia 2009 16 000 Hospital N=6 (Jama Ped, Clin Infect Dis, Vaccine, J Ped Inf Dis,
BMC Ped, Arch Dis Child)
IPD 2010 1000 Hospital N=2 (Clin Infect Dis)
IPD ECDC study (SPIDNET) 2013 250 Hospital N=1 (Lancet Resp Med)
E coli ESBL carriage 2010 3600 Ambulatory N=8 (BMC infect Dis, JAC, Emerg Infect Dis, Plos One, Vaccine)
GAS studies 2012 1600 Ambulatory N=14 (Clin Infect Dis, Plos one, CMAJ, J Clin Epidemio, Eur
J Microb, Int J Med Microbiol )
Pertussis 2002 800 Ambulatory N=3 (Vaccine, Emerg Infect Dis, Arch Ped)
Otorrhea 2015 600 Ambulatory N=1 (Plos One)
https://www.activ-france.com/Publis_en.php
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Epidemiology in primary care?
Yes ! if we address areas of concern for primary care physicians
Most of our research projects try to answer a “daily” clinical question related to professional practice in order to promote a pediatric best practices for the benefit of children
• Improving the diagnosis
• Improving the management of pediatric infectious diseases
• Quick practical application for pediatricians+++
Studies initially dealt with respiratory-tract infections, which are particularly
suitable for clinical or epidemiological studies
– their frequency
– the ease in obtaining samples (NP+++)
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A recipe? By co-opting
39
joinmynetwork#pediatricians#research
Conclusion
Always placed investigators and their training at the cornerstone of the research
system
Never forget to provide results of the studies and feedback to the investigators+++ (congress, publications)
Try to have fundings according to the objective of the study scheduled
(government, university and pharmaceutical industry)
Challenges : maintain several well-established
surveillance systems and increase the involvement of
young researcher-pediatricians
“Successes have a thousand fathers, failures are orphans”
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ACKNOWLEDGMENTS