2. Reduction of antibiotic prescriptions for children with RTI in primary care: a cluster RCT
Anne R.J. Dekker, Theo J.M. Verheij, Alike W. van der Velden
Julius Centrum, UMC Utrecht

3. Introduction Infectious diseases common in childhood
262 antibiotics prescribed per 1000 children1
Antibiotics only indicated for pneumonia and for children with specific symptoms/characteristics
Over-prescription in children with RTI: 32%2
Infectious diseases are common in childhood, especially in winterseason, the figure shows disease episodes per 1000 children per year.
262 antibiotics per 1000 children, mostly for RTI including ear infections as you can see in the figure.
Antibiotic treatment is only recommended for pneumonia, vulnerable children and for children with specific or severe signs and symptoms, because most RTIs are viral and self-limiting.3 Besides, the limited effect of antibiotics needs to be weighed against side effects, and the development of bacterial resistance.3
Even in a low prescribing country as the Netherlands, one third of antibiotic prescriptions for children are not indicated according to the guidelines.5
Dekker AR, Verheij TJ, van der Velden AW. Antibiotic management of children with infectious diseases in dutch primary care. Fam Pract
Dekker AR, Verheij TJ, van der Velden AW. Inappropriate antibiotic prescription for respiratory tract indications: Most prominent in adult patients. Fam Pract

4. Aim
To reduce antibiotic prescriptions for children with respiratory tract infections using an online training for GPs and an information booklet for parents.
Prudent antibiotic use is an important goal, in which general practice has a major contribution and responsibility.
We aimed to reduce antibiotic prescriptions for children with RTI using an online training for GPs and an information booklet for parents.
We studied the effectiveness of such an intervention during the RAAK trial.
What is the effectiveness of an online training for GPs and an information booklet for parents on antibiotic prescribing for children with symptoms of respiratory tract infections in primary care?
RAtioneel Antibioticabeleid voor Kinderen met Luchtweginfecties

5. Methods Pragmatic, cluster randomized, controlled trial
Baseline prescription audit in year preceding intervention
Study population:
Children <18 years
Symptoms of a RTI (nose, ear, throat and lower respiratory tract symptoms)
Primary outcome: Antibiotic prescription rate (GP’s registration)
Secondary outcomes
Number of reconsultations and referrals (medical record)
Total and types of dispensed antibiotics (pharmacy data)
The RAAK study was a pragmatic, cluster randomized, controlled trial.
We considered the practice as the unit of randomization and analysis to minimize contamination. GPs within a practice could influence on each other’s behaviour and patients within a practice be managed by different GPs.
In the year before the intervention antibiotic prescribing was assessed to be able to correct for differences in antibiotic prescribing at baseline.
GPs were asked to register 40 consecutive consultations of children younger than 18 years, presenting at the general practice with symptoms of a RTI (nose, ear, throat and lower respiratory tract symptoms) in the year prior and after the intervention.
The primary outcome was the antibiotic prescription rate, retrieved from the consultation report forms filled in by the GPs.
The following secondary outcomes were assessed from the patients’ medical records: number of reconsultations during the same disease episode, number of consultations for new RTIs episodes, and the number of hospital referrals during a follow-up of six months.
Total and types of dispensed antibiotic courses for children <18 were collected via the Dutch Foundation for Pharmaceutical Statistics (SFK).
were calculated by summing the following antibiotics: tetracyclines (J01AA), amoxicillin (J01CA), pheneticillin (J01CE), amoxicillin/clavulanate (J01CR) and macrolides (J01FA), and related to the number of registered children in the practice for the corresponding year.

6. Intervention- Online training
Part 1 General background
Relevance of prudent antibiotic use
Part 2 Information of the 4 national RTI guidelines
Assessment of disease severity and risk factors
Indications for antibiotic treatment
First and second choice antibiotic treatment
Part 3 Training in enhanced communication skills
Information about communication skills
Videos of consultations techniques
The intervention consisted of an online training for GPs and a written information booklet for parents. The online training consisted of three parts:
general background about the relevance of prudent antibiotic use and information about antibiotic related problems,
child specific information of the four national respiratory tract guidelines of the Dutch College of GPs3, including assessment of disease severity, risk factors, signs and symptoms as indications for antibiotic treatment, and the first and second choice antibiotic treatment advise,
training in enhanced communication skills supported with videos of consultation techniques and recorded explanations.
based on the elicit-provide-elicit framework, used in prior antibiotic intervention, adapted to communication with parents.

7. Intervention- Online training GP

8. Intervention- Online training GP
Summary of indications to prescribe antibiotics, type of antibiotic

9. Intervention-Online training GP
Print screens of videos with consultation techniques

10. Intervention- Information booklet parents
The booklet contained the following information in text and pictograms:
how often RTIs occur,
the often viral cause of RTIs and their self-limiting prognosis,
information about why most RTIs do not need to be treated with antibiotics, and antibiotic related problems, including bacterial resistance.
Additionally, self-management strategies for their child, and signs and symptoms when to consult the GP were explained.

11. Results
Characteristics of general practices allocated to intervention and control group
Intervention (n=15)
Control (n=17)
Median list size total (IQR)
2980 ( )
3275 ( )
Median list size children <18 years (IQR)
604 ( )
664 ( )
Participating general practitioners 40 35
Mean age GP (SD)
46.0 (11.0)
45.3 (9.5)
Characteristics of consultations of the follow-up audit after allocation to intervention and control group
Intervention (n=477)
Control (n=532)
Mean age (SD) (years)
4.7 (4.4)
4.4 (4.1)
Median duration of illness before consultation, days (IQR)
5.0 (3-14)
5.0 (3-10)
Mean GPs’ perception of illness severity (1 = not ill, 5 = severely ill) (SD)
1.6 (0.8)
1.9 (1.0)
Fever (%)
257 (53.9)
278 (52.3)
No (%) with symptoms of:
Earache
Runny nose
Sore throat
Cough
177 (37.1)
387 (81.1)
128 (26.8)
358 (75.1)
156 (29.3)
375 (70.5)
121 (22.7)
381 (71.6)
Practices of the intervention and control group were comparable with respect to their total list size and numbers of children, see Table 1. In intervention practices, 40 GPs registered consultations and in the control practices 35 GPs. Pharmacy data were analysed from the same general practices, except from one single-handed GP his pharmacy data could not be obtained reliably.
In total 1009 consultations were registered, 532 from control and 477  from intervention practices. Consultations were comparable with respect to children’s’ age (4.7 and 4.4), median duration of illness before consultation and presentation with fever. Number of symptoms appeared to be higher in the intervention group compared to the control group, especially for earache (37.1% vs 29.3). Illness severity (1.6 and 1.9) and fever (53.9% vs. 52.3%) were comparable, see Table 2.  In flow diagram staan de aantallen die geanalyseerd zijn (dus -3 waar de uitkomst van misten)

12. Results
Effectiveness of the intervention on antibiotic prescription rates in consultations (registered by GPs during consultation)
Intervention
Control
RR (95% CI)
Crude percentage
20% (95/475) 
37% (196/531) 
0.54 (95% CI ; p<0.0001)
Correction for baseline prescription
21%
33%
0.65 (95% CI ; p=0.013)
Effectiveness of the intervention on total and second choice dispensed antibiotics per 1000 registered children per year (pharmacy data)
Intervention
Control
RR (95% CI)
Total AB antibiotics/1000 children/year *
114 ( )
146 ( )
0.78 ( ); p=0.002
Second choice antibiotics/1000 children* 40 49
0.81 ( ); p=0.104
Second choice antibiotic/total number antibiotics*
34%
0.99 ( ); p=0.911
GPs from practices in the intervention group prescribed significantly less antibiotics based on a generlized linear model adjusted for baseline prescription rates (RR RATE RATIO, want count uitkomst door aggregatie praktijken) 0.645, 95% CI ) than from the control group, . In 21.4% of the consultations an antibiotic was prescribed in intervention practices, compared to 33.2% in the control group.
General practices exposed to the intervention reduced antibiotic dispensing with 32 courses per 1000 registered children per year, relative to the control group, according to the full year’s pharmacy data. Controlled for the year preceding the intervention, the mean number of dispensed antibiotics was 114 per 1000 children in the intervention group and 146 per 1000 children in the control group, see table 5. The number of dispensed second choice antibiotics in the intervention group seemed lower (39.9/1000 children) compared to the control group (49.2/1000 children), however, this difference was not significant. The rate of second choice antibiotics over the total amount of dispensed antibiotics did not differ between intervention (34.1%) and control group (34.3%).
*Correction for baseline prescription

13. Results
Effectiveness of the intervention on reconsultation, consultations for new RTI episodes and hospital referral (patient medical registries)
Intervention (n=311)
Control (n=197)
RR (95% CI)
Mean number of reconsultations within the same disease episode (0-8)
0.43
0.76
0.57 ( ; p=0.02)
Mean number of consultations for new RTI episodes within 6 months (0-9)
0.79
0.78
1.01 ( ; p=0.95)
Hospital referral 8%
13%
 0.65 ( ; p=0.23)
Reconsulting during the same disease episode differed significantly between intervention group (0.43), as compared to the control group (0.76),  with a RR of 0.57, see Table 4. There was no difference in the mean number of consultations for new RTIs within 6 months between the intervention (0.79) and control group (0.78), nor for hospital referrals 8% in the intervention and 13%  in the control group. The majority of referrals were to Ear-Nose-Throat specialists for relapsing acute otitis media, indication for tympanostomy tubes, tonsillectomy and/or adenectomy  

14. Summary Less antibiotic prescribed based on two outcomes:
GPs’ registration
Pharmacy data of total antibiotic dispensing during a full year
Proportion second choice antibiotics remained the same
Less reconsultations in the same disease episode
Consultation for new RTI episodes and hospital referral not affected by intervention
Our intervention showed a convincing effect on two outcomes.
Less antibiotic prescriptions, during a GPs’ registration period, as well as total antibiotic dispensing during a full year after the intervention.
The proportion of prescribed first and second choice antibiotics remained the same. The intervention did lower reconsultations in the same disease episode, but did not influence the number of new RTI episodes or hospital referrals.

15. Implications Intervention concise, feasible and valued
Expected to be cost-effective
Development for implementation on national level
Our intervention showed to be effective in reducing antibiotic prescribing, due to feasibility and acceptance.27,28
We expect this intervention to be cost-effective.
The best way to implement this intervention at a national level should be further developed. It is worth considering presentation of the information booklet electronically, via a nationwide evidence-based health website. The Dutch website endorses by Dutch GPs would be ideal,  given its popularity and ability of regulating healthcare usage.35  De tekst in het boekje heb ik eigenlijk voornamelijk van thuisarts.nl en de standaarden.
Furthermore, we would like to encourage other countries with much higher inappropriate antibiotic usage to develop comparable interventions. Effect and acceptance should be further explored in their local context

16. Questions?

18. Results

19. Strengths & Limitations
Convincing effect on two outcomes
Controlled for baseline prescribing
Intervention simple, feasible and valued
Limitations
Pharmacy data include GPs not involved in the trial
Study not powered to measure severe complications
Characteristics of registered consultations differ
Follow up data of a selected group

20. Online training

21. Statistical analysis
Generalized linear model, Poisson distribution for count outcomes and corrected for overdisperision.20 We calculated Rate Ratio’s (RR) with corresponding 95% Confidence Intervals (CI) and controlled for baseline prescription rates.
The pharmacy data were aggregated to the cluster level and analysed similarly as the primary outcome. We controlled for the number of prescription per 1000 registered children during the year preceding the intervention and the number of children within the practice as an offset variable.
We did not adjust for signs and symptoms or diagnoses. Clinical judgment of patients and discrimination of risk classification varies in primary care.21,22 The intervention itself could influence GPs’ assessment of children, which could change labelling and therefore decision making.23