Full text
Whi e Pape : B idging he gap be ween su eillance da a and
an imic obial s ewa dship in he ou pa ien sec o —p ac ical
guidance om he JPIAMR ARCH and COMBACTE-MAGNET
EPI-Ne ne wo ks
Fabiana A ie i
1
†, Si i Go¨pel
2,3
†, Ma cella Sibani
1
*, Elena Ca a a
1
, Ma ia Dile a Pezzani
1
, Ri a Mu i
4
,
Nico T. Mu e s
5
, Lo ena Lo`pez-Ce e o
6
, And eas Voss
7
, Robe o Cauda
4
and E elina Tacconelli
1,2,3
on behal o
he ARCH wo king g oup‡
1
In ec ious Diseases Sec ion, Depa men o Diagnos ics and Public Heal h, Uni e si y o Ve ona, Ve ona, I aly;
2
In ec ious Diseases,
Depa men o In e nal Medicine I, Tu¨bingen Uni e si y Hospi al, Tu¨bingen, Ge many;
3
Ge man Cen e o In ec ion Resea ch (DZIF),
Clinical Resea ch Uni o heal hca e associa ed in ec ions, Tu¨bingen, Ge many;
4
Ins i u e o In ec ious Diseases, Fondazione Policlinico
Uni e si a io A. Gemelli IRCCS, Uni e si a´ Ca olica del Sac o Cuo e, Rome, I aly;
5
Ins i u e o Hygiene and Public Heal h, Bonn
Uni e si y Hospi al, Bonn, Ge many;
6
Mic obiology and In ec ious Diseases Uni , Uni e si y Hospi al Vi gen Maca ena, Se illa, Spain;
7
Depa men o Clinical Mic obiology and In ec ious Diseases, Canisius-Wilhelmina Hospi al, Nijmegen, The Ne he lands
*Co esponding au ho . E-mail: ma cella.sibani@uni .i
†Equally con ibu ing i s au ho s.
‡Membe s a e lis ed in he Acknowledgemen s sec ion.
Backg ound: The ou pa ien se ing is a key scena io o he implemen a ion o an imic obial s ewa dship
(AMS) ac i i ies, conside ing ha o e consump ion o an ibio ics occu s mainly ou side hospi als. This publica-
ion is he esul o a join ini ia i e by he JPIAMR ARCH and COMBACTE-MAGNET EPI-Ne ne wo ks, which is
aimed a o mula ing a se o a ge ac ions o linking su eillance da a wi h AMS ac i i ies in he ou pa ien
se ing.
Me hods: A scoping e iew o he li e a u e was ca ied ou in h ee esea ch a eas: AMS leade ship and accoun -
abili y; an imic obial usage and AMS; an imic obial esis ance and AMS. Consensus on he ac ions was eached
h ough a RAND-modi ied Delphi p ocess in ol ing o e 40 expe s in in ec ious diseases, clinical mic obiology,
AMS, e e ina y medicine o public heal h, om 18 low-, middle- and high-income coun ies.
Resul s: E idence was e ie ed om 38 documen s, and an ini ial 25 a ge ac ions we e p oposed, di e en ia -
ing be ween essen ial o desi able a ge s acco ding o clinical ele ance, easibili y and applicabili y o se ings
and esou ces. In he i s consul a ion ound, p elimina y ag eemen was eached o all a ge s. Fu he o a se-
cond e iew, 6 s a emen s we e e-conside ed and 3 we e dele ed, leading o a inal lis o 22 a ge ac ions in
he o m o a p ac ical checklis .
Conclusions: This Whi e Pape is a p agma ic and lexible ool o guide he de elopmen o calib a ed
su eillance-based AMS in e en ions speci ic o he ou pa ien se ing, which is cha ac e ized by subs an ial in-
e - and in a-coun y a iabili y in he o ganiza ion o heal hca e s uc u es, main aining a global pe spec i e
and aking in o accoun he easibili y o he a ge ac ions in low- esou ce se ings.
In oduc ion
An imic obial s ewa dship (AMS) in he ou pa ien se ing is a c i ic-
al aspec wi hin a global scena io o he con inuous inc ease in
an imic obial esis ance (AMR) and o e consump ion o an ibio ics,
which mainly occu s (app oxima ely 80%–90%) ou side hospi-
als.
1–3
Hence, i is impossible o hypo hesize any AMS in e en ion
in he ou pa ien se ing wi hou he abili y o adequa ely ack
an imic obial use (AMU) and AMR. This p ocess can be done in se -
e al ways, om single p esc ibing uni s o la ge e i o ial a eas,
and should be able o gua an ee eedback o indi idual p esc ibe s
and allow benchma king wi h egional and na ional da a. Due o
V
CThe Au ho (s) 2020. Published by Ox o d Uni e si y P ess on behal o he B i ish Socie y o An imic obial Chemo he apy.
This is an Open Access a icle dis ibu ed unde he e ms o he C ea i e Commons A ibu ion Non-Comme cial License (h p://c ea i ecom
mons.o g/licenses/by-nc/4.0/), which pe mi s non-comme cial e-use, dis ibu ion, and ep oduc ion in any medium, p o ided he o iginal
wo k is p ope ly ci ed. Fo comme cial e-use, please con ac [email p o ec ed]
ii42
J An imic ob Chemo he 2020; 75 Suppl 2: ii42–ii51
doi:10.1093/jac/dkaa428
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he ele ance o hese da a, many e o s ha e been unde aken
a he in e na ional le el (WHO, ESAC ECDC, Canadian
An imic obial Resis ance Su eillance Sys em, Japanese
An imic obial Consump ion Su eillance) o s anda dize epo ing.
Howe e , he he e ogenei y o me ics o AMU su eillance, espe-
cially o he ou pa ien se ing, makes i di icul o o mula e clea
ecommenda ions on which me ic should bep e e ed.
4
While many AMS in e en ions ocus on educing consump ion,
i is impo an o poin ou ha in many se ings he AMS p o-
g amme is de eloped o educe AMR. In he ou pa ien se ing, a
numbe o ini ia i es (i.e. educa ional ools and awa eness cam-
paigns) ha e been p o ed o be success ul in enhancing app op i-
a eness o p esc ip ions. Howe e , al hough good examples o
bo om-up AMS ini ia i es in eg a ed in o ou pa ien daily clinical
p ac ice a e inc easingly being desc ibed,
5
high-quali y e idence
da a showing he impac o such ini ia i es on mic obiological ou -
comes a e s ill limi ed, mainly because o sca ce and he e oge-
neous epo ing o da a.
6
Indeed, when i comes o he o he pilla
o AMS in e en ions (i.e. moni o ing AMR), he ou pa ien se ing is
e en mo e challenging because mos he apeu ic decisions a e
made empi ically. Mic obiological da a, when a ailable, a e di i-
cul o in e p e and a e a ely ep esen a i e o he gene al
popula ion.
Despi e he a ailabili y o guidelines o implemen a ion and
managemen o AMS p og ammes in he communi y (CDC Co e
Elemen s and Field Guide, SHEA MITIGATE o Eme gency
Depa men and U gen Ca e, Join Commission An imic obial
S ewa dship Ambula o y Ca e), p ac ical ecommenda ions on
how p esc ibe s should ela e o local mic obiological and con-
sump ion da a o imp o e p esc ip ions a e a ely discussed.
Undoub edly, in a con ex whe e each coun y has i s own legisla-
ion egula ing bo h an ibio ic policies and ou pa ien en i ies, i is
di icul o issue widely applicable ecommenda ions. The ou -
pa ien se ing can be an elusi e concep o ou line and se e al
de ini ions a e ound in he li e a u e (Table1); addi ionally, i s o -
ganiza ion has been con inuously and apidly changing in ecen
decades, e en in low- and middle- income coun ies (LMICs).
7,8
Fo he pu poses o his esea ch pape , JPIAMR ARCH and
COMBACTE-MAGNET EPI-Ne
9,10
ha e ha monized e o s o
ou line a s uc u ed app oach ha p o ides a se o ac ions o
acili a e an ibio ic policy in e en ions and d i e he link be ween
su eillance da a on AMR and an ibio ic consump ion and imple-
men a ion o AMS ac i i ies.
The in e na ional expe panel has p oduced a se ies o Whi e
Pape s ocused on ou di e en se ings: hospi al; ou pa ien ;
long- e m ca e acili ies (LTCFs); and e e ina y. The esea ch
ques ions ha cons i u e he e idence base o he ecommenda-
ions ocused on h ee main a eas: (i) leade ship commi men ,
accoun abili y and AMS eam; (ii) AMU and AMS; and (iii) AMR and
AMS. The inal lis o a ge ac ions summa izes he epidemiologic-
al, mic obiological and an imic obial da a ha a e essen ial o
an ibio ic p esc ibing and policy. The en i e p ocess was unde -
pinned by a s ong ocus on he easibili y o he ac ions and he
One Heal h app oach. This pape ocuses on he ou pa ien se ing,
namely any ca e se ice p o ided o pa ien s who a e no admi -
ed oa hospi al o LTCF, anging om immedia e ea men o an
acu e and o en se ious illness (e.g. eme gency ou pa ien clinics)
o ou pa ien special y clinics and p ima y heal h ca e acili ies
ha p o ide p e en i e and cu a i e se ices (Table 1). The
in ended audience o his Whi e Pape is heal hca e p o essionals
and leade s wo king in ou pa ien clinics in high-income coun ies
who a e willing o es ablish o implemen an e ec i e AMS p o-
g amme; howe e , speci ic e e ences o LMICs a e also p o ided
whene e easible and ele an . The checklis s p oduced a e
a ailable o download on he ARCH websi e,
9
and can be used as
p ac ical ools by heal h p o essionals and policymake s o es ab-
lish and/o moni o s ewa dship ac i i ies. Dissemina ion will be
ensu ed by he ne wo ks in ol ed in he JPIAMR ARCH p ojec ha
a e lis ed in Table 1o he i s pape in his se ies.
11
Me hods
Using a One Heal h app oach, he p esen p ojec was concei ed o de elop
expe consensus based on e alua ion o he a ailable li e a u e and guid-
ance documen s on AMS and su eillance. This was ollowed by he de el-
opmen o a i s d a o a ge s and a RAND-modi ied Delphi p ocess o
he de ini i e alida ion o a ge s (p o ocola ailable a he ARCHwebsi e).
9
The en i e p ocess is desc ibed in he i s pape o his se ies, which ocuses
on he hospi al se ing.
11
B ie ly, he p ocess in ol ed he ollowing: de el-
opmen o key esea ch ques ions (lis ed in Table3o he i s Whi e Pape
o his se ies) de i ing om a sys ema ic e iew p e iously de eloped o
p o ide guidance on he AMR su eillance modali ies ha a e bes sui ed o
d i ing s ewa dship in e en ions in hospi als (EPI-Ne COACH p ojec );
12
a
na a i e e iew o he a ailable e idence; he p oduc ion o a i s d a o
a ge s p o ided o he expe s in a web-based su ey in which ag eemen
was exp essed on a nine-poin Like scale; a 2 day ace- o- ace mee ing
held a he end o Oc obe 2019. Fo he li e a u e sea ch, ele an publica-
ions in English, published in he las 10yea s, we e sc eened wi h a s ep-
wise app oach: i s , guidance ( om scien i ic socie ies, in e na ional and
na ional au ho i ies) and documen s included in he EU-JAMRAI eposi-
o y
13
we e assessed, and hen he sea ch was ca ied ou using MEDLINE
(Na ional Lib a y o Medicine, Be hesda, MD, USA) wi h a combina ion o he
ollowing e ms: an imic obial, consump ion, ou pa ien , an imic obial d ug
esis ance and su eillance.
Nex , du ing he ace- o- ace mee ing, he expe s we e p esen ed wi h
a summa y o he e idence, discussed he esul s o he online su ey and
inalized he lis o a ge s. Recommenda ions, s a e o he a , and o iginal
app oaches we e e alua ed by ocusing on easibili y and adap abili y o
di e en economic and heal hca e con ex s o compile a lis o ‘essen ial’
and ‘desi able’ a ge s. Ta ge s we e ecognized as ‘essen ial’ when widely
Table 1. De ini ions o ou pa ien se ings
Re e ence De ini ion
59 An ou pa ien is a pe son who goes o a heal hca e acil-
i y and who lea es he acili y wi hin 3 h o he s a o
consul a ion. An ou pa ien is no o mally admi ed o
a acili y.
60 Ca e p o ided in acili ies whe e pa ien s do no emain
o e nigh (e.g. hospi al-based ou pa ien clinics, non--
hospi al-based clinics and physician o ices, u gen
ca e cen es, ambula o y su gical cen es e c.).
61
a
Any ca e se ice p o ided o pa ien s who a e no admi -
ed as inpa ien s o a hospi al.
a
Fo he pu poses o his documen , we conside ed his b oad de ini ion
o ou pa ien se ing; howe e , mos o he e idence ound in he li e a-
u e e iew was ela ed o GP clinics, amily physician clinics and paedia -
ic clinics.
Linking su eillance wi h AMS in he ou pa ien se ing JAC
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p ac icable i no al eady b oadly accomplished, and ‘desi able’ in he case
o limi ed easibili y o esou ce cons ain s. Topics o which mo e e idence
was equi ed in o de o d aw up ecommenda ions we e de inedas p io i y
opics o u u e esea ch. A o al o 40 expe s om 18 coun ies and 30
ne wo ks de eloped he p o ocol, con ibu ed o eaching a consensus and
app o ed he inal lis o indica ions (see i s pape in his se ies).
Resul s
A o al o 38 documen s we e included o he app aisal,
2,6,14–49
co e ing all egions wo ldwide; howe e , he majo i y (32, 84%)
we e om Eu ope, No h Ame ica o he Eas Asia and Paci ic
egions. Mos o he e idence was e ie ed om guidelines, sys-
ema ic e iews, p ac ical guides o ools, s udies and su eillance
epo s, mos ly encompassing adul and paedia ic se ings.
A limi ed numbe o expe opinion and s udy p o ocol documen s
we e also included.
E idence o he leade ship commi men , accoun abili y and
AMS eam esea ch a ea was e ie ed om 10 guidelines, 3 sys-
ema ic e iews and 1 s udy p o ocol, while e idence ela i e
o AMU and AMS was ob ained om 8 guideline documen s, 6
e iews, 13 s udy a icles o epo s, 3 p ac ical ools and 1 expe
opinion. No guidelines speci ically add essing AMR and AMS we e
iden i ied, and e idence o his opic was e ie ed om eigh
documen s, including e iews, s udies, a ew p ac ical ools and
expe opinion.
P elimina y s a emen s o he h ee a eas o esea ch (leade -
ship commi men , accoun abili y and AMS eam; AMU and AMS;
and AMR and AMS) we e es ablished. Twen y expe s a ed he ini-
ial s a emen s h ough an online su ey and ag eemen was
eached o all o hem; howe e , du ing he ace- o- ace mee ing
(Oc obe 2019) some aspec s we e discussed u he : 6 s a e-
men s we e e-conside ed and e-ph ased and 3 we e dele ed,
leading o a lis o 22 a ge ac ions ha we e app o ed in hei
inal e sion by he en i e panel. Tables2–4, espec i ely, lis he
ecommended a ge s o he h ee a eas o esea ch. Due o lack
o e idence o expe ag eemen , i was no possible o o mula e
a ge s on one esea ch ques ion o AMU and AMS and on h ee
esea ch ques ions o AMR and AMS, highligh ing he gaps in he
li e a u e and expanding he lis o esea ch p io i ies (Table 5).
Discussion
Leade ship commi men , accoun abili y and
an imic obial s ewa dship eam
The ou pa ien se ing is cha ac e ized by consis en in e - and
in a-coun y a iabili y in he o ganiza ion o heal hca e s uc-
u es, which e lec s he complexi y in he design o AMS
p og ammes. Ne e heless, i is c ucial o iden i y a clea leade
(o leade s) o guide he AMS eam and ac i i ies.
19,50
In la ge ad-
minis a i e se ings such as ou pa ien clinics, an o ganiza ional
s uc u e ollowing he ‘hub and spoke’ model can be conside ed.
Fo example, in he case o an ou pa ien se ice linked o a hos-
pi al, esou ces such as he mic obiology labo a o y, pha macy, IT
s uc u e and guidance by in ec ious disease specialis s can be
used o d i e AMS ac i i ies, while in low-income coun ies exis ing
p og ammes such as hose o HIV, mala ia and ube culosis can
be in eg a ed wi h AMS o sa e esou ces. By con as , in he case
o smalle p esc ibing uni s such as single GPs, den is s o o he
special ies, a clea AMS leade should be iden i ied o each uni .
The wo king g oup highligh ed he c ucial ole o se e al di e en
p o essionals wi hin he ou pa ien se ing. GPs a e necessa ily he
pi o s o mos AMS ac i i ies in his se ing; howe e , depending on
he esou ces and speci ic cha ac e is ics, leading oles can be
assigned o o he physicians, a physician’s assis an , an ad anced
p ac ice egis e ed nu se o a pha macis . The inclusion o a dis ic
pha macis can be a key elemen o deli e messages o pa ien s
and physicians,
21,51
especially, bu no only, in low- esou ce se -
ings and in coun ies wi h a high p opo ion o unp esc ibed
Table 2. Leade ship commi men , accoun abili y and an imic obial s ewa dship eam in he ou pa ien se ing
Pa icipan s in he an imic obial s ewa dship eam
1.1. Essen ial
The AMS eam should be mul idisciplina y. Co e membe s should include leade s wi h expe ience in AMS and su eillance, a ep esen a i e o pha -
macies in he local dis ic and a ep esen a i e o gene al p ac i ione s.
1.2. Desi able
Include addi ional igu es in he co e g oup acco ding o he se ing, esou ces and ype o in e en ion (i.e. o he specialis s om a ge wa ds, in ec-
ion con ol nu ses and IT expe s).
Ins i u ional suppo o he o ganiza ion and managemen o an imic obial s ewa dship p og ammes: legal amewo k
1.3. Essen ial
Regula e and p omo e AMS ac i i ies a e e y le el o heal hca e o ganiza ion wi h well-de ined oles, esponsibili ies and a clea go e nance
s uc u e.
Ins i u ional suppo o he o ganiza ion and managemen o an imic obial s ewa dship p og ammes: s a ing pe sonnel
1.4. Essen ial
Include dedica ed ime and speci ic sala y suppo o AMS ac i i ies as pa o AMS p og ammes.
1.5. Essen ial
Alloca e ull- ime equi alen s acco ding o na ional equi emen s o he di e en se ings and le el o in e en ion, whe e a ailable.
A ie i e al.
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an ibio ic sales whe e pha macies and o he p i a e d ug s o es
ep esen he p ima y access poin s o an imic obials.
52
O he po-
en ial pa ne s, especially in he case o smalle adminis a i e
uni s, can be local heal hca e depa men s, heal h insu ance com-
panies, heal hca e p o essional socie ies, local mic obiology labo-
a o ies and LTCFs. In LMICs, he in eg a ion o AMS e o s in o
Table 3. An imic obial usage and an imic obial s ewa dship in he ou pa ien se ing
Which an ibio ics should be moni o ed?
2.1. Essen ial
Include as minimum equi emen s o moni o ing:
- o e all consump ion o an ibio ics
- IV and o al an ibio ics used in high olumes o acco ding o he local anking (5–10 mos used agen s)
- an imic obials included in he Wa ch and Rese e ca ego ies WHO Essen ial D ug Lis AWARE index
- an ibio ics used o ea ing in ec ions caused by locally clinically ele an esis an pa hogens as de ined by he AMS eam
2.2. Desi able
Moni o he o al consump ion o sys emic an imic obials (ATC J01 class), bo h IV and o al o mula ions, as o e all agg ega ed da a and as sub-
classes o indi idual agen s.
2.3. Desi able
S a i y da a by p esc ibing medical special y (i.e. gene al p ac i ione , paedia ician, den is ) o allow o benchma king. Ta ge indica ions/
synd omes o which an ibio ics should be moni o ed:
- Respi a o y ac in ec ion (RTI), including uppe and lowe RTI
- U ina y ac in ec ion
- Dia hoea (depending on local epidemiology and ele ance)
- Sexually ansmi ed diseases
- Skin and so issue in ec ions
Which me ics should be employed?
2.4. Essen ial
Fo na ional/ egional su eillance, moni o DDDs pe 1000 inhabi an s pe day and numbe o p esc ip ions pe 1000 inhabi an s pe yea
2.5. Essen ial
Fo su eillance a he p esc ibe le el, moni o numbe o p esc ip ions ei he pe 100 pa ien s/yea o 100 pa ien con ac s/yea
2.6. Desi able
Fo na ional/ egional su eillance, moni o numbe o p esc ip ions pe 100 physician con ac s/yea
2.7. Desi able
Fo su eillance a he p esc ibe le el, moni o DDD pe 100 pa ien s pe yea
2.8. Desi able
Fu he me ics should be based on logis ics and he ypes o An imic obial S ewa dship in e en ions ha will be implemen ed; o in e en ions a -
ge ing o e -p esc ip ion o speci ic diagnoses, moni o p esc ip ion a e o speci ic diagnoses [p esc ip ion/indica ion/p esc ibe /yea (mon h)].
Repo deli e y
2.9. Essen ial
Make local agg ega ed da a a ailable o physician ne wo ks and speci ic p esc ibing uni s. S a i ica ion by special y o indica ion should be done
whene e possible.
2.10. Desi able
I consump ion da a b oken down by single p esc ibe ac i i y (i.e. numbe o DDDs o p esc ip ions a ibu able o each indi idual gene al p ac i ione
o o he p esc ibe s) a e a ailable, deli e hem o he speci ic p esc ibing uni s, making hem a ailable o p esc ibe s and ca egi e s, bu also o
adminis a ion. Pe o m u he agg ega ion by special y o s a i ica ion by indica ion whene e possible.
Which ime in e al should be used o epo ing?
2.11. Essen ial
P o ide an imic obial consump ion da a on a egula basis, a leas annually.
2.12. Desi able
The da a should be agg ega ed a leas qua e ly o allow o desc ibing seasonal a ia ion in ends in high-usage indica ions o espi a o y
in ec ions.
Linking su eillance wi h AMS in he ou pa ien se ing JAC
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well-es ablished s uc u es o su eillance and ea men o com-
municable diseases such as HIV, mala ia and ube culosis was
iden i ied by he panel as a s a egy o use in he implemen a ion
o AMS ac i i ies.
In e ms o ins i u ional suppo h ough a legal amewo k,
he a ailable li e a u e mos ly ocuses on he ele ance o he
commi men o public heal h au ho i ies in p omo ing AMS
and communica ing wi h pa ien s and heal hca e p o essionals,
iden i ying AMS coo dina o s a a local le el and including AMS-
ela ed du ies wi hin job desc ip ions.
19,22,25,50
Some coun ies, o
example, ha e implemen ed inancial incen i es o p ima y ca e
p o ide s. Pay- o -pe o mance sys ems a e implemen ed wi hin
he UK’s Na ional Heal h Se ice, he na ional heal h se ice in
F ance and he heal hca e sys em in he USA.
An imic obial usage and an imic obial s ewa dship
The a ailable guidance on AMS in he ou pa ien se ing sugges s
moni o ing p esc ip ions o condi ions ypically associa ed wi h a
high a e o inapp op ia e p esc ibing wi hou indica ing speci ic
pha maceu ical ca ego ies. Cu en ly, mos high-income coun ies
and an inc easing numbe o LMICs ha e da a lows om eim-
bu semen o sales eco ds ha can p o ide da a o na ional o
in e na ional su eillance sys ems. Pe iodic epo s o elec onic
ools allow open consul a ion o hese su eillance da a a
he coun y o egional le el,
27,31
wi h he addi ional possibili y o
acking consump ion o sys emic an ibio ics (ATC J01) in dis inc
hospi als and communi ies. In some cases, he da a can be also
b oken down o J01 subg oups o o single agen s and p esen ed
as absolu e consump ion o single classes o as he a io o b oad-
spec um an ibio ics o o al consump ion. An imic obials o he
han an ibio ics (e.g. an imycobac e ials, an ipa asi ics) may also
be a ailable insome cases.
The AWARE index, in oduced by he WHO, appea s o be a
p omising globally o ien ed app oach o da a s a i ica ion and
e alua ion o pe o mance.
53,54
Mos na ional ac ion plans, as well
as he WHO ‘adop AWaRe’ ini ia i e, es ablish goals in e ms o
desi able shi s in consump ion (i.e. educ ion o inc ease in con-
sump ion o speci ic agen s, classes o o he de ined ca ego ies).
Conside ing he in insic need o benchma king and imp o e-
men s in acking, he a ge s p oposed by he expe panel a e
in ended o p omo e alignmen be ween local and e e al AMU
da a. T acking consump ion a he ATC J01 subclass o agen le el
ep esen s he mos desi able op ion, bu i s easibili y is es ic ed
o well-s uc u ed con ex s such as hospi al ou pa ien clinics o
coun ies whe e p ima y ca e se ices a e o ganized on a local
basis and include a cen alized pha macy se ice ha is able o
main ain a comple e and upda edda a low. Consis en wi h o he
human se ings, o he ou pa ien se ing he expe s p oposed a
less demanding, bundle app oach as an essen ial a ge , which
equi es moni o ing, beyond o e all consump ion, o he mos e-
quen ly p esc ibed agen s, including hose in he Wa ch and
Rese e ca ego ies o he WHO AWaRe index and o he an ibio ics
speci ically indica ed by he AMS eam, conside ing local epidemi-
ology (Table3).Thein oduc iono moni o ingo IVan ibio ics
(Table 3, a ge 2.1) inds i s a ionale in he g owing implemen a-
ion o se ices o IV adminis a ion wi hou hospi al s ay h ough
communi y-based managemen , such as ou pa ien pa en e al
an imic obial he apy (OPAT). Fo su eillance pu poses, consump-
ion in he communi y se ing is epo ed as DDDs pe 100 o 1000
inhabi an s. A p e ious consensus e o , aiming o de elop a se
o quan i a i e AMS me ics o be employed in ou pa ien s,
highligh ed he need o combine mo e han one me ic o o e -
come in insic pi alls and op imize in e p e a ion.
39
Conside ing
di e en AMS o ganiza ions and le els o in e en ion, he expe
panel p o ides dis inc s epwise app oaches (Table 3, a ge s 2.4–
2.8). Whe e a cen alized pha macy se ice is in place, DDD-based
me ics a e easy o ob ain and can be ou inely calcula ed o
moni o ing o consump ion, handling cos s and eimbu semen s;
in his con ex , ob aining he numbe o p esc ip ions equi es add-
i ional wo k and dedica ed esou ces. When ini ia i es o AMS
Table 4. An imic obial esis ance and an imic obial s ewa dship in he ou pa ien se ing
Which esis an pa hogens should be a ge ed?
3.1. Essen ial
Iden i y and moni o mos p edominan esis ance pa e ns among u ina y ac cul u es.
How should esis ance be moni o ed?
3.2. Desi able
All samples (ob ained inside and ou side he hospi al) should be clea ly ca ego ized in heal hca e-associa ed o communi y-acqui ed samples o
allow o isk s a i ica ion and di ec empi ical he apy in ou pa ien and hospi al se ings.
Wha ime in e al should be used o epo ing an imic obial esis ance su eillance da a?
3.3. Essen ial
P o ide esis ance su eillance da a a leas yea ly, epo ing only da a o which 30 o mo e isola es a e a ailable.
Should he epo be deli e ed o heal hca e p o essionals o he han he an imic obial s ewa dship eam?
3.4. Essen ial
Deli e a epo o p esc ibing uni s, making hem a ailable o p esc ibe s and ca egi e s, bu also o adminis a ion.
3.5. Desi able
Deli e a epo o p esc ibe s wi h a commen a y; conside highligh ing speci ic da a ha migh equi e e-e alua ion o he apeu ic guidelines.
A ie i e al.
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e o s come om small p esc ibing uni s, simple da abases can
eco d he numbe o p esc ip ions o e ime. As a u he s ep, he
panel encou ages da a s a i ica ion based on p esc ibe speciali y,
and sugges s he acking o p esc ip ions (o e all olumes as well
as ela i e consump ion o speci ic an imic obial agen s/classes)
ackling high-p io i y condi ions, such as hose o which an ibio ics
a e o e p esc ibed (e.g. acu e b onchi is, i al pha yngi is) o a e
likely o be ine ec i e due o inc easing esis ance a es [e.g. u in-
a y ac in ec ions (UTIs) and sexually ansmi ed diseases].
Al hough his app oach equi es de ailed eco ding o p esc ibing
indica ions ha is a ely in place, i s implemen a ion would allow
meaning ul benchma king andda a acking imp o emen s.
The da a collec ed should be egula ly dissemina ed o admin-
is a o s and p esc ibe s (Table 3 a ge s 2.9–2.12). The a o emen-
ioned s a i ica ion should be employed o ailo epo s,
which should also conside he speci ic in e en ion o be imple-
men ed and goals o be pu sued. Regional o local, agg ega ed,
popula ion-based da a should be p o ided o inc ease awa eness
o p esc ibe s and adminis a o s ega ding he dis ance om bes
p ac ice and p og ess made o e ime, as well as o p omo e
sha ed e o s wi hin he same a ea and ac oss he con inuum o
ca e (e.g. e e al hospi als and su ounding LTCFs). The impo -
ance o complemen ing da a dissemina ion wi h s uc u ed edu-
ca ional ac i i ies o os e unde s anding and enhancing desi able
p esc ibing p ac ice is u he s essed by he panel.
De ailed da a o single p esc ibing uni s (small p esc ibe
g oups, ambula o y ca e) o indi idual p esc ibe s allow pee
compa isons o pe o mance, an app oach ha has been demon-
s a ed o be highly e ec i e in ou pa ien AMS.
55,56
To p o ide
meaning ul and close- o-p ac ice da a, annual epo ing is sug-
ges ed. Qua e ly agg ega ed da a and co esponding epo ing,
when olume o use is la ge enough o p o ide eliable da a,
has he po en ial o e eal seasonal ends ha wa an u he
in es iga ion o speci ic coun e measu es.
Sel -medica ion and o e - he-coun e dis ibu ion we e also
acknowledged by he membe s o he panel as issues ha can
ha e an impo an impac on AMR, especially (bu no only) in
LMICs whe e policies egula ing he sale o an imic obials, includ-
ing he equi emen o a p esc ip ion o human use, a e no in
place.
57,58
Es ima ing he amoun o his dispensing ou e was
deemed o be o alue. Howe e , conside ing ha local and na-
ional heal hca e au ho i ies a e esponsible o his a he han
single p ac i ione s o a local AMS eam ac ing in small p esc ibing
uni s, a e discussion he a ge was dele ed om he lis and
ou lined as a opic o u u e esea ch (Table 5).
An imic obial esis ance and an imic obial s ewa dship
Wi h ega d o AMR su eillance, e idence on speci ic pa hogens
o be a ge ed in he ou pa ien se ing is limi ed. The majo i y o
guidance documen s sugges he acking o an ibio ic esis ance
ends among ‘common ou pa ien pa hogens’, communi y-
associa ed Clos idioides di icile in ec ions and in ec ion a es wi h
‘mul id ug- esis an o ganisms’ wi hou speci ying which pa ho-
gens.
22,38,47,48
This limi a ion is mainly ela ed o he ac ha , in
Table 5. Resea ch p io i ies
•De elop s anda dized and eliable su eillance de ini ions and ou come da a
Ra ionale
While c i e ia o disc imina e hospi al- om communi y-acqui ed in ec ions exis , mic obiological samples submi ed om ou pa ien se ings
may no e lec he ue o igin o in ec ions. Resis ance a e in he communi y could be o e es ima ed when o e ep esen a ion o samples om
pa ien s wi h speci ic isk ac o s (e.g. exposu e o heal hca e acili ies such as day se ice p ac ices, indwelling de ice ca ie s, ecu en in ec ions,
e c.) occu s. S anda dized de ini ions allowing unambiguous iews o he mos p obable se ing o in ec ion acquisi ion, u he pa ien -based
s a i ica ion c i e ia (e.g. age, gende , speci ic isk ac o ) and he es ablishmen o he minimum numbe o isola es necessa y o p o ide consis -
en da a, would help in collec ing mo e eliable su eillance da a o in o m p esc ibing p ac ice and empi ical he apy.
•App aise and es ablish new s a egies o AMU su eillance in communi y
Ra ionale
As cu en me ics and o ma s o AMU moni o ing we e de eloped o su eillance no di ec ly conside ing AMS goals and s a egy, he mos
e ec i e me hods o an imic obial consump ion da a collec ion in he communi y se ing s ill ha e o be iden i ied, especially in ega d o i s co -
ela ion wi h an imic obial esis ance ends. The easibili y/ eliabili y o poin p e alence su eys (PPSs) o an ibio ic use in he communi y se ing
ha e been poo ly explo ed un il now.
The assessmen o sel -medica ion and o e - he-coun e dispensing a na ional, egional and local le els ( h ough PPSs o o he sui able
me hodologies) would no only p o ide essen ial da a o co ec ly es ima e ac ual an imic obial consump ion, bu would also guide policymake s
in es ablishing an imic obial dispensing egula ions.
•Gene a e e idence o unde s and he ole o accina ion in AMS
Ra ionale
Many AMR egula o y documen s and AMS guidance poin ou accina ion as a p omising s a egy o limi AMR. E en hough he a ional o his en-
do semen appea s clea , limi ed s udies ha e analysed an imic obial consump ion and esis ance end a ia ions as di ec e ec s o accina ion
campaigns o he associa ion be ween accina ion co e age and an imic obial usage and esis ance a e. Mo e e idence is needed on he e ec
o accines on an ibio ic use and esis ance. Solid s a is ical ools and adequa e s udy designs o assess such a link should be e alua ed and
implemen ed.
Linking su eillance wi h AMS in he ou pa ien se ing JAC
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he ou pa ien con ex , mic obiological analysis o a ious speci-
mens o de e mine pa hogens and ela ed suscep ibili ies is o en
imp ac ical. Some e iew documen s ocus on he mos common
in ec ions, such as espi a o y ac in ec ions (RTIs) and UTIs.
Consequen ly, he mos ele an pa hogens a e S ep ococcus
pneumoniae,Haemophilus in luenzae,Mo axella ca a halis,
Mycoplasma pneumoniae and En e obac e iaceae.
47
Acknowledging he di icul ies associa ed wi h sample collec ion,
he panel conside ed ha moni o ing RTI esis ance in ou pa ien s
is no easible, as only a ew samples a e no mally submi ed o
mic obiological analysis. Acco dingly, i was decided o ocus on
synd omes displaying a g ea e bu den o esis ance, sugges ing
ha esis ance be moni o ed only o UTIs (Table 4, a ge 3.1).
Ne e heless, he impo ance o ca ego izing all samples
(ob ained bo h in and ou o hospi al) in heal hca e-associa ed o
communi y-acqui ed se ings o allow isk s a i ica ion and di ec
empi ical he apy in ou pa ien and hospi al se ings was unde -
lined. Fu he s a i ica ions by gende , age and isk ac o s we e
discussed, bu hey we e no included in he inal a ge s due o
lack o easibili y and eliabili y.
On AMR epo ing, he expe panel ag eed on he ac ha he
epo should be deli e ed o all p esc ibing uni s and heal hca e
au ho i ies. I should be made a ailable o adminis a ion, p e-
sc ibe s, ca egi e s and nu ses o all uni s. The expe panel u he
s essed he impo ance no only o passi ely deli e ing a epo ,
bu also o linking dissemina ion o su eillance da a wi h s uc-
u ed educa ional ac i i ies o imp o e unde s anding and d i e
clinical p ac ice. Howe e , conside ing possible esou ce con-
s ain s, his was held o be desi able and no essen ial ( a ge 3.5).
I was also sugges ed ha an English e sion o he epo be
included o os e he sha ing o in o ma ion be ween coun ies.
Mo eo e , as p e iously ad oca ed,
58
he panel highligh ed he
ac ha educa ional e o s should a ge no only physicians, bu
also unde g adua e s uden s. In his con ex , he unde g adua e
cu iculum could be expanded o allow eaching o he p inciples
o mic obiology, in ec ious diseases and clinical pha macology
wi h emphasis on AMR and p uden p esc ibing.
The a ailable li e a u e did no allow he de elopmen o
de ailed indica ions on a ew impo an ques ions ela ed o AMU
epo ing and AMR moni o ing and epo ing in he ou pa ien se -
ing. The esea ch ques ion ini ially o mula ed o opic 2, ‘Which
c i e ia should be used o de ine a anking o an ibio ic use?’, and
he esea ch ques ions o opic 3, ‘Should non-clinical samples (e.g.
sc eening) be moni o ed?’, ‘Should speci ic h esholds be es ab-
lished o d i ing AMS ecommenda ions o empi ical he apy?’
and‘Which s a i ica ion should be used o d i eselec i e epo ing
o an ibiog ams?’, should he e o e be conside ed p io i ies o u-
u e esea ch. Th ee main esea ch p io i ies including inpu s o
policymake s a e summa ized in Table5. Las ly, he panel dis-
cussed he impo ance o expanding a simila lis o consensus a -
ge s o ube culosis and o he pa hogens ( ungi and i uses) in
he u u e.
Conclusions
The 22 a ge s de eloped he ein we e concep ualized as a lis o
p agma ic and b oadly applicable ac ions o guide de elopmen o
an AMS p og amme in he ou pa ien se ing. Despi e he in insic
limi a ions gi en by he subjec i e na u e o expe opinion
me hodology, one s eng h o his wo k is ha he a ge ac ions
ha e been p oposed by a b oad panel o p o essionals, encom-
passing human and e e ina y medicine in a One Heal h app oach.
Ano he s eng h o his wo k is he ca ego iza ion o he a ge
ac ions as essen ial (conside ed as he minimum equi emen s)
and desi able (ac ions o be conside ed o he u he and op imal
implemen a ion o an AMS plan), aking in o accoun low- esou ce
se ings, including hose cha ac e ized by lack o quali ied pe son-
nel and labo a o y in as uc u e due o budge cons ain s.
Acknowledgemen s
We a e e y g a e ul o Ru h Joanna Da is o he suppo in he man-
agemen o he p ojec , and o Michaela Ha diman and Nadine
Conzelmann o hei adminis a i e suppo .
Membe s o he ARCH wo king g oup
Ayola Akim Adegnika, Cen e de Reche ches Me´dicales de Lamba e´ne´
(CERMEL), Lamba e´ne´, Gabon, and Ins i u u¨ T openmedizin and
Ge man Cen e o In ec ion Resea ch, pa ne si e Tu¨bingen,
Uni e si a¨ sklinikum, Wilhelms aße, Tu¨bingen, Ge many; Fabiana A ie i,
In ec ious Diseases Sec ion, Depa men o Diagnos ics and Public
Heal h, Uni e si y o Ve ona, Ve ona, I aly; Ni hya Babu Rajend an,
In ec ious Diseases, Depa men o In e nal Medicine I, Tu¨bingen
Uni e si y Hospi al, Tu¨bingen, Ge many, and Ge man Cen e o In ec ion
Resea ch (DZIF), Clinical Resea ch Uni o heal hca e associa ed in ec-
ions, Tu¨bingen, Ge many; Julia Bielicki, Pedia ic In ec ious Diseases,
Uni e si y Child en’s Hospi al Basel, Basel, Swi ze land, and Pedia ic
In ec ious Disease Resea ch G oup, Ins i u e o In ec ion and Immuni y,
S Geo ge’s Uni e si y o London, London, UK; S e en Bo mann, Cen e
de Reche ches Me´dicales de Lamba e´ne´ (CERMEL), Lamba e´ne´, Gabon,
and Ins i u u¨ T openmedizin and Ge man Cen e o In ec ion
Resea ch, pa ne si e Tu¨bingen, Uni e si a¨ sklinikum, Wilhelms aße,
Tu¨bingen, Ge many; Elena Ca a a, In ec ious Diseases Sec ion,
Depa men o Diagnos ics and Public Heal h, Uni e si y o Ve ona,
Ve ona, I aly; Robe o Cauda, Ins i u e o In ec ious Diseases,
Fondazione Policlinico Uni e si a io A. Gemelli IRCCS, Uni e si a` Ca olica
del Sac o Cuo e, Rome, I aly; Monica Comp i, In ec ious Diseases Sec ion,
Depa men o Diagnos ics and Public Heal h, Uni e si y o Ve ona,
Ve ona, I aly; Giulia De Angelis, Dipa imen o di Scienze Bio ecnologiche
di base, Cliniche In ensi ologiche e Pe iope a o ie, Uni e si a` Ca olica
del Sac o Cuo e, Rome, I aly; Raquel Du o, Uni o he P e en ion and
Con ol o In ec ion and An imic obial Resis ance, Cen o Hospi ala
Uni e si a´ io de S~
ao Jo~
ao, Opo o, Po ugal; Isabel F os , Cen e o
Disease Dynamics, Economics & Policy, New Delhi, India; Facul y o
Medicine, Depa men o In ec ious Disease, Impe ial College, London,
UK; Liliana Galia, In ec ious Diseases Sec ion, Depa men o Diagnos ics
and Public Heal h, Uni e si y o Ve ona, Ve ona, I aly; Pe a Gas meie ,
Ge man Cen e o In ec ion Resea ch Associa ion (DZIF), B aunschweig,
Ge many, and Ins i u e o Hygiene and En i onmen al Medicine, Cha i e´
- Uni e si a¨ smedizin Be lin, Ge many, co po a e membe o F eie
Uni e si a¨ Be lin, Humbold -Uni e si a¨ zu Be lin, and Be lin Ins i u e o
Heal h; Ch is ian Giske, Depa men o Clinical Mic obiology, Ka olinska
Uni e si y Hospi al, S ockholm, Sweden; Depa men o Labo a o y
Medicine, Ka olinska Uni e si y Hospi al, S ockholm, Sweden; Si i Go¨pel,
In ec ious Diseases, Depa men o In e nal Medicine I, Tu¨bingen
Uni e si y Hospi al, Tu¨bingen, Ge many, and Ge man Cen e o In ec ion
Resea ch (DZIF), Clinical Resea ch Uni o heal hca e associa ed in ec-
ions, Tu¨bingen, Ge many; He man Goossens, Depa men o Medical
Mic obiology, Vaccine & In ec ious Disease Ins i u e, Uni e si y o
An we p, An we p, Belgium; Gunna Kahlme e , Depa men o Clinical
Mic obiology, Va¨xjo¨ Cen al Hospi al, Va¨xjo¨, Sweden; Souha S. Kanj,
A ie i e al.
ii48
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Di ision o In ec ious Diseases, Depa men o In e nal medicine, and
In ec ion Con ol and P e en ion P og am, and An imic obial
S ewa dship P og am, Ame ican Uni e si y o Bei u Medical Cen e ,
Bei u , Lebanon; Tomisla Kos yane , Depa men o Medical
Mic obiology, Vaccine & In ec ious Disease Ins i u e, Uni e si y o
An we p, An we p, Belgium; Leona d Leibo ici, Medicine E, Rabin Medical
Cen e , Beilinson Hospi al, Pe ah Tik a, Is ael, and Facul y o Medicine,
Tel-A i Uni e si y, Tel-A i , Is ael; Jean-Ch is ophe Luce , In ec ion
Con ol Uni , Bicha -Claude Be na d Hospi al, AP-HP, Pa is, F ance; IAME,
UMR 1137, DeSCID eam, Uni e si e´ Pa is Dide o , So bonne Pa is Ci e´,
Pa is, F ance; Lo ena Lo´pez-Ce e o, Mic obiology and In ec ious Diseases
Uni , Uni e si y Hospi al Vi gen Maca ena, Se illa, Spain; Rodolphe
Made , Uni e si y o Lyon, F ench Agency o Food, En i onmen al and
Occupa ional Heal h and Sa e y (ANSES), Labo a o y o Lyon,
An imic obial Resis ance and Bac e ial Vi ulence Uni , Lyon, F ance;
Ful ia Mazza e i, In ec ious Diseases Sec ion, Depa men o Diagnos ics
and Public Heal h, Uni e si y o Ve ona, Ve ona, I aly; Elena Mazzolini,
Depa men o Epidemiology, Is i u o Zoop o ila ico Spe imen ale delle
Venezie, Legna o, Padua, I aly; Ma c Mendelson, Di ision o In ec ious
Diseases and HIV Medicine, Depa men o Medicine, Uni e si y o Cape
Town, Cape Town, Sou h A ica; Ri a Mu i, Ins i u e o In ec ious
Diseases, Fondazione Policlinico Uni e si a io A. Gemelli IRCCS, Uni e si a`
Ca olica del Sac o Cuo e, Rome, I aly; Nico T. Mu e s, Ins i u e o
Hygiene and Public Heal h, Bonn Uni e si y Hospi al, Bonn, Ge many;
Mical Paul, Diseases Ins i u e, Rambam Heal h Ca e Campus, Ru h and
B uce Rappapo Facul y o Medicine, Technion - Is ael Ins i u e o
Technology, Hai a, Is ael; Ma ia Dile a Pezzani, In ec ious Diseases
Sec ion, Depa men o Diagnos ics and Public Heal h, Uni e si y o
Ve ona, Ve ona, I aly; Elisabe h P es e l, Eu opean Commi ee on
In ec ion Con ol, Basel, Swi ze land, and Depa men o In ec ion
Con ol and Hospi al Epidemiology, Medical Uni e si y o Vienna, Vienna,
Aus ia; Hanna Renk, Uni e si y Child en’s Hospi al Tu¨bingen,
Depa men o Paedia ic Ca diology, Pulmology and In ensi e Ca e
Medicine, Tu¨bingen, Ge many; Oana Sandulescu, Depa men o
In ec ious Diseases I, Facul y o Medicine, Ca ol Da ila Uni e si y o
Medicine and Pha macy, Bucha es , Na ional Ins i u e o In ec ious
Diseases ‘P o . D Ma ei Bals¸’ Bucha es , Romania; Le Huu Song,
Vie namese Ge man Cen e o Medical Resea ch, Hanoi, Vie nam, and
108 Mili a y Cen al Hospi al, Hanoi, Vie nam; Mau izio Sanguine i,
Dipa imen o di Scienze Bio ecnologiche di base, Cliniche
In ensi ologiche e Pe iope a o ie, Uni e si a` Ca olica del Sac o Cuo e,
Rome, I aly, and Dipa imen o di Scienze di Labo a o io e
In e i ologiche, Fondazione Policlinico Uni e si a io A. Gemelli IRCCS,
Rome, I aly; Remco Sch ij e , Ve E ecT, Bil ho en, The Ne he lands;
Luigia Scudelle , Scien i ic Di ec ion o IRCCS Ca’ G anda Ospedale
Maggio e Policlinico di Milano, Milano, I aly; Mike Sha land, Paedia ic
In ec ious Diseases Resea ch G oup, Ins i u e o In ec ion and
Immuni y, S Geo ge’s Uni e si y o London, London, UK; Ma cella Sibani,
In ec ious Diseases Sec ion, Depa men o Diagnos ics and Public
Heal h, Uni e si y o Ve ona, Ve ona, I aly; E elina Tacconelli, In ec ious
Diseases Sec ion, Depa men o Diagnos ics and Public Heal h,
Uni e si y o Ve ona, Ve ona, I aly, and In ec ious Diseases, Depa men
o In e nal Medicine I, Tu¨bingen Uni e si y Hospi al, Tu¨bingen, Ge many,
and Ge man Cen e o In ec ion Resea ch (DZIF), Clinical Resea ch Uni
o heal hca e associa ed in ec ions, Tu¨bingen, Ge many; Didem
To umkuney, In e na ional Fede a ion o Pha maceu ical Manu ac u e s
and Associa ions (IFPMA), Gene a, Swi ze land; Thi umalaisamy P.
Vela an, Ins i u e o T opical Medicine, Uni e si a¨ sklinikum Tu¨bingen,
Ge many, and Vie namese Ge man Cen e o Medical Resea ch, Hanoi,
Vie nam, and Facul y o Medicine, Duy Tan Uni e si y, Da Nang, Vie nam;
And eas Voss, Depa men o Medical Mic obiology, Radboud Uni e si y
Medical Cen e, Nijmegen, The Ne he lands.
Funding
This esea ch p ojec has ecei ed unding om he Inno a i e
Medicines Ini ia i e Join Unde aking unde g an ag eemen No.
115737, esou ces o which a e composed o inancial con ibu ion om
he Eu opean Union Se en h F amewo k P og amme (FP7/2007-2013)
and Eu opean Fede a ion o Pha maceu ical Indus ies and Associa ions
(EFPIA) companies in-kind con ibu ion, and he Ge man Fede al Minis y
o Educa ion and Resea ch (BMBF) (P ojec ID 01KI1830) unde he Join
P og amme Ini ia i e on An imic obial Resis ance (JPIAMR) 2018 call.
T anspa ency decla a ions
The au ho s ha e none o decla e. Pa ick Moo e o Ad ia ic Heal h
Communica ions p o ided medical w i ing se ices o he edi ing and
p oo ing o his pape . This a icle o ms pa o a Supplemen .
Re e ences
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