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0niveisity Neuical Centie 0tiecht, 0tiecht, The Netheilanus.

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!"#$%&': To assess the effect of alcoholism on the suivival fiom multiuiug-iesistant
tubeiculosis in auults.
(')*%+&: A systematic seaich was peifoimeu in the Cochiane Libiaiy, Embase anu
PubNeu to iuentify ielevant aiticles. Stuuies with high ielevance anu valiuity weie
analyzeu.
,'&"-)&. 0ne aiticle was consiueieu as the best available eviuence. Nultivaiiate analysis
showeu a coiielation between moitality anu 'use of alcohol' (BR 1.S2 (9S% CI 1.26-
1.84)) anu between moitality anu 'alcoholism' (BR 1.49 (9S%CI 1.1S-1.96))
0%12-"&3%1. Alcohol use has a negative effect on the alieauy pooi suivival of multiuiug-
iesistant tubeiculosis. This unueilines the impoitance of both meuical anu non-meuical
help in uiscontinuing alcohol use in patients with this uisease.

Cl i ni cal Scenari o

A S4-yeai-olu man was inviteu to the municipal
health caie unit foi tubeiculosis eiauication in
light of contact tiacing. Be uiu not have pulmonaiy
complaints, but suffeieu fiom fatigue anu night
sweats. The chest X-iay showeu a consoliuation in
the iight uppei lobe. Both PCR testing anu
auiamine staining on sputum weie positive.
Antibiotic sensitivity assays weie not yet available
to us in light of the slow giowth of N. tubeiculosis,
but since the inuex patient hau multiuiug-iesistant
tubeiculosis (NBR-TB), the same was assumeu in
this patient. The patient, who iesiueu in a
homeless sheltei at the time of tieatment,
aumitteu to alcohol abuse anu inquiieu if this
woulu affect his chances of suivival.

Background

NBR-TB is tubeiculosis that has become
insensitive to the two most impoitant fiist-line
anti-tubeiculosis uiugs, isoniaziu anu iifampicin.
Resistance to antibiotics aiises fiom inauequate
tieatment of susceptible tubeiculosis. While a
iesistance to the afoiementioneu antibiotics is
uefining, auuitional iesistance is possible. When

theie is an auueu insensitivity to quinolones anu
one of the thiee seconu-line injectables
(kanamycin, amikacin, capieomycin), it has
become extensively uiug-iesistant tubeiculosis
(XBR-TB).
1,2


NBR-TB has become a seiious thieat to
tubeiculosis contiol anu public health. It
oiiginates pieuominantly in countiies with weak
tubeiculosis contiol piogiams, such as the Russian
Feueiation, China anu Inuia, but is becoming a
woiluwiue pioblem. ulobally, S.7% of new
tubeiculosis cases anu 2u% of pieviously tieateu
patients have a NBR stiain, 9% of which aie
XBR.
S,4


In countiies with low inciuence of tubeiculosis like
the Netheilanus, the uisease is most often founu in
immigiants anu inuiviuuals with impaiieu
immune function. 0ne gioup paiticulaily at iisk
foi contiacting the uisease aie the homeless, both
because they often suffei fiom impaiieu immunity
anu because of ciowuing in shelteis. In the geneial
population, the inciuence of alcohol abuse is
u,7S%.S The inciuence of alcohol abuse among the
homeless vaiies in uiffeient stuuies, but is thought
to be somewheie between ten anu fifty peicent in
the Netheilanus.
6

These numbeis come togethei in oui homeless
patient, who has the misfoitune of suffeiing fiom
both alcohol abuse anu NBR-TB.

Cl i ni cal questi on

Bow uoes alcohol use |ueteiminantj affect the S-
yeai suivival |outcomej in auults with multi-uiug
iesistant tubeiculosis |uomainj.

Methods

4'5#2* &)#5)'67 51+ &'-'2)3%1
A systematic seaich was peifoimeu in the
Cochiane Libiaiy, PubNeu anu Embase to iuentify
ielevant aiticles. vaiious synonyms foi multiuiug-
iesistant tubeiculosis weie combineu with
synonyms foi moitality anu suivival, visible in the
appenuix.

Results weie evaluateu on title anu abstiact to see
whethei inclusion ciiteiia weie met. Full texts
weie ieau to confiim. The iefeiences anu citations
of the selecteu aiticles weie scieeneu foi missing
aiticles.

Cri ti cal apprai sal

The aiticles weie evaluateu foi ielevance anu
valiuity baseu on pieueteimineu ciiteiia (figuie
1). Regaiuing ielevance, we evaluateu whethei it
was a piognostic stuuy that incluueu NBR
tubeiculosis patients, evaluateu alcohol use as a
piognostic factoi anu if the outcome was moitality
oi suivival. Regaiuing valiuity, we evaluateu foi
auequacy anu tianspaiency of stuuy uesign,
iesults anu uata analysis.

Since moitality is the outcome, stanuaiuization
was assumeu anu blinuing is not applicable.
Aiticles with low scoies foi eithei weie not taken
into account foi analysis (figuie 2).

Resul ts

4'-'2)3%1 %8 5#)32-'&
Thiee aiticles weie selecteu foi ciitical appiaisal
(figuie 2). Nathew et al.
7
anu Santa et al.
8
weie
both excluueu foi evaluating multiuiug-iesistance
anu alcoholism as sepaiate ueteiminants, theieby
making it impossible to ueteimine the effect of one
upon the othei.
Balabanova et al.
9
was ielevant anu attaineu
auequate valiuity scoies, making it suitable foi
analysis.

Outcome

Balabanova et al.
9
investigateu factois influencing
suivival among 18u7 Lithuanians uiagnoseu with
NBRXBRTBC in a ietiospective cohoit stuuy. The
majoiity of patients weie young Lithuanian males
living in uiban settings, unemployeu, with piimaiy
oi seconuaiy euucation anu fiequently using
cigaiettes anu alcohol. The 18u7 patients weie
followeu foi a total of 4u89.S peison-yeais.

Alcohol use is uesciibeu with the following teims:
'sometimes', 'often' oi 'alcoholism'. Bowevei, no
cleai uefinition is given.


;3701$ <= &+)>'#41(
Both multivaiiate anu univaiiate analysis weie
peifoimeu on factois thought to influence the
moitality. When aujusteu foi oluei age, iuial
living, meuication, unemployment, lowei level of
euucation, positive oi unknown BIv status, cavity
uisease anu being smeai positive at the time of
uiagnosis, theie is a coiielation between moitality
anu use of alcohol (BR 1.S2 (9S% CI 1.26-1.84))
anu between moitality anu alcoholism (BR 1.49
(9S%CI 1.1S-1.96)) (table 1).
Di scussi on

0thei stuuies have founu uiffeient suivival iates
between XBR anu NBR tubeiculosis patients.
Bowevei, once othei patient chaiacteiistics weie
aujusteu foi, theie was no significant suivival
benefit between the two in this aiticle (BR 1.19
(9S%CI u.91-1.81), so we felt justifieu in using all
patient uata foi answeiing oui clinical question.

Positive aspects of Balabanova et al.
9
aie the laige
stuuy population, the low peicentage of missing
uata (2%) anu the fact that they coiiecteu foi any
foim of tieatment, making it easily applicable to
othei NBR patients.

A uiawback is the uncleai uefinition foi alcoholism
that has been given, inhibiting iepiouucibility anu
iestiicting the claiity of the iecommenuation.

The pievalence of tubeiculosis in Lithuania is
much highei than in Westein Euiope, iesulting in
a uiffeient patient population. Wheieas in low-
inciuence settings such as the Netheilanus,
tubeiculosis commonly affects vulneiable
inuiviuuals, this is not tiue foi Lithuania. As a
iesult, the patient population is ielatively healthy
anu consequently moitality iates aie lowei.
7
The
"4:+$ <= 9$-0+(-
effect of alcohol use on the moitality iates is
alieauy quite pionounceu among this gioup. It can
be assumeu that the effect woulu be even moie
seveie on the compaiatively vulneiable Butch
NBR tubeiculosis patients. Consequently, the
uiffeience in population uoes not leau to an
oveiestimation the effect of alcohol on NBR
tubeiculosis.
The stiength of this EBCR is the methouical seaich
meaning all aiticles on this subject have likely
been iuentifieu. The scaicity of iesults implies a
lack of knowleuge on this subject, making this
aiticle all the moie ielevant. This also poses a
limitation; no piospective cohoit stuuy, the
piefeiieu stuuy uesign, coulu be iuentifieu on the
subject.

Recommendati on

Fiequent alcohol use negatively affects the
suivival of NBR tubeiculosis patients. Since the
piognosis is alieauy giim, an aggiessive appioach
shoulu be taken.

Theiefoie, we woulu stiongly iecommenu oui
patient to cease alcohol use immeuiately anu to
seek tieatment foi his alcohol abuse.

This EBCR unueilines the impoitance of explicitly
quantifying alcohol use, especially in NBR
patients, anu taking an aggiessive appioach in
piocuiing assistance in cases of alcohol abuse.

References

1
Woilu Bealth 0iganization (2u12) WB0 | Nultiuiug-iesistant tubeiculosis (NBR-TB). |onlinej Available
at: http:www.who.inttbchallengesmuien |Accesseu: 1S }an 2u1Sj.
2
Woilu Bealth 0iganization (2u1u) WB0 | XBR-TB. |onlinej Available at:
http:www.who.inttbchallengesmuixuieninuex.html |Accesseu: 1S }an 2u1Sj.
S
Woilu Bealth 0iganization (2u1S) NBR Factsheet. |onlinej Available at:
http:www.who.inttbpublicationsNBRFactSheet2u12.puf |Accesseu: 1S }an 2u1Sj.
4
Woilu Bealth 0iganization (2uu6) NBR-TB Repoit. |onlinej Available at:
https:extianet.who.intsieeRepoits.op=vs&path=WB0_BQ_Repoitsu2PR0BEXTNBRTB_I
nuicatois_map |Accesseu: 1S }an 2u1Sj.
S
Nationaalkompas (2uu7) Boe vaak komt afhankelijkheiu van alcohol vooi en hoeveel mensen steiven
eiaan. - Nationaal Kompas volksgezonuheiu. |onlinej Available at:
http:www.nationaalkompas.nlgezonuheiu-en-ziekteziekten-en-aanuoeningenpsychische-
stooinissenafhankelijkheiu-van-alcohol-uiugs-of-anueie-miuuelenafhankelijkheiu-van-
alcoholomvang |Accesseu: 1S }an 2u1Sj.
6
Neuisch Contact (2u1S) Psychiatiische aanuoeningen bij uaklozen. |onlinej Available at:
http:meuischcontact.aitsennet.nlnieuws-26aichief-6tijuschiiftaitikel2487Spsychiatiische-
aanuoeningen-bij-uaklozen.htm |Accesseu: 1S }an 2u1Sj.
7
Nathew, T. et al. (2uu6) Causes of ueath uuiing tubeiculosis tieatment in Tomsk 0blast, Russia. The
Inteinational }ouinal of Tubeiculosis anu Lung Bisease, 1u (8), p.8S7-86S.
8
Santha, T. et al. (2uu2) Risk factois associateu with uefault, failuie anu ueath among tubeiculosis
patients tieateu in a B0TS piogiamme in Tiiuvallui Bistiict, South Inuia, 2uuu. The Inteinational
}ouinal of Tubeiculosis anu Lung Bisease, 6 (9), p.78u-788.
9
Balabanova, Y. et al. (2uu6) Suivival of uiug iesistant tubeiculosis patients in Lithuania: ietiospective
national cohoit stuuy.. BN} 0pen, Available at:
http:bmjopen.bmj.comcontent12euuuSS1.full.siu=b926u297-uuS1-4cau-9aeS-28eSf1288f72
|Accesseu: 14th Bec 2u12j.


Appendi x