METHODOLOGY Open Access
T ajec o ies o a se o en unc ional
soma ic symp oms om adolescence
o middle age
Tapio Nummi
1*
, Pekka Vi anen
2
, Päi i Leino-A jas
3
and Anne Hamma s öm
4
Abs ac
Backg ound: Func ional soma ic symp oms (FSS), o symp oms wi hou a clea medical explana ion a e a
conside able challenge o heal h ca e sys ems. The e is no gene al consensus as o which symp oms should
be ega ded unc ional. Few longi udinal s udies on he de elopmen o FSS exis and hese ha e mainly been
based on he assump ion ha he ac o ial s uc u e o a FSS sco es a iable emains in a ian o e ime. When
he analysis co e s longe pe iods o he li e cou se, his may be challenged. The aim o ou s udy was o
in es iga e how en unc ional soma ic symp oms (FSS) e ol e when indi iduals a e ageing.
Me hods: The da a o he No he n Swedish Coho (n= 1001) om ques ionnai e su eys a ages 16, 18, 21, 30
and 42, we e analysed. Pa icipa ion a es emained e y high o e he i e su eys. The lis o symp oms included
backache, b ea hlessness, dizziness, a igue, headache o mig aine, nausea, o e s ain, palpi a ions, sleeplessness and
s omach ache. We used mul i a ia e ajec o y analysis (TA) wi h logis ic b oken-s ick eg ession models o desc ibe
sub-g oups in he da a. In mul i a ia e TA he join de elopmen o he se o i em a iables can be in es iga ed.
The e is no need o cons uc a special FSS summa y sco e a iable.
Resul s: Fou well sepa a ed ajec o ies we e iden i ied. In wo g oups, healing symp oms (25.4% o he sample)
and low symp om load (32.2% o he sample), he symp om le el s ayed ela i ely low in adul hood. In he hi d
g oup o high symp om load (17.2%) he p obabili y o ha ing symp oms was high o all FSS a iables. In he
ou h g oup o inc easing symp oms (25.3%) he le el o symp oms was i s in e media e, bu inc eased ma kedly
wi h age.
Conclusions: Ins ead o a single FSS sco e we we e able o assign each indi idual o one o ou ajec o ies
desc ibed join ly by 10 sepa a e symp oms. The p o ile o de elopmen , bu no he p obabili y le el, was a he
simila o e he symp oms wi hin he ajec o ies, wi h ew excep ions. The esul s p o ide be e unde s anding o
he longi udinal de elopmen o he symp oms om he adolescence o he middle age.
Keywo ds: Fini e mix u es, Logis ic eg ession, Longi udinal da a, Mul i a ia e ajec o y analysis, Pain
Backg ound
O e decades, ens o ques ionnai es ha e been con-
s uc ed o measu e he numbe , he equency and he
se e i y o soma ic symp oms in a ious clien o popu-
la ion g oups (see [18]). The ques ionnai es a e p inci-
pally in ended o p oduce a single quan i a i e indica o
o he la en a iable ha , depending on he heo e ical
assump ions, can be concep ualized in se e al ways. The
e iew e e ed o abo e assumes he e m ‘ unc ional
soma ic’, implying some kind o physiological dis u bance,
bu he symp oms ha e also been called ‘medically unex-
plained’in e ms o a lack o diagnosed disease, as ‘s ess’
in e ms o a s ain in he indi idual-en i onmen ela-
ionship, o as ‘psychosoma ic’o ‘in e nalized’in e ms o
unde lying men al heal h diso de . Ou choice in he
p esen pape is unc ional soma ic symp oms (FSS). I is
no clea om he li e a u e which speci ic symp oms
should be conside ed as FSS. Any one o he common
symp oms p esen ed by pa ien s seeking ca e o epo ed
* Co espondence: [email p o ec ed]
1
Facul y o Na u al Sciences, Uni e si y o Tampe e, 33014 Tampe e, Finland
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Nummi e al. A chi es o Public Heal h (2017) 75:11
DOI 10.1186/s13690-017-0178-8
in a ques ionnai e migh be conside ed as a ising om a
disease o a pa icula o gan sys em. Howe e , he mo e
symp oms a pe son has, he less likely i appa en ly is ha
hese e lec he p esence o a soma ic disease [9].
In he esea ch con ex , FSS summa y sco e indices
ha e mos ly been analysed wi h s a is ical me hods
in ended o c oss-sec ional da a such as logis ic eg es-
sion, p incipal componen analysis, ac o analysis and
analysis o co ela ion coe icien s (e.g. [6, 8, 16]). The e
a e only ew s udies ha analyse FSS in longi udinal se -
ings. Rousseau e al. [14] and Janssens e al. [3] ha e
used la en g ow h mix u e model [11] when in es iga ing
he ajec o ies o FSS and hei associa ion wi h back-
g ound cha ac e is ics in adolescence. The ajec o y ana-
lysis by Nagin [12] was used by Mul aney e al. [10] in he
s udy o child en su e ing om abdominal pain. Usually
hese ajec o y analyses ound 3 o 4 g oups sizes a ying
depending on he s a is ical models used, he sco e a i-
able u ilized and he age pe iod in es iga ed.
Longi udinal analysis o FSS sco es is based on he
assump ion ha he ac o ial s uc u e o he sco e
a iable emains in a ian o e ime. FSS sco e has been
analysed, o example, in a s udy o he No he n Swedish
Coho [2]. This coho is also he sou ce o he p esen
s udy. In o de o expand ou unde s anding o FSS, we
decided o es a di e en app oach, which akes in o
accoun he ac ha indi idual symp oms can de elop in
di e en ways a di e en s ages o li e. Thus, ou aim was
o in es iga e how en symp oms assumed as unc ional
e ol e when indi iduals a e ageing om age 16 o age 42
by applying mul i a ia e ajec o y analysis o he symp-
om se .
Me hods
The No he n Swedish Coho consis s o pupils who
s udied hei las yea o compulso y school in a
medium-sized Swedish indus ial own in 1981. Da a
we e collec ed a ages 16, 18, 21, 30 and 42 wi h su eys
comp ising hei heal h and heal h beha iou , labou
ma ke expe iences, amily si ua ion and socioeconomic
condi ions. The baseline su ey a age 16 ook place in
class ooms and he ollow-up su eys we e conduc ed in
classma e eunions o by pos o elephone. A he la es
ollow-up su ey in 2007 he pa icipa ion a e was s ill
94.3% (n= 1010; 522 men and 488 women). The s udy
was app o ed by he Regional E hical Re iew Boa d in
Umeå, Sweden.
The e we e ew d opou s o missing da a and he
e ec i e sample size o his s udy was n= 1001 (519 o
52% men and 482 o 48% women). The se o a iables
o measu ing FSS was cons uc ed by a panel consis ing
o 25 heal h p o essionals ( o mo e de ails see [2]). Fo
each o he lis ed 42 candida e symp oms, he panel was
asked o judge whe he he symp om belonged o FSS o
no . The ollowing en symp oms ecei ed he highes
suppo : 1) s omach ache o he han hea bu n, gas i is
o gas ic ulce (96%); 2) headache o mig aine (80%); 3)
a igue (76%); 4) dizziness (72%); 5) palpi a ions (72%);
6) nausea (68%); 7) sleeplessness (68%); 8) backache, hip
pain o scia ica (64%); 9) b ea hlessness (64%) and 10)
o e s ain (64%). In he su ey he occu ence o hese
10 symp oms du ing he pas 12 mon hs was inqui ed
using h ee esponse al e na i es (no; yes, ligh ; yes
se e e). Fo ou analyses each symp om a iable was
dicho omized as no s. yes.
The longi udinal da a o FSS we e analysed using
ajec o y analysis (TA), which can be used o model he
unobse ed he e ogenei y in longi udinal da a. The
TA by Nagin [12, 13], Jones and Nagin [5] and Jones
e al. [4] applies he gene alized linea models heo y
(exponen ial amily o dis ibu ions) wi h Fini e Mix-
u es unde he assump ion ha obse a ions wi hin a
gi en ajec o y a e independen . Ou main analysis
used he mul i a ia e e sion o his basic TA, whe e
ou comes a e ela ed bu dis inc a iables (see e.g.
[4, 13]). The compu a ions we e ca ied ou by R
package Flexmix [7].
As can be obse ed om Fig. 1, he o e all end is
ha he p e alence o symp oms i s dec eases and hen
inc eases wi h age. Howe e , some symp oms inc ease
only sligh ly (b ea hlessness, dizziness, o e s ain and
palpi a ion) and some e en dec ease (nausea). The high-
es pe cen ages we e ob ained o a igue and headache.
I is u he obse ed ha age 21 is a kind o u ning
poin , om which mos FSS a iables de elop ai ly s a-
bly o e adul hood. The basic linea model ha can be
used o modelling such de elopmen is he so-called
b oken-s ick model ha joins wo eg ession lines a a
gi en kno poin [15]. He e we ake he kno poin as
21 yea s o age. Figu e 1 also shows ha FSS a e ai ly
simila o bo h gende s, bu o women he le el ends
o be highe .
This is in line wi h many ea lie s udies and mus also
be accoun ed o when cons uc ing s a is ical models.
The join model used o each o he 10 symp oms a i-
ables akes he o m o he b oken-s ick
logi pðÞ¼b0 þb1 sex þb2 þb3 þ;
whe e is age and + is he posi i e pa o ( −21) and
ze o o he wise. This o mula ion spli s he model in o
wo pa s. The i s co e s he age pe iod (16, 21) and
he second pa adds he age pe iod [21, 42]. The mul i-
a ia e ajec o y analysis model consis s o 10 logis ic e-
g ession models in oduced abo e, whe e wo eg ession
lines a e joined oge he a he kno poin = 21 and he
in e cep e m is es ima ed sepa a ely o men and
women. No e ha in his kind o mul i a ia e o mula ion
Nummi e al. A chi es o Public Heal h (2017) 75:11 Page 2 o 7
he ull po en ial o all he 10 a iables a e used in
TA. This is in con as o mo e common FSS sum-
ma y sco e analysis ha can po en ially mask some
impo an de elopmen o a single i em a iables in
he analysis, because he symp oms beha e in di e -
en waysa di e en pe iodso age.
Resul s
The numbe o ajec o ies o be es ed was k = 1, …,7.
To ensu e con e gence, each un was epea ed 10 imes
using di e en s a ing alues. The ob ained alues o
he in o ma ion c i e ia BIC we e hen 41011.46,
38655.49, 38490.46, 38375.48, 38500.89, 38628.52 and
38799.41. The minimum BIC = 38375.48 was clea ly
a ained when k = 4 and his is he e o e aken as he
numbe o ajec o y g oups o ou analysis. The size
o he ajec o ies a ied be ween 17 and 32%; he es i-
ma ed mix u e p opo ions we e p1 = 0.254, p2 = 0.322,
p3 = 0.172 and p4 = 0.253. The so-called oo og am plo
o pos e io p obabili ies (Fig. 2) con i med ha he
ou g oups we e e y well sepa a ed.
Figu e 3 illus a es he de elopmen o each symp om
in each ajec o y g oup, and es ima es o he model pa-
ame e s a e displayed in Table 1. Using his in o ma ion
Fig. 1 Plo s o pe cen age o subjec s epo ing unc ional soma ic symp oms as a unc ion o age. Solid cu e is o women and do ed cu e is o men
Fig. 2 Roo og am plo o pos e io p obabili ies
Nummi e al. A chi es o Public Heal h (2017) 75:11 Page 3 o 7
oge he wi h he mean o he numbe o symp oms as a
unc ion o age (Fig. 4), we cha ac e ised he ajec o y
g oups as ollows.
Healing symp oms, 25.4%
Fo mos a iables he de elopmen cu e i s de-
c eased and a e age 21 ei he u he dec eased o
s ayed a he low le el (in he model b2, b3 and
Fig. 3). Al hough he p obabili y o mos o he symp-
oms was a he high in adolescence i became ela-
i ely low a he end o he ollow-up in middle-age
(Figs. 3 and 4). The e we e wo excep ions: changes
in he p obabili y o palpi a ions we e small h ough-
ou (b1 and b2) and ha o backache inc eased mod-
e a ely o e ime (Fig. 3). The le el o he symp oms
(b1) was lowe o men conside ing he a iables diz-
ziness, a igue, headache and palpi a ion. Howe e , o
nausea he cons an e m (b1) was signi ican ly highe
o men. The odds o de eloping symp oms o nausea
o males in his g oup we e abou OR = 1.5 when
compa ed o emales.
Low symp om load, 32.2%
The mean numbe o symp oms was lowes in compa i-
son o o he ajec o ies (Figs. 3 and 4), bu a e age 21
i ended o inc ease sligh ly (b2, b3, Figs. 3 and 4). The
le el o he symp oms was (signi ican ly) lowe in men
han in women conside ing Dizziness, Fa igue, Headache
and Sleeplessness (b1).
High symp om load, 17.2%
In his g oup he le el o he symp oms was high o
each FSS a iable, especially o a igue, headache, nau-
sea and sleeplessness (Fig. 3). Fo headache he cu e in-
c eased sligh ly o e he whole ollow-up pe iod (b2)
and o a igue and s omach ache (b2 and b3) i in-
c eased a e he age 21. The le el o he symp oms (b1)
in men was (signi ican ly) lowe o dizziness, headache
and nausea, bu highe o o e s ain (OR = 1.5) and
sleeplessness (OR = 1.6) han in women.
Inc easing symp oms, 25.3%
The baseline le el o he numbe o symp oms was low o
in e media e, bu inc eased by age especially o a igue
(Fig. 3), sleeplessness (Fig. 3), backache (Fig. 3, b2 and b3)
and headache (Fig. 3, b2 and b3). The symp om le el in
men was signi ican ly lowe han in women o dizziness,
a igue, headache, nausea and palpi a ions (b1).
The g oups o healing and inc easing symp oms a e
sligh ly domina ed by women (52.0 and 52.2%, espec -
i ely), while he g oup o low symp om load is domi-
na ed by men (57.6%). In he g oup o high symp om
load he p opo ions a e abou he same as in he o i-
ginal sample.
In he g oup o inc easing symp oms, he a e age
numbe o symp oms clea ly inc eased o e ime, bu in
he o he g oups, he numbe o symp oms emained
ai ly s able in adul hood. The highes o e all numbe o
symp oms by he end o he ollow-up was ob ained in
he g oup o pe manen ly high symp om load, and he
second highes in he g oup o inc easing symp oms.
Fig. 3 Plo o 10 FSS a iables o each ajec o y g oup as a unc ion o age. Solid cu e is o he g oup o healing symp oms, dashed cu e o
he g oup o pe manen ly low symp om load, do ed cu e o he g oup o pe manen ly high symp om load and he semi-dashed cu e is o
he g oup o inc easing symp oms
Nummi e al. A chi es o Public Heal h (2017) 75:11 Page 4 o 7
These wo g oups a e in e es ing om he esea ch
poin o iew, bu he deepe analysis goes beyond he
scope o his pape .
Discussion
We explo ed he ajec o ies o en FSS o e a 26-yea
ime span among, o iginally, 16-yea -old Swedes. Fou
dis inc sub-g oups we e ound, labelled as healing, low
symp om load, high symp om load, and inc easing
symp oms. When summa izing he main indings we
no e ha in he i s wo ajec o y g oups (healing and
low symp om load), he symp om le els s ay ela i ely
low in adul hood. This applies o all symp oms. Sligh ly
mo e han one hal o he sample belonged o hese
g oups wi h a a ou able long- e m de elopmen . Po en-
ially mo e clinically ele an a e he hi d g oup ha
comp ises indi iduals ha ha e a high le el o FSS
al eady in hei eens, and he ou h g oup whe e he
le el o he symp oms is low o in e media e a baseline,
bu unde goes a s eep inc ease ill midli e. The la e
Table 1 Es ima es o he pa ame e s o he b oken-s ick model o each ajec o y g oup
G oup Pa . B ea h. Dizzi. Fa igue Head. Nausea O e s . Palpi. Sleep. S omach Back
Healing b0 3.919* 3.405* 4.647* 3.850* 5.772* 0.373 −0.646 2.836* 5.452* −1.119
b1 0.194 −1.149* −0.540* −0.723* 0.395* −0.184 −1.238* −0.221 0.032 −0.062
b2 −0.318* −0.230* −0.207* −0.124* −0.306* −0.098 −0.095 −0.186* −0.325* 0.036
b3 0.322* 0.182* 0.191* 0.120* 0.258* 0.058 0.100 0.211* 0.299* −0.010
Low b0 2.340 1.958 2.094* −0.792 3.276* −2.897 −1.072 −0.397 4.236* −1.981*
b1 −0.381 −0.850* −0.593* −0.700* 0.237 −0.543 −1.243 −0.494* −0.482 0.079
b2 −0.279* −0.265* −0.154* 0.024 −0.276* 0.008 −0.145 −0.048 −0.363* 0.012
b3 0.319* 0.293* 0.188* 0.014 0.271* −0.006 0.117 0.074 0.410* 0.028
High b0 −0.301 0.781 4.744* −0.565 3.409* −1.538 −2.214* 1.642 2.801* −1.192
b1 −0.040 −0.510* −0.422 −1.583* −0.774* 0.388* −0.582* 0.474* −0.226 −0.159
b2 −0.011 −0.050 −0.165* 0.152* −0.110* 0.030 0.065 −0.071 −0.144* 0.082
b3 0.030 0.083 0.222* −0.110 0.098 0.007 −0.045 0.101 0.164* −0.030
Inc ease b0 −2.670* −2.472 −0.453 −2.970* −1.767 −2.925* −4.206* −0.824 −0.739 −6.335*
b1 −0.047 −0.785* −0.712* −1.059* −0.705* −0.322 −0.916* 0.068 −0.190 −0.234
b2 0.027 0.026 0.047 0.189* 0.053 0.065 0.095 −0.001 −0.041 0.285*
b3 0.038 0.043 0.052 −0.151* −0.022 −0.014 −0.031 0.085 0.103 −0.226*
Es ima es o he male gende (di e ence om emales) a e deno ed by b1
Coe icien b2 is he eg ession coe icien o age pe iod (16, 21) and b2 and b3 join ly a e coe icien es ima es o he age pe iod [21, 42]
S a is ically signi ican es ima es (a 5% le el o signi icance) a e ma ked wi h an as e isk
Fig. 4 Mean numbe o symp oms by age. Solid cu e is o he g oup o healing symp oms, dashed cu e o he g oup o pe manen ly low symp om
load, do ed cu e o he g oup o pe manen ly high symp om load and hesemi-dashedcu eis o heg oupo inc easingsymp oms
Nummi e al. A chi es o Public Heal h (2017) 75:11 Page 5 o 7

wo g oups call o u he esea ch, because high le els
o FSS may be associa ed wi h psychia ic diso de s such
as anxie y and dep ession, lowe quali y o li e, and so-
cial p oblems [1, 10, 17] in addi ion o being hemsel es
dis u bing. Howe e , a deepe analysis goes beyond he
scope o his mo e me hodologically o ien ed pape .
Ou analysis e ealed a he simila pa e ns o he
a ious single symp om a iables wi hin he g oups, bu
in he g oup o inc easing symp om he inc ease is
mainly due o inc ease o pain symp oms (Headache and
Backache, b2 and b3) as well as a igue and sleeplessness
(Fig. 3). This sugges s a somewha di e en ae iology in
symp oms o ma ion.
Compa ing ou esul s o he ew o he ajec o y ana-
lyses o FSS is di icul , since hey a e ca ied ou among
pa icipan s wi h a sho e ollow-up in he you h and a
single FSS sco e a iable. Janssens e al. [3] s udied he
de elopmen o a sco e o se en FSS o e a 7-yea s ime
span among Du ch eens aged om 11 o 16 yea s on
a e age in he h ee wa es o da a collec ion. In hei
ou - ajec o y solu ion he g oup wi h low symp oms
was he la ges and he g oup wi h pe sis en FSS he
smalles , simila o ou indings. The g oup sizes we e
di e en , howe e , p esumably due o he di e ences in
age and leng h o ollow-up be ween s udies. The g oup
wi h healing symp oms comp ised abou a qua e o he
subjec s in ou s udy, while one en h o he Du ch eens
belonged o he g oup wi h dec easing symp oms. In he
ajec o y analysis by Mul aney e al. [10] he long- e m
isk g oup consis o 14% o paedia ic pa ien s.
Longi udinal analysis o FSS is o en based on he as-
sump ion ha ac o ial s uc u e o he sco e a iable e-
mains in a ian o e ime. This was also es ed in a s udy
o he No he n Swedish Coho [2] pa ly o he same
a iables ha is conside ed in his s udy. Howe e , in
o de o expand ou unde s anding abou he de elop-
men o FSS we decided o es a di e en app oach,
which akes in o accoun ha indi idual symp oms can
de elop in di e en ways a di e en s ages o li e. So, he
ocus was no on he sco e a iable; ins ead he aim is o
lea n o unde s and po en ial a ia ion in he ole o indi-
idual symp oms when he de elopmen om adolescence
o middle age is elucida ed.
As discussed in Beck [1], longi udinal s udies mus
eplace c oss-sec ional designs ha use la ge and a ied
age anges wi h s udies ha gi e us ools o unde s and
he ex en o which FSS a e no ma i e a ce ain de el-
opmen pe iods. Ou esul s a e also suppo ed by he
iew o Wessey e al. (1999), who emphasize a dimen-
sional classi ica ion o symp oms. This s udy uses good-
quali y longi udinal da a. The sample size is adequa e
and he a i ion a e is ex emely low. In addi ion, he
ime pe iod in es iga ed is long enough o assess he de-
elopmen o symp oms om adolescence o adul hood.
He e we ha e used he mul i a ia e ajec o y analysis
model o FSS ha , o ou knowledge, has no been u i-
lized ea lie . The model gi es us means o assess how
he indi idual symp oms de elop as a unc ion o age o
each iden i ied ajec o y g oup. The ajec o ies wi h
hei quali a i e in e p e a ion yield no el pe spec i es
o he longi udinal de elopmen o he symp oms. The
impo an limi a ion o he analysis me hod is ha ob-
se a ions wi hin each ajec o y class a e assumed o be
independen wi hin and be ween each a iable. This may
p oduce some small bias in pa ame e es ima es o he
ajec o y model pa ame e s. Howe e , his small bias e -
ec may no ha e a ema kable in luence on he main
conclusions o he s udy.
Conclusions
I has been shown ea lie ha he ac o ial in a iance
o e ime applies o he FSS sco e a iable ha is based
on se en FSS symp oms [2]. Howe e , he ull mul i a i-
a e ajec o y analysis o en FSS a iables applied he e
has he ad an age ha i akes in o accoun he ac ha
indi idual symp oms wi hin la en g oups may no
e ol e on he same way o each s udy pa icipan in
each pe iod o age. Ins ead o he single alue o an FSS
sco e a iable we can assign each indi idual o one o
he ou ajec o ies, which gi es a nice quali a i e in e -
p e a ion. This yields a be e unde s anding abou he
longi udinal de elopmen o he symp oms and espe-
cially be e ools o he iden i ica ion o he isk g oup
o indi iduals whose symp oms o ma ion should be in-
es iga ed in mo e de ail in u he s udies.
Abb e ia ions
FSS: Func ional soma ic symp oms; TA: T ajec o y analysis
Acknowledgemen
No applicable.
Funding
The s udy has been inanced by he Swedish Resea ch Council Fo mas dn
259-2012-37.
A ailabili y o da a and ma e ials
The da ase is pa o he No he n Swedish Coho (NSC). The Swedish Da a
P o ec ion Ac (1998:204) does no pe mi sensi i e da a on humans (like in
he NSC ques ionnai es) o be openly sha ed. Agg ega e da a is a ailable
upon eques om he P incipal In es iga o Anne Hamma s öm
([email p o ec ed]), pending e hical app o al.
Au ho s’con ibu ions
TN designed and pe o med he s a is ical analyses and w o e he main pa
o he pape . PV and PLA ex ended and commen ed AH commen ed he
pape . All au ho s ead and app o ed he inal manusc ip .
Compe ing in e es s
The au ho s decla e ha hey ha e no compe ing in e es s.
Consen o publica ion
No applicable.
Nummi e al. A chi es o Public Heal h (2017) 75:11 Page 6 o 7
E hics app o al and consen o pa icipa e
This s udy was conduc ed wi h he app o al o he Regional E hical Re iew
Boa d in Umeå, Sweden. Each pa icipan ag eed o pa icipa e o he s udy
and w i en in o ma ion was gi en o hem, as well as o hei pa en s.
Au ho de ails
1
Facul y o Na u al Sciences, Uni e si y o Tampe e, 33014 Tampe e, Finland.
2
School o Heal h Sciences, Uni e si y o Tampe e, 33014 Tampe e, Finland.
3
Finnish Ins i u e o Occupa ional Heal h, Cen e o Expe ise o Heal h and
Wo k Abili y, Helsinki, Finland.
4
Depa men o Public Heal h and Ca ing
Sciences, Uppsala Uni e si y, Uppsala, Sweden.
Recei ed: 12 Oc obe 2016 Accep ed: 13 Janua y 2017
Re e ences
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