Impact of an oral nutritional protocol with oligomeric enteral nutrition on the quality of life of patients with oncology treatment-related diarrhea

nu ien s A icle Impac o an O al Nu i ional P o ocol wi h Oligome ic En e al Nu i ion on he Quali y o Li e o Pa ien s wi h Oncology T ea men -Rela ed Dia hea Alejand o Sanz-Pa is 1,2,*, Ja ie Ma inez-T u e o 3, Julio Lambea-So osal 4, Raimon Milà-Villa oel 5, Fe nando Cal o-G acia 6and on behal o he DIAPOENO S udy †   Ci a ion: Sanz-Pa is, A.; Ma inez- T u e o, J.; Lambea-So osal, J.; Milà-Villa oel, R.; Cal o-G acia, F.; DIAPOENO S udy. Impac o an O al Nu i ional P o ocol wi h Oligome ic En e al Nu i ion on he Quali y o Li e o Pa ien s wi h Oncology T ea men -Rela ed Dia hea. Nu ien s 2021,13, 84. h ps://doi.o g/10.3390/nu13010084 Recei ed: 24 No embe 2020 Accep ed: 26 Decembe 2020 Published: 29 Decembe 2020 Publishe ’s No e: MDPI s ays neu- al wi h ega d o ju isdic ional clai- ms in published maps and ins i u io- nal a ilia ions. Copy igh : © 2020 by he au ho s. Li- censee MDPI, Basel, Swi ze land. This a icle is an open access a icle dis ibu ed unde he e ms and con- di ions o he C ea i e Commons A - ibu ion (CC BY) license (h ps:// c ea i ecommons.o g/licenses/by/ 4.0/). 1Depa men o Endoc inology and Nu i ion, Miguel Se e Hospi al, 50009 Za agoza, Spain 2Ins i u o de In es igación Sani a ia A agón (IIS A agon), 50009 Za agoza, Spain 3Depa men o Medical Oncology, Miguel Se e Hospi al, 50009 Za agoza, Spain; jm [email p o ec ed]g 4Depa men o Oncology, Uni e si y Clinic Hospi al, 50009 Za agoza, Spain; [email p o ec ed] 5G oup Resea ch on Wellbeing (GRoW), Blanque na School o Heal h Sciences-Uni e si a Ramon Llull, 08025 Ba celona, Spain; [email p o ec ed] 6Depa men o Endoc inology and Nu i ion, Uni e si y Clinic Hospi al, 50009 Za agoza, Spain; [email p o ec ed] *Co espondence: [email p o ec ed]; Tel.: +34-651667352 † Membe ship o he DIAPOENO S udy is p o ided in he Acknowledgmen s. Abs ac : (1) Backg ound: Nu i ional s a us can in luence he quali y o li e (QoL) o cance pa ien s. (2) Me hods: This subanalysis e alua ed he impac o an o al oligome ic en e al nu i ion (OEN) p o ocol on he QoL o pa ien s wi h oncology ea men - ela ed dia hea (OTRD) in a mul icen e , obse a ional, p ospec i e s udy (DIAPOENO s udy). QoL was assessed wi h he No ingham Heal h P o ile (NHP) a baseline and a e eigh weeks o OEN ea men . (3) In he o e all popula ion, all he NHP ca ego ies signi ican ly imp o ed a e eigh weeks o OEN ea men : ene gy le els (p< 0.001), pain (p< 0.001), emo ional eac ions (p< 0.001), sleep (p< 0.001), social isola ion (p= 0.023), and physical abili ies (p= 0.001). QoL imp o emen was highe in pa ien s wi h imp o ed o main ained nu i ional s a us and in hose wi h imp o ed consis ency o s ools wi h he OEN p o ocol. Howe e , QoL did no signi ican ly imp o e in pa ien s wi h wo se nu i ional s a us and wi h wo se o main ained s ool consis ency wi h he OEN p o ocol. QoL imp o ed ega dless o disease se e i y. Mul i a ia e logis ic eg ession analysis showed ha weigh change was signi ican ly associa ed wi h imp o ed QoL (OR 2.90–5.3), excep o social isola ion, in models unadjus ed and adjus ed o age, sex, oncology ea men , and s ool consis ency. (4) Conclusion: In his subanalysis, he OEN p o ocol was associa ed wi h imp o ed QoL. Keywo ds: oligome ic en e al nu i ion; quali y o li e; oncology ea men - ela ed dia hea; nu i- ional p o ocol 1. In oduc ion Cance pa ien s equen ly su e om gas oin es inal symp oms ha se e ely impai hei nu i ional s a us [ 1 ]. Nu i ional s a us can be u he comp omised by an icance he apy side e ec s, including as e changes, nausea, cons ipa ion, and dia hea [ 2 ]. On- cology ea men - ela ed dia hea (OTRD) is a common side e ec [ 3 ], esul ing in low pe o mance, equen hospi al admissions, educed su i al, and impai ed quali y o li e (QoL) [ 4 ]. The de elopmen o a ge ed he apies ha a e o en main ained o p olonged pe iods has inc eased he equency o OTRD [5]. QoL e lec s people’s wellbeing by conside ing emo ional, social, and physical aspec s o li e [ 6 ]. This mul idimensional measu e is key in oncology, gi en he impai men ha cance and oncology ea men s p omo e in physical and psychological sphe es o li e [ 7 ]. Common psychological consequences o malnu i ion and dia hea a e anxie y Nu ien s 2021,13, 84. h ps://doi.o g/10.3390/nu13010084 h ps://www.mdpi.com/jou nal/nu ien s Nu ien s 2021,13, 84 2 o 13 and dep ession, which can se e ely es ic daily li e ac i i ies [ 8 ]. Mo eo e , he highe incidence o hospi al admissions, longe hospi al s ays, and educed ole ance o an icance ea men s associa ed wi h malnu i ion and dia hea esul in poo e ou comes, educed QoL, and sho e su i al [ 9 , 10 ]. A sys ema ic e iew iden i ied ha dia hea episodes co ela ed wi h he lowes QoL pe cep ion in cance pa ien s [7]. Gi en he impac o nu i ion on disease ou comes and QoL, nu i ional suppo is expec ed o imp o e he wellbeing o cance pa ien s by educing weigh loss and o he gas oin es inal complica ions, sho ening he leng h o hospi al s ays, and imp o ing ole ance o ea men s [ 11 ]. Howe e , he associa ion be ween QoL and nu i ion in cance pa ien s has been sca cely s udied [12]. A sys ema ic e iew showed ha o al nu i ional suppo bene i ed some aspec s o QoL (emo ional unc ioning, dyspnea, loss o appe i e, and global QoL) [ 13 ]. A mo e ecen sys ema ic e iew only ound signi ican di e ences in some QoL domains wi h high-p o ein, n-3 polyunsa u a ed a y-acid-en iched o al nu i ional supplemen s [ 9 ]. Howe e , bo h sys ema ic e iews we e limi ed by he educed numbe o s udies included and hei he e ogenei y. Nu i ional suppo comp ises die a y counseling, ood supplemen s, and nu i ion he apy [ 14 ]. Howe e , clinical guidelines mainly p o ide a pha macological app oach o ea dia hea, and he nu i ional suppo o pa ien s is o en dis ega ded [3,4,15–18] . We ecen ly published an o al oligome ic en e al nu i ion (OEN)-based p o ocol and showed i s e ec i eness in pa ien s wi h OTRD [ 19 , 20 ]. OEN is whe e p o eins a e p o ided as pep ides ins ead o whole p o eins and a s as medium-chain iglyce ides wi h he aim o inc easing nu ien abso p ion. The p o ocol was p o en e ec i e in imp o ing he nu i ional s a us and consis ency o s ools in pa ien s wi h OTRD [ 20 ]. Since he e is li le e idence on he e icacy o OEN in OTRD [ 19 , 20 ] and, o ou knowledge, no p e ious s udy has e alua ed i s impac on QoL in pa ien s wi h cance , his subanalysis e alua ed whe he he e ec i eness o he OEN p o ocol ansla ed in o an imp o ed QoL in pa ien s wi h OTRD. 2. Ma e ials and Me hods 2.1. S udy Design This s udy epo s he subanalysis o QoL da a om he DIAPOENO s udy: a mul i- cen e , obse a ional, p ospec i e coho s udy [ 20 ]. The s udy was conduc ed a 15 cen e s ac oss Spain and was app o ed by he E hics Commi ee o Comunidad Au ónoma de A agón (CEICA, Code CP-CI.PI 15/0319). The s udy was pe o med in acco dance wi h he ene s o he Decla a ion o Helsinki and w i en in o med consen was ob ained om all pa icipan s. The design and p ocedu es o he s udy ha e been p e iously desc ibed in de ail [ 20 ]. In b ie , pa ien s ecei ed, a he onse o OTRD, Su imed OPD D ink ® (F esenius Kabi, Bad Hombu g, Ge many), a nu i ionally comple e o mula. This o al nu i ional suppo is composed o hyd olyzed p o eins (18.6%), ca bohyd a es (56.4), and a con en (25%). Depending on nu i ional s a us and in es inal unc ion, 2 o 3 bo les we e adminis e ed pe day (200 mL/bo le wi h a calo ic densi y o 1 Kcal/mL) o o al OEN [19]. Inclusion c i e ia we e age ≥ 18 yea s, cance diagnosis, ea men wi h cance he apy ( a ge ed he apy, chemo he apy, adio he apy, o chemo he apy and adio he apy), and OTRD- ela ed malnou ishmen o isk o malnou ishmen . Exclusion c i e ia included: li e expec ancy <3 mon hs, dia hea associa ed wi h an ibio ics, H 2 - ecep o an agonis s o p okine ics, laxa i es o osmo ically ac i e agen s ea men s, Clos idium di icile in ec ion, and he p esence o o he gas oin es inal condi ions ha could in e e e wi h he s udy assessmen s [20]. 2.2. S udy Ou comes The main objec i e o his subanalysis was o e alua e he impac o he OEN p o ocol on he QoL o pa ien s. The seconda y objec i es o he s udy we e: o assess whe he he Nu ien s 2021,13, 84 3 o 13 imp o emen in QoL co ela ed wi h nu i ional s a us, disease se e i y, and consis ency o s ools; and o iden i y independen ac o s signi ican ly associa ed wi h he imp o emen o QoL ca ego ies. QoL was assessed using he No ingham Heal h P o ile (NHP). The NHP is a mul idi- mensional measu e o heal h comp ising a i s pa wi h 38 ques ions ac oss 6 suba eas: ene gy le els (n= 3), pain (n= 8), emo ional eac ions (n= 9), sleep (n= 5), social isola ion (n= 5), and physical abili ies (n= 8). S a emen s a e assigned a weigh ed alue using he Thu s one me hod o pai ed compa isons, gi ing a sco e ha can ange om 0 (minimum se e i y) o 100 (maximum se e i y) [21]. The NHP was adminis e ed a baseline and ollowing 8 weeks o OEN ea men . In his s udy , he Spanish- alida ed e sion o he ques ionnai e was employed unde he use license o he copy igh ed ma e ial [22]. QoL change was also assessed in pa ien subg oups based on nu i ional s a us, disease se e i y, and s ool consis ency. The p o ocol was deemed e ec i e in he p e ious s udy when nu i ional s a us was main ained a isk o malnou ishmen o imp o ed 1 o 2 le els ( om mode a e o se e e malnou ishmen ). Wo sening o nu i ional s a us was conside ed when: nu i ional s a us wo sened 1 ( om a isk o malnou ishmen o om mode a e malnou ishmen ) o 2 le els ( om a isk o malnou ishmen ). The p o ocol was conside ed e ec i e when s ool consis ency, e alua ed wi h he B is ol S ool o m scale [ 16 ], was main ained a no mal s ool ypes o imp o ed by 1, 2, o 3 le els. S ool consis ency wo sened when s ool classi ica ion inc eased by 1 o 2 le els [ 20 ]. In his subanalysis, QoL changes we e assessed in pa ien s wi h imp o ed, main ained, o wo sened nu i ional s a us wi h he OEN p o ocol, wi h imp o ed, main ained, o wo sened s ool consis ency wi h he OEN p o ocol and in pa ien s wi h se e e (p esence o me as asis o pallia i e ea men ) o nonse e e disease. 2.3. S a is ical Analyses Dis ibu ion o da a dis ibu ion was assessed wi h he Kolmogo o –Shapi o–Wilks es and no mali y plo s. Con inuous a iables we e desc ibed as mean and s anda d de ia ions and ca ego ical a iables as numbe s and pe cen ages. Di e ences in QoL om baseline o Week 8 we e es ima ed using he Wilcoxon pai ed es . Logis ic eg ession models we e pe o med o de e mine ac o s independen ly as- socia ed wi h he imp o emen in QoL ca ego ies. The independen e ec s o sex, age, pallia i e ea men , weigh change, and s ool consis ency imp o emen on QoL we e assessed, and esul s we e exp essed as odds a ios (OR) wi h 95% CI. The e ec o weigh change was assessed in adjus ed and unadjus ed models. Analyses we e pe o med wi h he s a is ical package IBM SPSS S a is ics .24.0 (IBM Co p, A monk, NY, USA). S a is ical signi icance was se a p< 0.05. 3. Resul s 3.1. S udy Popula ion Ou o a o al o 162 pa ien s wi h OTRD, 149 comple ed he s udy, and QoL da a we e a ailable o 135. In he o e all popula ion, mean ± SD age was 68.6 ± 12.6 yea s, and 55% we e men and no pa ien ecei ed p e ious en e al nu i ion [ 20 ]. Table 1shows baseline cha ac e is ics ca ego ized by disease se e i y. Se e e disease was conside ed o pa ien s wi h me as ases o on pallia i e ea men . Nu ien s 2021,13, 84 4 o 13 Table 1. Demog aphic and clinical cha ac e is ics o s udy pa icipan s. Se e e (n= 83) Nonse e e (n= 52) p-Value Age (yea s), Mean (SD) 69.5 (12.8) 66.2 (12.4) 0.433 Gende , (%) Men 47 (56.6%) 28 (53.8%) 0.752 Women 36 (43.4%) 24 (46.2%) Weigh (kg), Mean (SD) 60.1 (12.1) 65.4 (11.6) 0.255 BMI (kg/m2), Mean (SD) 21.4 (3.2) 23.6 (4.1) 0.512 Resec abili y (* n= 132) Un esec able 64 (80.0%) 0 (0%) <0.001 Localized 16 (20.0%) 52 (100%) Type o ea men Pallia i e 62 (74.7%) 0 (0%) <0.001 Cu a i e 21 (25.3%) 52 (100%) T ea men modali y Chemo he apy 46 (55.4%) 7 (13.5%) <0.001 Radio he apy 9 (10.8%) 12 (23.1%) Chemo he apy + Radio he apy 28 (33.7%) 33 (63.5%) Ta ge ed he apy (* n= 134) Yes 23 (27.7%) 3 (5.9%) 0.002 No 60 (72.3%) 48 (94.1%) Type o umo Gynecologic/u ologic 9 (10.8%) 14 (26.9%) 0.023 Diges i e 67 (80.7%) 37 (71.2%) O he 7 (8.4%) 1 (1.9%) * indica es pe cen ages ob ained conside ing he numbe o pa ien s wi h a ailable da a. BMI, Body Mass Index. Se e i y is de ined by he p esence o me as ases o he ype o ea men (pallia i e). 3.2. QoL Imp o emen A baseline, ene gy le els (38.97) and sleep (35.47) sco ed highe (wo se pe cei ed QoL) han o he ca ego ies, whe eas social isola ion (14.34) and pain (16.15) showed lowe sco es (be e pe cei ed QoL). A e eigh weeks o OEN ea men , all he NHP ca ego ies signi ican ly imp o ed: ene gy le els (p< 0.001), pain (p< 0.001), emo ional eac ions (p< 0.001), sleep (p< 0.001), social isola ion (p= 0.023), and physical abili ies (p= 0.001). Di e ences a e eigh weeks o OEN ea men we e mo e p onounced o ene gy le els (di e ence o 13.12) and emo ional eac ions (di e ence o 10.38). Lowe di e ences a e eigh weeks o OEN ea men we e obse ed o social isola ion (di e ence o 3.84) and sleep (di e ence o 5.81) (Figu e 1). We nex assessed he subg oup o pa ien s ha be e imp o ed hei QoL. To his end, QoL sco es we e analyzed acco ding o nu i ional s a us, disease se e i y, and consis ency o s ools. A e eigh weeks o OEN ea men , all he NHP ca ego ies we e imp o ed, wi h signi ican ly highe di e ences in hose who imp o ed o main ained nu i ional s a us s. hose wi h wo sened nu i ional s a us o ene gy le els (p= 0.002, p= 0.001), pain (p = 0.002, p= 0.001), emo ional eac ions (p= 0.001, p= 0.001), sleep (p= 0.036, p= 0.021), and physical abili ies (p= 0.001, p= 0.026). In con as , social isola ion showed signi ican di e ences in pa ien s wi h wo sened nu i ional s a us (p= 0.024) (Figu e 2). Nu ien s 2021,13, 84 5 o 13 Nu ien s 2021, 13, x FOR PEER REVIEW 5 o 13 Figu e 1. Change in quali y o li e a e 8 weeks o oligome ic en e al nu i ion (OEN). The plo s show mean sco es ±95% CI o each ca ego y o he No ingham Heal h P o ile a baseline and a e 8 weeks o OEN ea men . * indica es p < 0.05 ( om baseline o Week 8). The No ingham Heal h P o ile (NHP) sco e anges om 0 (does no pe cei e any heal h p oblem) o 100 (maxi- mum heal h p oblems pe cei ed by he pa ien ). We nex assessed he subg oup o pa ien s ha be e imp o ed hei QoL. To his end, QoL sco es we e analyzed acco ding o nu i ional s a us, disease se e i y, and con- sis ency o s ools. A e eigh weeks o OEN ea men , all he NHP ca ego ies we e im- p o ed, wi h signi ican ly highe di e ences in hose who imp o ed o main ained nu i- ional s a us s. hose wi h wo sened nu i ional s a us o ene gy le els (p = 0.002, p = 0.001), pain (p = 0.002, p = 0.001), emo ional eac ions (p = 0.001, p = 0.001), sleep (p = 0.036, p = 0.021), and physical abili ies (p = 0.001, p = 0.026). In con as , social isola ion showed signi ican di e ences in pa ien s wi h wo sened nu i ional s a us (p = 0.024) (Figu e 2). Figu e 1. Change in quali y o li e a e 8 weeks o oligome ic en e al nu i ion (OEN). The plo s show mean sco es ± 95% CI o each ca ego y o he No ingham Heal h P o ile a baseline and a e 8 weeks o OEN ea men . * indica es p< 0.05 ( om baseline o Week 8). The No ingham Heal h P o ile (NHP) sco e anges om 0 (does no pe cei e any heal h p oblem) o 100 (maximum heal h p oblems pe cei ed by he pa ien ). Nu ien s 2021, 13, x FOR PEER REVIEW 5 o 13 Figu e 1. Change in quali y o li e a e 8 weeks o oligome ic en e al nu i ion (OEN). The plo s show mean sco es ±95% CI o each ca ego y o he No ingham Heal h P o ile a baseline and a e 8 weeks o OEN ea men . * indica es p < 0.05 ( om baseline o Week 8). The No ingham Heal h P o ile (NHP) sco e anges om 0 (does no pe cei e any heal h p oblem) o 100 (maxi- mum heal h p oblems pe cei ed by he pa ien ). We nex assessed he subg oup o pa ien s ha be e imp o ed hei QoL. To his end, QoL sco es we e analyzed acco ding o nu i ional s a us, disease se e i y, and con- sis ency o s ools. A e eigh weeks o OEN ea men , all he NHP ca ego ies we e im- p o ed, wi h signi ican ly highe di e ences in hose who imp o ed o main ained nu i- ional s a us s. hose wi h wo sened nu i ional s a us o ene gy le els (p = 0.002, p = 0.001), pain (p = 0.002, p = 0.001), emo ional eac ions (p = 0.001, p = 0.001), sleep (p = 0.036, p = 0.021), and physical abili ies (p = 0.001, p = 0.026). In con as , social isola ion showed signi ican di e ences in pa ien s wi h wo sened nu i ional s a us (p = 0.024) (Figu e 2). Figu e 2. Change in quali y o li e a e 8 weeks o oligome ic en e al nu i ion (OEN) by nu i ional s a us e olu ion. The ba s show mean sco es ± 95% CI o each ca ego y o he No ingham Heal h P o ile a baseline and a e 8 weeks o OEN ea men o pa ien s who imp o ed, main ained, o wo sened hei nu i ional s a us wi h he OEN p o ocol. * indica es p < 0.05 ( om baseline o Week 8). The NHP sco e anges om 0 (does no pe cei e any heal h p oblem) o 100 (maximum heal h p oblems pe cei ed by he pa ien ). Disease se e i y was no associa ed wi h signi ican di e ences in QoL imp o emen . Pa ien s wi h se e e disease signi ican ly imp o ed QoL sco es o ene gy le els (p= 0.001), pain (p= 0.030), emo ional eac ions (p= 0.001), and sleep (p= 0.044). Simila ly, he subg oup o pa ien s wi h nonse e e disease signi ican ly imp o ed ene gy le els (p = 0.001), pain (p= 0.001), emo ional eac ions (p= 0.001), and sleep (p= 0.002). Fo social isola ion and physical abili ies, di e ences we e no signi ican in pa ien s wi h se e e and nonse e e disease (p= 0.124, p= 0.070), espec i ely (Figu e 3). Nu ien s 2021,13, 84 6 o 13 Nu ien s 2021, 13, x FOR PEER REVIEW 6 o 13 Figu e 2. Change in quali y o li e a e 8 weeks o oligome ic en e al nu i ion (OEN) by nu i ional s a us e olu ion. The ba s show mean sco es ±95% CI o each ca ego y o he No ingham Heal h P o ile a baseline and a e 8 weeks o OEN ea men o pa ien s who imp o ed, main ained, o wo sened hei nu i ional s a us wi h he OEN p o ocol. * indica es p < 0.05 ( om baseline o Week 8). The NHP sco e anges om 0 (does no pe cei e any heal h p oblem) o 100 (maximum heal h p oblems pe cei ed by he pa ien ). Disease se e i y was no associa ed wi h signi ican di e ences in QoL imp o emen . Pa ien s wi h se e e disease signi ican ly imp o ed QoL sco es o ene gy le els (p = 0.001), pain (p = 0.030), emo ional eac ions (p = 0.001), and sleep (p = 0.044). Simila ly, he subg oup o pa ien s wi h nonse e e disease signi ican ly imp o ed ene gy le els (p = 0.001), pain (p = 0.001), emo ional eac ions (p = 0.001), and sleep (p = 0.002). Fo social isola ion and physical abili ies, di e ences we e no signi ican in pa ien s wi h se e e and nonse e e disease (p = 0.124, p = 0.070), espec i ely (Figu e 3). Figu e 3. Change in quali y o li e a e 8 weeks o oligome ic en e al nu i ion (OEN) by disease se e i y. The ba s show mean sco es ±95% CI o each ca ego y o he No ingham Heal h P o ile a baseline and a e 8 weeks o OEN ea men o pa ien s wi h o wi hou disease se e i y. * indica es p < 0.05 ( om baseline o Week 8). The NHP sco e anges om 0 (does no pe cei e any heal h p oblem) o 100 (maximum heal h p oblems pe cei ed by he pa ien ). The imp o emen in QoL ca ego ies was highe in pa ien s wi h imp o ed con- sis ency o s ools om baseline o Week 8, and signi ican o ene gy le els (p = 0.001), pain (p = 0.001), emo ional eac ions (p = 0.001), sleep (p = 0.003), social isola ion (p = 0.003), and physical abili ies (p = 0.001). In pa ien s wi h main ained o wo sened consis ency o s ools, signi ican di e ences om baseline o Week 8 we e ound only in he pe cep ion o pain (p = 0.044, p = 0.039) (Figu e 4). Figu e 3. Change in quali y o li e a e 8 weeks o oligome ic en e al nu i ion (OEN) by disease se e i y. The ba s show mean sco es ± 95% CI o each ca ego y o he No ingham Heal h P o ile a baseline and a e 8 weeks o OEN ea men o pa ien s wi h o wi hou disease se e i y. * indica es p< 0.05 ( om baseline o Week 8). The NHP sco e anges om 0 (does no pe cei e any heal h p oblem) o 100 (maximum heal h p oblems pe cei ed by he pa ien ). The imp o emen in QoL ca ego ies was highe in pa ien s wi h imp o ed consis ency o s ools om baseline o Week 8, and signi ican o ene gy le els (p= 0.001), pain (p= 0.001), emo ional eac ions (p= 0.001), sleep (p= 0.003), social isola ion (p= 0.003), and physical abili ies (p= 0.001). In pa ien s wi h main ained o wo sened consis ency o s ools, signi ican di e ences om baseline o Week 8 we e ound only in he pe cep ion o pain (p = 0.044, p= 0.039) (Figu e 4). Mul i a ia e logis ic eg ession analysis was pe o med o de e mine independen ac o s signi ican ly associa ed wi h he imp o emen in QoL. The ollowing a iables we e associa ed wi h an imp o ed pe cep ion o ene gy le els: women (OR, 0.39; 95% CI, 0.15–0.998), pallia i e ea men (OR, 0.26; 95% CI, 0.10–0.64), and weigh change (OR, 4.90; 95% CI, 1.83–9.03). The imp o emen in pain pe cep ion was associa ed wi h weigh change (OR, 3.79; 95% CI, 1.42–1.42) and imp o emen in s ool consis ency (OR, 3.76; 95% CI, 1.38–10.56) . Weigh change was he only de e minan signi ican ly associa ed wi h imp o ed emo ional eac ions (OR, 5.30; 95% CI, 2.1–2.05) and sleep (OR, 4.19; 95% CI, 1.57–11.20). Pa ien s unde pallia i e ca e we e less likely o imp o e social isola ion pe - cep ion (OR, 0.29; 95% CI, 1.0–0.88). The imp o emen in physical abili ies was signi ican ly associa ed wi h age (OR, 1.04; 95% CI, 1.00–1.08), pallia i e ea men (OR, 0.14; 95% CI, 0.06–0.35), weigh change (OR, 4.95; 95% CI, 1.92–12.79) and imp o ed s ool consis ency (OR, 3.74; 95% CI, 1.40–12.50). Since weigh change was an independen ac o o imp o e- men o all he ca ego ies bu social isola ion, we calcula ed he e ec o weigh change in adjus ed and unadjus ed models (Table 2). Nu ien s 2021,13, 84 7 o 13 Nu ien s 2021, 13, x FOR PEER REVIEW 7 o 13 Figu e 4. Change in quali y o li e a e 8 weeks o oligome ic en e al nu i ion (OEN) by he consis ency o s ool e olu ion. The ba s show mean sco es ± 95% CI o each ca ego y o he No ingham Heal h P o ile a baseline and a e 8 weeks o OEN ea men o pa ien s who imp o ed, main ained, o wo sened he consis ency o s ools wi h he OEN p o ocol. * indica es p < 0.05 ( om baseline o week 8). The NHP sco e anges om 0 (does no pe cei e any heal h p oblem) o 100 (maximum heal h p oblems pe cei ed by he pa ien ). Mul i a ia e logis ic eg ession analysis was pe o med o de e mine independen ac o s signi ican ly associa ed wi h he imp o emen in QoL. The ollowing a iables we e associa ed wi h an imp o ed pe cep ion o ene gy le els: women (OR, 0.39; 95% CI, 0.15–0.998), pallia i e ea men (OR, 0.26; 95% CI, 0.10–0.64), and weigh change (OR, 4.90; 95% CI, 1.83–9.03). The imp o emen in pain pe cep ion was associa ed wi h weigh change (OR, 3.79; 95% CI, 1.42–1.42) and imp o emen in s ool consis ency (OR, 3.76; 95% CI, 1.38–10.56). Weigh change was he only de e minan signi ican ly associa ed wi h im- p o ed emo ional eac ions (OR, 5.30; 95% CI, 2.1–2.05) and sleep (OR, 4.19; 95% CI, 1.57– 11.20). Pa ien s unde pallia i e ca e we e less likely o imp o e social isola ion pe cep ion (OR, 0.29; 95% CI, 1.0–0.88). The imp o emen in physical abili ies was signi ican ly asso- cia ed wi h age (OR, 1.04; 95% CI, 1.00–1.08), pallia i e ea men (OR, 0.14; 95% CI, 0.06– 0.35), weigh change (OR, 4.95; 95% CI, 1.92–12.79) and imp o ed s ool consis ency (OR, 3.74; 95% CI, 1.40–12.50). Since weigh change was an independen ac o o imp o emen o all he ca ego ies bu social isola ion, we calcula ed he e ec o weigh change in ad- jus ed and unadjus ed models (Table 2). Figu e 4. Change in quali y o li e a e 8 weeks o oligome ic en e al nu i ion (OEN) by he consis ency o s ool e olu ion. The ba s show mean sco es ± 95% CI o each ca ego y o he No ingham Heal h P o ile a baseline and a e 8 weeks o OEN ea men o pa ien s who imp o ed, main ained, o wo sened he consis ency o s ools wi h he OEN p o ocol. * indica es p< 0.05 ( om baseline o week 8). The NHP sco e anges om 0 (does no pe cei e any heal h p oblem) o 100 (maximum heal h p oblems pe cei ed by he pa ien ). Nu ien s 2021,13, 84 8 o 13 Table 2. Mul i a ia e logis ic eg ession models o assess he e ec o weigh change on QoL imp o emen . The able shows he model unadjus ed ( aw) and adjus ed o sex, age, pallia i e ea men , and s ool consis ency imp o emen . Da a a e exp essed as odds a ios (OR) wi h 95% CI and p- alues. Bold ex indica es signi ican de e minan s. Ene gy Le els Pain Emo ional Reac ions Sleep Social Isola ion Physical Abili ies Weigh Change OR (95% CI) pOR (95% CI) pOR (95% CI) pOR (95% CI) pOR (95% CI) pOR (95% CI) p OR ( aw) 3.28 (1.55–6.95) 0.002 2.65 (1.2–5.9) 0.017 4.2 (1.90–9.20) <0.001 2.90 (1.30–6.50) 0.012 0.96 (0.23–1.83) 0.329 3.81 (1.79–8.12) 0.001 OR (adjus ed) 4.90 (1.83–9.03) 0.000 3.79 (1.42–1.42) 0.008 5.30 (2.1–2.05) 0.001 4.19 (1.57–11.20) 0.004 1.12 (0.39–3.27) 0.83 4.95 (1.92–12.79) 0.001 Nu ien s 2021,13, 84 9 o 13 4. Discussion This subanalysis showed he o e all imp o emen in he QoL o pa ien s ea ed wi h he p e iously desc ibed OEN p o ocol [ 20 ]. This imp o emen ag ees wi h he main ind- ings o he DIAPOENO s udy, showing ha he OEN p o ocol was e ec i e in imp o ing nu i ional s a us and consis ency o s ools in pa ien s wi h OTRD. In his subanalysis, we e eal ha he e ec i eness o he OEN p o ocol ansla es in o QoL imp o emen , wi h signi ican di e ences in all he NHP ca ego ies in he o e all popula ion. The imp o e- men in QoL was mo e p onounced in pa ien s wi h imp o ed o main ained nu i ional s a us and in hose wi h imp o ed consis ency o s ools bu was independen o he se e i y o he disease. S udies add essing he impac o nu i ional suppo on he wellbeing o cance pa ien s a e sca ce, al hough a s udy e ealed ha global QoL sco es a e signi ican p e- dic o s o su i al in lung cance pa ien s [ 23 ]. Mo eo e , sys ema ic e iews include he e ogeneous s udies wi h inconclusi e esul s, making i di icul o ob ain eliable con- clusions. Whe eas some s udies ound a posi i e e ec o nu i ional suppo on pa ien s’ QoL [9,13,24], o he s did no [25,26]. We obse ed ha a baseline, he mos comp omised NHP ca ego ies we e ene gy le els and sleep, whe eas social isola ion and pain we e be e pe cei ed. This ag ees wi h p e ious s udies in pa ien s ea ed wi h adio he apy o o opha yngeal o epipha yngeal cance [ 27 ] and wi h non unc ioning pi ui a y adenomas [ 28 ], showing highe sco es o ene gy le els and lowe o pain and social isola ion. A e ecei ing he OEN p o ocol, pa ien s signi ican ly imp o ed he pe cep ion o all he NHP ca ego ies, indica ing an o e all imp o ed QoL upon his nu i ional suppo . Social isola ion, physical abili ies, and sleep we e he ca ego ies wi h mo e sub le di e ences om baseline. O no e, social isola ion was no se e ely comp omised a baseline (lowes sco e among all he ca ego ies), which could indica e ha his ca ego y is no ep esen a i e o he dis ess caused by malnu i ion in OTRD pa ien s. Rega ding sleep, al hough pa ien s showed a nega i e pe cep ion a baseline, i was among he ca ego ies wi h lowe di e ences om baseline. A possible explana ion could be ha sleep a ec a ion is in insically ela ed o cance i sel and does no depend on he nu i ional s a us o pa ien s. Howe e , his assump ion equi es u he con i ma ion. A p e ious mul i a ia e logis ic eg ession analysis ound ha sleep diso de s we e s ongly associa ed wi h low QoL and he au ho s poin ed o p obable unde ea men o he condi ion by physicians [29]. The mos ema kable imp o emen was obse ed in ene gy le els (di e ence o 13.12) and emo ional eac ions (di e ence o 10.38). Such an imp o emen in ene gy le els ag ees wi h he posi i e e ec o he OEN p o ocol on nu i ional s a us [ 20 ]. Low ene gy and a igue a e commonly obse ed in cance pa ien s ecei ing he apy. This is because he me abolism o cance pa ien s is al e ed, wi h highe p o eolysis and lipolysis, inc eased hepa ic p oduc ion, educed insulin sensi i i y, and, he e o e, inc eased ene gy expendi u e. In his con ex , nu i ional suppo can help main ain he balance be ween ene gy expendi u e and ood in ake, inc easing ene gy le els [ 30 ]. The imp o emen in emo ional eac ions could also be he consequence o he imp o emen in he consis ency o s ools p e iously epo ed [ 20 ], as OTRD is associa ed wi h anxie y and dep ession, which, in u n, can comp omise daily li e ac i i ies [7]. One o he mos in e es ing esul s o his s udy is ha he imp o emen in QoL was signi ican ly highe in pa ien s showing an imp o emen o main enance o nu i ional s a us wi h he OEN p o ocol and in hose wi h imp o ed consis ency o s ools. Howe e , i was obse ed ega dless o disease se e i y. These esul s sugges ha he posi i e e ec o he OEN p o ocol on nu i ional s a us and consis ency o s ools in luences he QoL o pa ien s independen ly o disease se e i y. The sco es o NHP ca ego ies we e highe a baseline (mo e se e e QoL impai men ) o pa ien s in ou s udy compa ed o he gene al popula ion in a subg oup o 1220 Spanish pa icipan s [ 22 ]. A e he OEN ea men , howe e , he sco e o emo ional eac ions was