När barnet blir vuxen, och fetman finns kvar: Vikten av att behandla fetma i tid

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1 Vad händer sedan? När barnet blir vuxen, och fetman finns kvar: Vikten av att behandla fetma i tid , Barnveckan Helena Dreber, med dr, specialist i allmänmedicin, Vårdcentralen Hökarängen

2 Vilka är fetmans drivkrafter? - Födelsevikt - BMI peak - Adiposity rebound (Aris et al, Int J Epid, 2019; Geserick et al, NEJM, 2018) Helena Dreber 2

3 Andel barn med fetma som går till svår fetma/övervikt/normalvikt: Helena Dreber 3

4 Förändring i ålder och BMI SDS uppdelat på ålder och grad av fetma vid behandlingsstart Helena Dreber 4

5 Är kirurgisk behandling ett alternativ? AMOS - Adolescent morbid obesity surgery BORIS-registret Studiegrupp: n=81, medelålder 16,5 år Kontrollgrupp: n=8o, medelålder 15,8 år Kontrollgrupp: n=81, medelålder 39,7 år (Olbers et al, Lancet Diabetes Endocrinol, 2018) Helena Dreber 5

6 AMOS, 5-årsuppföljning BMI (kg/m 2 ) T2DM/IGT (%) DYS- LIPIDEMI (%) FÖRHÖJT BLODTRYCK (%) STUDIE- GRUPP 45.5 à à à à2.8 BORIS- KTRL 42.2 à VUXNA KTRL 43.5 à 31.0 (Olbers et al, Lancet Diabetes Endocrinol, 2018) Helena Dreber 6

7 AMOS, 5-årsuppföljning: Fler näringsbrister i kirurgigruppen jämfört med BORIS-gruppen: Anemi: 32% vs 10% B-12 brist: 22% vs 6% Järnbrist: 66% vs 29% Komplikationer i kirurgigruppen: Tarmvred (14%), gallsten (11%), blodtransfusion (2%), laparotomi pga kraftig buksmärta (1%), observation pga buksmärta (11%), drogmissbruk (7%) (Olbers et al, Lancet Diabetes Endocrinol, 2018) Helena Dreber 7

8 AMOS: livskvalitet och psykisk ohälsa 2 år efter gastric-bypass sågs klara förbättringar i: Depressivitet Ångest Ilska Självkänsla Fetmarelaterade problem Men: 20% uppvisade symtom på klinisk depression och 14% rapporterade suicidtankar. (Järvholm et al, SOARD, 2016; Järvholm et al, Obesity, 2015) Helena Dreber 8

9 men vad händer med de som inte opereras? Helena Dreber 9

10 Viktutveckling efter tonåren: (Ng M et al, Lancet, 2013) Helena Dreber 10

11 Och vad händer på lång sikt? (Schmidt M et al, BMJ Open, 2013) Helena Dreber 11

12 Helena Dreber 12

13 Vad utmärker unga vuxna? Neurologisk Psykologisk Social Flytt från föräldrahemmet Påbörjar högre utbildning/börjar arbeta Ökad autonomi Helena Dreber 13

14 Bakgrund: Avhandling på fetma bland unga vuxna: 1. Kliniska observationer av unga vuxna med fetma: Metabol sjuklighet Psykisk ohälsa? Viktnedgång? 2. Är fetmakirurgi av unga vuxna en bra idé?!! Viktnedgång? Komplikationer? Uppföljning? Livskvalitet? Helena Dreber 14

15 Vem är den unga vuxna vi möter på fetmamottagningen? Dyslexi: 20% 39.2 kg/m 2 (SD: 5.2) Student: 64% Anställd: 20% Arbetslös: 10% Sjukskrivning>30 dagar Föregående år: 12%? 19.7 år (SD: 2.7) 80% kvinnor n=165 " Andra generationens invandrare: 19%! Dagligrökare: 22% # Dålig ell mycket dålig kondition (Åstrand): 92% Insomni: 54% (Dreber et al, PlosOne, 2015) Helena Dreber 15

16 Samsjuklighet? Hypertoni: 2% Diabetes typ 2: 3% Hyperkolesterolemi: 3% PCOS: 10% Depressiv episod: 13% Ångestsjukdom: 12% ADHD: 13% Annan neuropsykiatrisk sjd: 5% 1 psykiatrisk sjd: 29% 1 psykofarmaka: 21% Insulinresistans a: 82% 1 plasmalipid-abnormalitet b: 62% 1 vitamin-/mineralbristc: 48% Severe Obesity-related Problems (score 60): 55% Självrapporterade suicidförsök: 12% Låg självkänsla (Rosenberg 15): 42% A According to HOMA-index. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics. 2011;128 Suppl 5:S c Vitamin-D <25 nmol/l, b-folate <305 nmol/l, b-cobalamine <100 or <150 pmol/l and/or zink <10.7 mol/l. b

17 Helena Dreber 17

18 vs n=121 n=363 Relativ risk (95% CI) *: 52% 30% 1.8 ( ) Psykisk ohälsa (GHQ 3)! Självrapporterad depression 22% 8% 2.2 ( ) 12% 6% 2.0 ( ) Självrapporterat SU-försök (Dreber et al, Clin Obes, 2017) Helena Dreber 18

19 Study II: vs. 5,0 General Health Questionnaire-12 (GHQ-scoring, min-max distress: 0 to 12) 4,0 Total score 3,0 2,0 1,0 0, Population controls with class I obesity mean-bmi=32.1 kg/m2, SD:1.3 (n=102) Population controls with severe obesity mean-bmi=39.7 kg/m2, SD:5.3 (n=41) Young adult treatment-seekers mean-bmi=39.8 kg/m2, SD:5.3 (n=120) (Dreber et al, Clin Obes, 2017) Helena Dreber 19

20 Kirurgi nu, då? Helena Dreber 20

21 Metod: Matchade på BMI, kön, operationsår: Young adult Older adult n=3,531 Medelålder: 22.2 år (SD:2.1), span: år n=17,137 Medelålder: 52.6 år (SD:9.6), span: år Gastric bypass! Uppföljning 6 veckor /1 år/ 2 år/ 5 år Viktnedgång?! Loss-tofollow-up? Komplikationer? Livskvalitet? Helena Dreber 21

22 Resultat: Viktnedgång Young adult Older adult 45 * 43,7 43,4 * p BMI (kg/m 2 ) 35 * * 29,5 29,2 * 31,4 25 Before LCD 30,3 28,6 28,3 1 year 2 years 5 years N Young adults : 1 y=2,900, 2 y=1,831, 5 y=369 N Older adults : 1 y=15,298, 2 y=9,959, 5 y=1,525 (Dreber et al, SOARD, 2018) Helena Dreber 22

23 Komplikationer: Young adult Older adult * * Error bars represent 95% confidence intervals. * p <0.05 when adjusted for body mass index at baseline, gender, year of surgery, comorbidity at baseline (yes/no), surgical access (open/laparoscopic), duration of surgery (minutes), center volume (low/high) N Young adults intraoperatively=3,531, 6 weeks=3,330, 1 year=2,900, 2 years=1,832, 5 years=371. N Older adults intraoperatively=17,137, 6 weeks=16,632, 1 year=15280, 2 years=9,949, 5 years=2,210. (Dreber et al, SOARD, 2018) Helena Dreber 23

24 (Dreber et al, SOARD, 2018) Error bars represent 95% confidence intervals. * p <0.05 when adjusted for body mass index at baseline, gender, year of surgery, comorbidity at baseline (yes/no), surgical access (open/laparoscopic), duration of surgery (minutes), center volume (low/high) 24

25 Resultat fem år efter kirurgi: Young adult vs Older adult n=3,351 n=17,137 % viktnedgång 31.8% 28.2% p <0.001! % komplikationer* (mellan 2-5 år efter op) 20.3% 12.7% vs. Odds ratio *: 1.7, 95% CI: ! % loss-to-follow-up * (mellan 2-5 år efter op) 63.0% 53.9% Relativ risk *: 1.2, 95% CI: Helena Dreber 25 * Justerad för body mass index vid baseline, kön, ålder, samsjuklighet, kirurgisk access, operationstid, centervolym.

26 Livskvalitet fem år efter kirurgi bland unga vuxna: Den fysiska livskvaliteten ökade: Physical component score 40.7 à47.1 (effektstorlek: 0.6) Den emotionella livskvaliteten ökade inte: Mental component score 40.7 à 40.9 (effektstorlek: 0.02) Fetmarelaterade problem minskade vs. avsevärt: Obesity-related problems 75.0 à 39.6 (effektstorlek: 1.11) (Dreber et al, Obes Surg, 2018) Helena Dreber 26

27 Obehandlad fetma i barndom Fetma i ungdomen Ännu mer svårbehandlat! Samsjuklighet: psykiatriska sjd, metabola riskmarkörer, näringsbrister Kirurgi? Ok viktnedgång Fler komplikationer? Sämre uppföljnings -grad Bättre fysisk QoL Helena Dreber 27

28 Diskussion: Samexisterande psykisk sjukdom och fetma Bariatrisk kirurgi nu, senare eller aldrig? Helena Dreber 28

29 Tack! Helena Dreber 29

30 Sammanfattningsvis: hur mår unga vuxna med fetma, och vad händer efter fetmakirurgi? - Tänk på näringsbrister även hos unga med fetma som inte har opererats. - Hög andel psykiatriska sjukdomar. - Kirurgi: bra viktnedgång, men låg uppföljningsgrad à vad händer med de ungdomar som inte följs upp? - Oklart kring komplikationer efter kirurgi. - Klart förbättrad fysisk livskvalitet, men vi vet mindre om psykisk dito. Helena Dreber 30

31 Sammanfattningsvis: hur mår unga vuxna med fetma, och vad händer efter kirurgisk behandling? Kohort med vårdsökanden: " Vårdsökanden VS normalviktiga kontroller: 1 psykiatrisk sjukdom: 29% 1 psykiatrisk medicinering: 21% Kardiovaskulära risk-markörer: 22-82% - sjukdomar: 3-10% Näringsbrister: 48% Psykisk ohälsa: 52% vs 30%, RR: 1.8 Unga vuxna VS äldre vuxna 5 år efter RYGB:!! Viktnedgång: 31.8 vs 28.2% Komplikationer 6 veckor post-op: Justerad OR: Loss-to-follow-up: Adj RR: Livskvalitet: Ingen skillnad eller sämre förbättringar Helena Dreber 31

32 Extra slides Helena Dreber 15/06/

33 Study I: Results: Anthropometric, sociodemographic and lifestyle characteristics: Total (n=165) Age 19.7 y (SD: 2.7) Body mass index 39.2 kg/m 2 (SD: 5.2) Obesity class II-III 82% (135) Student 64% (106) Employed 20% (33) Unemployed 10% (17) Sickness benefit >30 days last year 12% (20) Dyslexia (self-reported) 20% (33) Second generation immigrant 19% (31) Poor or very poor cardiorespiratory fitness (Åstrands test) 92% (90) Daily tobacco smoker 22% (36) Insomnia 54% (88) Helena Dreber 15/06/

34 Study I: Results: Physical co-morbidities (ICD-10) and micronutritional deficiencies: Diabetes mellitus type 2 3% (5) Hypercholesterolemia 3% (5) Hypertension 2% (4) Total (n=165) Polycystic ovary syndrome (of women only) 10% (13) Insulin resistant according to HOMA-index 82% (129) 1 plasma lipid abnormality a 62% (98) Elevated ALT b 22% (35) Deficiency in: s-cobalamine c (<100 or <150 pmol/l) 8% (12) b-folate (<305 nmol/l) 7% (10) s-25-oh-vitamin D (<25 nmol/l) 35% (55) 1 micronutritional deficiency (cobalamine, folate, 25-OH-vitamin D, zink) 48% (76) a Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics. 2011;128 Suppl 5:S b Women: <18 years: >0.37 µkat/l, 18 years: 0.76 µkat/l, men: <18 years: >0.42 µkat/l, 18 years: 1.20 µkat/l. c Reference values according to Beckman Coulter Inc (DxI, low cut-off) and Roche Diagnostics (Modular E120, high cut-off). Helena Dreber 15/06/

35 Study I: Results: Present psychiatric disorders (ICD-10 coded), medications and self-reported mental health indices: Total (n=165) Depressive episode 13% (22) Anxiety disorder 12% (20) Attention deficit hyperactivity disorder 13% (21) Other neurodevelopmental disorder 5% (8) 1 psychiatric disorder 29% (47) Medication for any psychiatric disorder (ATC-classified) 21% (35) Self-reported suicide attempt 12% (20) HADS anxiety subscale, clincial or subclinical score ( 8) 47% (77) HADS depression subscale, clincial or subclinical score ( 8) 27% (45) Low self-esteem according to Rosenberg self-esteem scale ( 15) 42% (69) Severe impairment according to Obesity-related Problems scale ( 60) 55% (91) Abbreviations: HADS, Hospital Anxiety and Depression Scale Helena Dreber 15/06/

36 Study I: Anxiety Depression Helena Dreber 36

37 Study II: Results: Mental health 20.8 y (SD:2.3) 21.4 y (SD:2.2) 21.8 y (SD:2.3) 81% women 49% women 78% women Economic strain: 25% Economic strain: 31% Economic strain: 42% BMI: 39.8 kg/m 2 (SD: 5.3) BMI: 32.1 kg/m 2 (SD:1.3) BMI: 39.7 kg/m 2 (SD: 5.3) n=121 n=105 n=41 GHQ-score (likert-scoring) (Min-max distress: 0-36) * 10.2 * GHQ-score (ghq-scoring) (Min-max distress: 0-12) Poor mental health (GHQ-12 3) % 2.3 * 2.1 * 27% 39% Helena Dreber Data were adjusted for age, gender, economic strain and body mass index. 37 * p <0.05 for difference in treatment-seekers vs obesity class I and severe obesity respectively.

38 Study II: Results: vs. Baseline characteristics: Characteristic Treatment-seekers (n=121) Women, % (n) 81 (98) 81 (294) Age, y (SD) 20.8 (2.3) 20.8 (2.3) Economic strain, % (n) 25.0 (30) 25.0 (90) Body mass index, kg/m 2 (SD) 39.8 (5.3) 22.4 (4.0) Overweight, % (n) 0 (0) 14 (50) * Obesity, class I, % (n) 17 (20) 4 (13) * Severe obesity, % (n) 83 (91) 2 (5) * Student, % (n) 52 (63) 59 (211) Unemplyed/on sick leave/other, % (n) 17 (21) 6 (20) * Born in Sweden, % (n) 87 (105) 89 (322) Population controls (n=363) * p <0.05 for difference population controls vs treatment-seekers. Helena Dreber 15/06/

39 Study II: Results: vs. Mental health indices and quality of life in treatment-seekers versus population controls: Variable Treatmentseekers (n=121) Population controls (n=363) Adjusted difference or RR (95% CI) a GHQ-12 (Likert scoring b ), mean (SE) 15.5 (0.57) 10.8 (0.34) 4.55 (3.24, 5.86) GHQ-12 (GHQ scoring c ), mean (SE) 3.9 (0.30) 2.2 (0.17) 1.75 (1.08, 2.42) Mental distress (GHQ scoring 3), % (n) 52 (63) 30 (109) 1.76 (1.38, 2.24) Depression (self-reported), % (n) 22 (32) 8 (27) 2.18 (1.34, 3.55) Suicidal ideation (self-reported), % (n) 41 (50) 19 (69) 1.98 (1.43, 2.73) Suicide attempt (self-reported), % (n) 12 (14) 6 (20) 2.04 (1.06, 3.95) EQ5D, mean (SE) 0.64 (0.019) 0.86 (0.011) (-0.27, -0.18) a Matched and adjusted for age, gender, socioeconomic status, tobacco smoking, hazardous alcohol drinking, physical disease, sexual orientation and social support. b Min max (0 36). c Min max (0 12). Helena Dreber 15/06/

40 Study III: Results: Young adult vs. Older adult Baseline characteristics: Characteristic: Young adult Older adult p-value (n=3,531) (n=17,137) Age, y (SD) 22.2 (2.1) 42.6 (9.6) <0.001 Female, % (n) 81.6 (2882) 82.0 (14.052) 0.60 Year of surgery, % (n) 0.81 Body mass index, kg/m 2 (SD) 43.7 (5.4) 43.4 (5.0) Co-morbidities, % (n) Any disorder 22.3 (786) 52.8 (9054) <0.001 Diabetes mellitus type (104) 14.0 (2403) <0.001 Hypertension 2.0 (70) 26.7 (4577) <0.001 Dyslipidemia 1.2 (43) 9.9 (1696) <0.001 Sleep apnea 1.5 (52) 9.8 (1680) <0.001 Depression 9.4 (331) 15.4 (2641) <0.001 Current smoking, % (n) 26.7 (648) 13.8 (1646) <0.001 Laparoscopic access, % (n) 98.0 (3461) 96.4 (16.527) <0.001 Concurrent surgery, % (n) 0.4 (13) 1.4 (245) <0.001 Helena Dreber 15/06/

41 Study IV: Results: Short Form-36 and Obesity-related problems scale at baseline and 5 years after Roux-en-Y gastric bypass in young (18-25 y) and older (26-74 y) adults. Variable Young adult Older adult p-value (n=2.425) (n=12,425) Physical component score, mean (SD) Baseline 40.7 (10.0) 36.8 (10.9) < years after Roux-en-Y gastric bypass 47.1 (11.3) ** 45.3 (12.4) ** Effect size Baseline - 5 years Mental component score, mean (SD) Baseline 40.7 (12.6) 45.4 (12.5) < years after Roux-en-Y gastric bypass 40.9 (14.0) 43.5 (14.4) ** Effect size Baseline - 5 years Obesity-related Problems scale, median (IQR) Baseline 75.0 (33.3) 70.8 (35.7) < years after Roux-en-Y gastric bypass 39.6 (45.8) ** 20.8 (45.8) ** <0.001 Effect size Baseline - 5 years ** p for difference between baseline and 5 years Helena Dreber 15/06/

42 Study IV: Results: Young adult vs. Older adult Effect of matching group (1=young adults) on 5-year change in Short Form-36 and Obesity -related Problems scale in 138 young (18-25 years) and 1,021 older (26-74 years) adult Roux-en Y gastric bypass patients. Variable Adjusted model Beta (95% CI) a p-value Short Form-36 Physical functioning -2.0 (-5.5, 1.5) 0.27 Physical role -7.2 (-14.0, -0.47) Bodily pain -2.0 (-7.4, 3.4) 0.47 General health -6.6 (-10.9, -2.3) 0.02 Vitality -6.2 (-10.9, -1.4) Social functioning -5.7 (-11.0, -1.4) Role emotional 4.7 (-12.0, 2.7) 0.21 Mental health -1.3 (-5.4, 2.8) 0.54 Physical component score -2.1 (-4.0, -0.14) Mental component score -2.0 (-4.7, 0.58) 0.13 Obesity-related Problems scale 13.6 (8.7, 18.4) <0.001 a Negative numbers for Short Form-36 denote a smaller change in young versus older adults, positive numbers for obesity-related problems scale denotes a smaller change in young versus older adults. Data are adjusted for healthrelated quality of life at baseline, comorbidity, weight loss at 5 years, adverse event, surgical access. Helena Dreber 15/06/

43 Study III: Scandinavian Obesity Surgery Registry Data collection: May 2, 2007 Sept 15, 2015 Young adults (18-25 y) Older adults (26-74 y) Baseline n=3,531 6 weeks n=3,328 Missed appointment (n=175) No attempt to contact patient (n=23) Missing data (n=5) Baseline n=17,137 6 weeks n=16,631 Missed appointment (n=381) No attempt to contact patient (n=94) Deceased (n=4) Missing data (n=27) 1 year n=2,900 Missed appointment (n=430) No attempt to contact patient (n=149) Deceased (n=2) Missing data (n=50) 1 year n=15,298 Missed appointment (n=1,088) No attempt to contact patient (n=414) Deceased (n=16) Missing data (n=321) 2 years n=1,831 Missed appointment (n=632) No attempt to contact patient (n=381) Surgery after (n=242) Deceased (n=4) Missing data (n=441) 2 years n=9,959 Missed appointment (n=1,965) No attempt to contact patient (n=1,547) Surgery after (n=1,203) Deceased (n=30) Missing data (n=2,436) 5 years n=369 Missed appointment (n=257) No attempt to contact patient (n=95) Surgery after (n=2,533) Deceased (n=6) Missing data (n=275) 5 years n=2,210 Missed appointment (n=955) No attempt to contact patient (n=311) Surgery after (n=12,345) Deceased (n=36) Missing data (n=1,208) = 37.0% of eligible patients = 46.1% of eligible patients Helena Dreber 43

44 Study III: Results: Loss-to-follow-up Young adult vs. Older adult Relative risk (RR) of loss-to-follow-up: Young adult Older adult Adjusted RR (95% CI) a, p-value 1 year, % (n) Visits 82.1 (2,900) 89.3 (15,298) Missed appointment 12.2 (430) 6.3 (1,088) 1.81 ( ), <0.001 No attempt to contact patient 4.2 (149) 2.4 (414) 1.50 ( ), <0.001 Total loss-to-follow-up 17.9 (631) 10.7 (1,839) 1.57 ( ), < years, % (n) Visits 55.7 (1,831) 62.5 (9,959) Missed appointment 19.2 (632) 12.3 (1,965) 1.47 ( ), <0.001 No attempt to contact patient 11.6 (381) 9.7 (1,544) 1.18 ( ), Total loss-to-follow-up 44.3 (1,458) 37.5 (5,975) 1.20 ( ), < years, % (n) Visits 37.0 (369) 46.1 (2,210) Missed appointment 25.8 (257) 19.9 (955) 1.25 ( ), <0.001 No attempt to contact patient 9.5 (95) 6.5 (311) 1.33 ( ), Total loss-to-follow-up 63.0 (629) 53.9 (2,582) 1.16 ( ), <0.001 a Adjusted for body mass index at baseline, gender, year of surgery, comorbidity at baseline, surigcal access, duration of surgery, center volume. Helena Dreber 15/06/

45 Study II: Results: Baseline characteristics 22.2 y (SD: 2.1) 42.6 y (SD:9.6) 81.6 % women BMI: 43.7 kg/m 2 (SD: 5.4) vs 82.0 % women BMI: 43.4 kg/m 2 (SD: 5.0) n=3,351 n=17,137 Diabetes type 2 2.9% p < % Hypertension! Depression 2.0% 26.7% 9.4% 15.4% p <0.001 p <0.001 " Current smokers 26.7% (n=648) 13.8% (n=1646) p <0.001 Helena Dreber 45

46 AMOS, 5-årsuppföljning Anemi (%) B12- brist (%) STUDIE- GRUPP 10 à 32 1à 22 BORIS- KTRL 7 6 Helena Dreber 46

47 Study II: Methods: Stockholm Public Health Cohort: Treatment-seekers: Normal-weight: Obesity class I: Severe obesity: Mean BMI: 39.8 kg/m 2 (SD: 5.2) Mean BMI: 22.4 kg/m 2 (SD: 4.0) Mean BMI: 32.1 kg/m 2 (SD: 1.3) Mean BMI: 39.7 kg/m 2 (SD: 5.3) vs. vs. Matched cohort 1:3 for age, gender and socioeconomic strain Unmatched cohort Helena Dreber 47

48 Study II: Results: Baseline characteristics 20.8 y (SD: 2.3) 81% women Economic strain: 25% vs 20.8 y (SD: 2.3) 81% women Economic strain: 25% BMI: 39.8 kg/m 2 (SD: 5.3) BMI: 22.4 kg/m 2 (SD: 4.0)! Regular smoker n=121 25% n=363 16% p=0.043 " Hazardous alcohol drinking a 11% 30% p<0.001 # Heterosexual orientation $ Social support b 83% 88% 91% 94% p=0.012 p=0.024 a Helena Dreber Weekly consumption of 14 (men) or 9 (women) units; or 5 (men) or 4 (women) units at the same occasion. 48 b According to single question in Stockholm Public Health Questionnaire.

49 Study III: Results: Health-related quality of life and effect size baseline à 5 years after gastric bypass surgery *: Physical component score (SF-36) Min-max health: Young adult vs Older adult n=138 n=1, à 47.1 * Effect size: à 45.3 * Effect size: 0.73 Between-group difference in change baseline-5 years in young vs older adults Adjusted a Beta (95% CI) -2.1 (-4.0, -0.14) * Mental component score (SF-36) Min-max health: à 40.9 Effect size: 0.02 vs à 43.5 * Effect size: (-4.7, 0.58) Obesity-related Problems Min-max problems: à 39.6 * Effect size: à 20.8 * Effect size: (8.7, 18.4) * Helena Dreber * p <0.05 for intra/between group differences. 49 a Adjusted for health-related quality of life at baseline, comorbidity, weight loss at 5 years, adverse event and surgical access.