BASUN - komplikationsrisk avseende nutritionsstatus, skelett och munhälsa efter obesitasbehandling -relaterat till socioekonomi och psykiatrisk hälsa.
Project number : 137801
Created by: Malin Werling, 2013-11-28
Last revised by: Researchweb Support 7, 2018-03-21 Verified: 2018-12-17
Project created in: FoU i Västra Götalandsregionen

PublishedPublished

1. Översiktlig projektbeskrivning

Engelsk titel

BASUN - Risks for malnutrition, metabolic bone disease and impaired oral health after obesity treatment - interaction with gastrointestinal microbiota, psychiatric morbidity and socioeconomics

Populärvetenskaplig sammanfattning av projektet

PROJEKTSAMMANFATTNING:
Prevalensen av övervikt och obesitas ökar stadigt. Följdkostnader för sjukvård och nedsatt arbetsförmåga utgör en betydande belastning på samhällsresurserna. BMI korrelerar positivt till sjuklighet samt sjukskrivning. Obesitas ger >30% ökning av både kort- och långtidssjukskrivning jämfört med hos normalviktiga.
Konventionell obesitasbehandling har ringa och kortvarig effekt. Obesitaskirurgi blir allt vanligare med god långtidseffekt på vikt, livskvalitet och följdsjuklighet samt är kostnadseffektiv. Viktnedgången varierar dock stort och det förekommer ibland viktrecidiv. Därtill förekommer komplikationer med smärtsyndrom, diarréer, vitamin- och mineralbrist samt nedsatt skelett- och munhälsa. Ovan resulterar i minskad vinst av behandlingen både ur ett individuellt och hälsoekonomiskt perspektiv. Det saknas idag prediktorer för utfall samt komplikationer efter obesitaskirurgi.
BASUN utgör en detaljerad prospektiv 10 års jämförelse av konventionellt och kirurgiskt behandlade (n=1400) avseende utfall, komplikationer och hälsoekonomisk effekt.
Psykiatrisk sjuklighet och socioekonomi kartläggs utifrån om de utgör riskfaktorer för komplikationer och sämre utfall. Prover sparas i Sahlgrenska Biobank. BASUN utförs i ett brett samarbete i VGR mellan olika expertisområden. BASUN kommer att skapa en hälsoekonomisk vinstökning genom ökad behandlingseffektivitet och minskade komplikationer samt i förlängningen förbättrad hälsa, livskvalité och ökad arbetsförmåga på individnivå.

BAKGRUND:
Diagnosen obesitas utgör en stor belastning på samhälls- och sjukvårdsresurserna internationellt genom direkta och indirekta kostnader pga. följdsjukdomar respektive nedsatt arbetsförmåga. BMI korrelerar positivt till både sjukvårdsutnyttjande samt kort- och långtidssjukskrivning. Obesa har >30% ökad sjukfrånvaro jämfört med normalviktiga. Utan effektiv behandling tenderar sjukligt obesa individer öka i vikt under sin livslängd med ytterligare ökade samhällskostnader som följd. 2013 hade över 35% av jordens och närmare 50% av Sveriges befolkning övervikt eller obesitas, och andelen med obesitas var drygt 10% respektive 14%. Övervikt och obesitas är i dag, via följdsjukdomar som diabetes och hjärt- och kärlsjukdom, orsak till fler dödsfall i världen än undervikt och svält. Konventionell behandling, trots multidisciplinära och komplexa insattser, har generellt dålig och kortvarig viktsänkande effekt, frekventa viktrecidiv samt saknar tydliga bevis avseende kostnadseffektivitet. Kirurgisk obesitasbehandling blir allt vanligare med positivare långvarig effekt på vikt och följdsjuklighet samt har tydligare bevis på kostnadseffektivitet för samhället. 400 000 obesitasoperationer görs per år i världen varav ca 8000 operationer i Sverige. Idag finns det tiotusentals obesitasopererade i Sverige och gruppen ökar stadigt. Det finns många studier gjorda kring de goda effekterna av obesitaskirurgi men långtidsstudier kring de negativa bieffekterna saknas. Kirurgisk behandling uppvisar, trots generellt goda resultat, stor variation avseende viktnedgång och viktrecidiv samt vidare tecken till grava komplikationer avseende smärtsyndrom, diarréer, vitamin och mineralbrist samt försämrad skelett- och tandhälsa. Det finns ingen vetenskaplig grund för dagens vårdprogram efter kirurgisk obesitasbehandling som inkluderar årliga läkarbesök med provtagning och receptförskrivning livet ut för alla patienter utan hänsyn till individuella behov eller fysiska och mentala förutsättningar. Det saknas idag kunskap om hur snabbt komplikationerna uppstår och hur man bäst följer upp patientgruppen för att ge bästa vårdkvalitét. Det saknas idag kunskap kring prediktorer för vilka patienter som får ett sämre viktutfall, drabbas av viktrecidiv eller allvarliga komplikationer efter olika behandlingsalternativ. Vi vet att psykisk ohälsa är hög bland obesa. Det är känt att socioekonomisk status korrelerar positivt till generell hälsa i befolkningen. Det är dock okänt om psykiatrisk sjuklighet och lägre socioekonomisk status utgör riskfaktorer för ökade komplikationer samt sämre behandlingsresultat generellt efter obesitasbehandling. På grund av kunskapsbrist erhåller vi idag långt ifrån den fulla vinst som obesitasbehandling kan ge på individ- och samhällsnivå. Ur både ett individuellt och samhälleligt perspektiv beror den långsiktiga totala effekten, efter all sorts obesitasbehandling, av tillräckligt stor viktnedgång, frånvaro av viktrecidiv och frånvaro av komplikationer. Ofullständig behandlingseffekt och komplikationer minskar drastiskt den hälsoekonomiska vinsten. Genom den brist på kunskap som idag råder utnyttjar och optimerar vi inte de behandlingsalternativ mot obesitas vi har i sjukvården. Det behövs kraftigt utökad kunskapskap för att skapa ett jämlikt behandlingsresultat, minska riskerna för komplikationer och för att bättre utnyttja tillgängliga samhälls- och sjuvårdsresurser. BASUN-studien kommer bidra till utökad kunskap kring aktuella frågeställningar som direkt kan implementeras i sjukvården i Sverige och som är av högt intresse för FoU-verksamhet internationellt.

FRÅGESTÄLLNINGAR:
•Till vilken grad och när uppstår vitamin- och mineralbrist, försämrad skelett- och tandhälsa efter obesitaskirurgi jämförande konventionell behandling mot obesitas?
•Utgör psykiatrisk sjuklighet samt lägre socioekonomiskt status riskfaktorer för sämre behandlingsutfall och större grad av komplikationer efter obesitasbehandling?
•Hur ser den psykiatriska hälsan ut i gruppen av patienter som genomgår obesitasbehandling samt hur påverkas den psykiatriska sjukligheten av behandlingen?
•Hur utfaller en detaljerad hälsoekonomisk analys, inkluderandes patientnöjdhet/livskvalitet, jämförande obesitasbehandling med kirurgisk och konventionell metod?

RELATION TILL SVENSK OCH INTERNATIONEL FoU INOM OMRÅDET:
BASUN ämnar svara på vetenskapliga frågeställningar med likväl nationell som internationell betydelse då grunddiagnosen obesitas och behandlingsmetoderna är spridda över hela världen. Resultaten av BASUN kommer ligga i framkant av den totala kunskapsbasen kring obesitasbehandling nationellt och internationellt tack vare sin bredd. Den nya kunskapen kommer generera i en bred bas för interventionsstudier redan efter 2 års tid för att ytterligare kunna bidra till utökad kunskap och hypotestestning inom området.

METOD:

1.Forskningspersonerna (Antalet tillåter 20% bortfall och ger >80% power)
•Tusen kirurgiskt behandlade obesitaspatienter
•Fyra hundra intensivt konventionellt behandlade obesitaspatienter

2.Inklusion
Patienterna tillfrågas för inkludering i BASUN-studien konsekutivt från mars 2015 via Regionalt Obesitascentrum/SU (ROC). Samtliga remisser för obesitaskirurgi och intensiv konventionell behandling i Västra Götaland bedöms via ROC vilket gör att BASUN kommer kunna täcka in hela regionen vid inklusion för ett väl representativt urval. Inklusionsperioden beräknas till två år. Den intensiva konventionella behandlingen består av fyra månaders pulverdiet under uppföljning av ett multidisciplinärt team. Antalet inkluderade begränsas av inklusionstiden för kirurgpatienterna; uppskattningsvis kommer 400 patienter genomgå konventionell behandling och kunna tillfrågas under denna period. Den konventionella behandlingen ger under de första månaderna, vid god följsamhet, ett viktnedgångsresultat motsvarande efter kirurgi, utan den livslånga anatomiska förändring i mag-tarmkanalen som en operation innebär. Den konventionella gruppen utgör, avseende alla uppföljningsparametrar, en kontrollgrupp för differentiering avseende kirurgins inverkan på nutritionsstatus, skelett- och tandhälsa utöver den effekt som viktnedgången ger per se. De två behandlingsarmarna kommer vidare jämföras avseende riskfaktorer för komplikationer och försämrat behandlingsresultat samt avseende hälsoekonomisk effekt och livskvalitet.

3.Beskrivande uppföljning och kartläggning av patientgrupperna:
Årligen från baseline upp till 10 år efter behandling (Samtliga forskningspersoner (FP)):
•Behandlingsresultat; vikt, samsjuklighet, medicinering, komplikationer.
•Följsamhet till ordinationer avseende kosttillskott; vitaminer och mineraler

Baseline samt 2, 5, och 10 år efter behandling (Samtliga FP):
•Näringsstatus; bred blodprovstagning avseende vitaminer, mineraler, metabola riskfaktorer och benmetabolism. (Blodprover biobankas för samanalys i batcher)
•Kostintag; detaljerad kostanalys av mikro- och makronutrienter via dietist.
•Gastrointestinala symtom; anamnes samt frågeformulär; kartläggning av utveckling av redan befintliga GI-symtom, nya symtom samt komplikationer efter intervention.
•Microbiota; avföringsprover insamlas; sambandet mellan microbiota och effekten av obesitasbehandling avseende näringsstatus och skeletthälsa.

Baseline samt 2, 5, och 10 år efter behandling (Alla kvinnor <35 år: totalt ca 500 FP):
(Kommentar; pgav höga kostnader för ingående undersökningar väljs detta att genomföras på en subgrupp. Valet av subgrupp baseras på att ca 70% av alla patienter som genomgår behandling utgörs av kvinnor samt att unga kvinnor skall leva längre med sin nya gastrointestinala anatomi och risken för komplikationer som detta innebär. Aktuell subgrupp bedöms därav vara av störst intresse för analys)
•Skeletthälsa; kroppssammansättning, skelettstyrka och benmetabolism kommer mätas med DXA, högupplösande CT samt benstyrkedetektor.
•Tandhälsa; detaljerat mun- och tandstatus, oral microbiota och röntgen av tänder/käke via tandläkare.

4.Kartläggning av eventuella riskfaktorer
Baseline samt 2, 5, och 10 år efter behandling (Samtliga FP):
•Psykiatri; Screening via frågeformulär samt telefonintervjuer avseende; depression, ångest, ADHD, ätstörning.
•Socioekonomi; Intervju, frågeformulär, registerutdrag.

5.Hälsoekonomi
Från 5 år före samt vid baseline och årligen upp till 10 år efter behandling (Samtliga FP):
•Via register och frågeformulär; patientnöjdhet, livskvalitet, behandlingskostnader, sjukvårdsförbrukning, läkemedelsanvändning, sjukskrivning.

6.Blodprover
Baseline samt 2, 5, och 10 år efter behandling (Samtliga FP):
Blodprovstagning kommer i största möjliga mån ske då FP uppsöker behandlande/uppföljande klinik eller primärvårdsenhet enligt ordinarie kliniska rutiner. Blodproverna kommer att sparas i Sahlgrenska (VGR’s) Biobank för samanalysering i ”batcher” för bästa jämförbara analysresultat. Några prover behöver direktanalyseras efter blodprovsdragning då de inte klarar att frysas.

7.Frågeformulär
Baseline samt 2, 5, och 10 år efter behandling (Samtliga FP):
GI symtom; ROME III, Kostintag; 4 dagars kostregistrering, Ätstörningar; QEWP, Fysisk aktivitet; IPAQ, Skeletthälsa; frågeformulär livsstilsfaktorer, Oral hälsa; OHIP, Psykiatri; PHQ-9, BAI, ASRS, WURS, MINI, Livskvalitet; SF-36, Alkohol/Droger; AUDIT/DUDIT, Hälsoekonomi; EQ5D (årligen).

8.Register
Baseline samt 2, 5, och 10 år efter behandling (Samtliga FP):
Patientregistret, Läkemedelsregistret, SOReg; Scandinavian Obesity Surgery Register, NDR; Nationella Diabetesregistret, SCB; Statistiska centralbyrån, Frakturregistret/Röntgenregistret, BVC/Skolhälsovård, Dödsorsaksregistret, Cancerregistret

ARBETSPLAN:
Studiecentrum finns på Sahlgrenska Universitetssjukhuset/SS. Studiepersonal har god kännedom och vana kring patientgruppen och kliniska studier. Studien startar april 2015 och kommer fortgå tom 2027. Data kommer att samlas i ett elektronisk e-CRF och i en lokal databas.

ETISKA FRÅGOR:
Regionala Etikprövningsnämnden i Göteborg godkände studien 14-09-24. Genomförandet av BASUN kan anses etiskt försvarbart då deltagande i studien innebär en klart utökad uppföljning och kvalitetskontroll som forskningspersonerna (FP) annars inte skulle få. De kan således direkt få egen nytta av studiedeltagande samtidigt som detta ökar den generella kunskapsbasen betydligt och kommer bidra till en bättre vård för framtida patienter. De risker och det obehag som deltagande i studien kommer innebära kan bedömmas som ringa jämfört med fördelarna. Samtliga FP kommer informeras muntligen och skriftligen samt skriva under ett skriftligt informerat samtycke innan studiestart.

KONTAKTER OCH SAMARBETE:
Studien utförs som ett regionsövergripande (Västra Götalandsregionen) projekt i aktivt samarbete mellan expertis inom endokrinologi, hematologi, kirurgi, diabetologi, psykiatri, gastroenterologi, socialmedicin, allmänmedicin, oralmedicin samt molekylärbiologi (fecal microbiota). BASUN kommer dra fördel av samarbetspartnernas internationella kontakter för provanalyser och utökad expertkunskap. Huvudsökande (MW) är med i en regionsgemensam (VGR) arbets- och HTA-grupp för uppdatering av behandlingsriktlinjer för obesitas i regionen. Studien innebär en naturlig länk in mot forskning kring kunskapsluckan i detta ämne för att främja bättre utnyttjandet av hälso-och sjukvårdsresurser.

FÖRVÄNTAT RESULTAT/BETYDELSE OCH PATIENTNYTTA:
BASUN har som övergripande syfte att öka den hälsoekonomiska vinsten av existerande obesitasbehandlingar inom sjukvården idag – nationellt och internationellt. Syftet uppnås genom att öka kunskapen kring hur vi förbättrar den kliniska effektiviteten och minskar komplikationsfrekvensen. Därigenom kan vi långsiktigt skapa förbättrad hälsa, livskvalitét och arbetsförmåga hos patienterna. BASUN kommer generera eftersökt kunskap kring hur olika behandlingsmetoder påverkar nutritionsstatus, skelett- och munhälsa samt psykiatrisk hälsa långsiktigt. Studien kommer vidare generera kunskap om vilka subgrupper av patienter som lider störst risk för komplikationer och sämre behandlingsresultat generellt. Resultaten kommer kunna appliceras direkt i den kliniska vardagen via förbättrade rutiner och medicinska riktlinjer avseende utredning och förberedelse innan behandling samt högkvalitativ och individuellt anpassad uppföljning efteråt.

KOMMUNIKATIONSPLAN:
Resultaten från BASUN kommer att publiceras i vetenskapliga artiklar från två år efter studiestart då baselinedata kommer vara tillgänglig. Regelbunden sammanställning av data kommer sedan göras utmed studiens gång. Resultaten kommer att redovisas på lokala, regionala, nationella och internationella möten och konferenser. Resultaten kommer kunna bidra till förbättrade medicinska riktlinjer och vardagliga rutiner kring obesitasvård samt därav ge en ökad hälsoekonomisk vinst av befintliga behandlingsmetoder.

Vetenskaplig sammanfattning av projektet

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Typ av projekt

Forskningsprojekt

MeSH-termer för att beskriva typ av studier

checked Kontrollerade kliniska prövningar (Controlled Clinical Trial)


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MeSH-termer för att beskriva ämnesområdet

information Added MeSH terms
Gastrointestinal Tract
Generally refers to the digestive structures stretching from the MOUTH to ANUS, but does not include the accessory glandular organs (LIVER; BILIARY TRACT; PANCREAS).
Osteoporosis
Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis (OSTEOPOROSIS, POSTMENOPAUSAL) and age-related or senile osteoporosis.
Bone Demineralization, Pathologic
Decrease, loss, or removal of the mineral constituents of bones. Temporary loss of bone mineral content is especially associated with space flight, weightlessness, and extended immobilization. OSTEOPOROSIS is permanent, includes reduction of total bone mass, and is associated with increased rate of fractures. CALCIFICATION, PHYSIOLOGIC is the process of bone remineralizing. (From Dorland, 27th ed; Stedman, 25th ed; Nicogossian, Space Physiology and Medicine, 2d ed, pp327-33)
Osteomalacia
A condition marked by softening of the bones (due to impaired mineralization, with excess accumulation of osteoid), with pain, tenderness, muscular weakness, anorexia, and loss of weight, resulting from deficiency of vitamin D and calcium. (Dorland, 27th ed)
Gastrointestinal Diseases
Diseases in any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM.
Anemia
A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin.
Calcium Metabolism Disorders
Disorders in the processing of calcium in the body: its absorption, transport, storage, and utilization.
Iron Metabolism Disorders
Disorders in the processing of iron in the body: its absorption, transport, storage, and utilization. (From Mosby's Medical, Nursing, & Allied Health Dictionary, 4th ed)
Celiac Disease
A malabsorption syndrome that is precipitated by the ingestion of GLUTEN-containing foods, such as wheat, rye, and barley. It is characterized by INFLAMMATION of the SMALL INTESTINE, loss of MICROVILLI structure, failed INTESTINAL ABSORPTION, and MALNUTRITION.
Lactose Intolerance
The condition resulting from the absence or deficiency of LACTASE in the MUCOSA cells of the GASTROINTESTINAL TRACT, and the inability to break down LACTOSE in milk for ABSORPTION. Bacterial fermentation of the unabsorbed lactose leads to symptoms that range from a mild indigestion (DYSPEPSIA) to severe DIARRHEA. Lactose intolerance may be an inborn error or acquired.
Avitaminosis
A condition due to a deficiency of one or more essential vitamins. (Dorland, 27th ed)
Protein Deficiency
A nutritional condition produced by a deficiency of proteins in the diet, characterized by adaptive enzyme changes in the liver, increase in amino acid synthetases, and diminution of urea formation, thus conserving nitrogen and reducing its loss in the urine. Growth, immune response, repair, and production of enzymes and hormones are all impaired in severe protein deficiency. Protein deficiency may also arise in the face of adequate protein intake if the protein is of poor quality (i.e., the content of one or more amino acids is inadequate and thus becomes the limiting factor in protein utilization). (From Merck Manual, 16th ed; Harrison's Principles of Internal Medicine, 12th ed, p406)
Obesity
A status with BODY WEIGHT that is grossly above the acceptable or desirable weight, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).
Gastric Bypass
Surgical procedure in which the STOMACH is transected high on the body. The resulting small proximal gastric pouch is joined to any parts of the SMALL INTESTINE by an end-to-side SURGICAL ANASTOMOSIS, depending on the amounts of intestinal surface being bypasses. This procedure is used frequently in the treatment of MORBID OBESITY by limiting the size of functional STOMACH, food intake, and food absorption.

Projektets delaktighet i utbildning

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2. Projektorganisation och finansiering

Arbetsplatser involverade i projektet

information Added workplaces
Regioner - Västra Götalandsregionen - Specialiserad vård - Sahlgrenska Universitetssjukhuset - Område 6 - Medicin, Sahlgrenska workplace verified by Västra Götalandsregionen on 2018-02-27
Regioner - Västra Götalandsregionen - Specialiserad vård - Sahlgrenska Universitetssjukhuset - Område 5 - Kirurgi Sahlgrenska workplace verified by Västra Götalandsregionen on 2018-02-27
Företag - Privata vårdgivande bolag - inom Västra Götalandsregionen - Vårdcentraler - Göteborg - Capio Närsjukvård AB - Capio Vårdcentral Axess workplace verified by Västra Götalandsregionen on 2018-02-27
Capio Axess Vårdcentral

Coworker

Cecilia Björkelund
Professor, specialistläkare allmänmedicin, Avdelningen för samhällsmedicin och folkhälsa, Lokalkontor Göteborg
Björn Eliasson
Professor, Medicin, Sahlgrenska
Lars Fändriks
Professor, Avdelningen för gastrokirurgisk forskning och utbildning, Kirurgi Sahlgrenska
Karin Mossberg
Leg läk, specialist i allmänmedicin, Närhälsan Herrestad vårdcentral (Uddevalla), Närhälsan FoUU-centrum Fyrbodal
My Engström
Universitetslektor i omvårdnad med inriktning mot kirurgisk vård, förenad med befattning som sjukskö, Kirurgi Sahlgrenska, Institutionen för vårdvetenskap och hälsa, Sektion omvårdnad avancerad nivå, Kirurgi Sahlgrenska
Bo Söderpalm
Professor, Universitetssjukhusöverläkare, Sektionen för psykiatri och neurokemi, Beroendevård
Kerstin Landin Wilhelmsen
Professor Överläkare, Avdelningen för invärtesmedicin och klinisk nutrition, Medicin, Sahlgrenska
Herman Nilsson-Ehle
Universitetssjukhusöverläkare, docent, Regionalt Cancercentrum Väst, Medicin, Sahlgrenska
Mattias Lorentzon
Professor, senior physician, Avdelningen för invärtesmedicin och klinisk nutrition, Geriatrik Mölndal
Fredrik Bäckhed
PhD, Föreståndare, Institutionen för medicin
Anna Elmered
Överläkare, Skaraborgs sjukhus - Verksamhetsområde K2
Almantas Maleckas
Gästprofessor, Kirurgi Sahlgrenska
Anna-Lena Östberg
leg tandläkare, Forskning och utbildning

Finansiering

Grants

Anders Bergvalls Stiftelse (.)
50 000 SEK (applied sum: 100 000 SEK)
Malin Werling/BASUN

2015, Förberedande och uppstartskostnader.\r\n

Svenska Läkaresällskapet (SLS-502001)
300 000 SEK (applied sum: 500 000 SEK)
Malin Werling/BASUN

2015, Malin Werling/BASUN

Ihre Projektanslag (SLS-505821)
175 000 SEK (applied sum: 200 000 SEK)
Malin Werling

2015, Malin Werling/BASUN

Regionala FoU (VGFOUREG 383 981)
2 015 000 SEK (applied sum: 500 000 SEK)
Malin Werling

2013, Förberedande och uppstartskostnader.\r\n

Göteborgs läkaresällskap (GLS 332081)
90 000 SEK (applied sum: 150 000 SEK)
Malin Werling/BASUN

2013, Förberedande och uppstartskostnader

3. Processen och projektets redovisning

Detaljerad projektbeskrivning

ABSTRACT

Obesity represents a major burden on social and health care resources due to co morbidities and reduced work capacity. Overweight and obesity are today the cause of more deaths in the world than underweight and starvation. Conventional obesity treatment has a generally poor weight loss effect and lacks cost effectiveness. Surgical obesity treatment is increasingly common with higher degree of positive long-term effect on weight and co-morbidities as well as with clearer evidence of cost-effectiveness. 400 000 surgical obesity procedures are performed annually worldwide and about 8000 in Sweden. The two most common techniques are gastric bypass and sleeve gastrectomy which both include major anatomical changes of the gastrointestinal anatomy. There are many studies over the benefits of obesity surgery. Long-term comparative studies, between conventional and surgical regimens, over adverse side-effects, risk factors for complications and poor outcome results are nevertheless missing. Obesity surgery exhibit a great variety of weight loss results, cases of weight regain, bowel pain syndrome, chronic diarrhea, vitamin and mineral deficiency and severe osteoporosis and impaired dental health. Knowledge is missing about how quickly complications occur, the prevalence of different complications, risk factors for poor treatment outcome or complications as well as how to best detect them early while still treatable. There is no scientific basis for today's medical guidelines for assessment before or after obesity surgery. There is an urgent need to develop the treatment options available by increased treatment effect and decreased complication rate to improve resource utilization during the current international epidemic of obesity. The BASUN study includes a detailed prospective 10-year comparison of conventionally (n = 400) and surgically (n = 1000) treated obese individuals as well as a subgroup analysis between the two surgical techniques gastric bypass and sleeve gastrectomy:

1. Nutritional status before and after obesity treatment:
•prevalence of vitamin and mineral deficiencies?
•interconnections to fecal microbiota?

2. Bone metabolism before and after obesity treatment:
•prevalence of impaired bone metabolism?
•interconnection to nutritional status?
•interconnections to fecal microbiota?

3. Oral health before and after obesity treatment:
•prevalence of impaired oral health?
•interconnection to nutritional status?
•interconnections to fecal microbiota?

4. Psychiatric disorders before and after obesity treatment:
•prevalence of depression, anxiety disorder and ADHD?
•interconnections to fecal microbiota?
•interconnections to socioeconomic status?

5. Do psychiatric disorders or low socioeconomic status constitute risk factors for
•poor weight loss after obesity treatment?
•complications after obesity surgery?
•vitamin and mineral deficiencies?
•impaired bone metabolism?
•Impaired oral health?

6.Detailed health economic analysis including primary and secondary costs.

Data will be collected by interviews, blood and fecal samples, questionnaires, patients’ record and registries. The study consists of annual checkups and detailed full protocol at Baseline and at 6 months, 2, 5 and 10 years after the intervention. Samples are saved in Sahlgrenska Biobank. The BASUN study is carried out in close cooperation with senior experts in surgery, medicine, psychiatry, endocrinology, gastroenterology, hematology, molecular biology, osteoporosis, oral medicine, physiology and general medicine.
The BASUN study will increase the knowledge about prevalence, type and detection methods for complication after obesity treatment. Through a structured search of prognostic tools and risk groups with higher predisposition for complications and poor treatment result the BASUN study will be able to form the basis for more individualized medical guidelines with the objective of higher medical quality, more equal treatment result and better utilization of health care resources.

ETHICAL CONSIDERATIONS

The study will be performed according to the Helsinki Declaration (64th WMA General Assembly, Fortaleza, Brazil; October 2013). The study has been approved by the Regional Ethical Review Board in Gothenburg, Sweden (no: 740-10). All study participants will get information, orally and in writing, and will sign a written informed consent before participation. Study subjects will be protected by the Swedish patients’ insurance “Patient försäkringen” in case of severe adverse events. Study participants integrity is protected by the Swedish law “Personuppgifts lagen”. The study is currently undergoing the registration process at Clinicalrials.gov.

For the individual study participant, inclusion in the study will extend the general assessment both before the clinical obesity intervention and during follow up afterwards. As the BASUN study is targeting prevalence of and risk factors for complications, vulnerable individuals will therefore benefit from study participation rather than be at risk for adverse effects during study duration. Participation in the study is considered including negligible risks and uncomfortable experiences for the study subjects in relation to the individual benefits originate from the extended assessments. Due to that the individual disadvantages are so few and the overall benefits will include largely increased knowledge in the clinical field, the execution of the study is considered ethically justified. A detailed pre-defined security plan will be included in the study protocol as well as in every individual CRF to ensure attention of all possible adverse events. Detailed plans will in addition exist for necessary arrangements in case of adverse events to make sure that study participants will receive all necessary assessments and additional clinical care when needed.

The conventional and surgical obesity treatment regimes in Sweden and in other countries are most often based on scientific evidence. Nevertheless both the need for, and the ideas behind the BASUN study are based on the fact that the medical guidelines for assessment before and follow after both conventional and surgical treatments are designed without sufficient scientific evidence. Furthermore knowledge is lacking about predictive factors regarding treatment outcome and need for individual adjustments for possible outcome optimizing.

There is an ongoing intense international debate on equal health care based on gender, age, ethnicity, sexual orientation, physical and mental disability etc. The debate is unfortunately mostly focused on equal medical interventions but more rarely on equal treatment results. The BASUN study aims to create more effective obesity treatments with more equal treatment results, lower degree of complications and better utilizations of health care resources.

The lack of knowledge and the lack of initiatives for scientific studies in these areas are today causing an ineffective utilization of social care resources. The long term health economic benefits from obesity treatments could be substantially increased. The BASUN study is intended to save social care resources through wiser alignment of medical interventions. It would be unethical not to extend our knowledge about how to utilize the medal resources better. The rationale behind the BASUN study could therefore be argued being constituted by an ethical dilemma.

BACKROUND

Obesity represents a major burden on social and health care resources internationally through direct and indirect costs due to secondary diseases and reduced work capacity. (1, 2) BMI correlates positively to long as well as short term sick leave. Obese individuals have > 30% increased absenteeism compared to normal weight subjects. (3-6) Without effective treatment strategies, obese individuals tend to increase their weight over time resulting in further increased costs for the society. In 2013 more than 35% of the world population and almost 50% of the Swedish population were overweight or obese. In the same year the rate of obesity were exceeding 10% and 14% respectively. (7, 8) Overweight and obesity are today, due to complications such as diabetes and cardiovascular disease, the cause of more deaths in the world than underweight and starvation. (7, 8)
Conventional obesity treatment has, despite of multidisciplinary and intense interventions, a generally poor weight loss effect, high weight regain frequency and lacks clear evidence regarding cost effectiveness. (9-11) Surgical obesity treatment is increasingly common with higher degree of positive long-term effect on weight and co-morbidities as well as with clearer evidence of cost-effectiveness. (12-15) 400 000 surgically procedures for morbid obesity are performed annually worldwide, of which about 8000 operations are performed in Sweden and 1000 in the region Västra Götaland. The two most used surgical techniques are gastric bypass and sleeve gastrectomy. Both of them include major anatomically irreversible changes of the gastrointestinal anatomy. (16-18) Today there are tens of thousands of surgically treated individuals in Sweden and the group is steadily increasing.
There are many studies conducted over the benefits of surgical obesity treatment regimes. Long-term comparative studies, between conventional and surgical regimens, over the adverse side-effects, risk factors for complications and poor outcome results are nevertheless missing. Surgical treatment exhibit, despite generally good results, a great variety of weight loss results, frequent weight regain, bowel pain syndrome, chronic diarrhea, vitamin and mineral deficiency and sever impaired bone and dental health. (18-22) There is an obvious lack of knowledge about how quickly complications occur, the prevalence of different complications and risk factors for poor treatment outcome or developing complications. (23, 24) It is known that the prevalence of mental illness is high among obese individuals. It is also known that socioeconomic status correlates positively to good health in the general population. However, it is unknown whether psychiatric morbidity and low socioeconomic status constitute risk factors for increased complication rate and inferior treatment results after obesity treatment. (23, 24) Today's healthcare program regarding assessment before or follow up after operation lacks scientific support. Medical guidelines include annual physician visits, life long, with blood sampling and prescription of vitamin and mineral supplementation for all patients without regard to individual needs or physical and mental conditions. Knowledge is missing about how to design assessment and follow up to avoid complications and how to create a high-quality care and best utilization of health care resources. Earlier comparative health economic studies use economic calculation models without including long term complications and poor treatment results. The more accurate scientific method would instead be to in detail prospectively mapp actual primary and secondary social and health care costs from a predefined study population, comparing conventional and surgical obesity treatment regimes. Incomplete treatment effect and high complication rate drastically reduces the health economic benefit from all kinds of obesity treatment strategies. The lack of knowledge and the lack of initiatives for scientific studies in these areas are today causing an ineffective utilization of social and health care resources. The long term health economic benefits from obesity treatments could be substantially increased both on the individual and societal level. (19, 25) The conditions in the clinic; with insufficient treatment results and complications, together with conclusions from the scientific literature demonstrates an evident need of a long term prospective study that in detail compares surgical and conventional obesity treatment regarding prognostic parameters and risk factors for poor outcome and complications together with a detailed health economic analysis.

SPECIFIC AIMS:
(All aims include a comparison between conventional and surgical treatment regimens as well as a subgroup analysis between the two surgical techniques gastric bypass and sleeve gastrectomy)

1. Nutritional status before and after obesity treatment:
a. What is the prevalence of vitamin and mineral deficiencies?
b. Are there any interconnections between nutritional status and fecal microbiota?

2. Bone metabolism before and after obesity treatment:
a. What is the prevalence of impaired bone metabolism, bone microarchitecture and bone strength?
b. Are there any interconnection between bone metabolism and nutritional status?
c. Are there any interconnections between bone metabolism and fecal microbiota?

3. Oral health before and after obesity treatment:
a. What is the prevalence of impaired oral health?
b. Are there any interconnection between oral health and nutritional status?
c. Are there any interconnections between oral health and fecal microbiota?

4. Psychiatric disorders before and after obesity treatment:
a. What is the prevalence of depression, anxiety disorder and attention deficit disorder (ADHD)?
b. Are there any interconnections between psychiatric disorders and fecal microbiota?
c. Are there any interconnections between psychiatric disorders and socioeconomic status?

5. Risk factors after obesity treatment: Do psychiatric disorders, such as depression, anxiety or ADHD or low socioeconomic status constitute risk factors for
a.poor weight loss after obesity treatment?
b.complications after obesity surgery such as pains syndrome, negative gastrointestinal symptoms and eating disorders?
c.vitamin and mineral deficiencies?
d.impaired bone metabolism, bone microarchitecture and bone strength?
e.Impaired oral health?

6.To make a detailed health economic analysis including primary and secondary costs.

THEORY AND SURVEY OF THE FIELD

Obesity surgery and nutritional health: Studies indicate that the obese population approved for obesity surgery to a great part is nutritionally deficient already before the operation. (26, 27) There is today no consensus, in Sweden or internationally, regarding detailed assessment or routinely substitution of the patients before surgery. Patients are operated on regardless. It is yet unknown how gastric bypass and sleeve gastrectomy in detail influence on nutritional uptake, bone metabolism or on oral health, neither in patients that are well nourished nor in patients already undernourished before their operation. The literature shows that deficiency regarding vitamin A (28-30), B (28, 29, 31, 32) and D (28, 29, 31-34) is common both short time and median term after surgery. Iron deficiency, with or without anemia, is also common irrespectively of time after surgery. (31, 32) Protein deficiency is furthermore present in some patients regardless of possible presence of micronutrient deficiency or other complications. (29, 35) However, studies over nutritional status in this group of patients are in most cases small, have short follow up time, lack regulated protocol and high quality analysis methods. Data show an obvious need of supplementation treatment after surgery, nevertheless dosage and time points for follow up are not scientifically supported. Compliance is known to be low both regarding intake of nutritional supplementation and visiting the healthcare for checkups, which impairs the matter further. (36)

Obesity surgery and bone metabolism: Earlier data indicate that obesity surgery has a negative impact on bone metabolism creating cases of osteopenia and osteoporosis. (18, 29, 31, 33, 34, 37, 38) Measuring changes in bone metabolism and bone strength requires, however, very high quality analyzing equipment and well standardized protocols. Those conditions are nevertheless missing in most of the studies performed over the surgically treated obese population. Most studies concentrate on comparing bone status preoperatively to only one occasion and mostly short term after surgery and therefor lack the possibility of describing the clinically interesting long term change development after the intervention. Bone mineral density (BMD) is affected by nutritional status, hormonal influences and physical activity. Gold standard measurement method is Dual X-ray Absorptiometry (DXA) which also provides information on total bone, muscle and fat mass. High-resolution peripheral Computed Tomography (HRpCT) gives information about the bone formation eg. the distribution between trabecular and cortical bone microarchitecture which contributes to the strength characteristics of the skeleton. HRpCT can also be used to define bone strength using finite element analyses but does not capture changes in bone material properties due to early changes in bone formation as for example in response to rapid weight loss. Microindentation has recently been introduced as a new method to measure the material properties and the actual bone strength of the bone tissue. (39) This minimal invasive method can now be used routinely in the clinic to measure the bone material properties of the tibia in patients.

Fecal Microbiota: During the last few years increasing interest has been directed towards the role of gastrointestinal microbiota in relation to obesity and the different parts of the metabolic syndrome. (40-42) Recently, an interesting connection between the microbiota and calcium metabolism and bone remodeling has been revealed. (43-46) Studies are mostly performed in mice and in smaller population of humans. Larger studies with the possibility to follow humans from preoperative state through a longer time perspective as well as in relation to other health parameters after surgery are missing but would be of considerable interest and essential to generate new knowledge in the area.

Obesity surgery and psychiatric disorders: Studies show that depression and anxiety disorders are more prevalent in the obese population compared to the population as a whole. The group included for surgery appears to have more symptoms at the time point for surgery and as well during life history compared to normal weight subjects. Weight loss results after surgery in correlation to psychiatric disorders vary in different studies. (47, 48) Psychiatric morbidity as a risk factor for nutritional complications or impaired bone and oral health after obesity surgery is furthermore not dealt with. Studies conclude that further research and greater studies in this area are needed. The prevalence of Attention Deficit Disorders (AD and ADHD) in children amounts to 5-7 % and the prevalence among adults to approx. 4%. (49-51) Large studies show that both children and adults with AD or ADHD have a higher prevalence of obesity compared to the rest of the population. (52, 53) Furthermore children and adults with obesity have a higher prevalence of AD and ADHD compared to normal weight subjects. (52, 53) AD or ADHD have been shown to interfere negatively on conventional weight loss regimens and is discussed as a possible negative predictor for poor weight loss outcome after obesity surgery compared to subjects without any mental disorder but no scientific evidence exist due to lack of targeted studies. (54-59) Studies involving obesity treatment and AD or ADHD all conclude that a more studies are needed and thorough assessment is necessary before intervention due to the close connection between the syndromes. (60)

Socioeconomic status: Studies concerning the socioeconomic background of the surgically and conventionally treated obese population show diverse results regarding impact on weight outcome. (60-62) Low socioeconomic status correlates to poorer health and higher BMI in the general population. (62-65) No survey has yet evaluated socioeconomic background as a potential risk factor for malnutrition or complications of bone metabolism or oral health after obesity surgery. Weight loss is just one of the goals with obesity treatment; conventionally or by surgery. Improved health is the most important and overall objective of the treatment. Avoidance of complications both short and long term after intervention is obviously crucial to get the best health benefits from the treatment. A large long term prospective study with a detailed protocol comparing surgically and conventionally obesity treatment is needed to increase the knowledge regarding risk factors, such as psychiatric morbidity and socioeconomic status, for poor general treatment outcome and clinically relevant complications such as under nutrition and impaired bone and oral health.

PROJECT DESCRIPTION – METHODS:

1.Study subjects (The number included will allow 20% drop out and will give >80% power.)
•One thousand surgically treated subjects (gastric bypass and sleeve gastrectomy operations)
•Four hundred conventionally treated subjects

2.Inclusion/exclusion:
All patients approved for obesity surgery and conventional obesity treatment in the region Västra Götaland will be asked consecutively for participation in the study. Only exclusion criteria will be lack of understanding Swedish orally or in writing as well as not being able to speak Swedish. 1000 surgically and 400 conventionally treated individuals will be included. The inclusion period will last about 1.5 to 2 years as between 800 and 1000 patients are operated in the region per year. The conventional treatment is carried out by a multidisciplinary team and consists of a strict VLCD powder diet during four months followed by an ordinary low caloric diet during eight months. The conventional treatment will, during the first six months, create a weight loss comparable to the results after surgery but without the life-long anatomical changes in the gastrointestinal tract as an operation involves. The conventional treatment group will therefor form a very suitable control group to the surgically treated group regarding 1/ all study parameters and 2/ for differentiation of the effect from the surgically treatment on nutritional status, skeletal and dental health in addition to the impact that weight loss gives per se. The two treatment arms will also be compared with respect to risk factors for complications and poor treatment outcome as well as health economic impact and quality of life. All patients will be given study information orally and in writing. After inclusion all study subjects will sign a written informed consent. A computerized CRF will be issued for every patient and stored safely in a database at the study center at Sahlgrenska University Hospital. Study participation will be documented in the patients’ record at Sahlgrenska University Hospital according to normal clinical study routine.

3.Descriptive mapping of the conventionally ant surgically treatment groups:

Baseline; extended assessment before obesity treatment (all study subjects (SS)):
All subjects will undergo extended assessment before treatment start, compared to regular clinical routine, to exclude diagnoses that might interfere on study parameters regarding:
•Irritable Bowel Syndrome; screening according to Rome III Diagnostic Criteria
•Inflammatory Bowel Disease; by anamnestic information and samples
•Celiac disease; Transglutaminas-IgA antibody sample
•Lactose intolerance; Beta-lactase genetic sample
•Helicobacter Pylori; Urea Breath Test
The possible diagnoses above will not exclude the subjects from the study. Data on the prevalence of IBS, IBD, lactose intolerance or celiac disease in the gastric bypass population are missing in the literature today. Results from the extended assessment will therefore be included in analyzes of the study results and will create new interesting knowledge to the scientific field.

Annually from baseline and up to ten years after obesity intervention (all SS):
•Treatment result; weight, diagnoses, medication, treatment complication
•Compliance to prescription regarding vitamin and mineral supplementation

Baseline and 6 months, 2, 5 and 10 years after obesity intervention (all SS):
•Nutritional and health status; by detailed blood sampling for vitamins, minerals, bone metabolism and risk factor markers regarding metabolic and cardiovascular disease.
•Diet intake; detailed four days diet registry and interview as well as screening for eating disorders through questionnaires by a dietician.
•Gastrointestinal symptoms; by anamnestic interview and validated questionnaires.
•Microbiota; fecal samples will be analyzed regarding the correlation between the microbiota and nutritional status, psychiatric health, bone and oral health. Fecal DNA will be isolated by using a well-validated protocol (41, 66), DNA will be amplified by using barcoded primers and sequence on the MiSeq platform. (67) Resulting sequences will be analyzed using Qiime. (68) Note that Fredrik Bäckhed (coapplicant) has established this platform and the analyses will be performed in collaboration with his group.

Baseline and 2, 5 and 10 years after obesity intervention (all women under 35 years of age):
(Comment; due to high costs for these analyzes only a subgroup of patients will be surveyed. Women under age 35 are selected due to that about 70% of all patients who undergo surgically treatment are women and due to our hypothesis that complication risks increase the longer the patients live with their new anatomical construction. This subgroup is there for deemed to be of greatest interest for analyses.)
•Bone health; body composition will be analyzed by Dual Energy X-ray Absorptiometry (DXA), bone microstructure; distribution of trabecular and cortical bone mass, will be analyzed by high-resolution peripheral Computed Tomography (CT) and bone material properties and strength (at tibia diaphysis) will be analyzed by micro indentation using the Osteoprobe device. (39)
•Oral health; detailed oral and dental status, oral microbiota and x-rays of teeth/jaw will be performed by dentist.

4.Descriptive mapping of risk factors:
Baseline and 2, 5 and 10 years after obesity intervention (all SS):
•Psychiatric health; will be analyzed through screening by validated questionnaires and personal interview regarding anxiety, depression and Attention Deficit and Hyperactivity Disorder (ADHD).
•Socioeconomic status; will be analyzed by anamnestic interview, medical record and registries.

5.Health economy
From 5 years before obesity intervention, at baseline and annually up to 10 years after intervention (all SS).
•Patient satisfaction, quality of life, treatment costs, health care usage, medical usage and costs, sick leave etc will be analyzed by questionnaires, registry and anamnestic interviews.

6.Tools and methods
Blood samples will be collected at Baseline, 6 months, 2, 5 and 10 years after intervention. Blood samples will be stored in the bio bank at Sahlgrenska University hospital under high quality standards.
Validated questionnaires will be used at Baseline and annually covering screening and mapping for gastrointestinal symptoms (ROME III, TFEQ, Bristol Stool Chart), diet intake (4 days food intake registry), eating disorders (QEWP-R), physical activity (Saltin-Grimby), oral health (OHIP), psychiatric health (PHQ-9, BAI, ASRS, WURS, MINI), quality of life (SF-36), alcohol and drug use (AUDIT/DUDIT), health economy (EQ5D).
Register: Medical and social registers will be searched for patients’ data. Registers: SOReg; Scandinavian Obesity Surgery Register - includes patients treated with bariatric surgery since 2007 in Sweden, Patients’ registry; Patientregistret, Registry of childrens’ health; MVC, BVC, Skolhälsovården, Drug registry; Läkemedelsregistret, Fracture registry; Frakturregistret, Radiology registry; Röntgenregistret, The Insurance Office; Försäkringskassan, National Board; Socialstyrelsen, Employment services; Arbetsförmedlingen.
Registry studies: With the intention to create a background information that is missing in the literature today regarding prevalence of fractures and mental disorders in the population treated with surgical strategies for their obesity, an interconnection will be performed between SOReg and the Fracture registry; Frakturregistret and the Radiology registry; Röntgenregistret, as well as for SOReg and the Patients’ registry; Patientregistret and the Drug registry; Läkemedelsregistret.
Statistics: Routine statistical methods will be applied and statistical support is included. The
numbers of included subjects, as a whole and in subgroups, intend to reach normal distributed materials. For comparisons at group level traditional pairwise tests will be used. In addition Kaplan-Meyer methodology for survival and hazard ratios will be used during analysis of event-free survival and; defined as the time from study entry to a significant event, for example to meet the clinically accepted criteria for deficiency regarding a vitamin level. Multivariate statistical methods will be used analyzing groups of data. Correlation analyses will be performed pre and post intervention within the whole subject population and within the two different intervention groups; conventionally and surgically treated subjects. Power analysis is based on the criteria of allowance of 20% drop out and >80% power. The most critical and demanding parameter for power calculation was to detect a significant and clinically relevant change in ionized calcium, both as paired and unpaired repeated analysis.

PROJECT DESCRIPTION - TIME FRAME AND IMPLEMENTATION

The BASUN study will start in April 2015. The inclusion will be finished within 1.5 to 2 years. The follow up will continue until 10 years after intervention. All referrals for specialized obesity care with surgery or conventional methods in the region Västra Götaland are assessed and approved centrally at ROC (the Regional Obesity Centre); led by professor Björn Eliasson (co-applicant), located at Sahlgrenska University hospital in Gothenburg. This is a unique procedure which stands model for future handling of other diagnostic groups and gives a unique research possibility to cover a large geographical area for inclusion and create a study population with high generalizability. All patients approved for specialized obesity care will be asked for participation in the study. As study participation could be considered beneficial for the patients on an individual level including an extended assessment and follow up after obesity intervention, acceptance frequency for study participation are expected to be high. The study follow up points coincides with the normal clinical assessment time points making the participation in the BASUN study less time and effort demanding for the study subjects. Blood samples will be collected at a clinical laboratory close to the home of the study subjects for their best comfort. Blood samples will be sent by the ordinary transportation network in the region of Västra Götaland to Sahlgrenska University Hospital and the bio bank for storing. Contact from the study center with the study subjects will be managed in person, by phone, by e mail and by post. Results from the study after analyses will be available for the study participants on demand. The head of primary care and the head of the department of Research and Educational in the region Västra Götaland have been informed about and approved the study. At start of inclusion in the study, the patients’ primary care center (PCC) will be contacted with an information letter including general information about the study and specialized obesity treatment; both surgical and conventional. The PCC will get contact information to the study staff and principal investigator. The information will conclude that study participation will increase security for the individual patient as well as facilitate the clinical post interventional follow up for the PCC; if questions occur easily accessible consultation will be provided by study staff and principal investigator. If samples or examination included in the study protocol will detect any anomalies, patients’ PCC will be contacted for further clinical action and follow up, with the patients’ best interest in focus.

PROJECT ORGANIZATION

Principal applicant and principal investigator for the BASUN study, Malin Werling, has been working with obese patients and specialized obesity treatment during many years both in research and in clinical settings. Study center will be located at Sahlgrenska University Hospital (SU) in Gothenburg at the Department of Gastrosurgical Research and Education (DGRE) led by professor Lars Fändriks, and at the Regional Obesity Center (ROC). The staff, study coordinators and research nurses, working in the study at the laboratory of DGRE is very well familiar with the obese population, have performed and are currently coordinating other prominent studies on patients undergoing specialized obesity treatment, both conventional and surgical. The study center is strategically located close to both ROC and the surgical and medical department at SU.

INTERNATIONAL AND NATIONAL COLLABORATION

The senior co-workers involved in the study will contribute by their detailed knowledge of expertise and by examination equipment. They have been and will work as valuable mentors to primary investigator Malin Werling throughout the study. They have contributed to the development of the study protocol, and will further contribute to general extension of the network of contacts as well as to analyses of study data and writing scientific reports.
Cecilia Björkelund, MD, Professor in Primary Health Care, director of the Department of Public Health and Community Medicine/Primary Health Care at the Sahlgrenska Academy, University of Gothenburg.
Fredrik Bäckhed, Professor in Molecular Medicine and director of the Wallenberg Laboratory for cardiovascular and metabolic research at the Sahlgrenska Academy, expert of the role of microbiota in metabolic disease.
Björn Eliasson, MD, Professor in Internal Medicine and Diabetology at SU, director of the Regional Obesity Centre (ROC) at SU.
Lars Fändriks, MD, Professor in Integrative Physiology and Pharmacology, director of Department of Gastrosurgical Research and Education, Sahlgrenska Academy/GU.
Kerstin Landin-Wilhelmsen, MD, Professor in Medicine and Endocrinology at the Department of Medicine/SU. Expert in metabolic bone diseases.
Mattias Lorentzon, MD, Professor in Geriatric Medicine, director of the national Clinical Osteoporosis Research School (CORS) and president of the Swedish Osteoporosis Society.
Almantas Maleckas, MD, Professor in surgery at the Department of Gastrosurgical Research and Education, Sahlgrenska Academy/GU.
Herman Nilsson-Ehle, MD, PhD, Assoc Professor in Hematology at the Department of Medicine/SU.
Magnus Simrén, MD, Professor in Medicine and Gastroenterology at the Department of Medicine/SU.
Bo Söderpalm, MD, Professor in Psychiatry at the Department of Psychiatry and neurochemistry at SU.
Anna Lena Östberg, Dentist, PhD, Assoc Professor in Odontology at the Department of Odontology, Sahlgrenska Academy/GU.
Carel W le Roux, MD, professor and director of Diabetes Complications Research Centre, UCD Conway Institute, School of Medicine and Medical Science, University College Dublin, Ireland and professor at the Department of Gastrosurgical Research and Education, Sahlgrenska Academy, GU.

SCIENTIFICAL AND CLINICAL SIGNIFICANCE

The BASUN study will contribute with a broad variety of new, both clinically and scientifically, significant knowledge that are apparently missing and asked for today. The overall aim of the BASUN study is to improve existing obesity treatment regimens by decreased complication rate and long term improved treatment outcome with a better utilization of health care resources as a consequence. By a prospective long term comparison between conventional and surgical obesity treatment including detailed mapping of the prevalence and type of complications after obesity intervention in relation to identification of risk factors, such as psychiatric disorders and low socioeconomic status for poor outcome and complications the BASUN study will be able to contribute to improved medical guidelines directly implacable in the clinic both in Sweden and internationally. By its detailed study protocol the BASUN study will be able to clarify which type of complications will occur and when the first signs are detectable after obesity intervention. These study results can directly be applied in the clinic by improvement of the time course and content of the assessment and follow up after obesity treatment with the aim to earlier detect and prevent complications. By comparing conventional and surgical intervention it will be possible to show whether possible complications are caused by weight loss per se or by the gastro intestinal anatomical change caused by the surgery. Furthermore through a structured search of prognostic tools and risk groups with higher predisposition for complications and poor treatment result the BASUN study will be able form the basis for more individualized medical guidelines with the objective to allocate the health care resources were they are needed the most for a higher medical quality and a more equal treatment result. The study results will be presented in international scientific journals and at conferences as well as in a more local context in Sweden and in the region Västra Götaland during clinical meetings and publications as well as used during development work in clinical setting.

FUTURE PERSPECTIVES

The BASUN study is needed to create a great baseline and follow up database regarding all included study parameters and the study subjects are not planned for inclusion in any intervention studies. Nevertheless the baseline and follow up results from the BASUN study will provide the background data for randomized interventional studies. A/ If the BASUN study (from baseline data and forward) show significant malnutrition regarding vitamins and minerals a randomized clinical study will be performed including randomization between normal or intense substitutional regimen. B/ If the BASUN study (from 6 months data and forward) show significant correlation between microbiota and nutritional status or bone metabolism (through blood samples) a randomized clinical study will be performed including randomization between treatment with probiotics and placebo. C/ If the BASUN study (from 2 years data and forward) show significant negative impact on bone health a randomized clinical study will be performed including randomization between normal or intense substitutional regimen as well as randomization between high level of physical activity or normal life activity. D/ If the BASUN study (from 2 years data and forward) show significant negative impact on oral health a randomized clinical study will be performed including randomization between normal or intense substitutional regimen. E/ If the BASUN study (from 6 months data and forward) show significant difference regarding treatment outcome, nutritional status, bone health or oral health depending on psychiatric illness (depression, anxiety or ADHD) a clinical randomized study will be performed including randomization between normal assessment (= no screening or evaluation of psychiatric illness) or clinical systematic evaluation of psychiatric and neuropsychiatric diagnoses and appropriate treatment if necessary before starting the obesity treatment regimen. The purposes with the planned follow up studies are to search for possible treatment options to prevent complications after obesity treatments or to find improvement opportunities of medical guidelines for obesity treatments regimens for better utilization of existing medical and social resources. Results from the BASUN study will be used for exact power calculations for each individual study.

PRELIMINARY RESULTS

In earlier studies we have described body composition, including bone density, in smaller cohorts of gastric bypass patients short term after surgery and in comparison to restrictive bariatric surgical technique up to six years after surgery. (69) Our long term study showed an increase in bone density in the gastric bypass group and one out of 17 patients reach osteopenia. In other studies by our research group we have found changes in gastric bypass patients regarding markers for D-vitamin and calcium uptake in the small intestine possibly contributing negatively to the bone metabolism. (70)

EQUIPMENT

A large number of blood samples will be collected throughout the study and freezer space will be needed for long term storage until analyses will be performed. Samples will be stored in a freezer short term before analysis at the study center and in the Bio bank of Sahlgrenska University Hospital (SaB).

INDEPENDENT LINE OF RESEARCH

The main applicant Malin Werling (MW) is a general medicine physician who defended her doctoral thesis in bariatric surgery; “Roux-en-Y gastric bypass – clinical outcome and mechanisms of action” in June 2013. (71) Within her clinical position she will develop the current study in order to establish her independent research profile. This profile; a combination of primary care physician and researcher with special interest and expertice in obesity and specialized obesity care is currently missing in both the clinic and in the research establishment of today. MW has currently a very advantageous position with half time specialist service at a primary care unit in central Gothenburg and half time postdoctoral research position including salary founds from ALF for the next 2 years. The graduate program was carried out at the Department of Gastrosurgical Research and Education at the University of Gothenburg and at the Department of Surgery at Sahlgrenska University Hospital (SU) with principal supervisor Torsten Olbers, MD, PhD, Ass Prof, bariatric surgeon, and co-supervisors Lars Fändriks, MD, Prof, director of the Dep of Gastrosurgical Research and Education and Hans Lönroth, MD, Prof, bariatric surgeon, director of the Dep of Surgery/SU. Through the thesis and by other projects carried out during the last years MW have gain profound knowledge of obesity surgery and of the surgical department of Sahlgrenska as well as other bariatric surgical units in the country. MW has also created an extensive network of contacts in many different disciplines around the obese patient population. MW’s clinical primary care position provides a stable foundation and a wide contact network for successful implementation of the current study in the primary care of the region Västra Götaland. The BASUN study complements and broadens the current ongoing research work and projects at the Institute of Clinical Sciences and Medicine at Sahlgrenska Academy. The BASUN study is a unique project which fills a knowledge gap in the clinic and research society internationally of today.

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BASUN - komplikationsrisk avseende nutritionsstatus, skelett och munhälsa efter obesitasbehandling -relaterat till socioekonomi och psykiatrisk hälsa., from FoU i Västra Götalandsregionen
http://www.researchweb.org/is/html/vgr/project/137801