Ph.D. Dissertation Hanne Bækgaard Larsen

FACULTY OF HEALTH SCIENCES UNIVERSITY OF COPENHAGEN Ph.D. Dissertation Hanne Bækgaard Larsen The Effects of a Controlled Family Navigator Nurse Directed Intervention Program for Parents Hospitalized with Children Undergoing Allogeneic Haematopoietic Stem Cell Transplantation (HSCT) Faculty of Health Sciences University of Copenhagen Department of Pediatrics, The Juliane Marie Centre & Department of Hematology, The Finsen Centre The University Hospitals Center for Nursing and Care Research Copenhagen University Hospital, Rigshospitalet Academic advisor: Professor, ph.d. Lis Adamsen Submitted: 31 July 2011

PhD Dissertation: The Effects of a Controlled Family Navigator Nurse Directed Intervention Program for Parents Hospitalized with Children Undergoing Allogeneic Haematopoietic Stem Cell Transplantation (HSCT) Hanne Bækgaard Larsen The dissertation will be defended on Official opponents Associate Professor Ole Weis Bjerrum, MD, DMSc Department of Surgery and Internal Medicine, University of Copenhagen Copenhagen, Denmark Professor Henrik Hasle, MD, DMSc Department of Pediactrics, Aarhus University Hospital, Skejby Aarhus Denmark Professor Kristian Larsen,RN, MSc, Ed.st., Ph.D. Oslo University College, Faculty of Nursing Oslo, Norway Scientific Advisors Professor Lis Adamsen, RN, MSc. Soc., Ph.D. The University Hospitals Center for Nursing and Care Research Institute of Public Health, Faculty of Health Sciences Copenhagen University, Copenhagen Denmark Professor Carsten Heilmann, MD, DMSc Department of Pediatrics, Copenhagen University Hospital, Rigshospitalet Copenhagen, Denmark Professor Christoffer Johansen, MD, DMSc, Ph.D. Department of Psychosocial Cancer Research, Danish Cancer Society Copenhagen, Denmark The University Hospitals Center for Nursing and Care Research (UCSF), Copenhagen University Hospital, Department 7001, Blegdamsvej 9, DK-2100 Copenhagen, Denmark ucsf@ucsf.dk

Tak Undersøgelserne i denne afhandling er gennemført med finansiel støtte fra Børnecancerfonden, Helsefonden, Lundbeckfonden, Gangstedfonden samt Rigshospitalets 2½-årige forskerdelestilling. Tusind tak for jeres støtte og medindlevelse i projektet undervejs. Jeg vil også rette en stor tak til jer forældre og børn, der i forbindelse med jeres behandling med allogen knoglemarvstransplantation har sagt Ja til at dele denne, for jer, svære tid med mig. I har åbnet ikke kun jeres isolationsstue på Rigshospitalet for mig, men også jeres familier. I har haft overskud til at dele jeres bekymringer, følelser, tanker og meninger med mig, svare på spørgsmål og udfylde talrige spørgeskemaer. Hvis I ikke havde udvist det storsind i en svær tid, kunne dette projekt ikke være lykkedes. Jeg ønsker jeg alle det bedste for fremtiden. Jeg er ligeledes dybt taknemmelig og fuld af beundring for den støtte, vejledning og læring jeg har fået gennem min hovedvejleder i ph.d. forløbet Professor Lis Adamsen fra Universitetshospitalernes center for Sygepleje- og Omsorgsforskning (UCSF). Lis, du har en beundringsværdig, utrættelig energi, som du investerer i forskning for derved at medvirke til at ændre verden til det bedre. Dette gør du enten direkte gennem din egen forskning eller ved at investere din tid og kræfter i andres projekter, hvilket i særdeleshed er kommet mig til gode i dette forløb. Lis, det er sjældent at møde mennesker der, i samme grad som dig, er i stand til at holde fanen højt, stille skarpt på de forskningsmæssige problemer, gennemskue svagheder, inspirere, nytænke og vedvarende holde fast i den røde tråd. Disse evner har jeg nydt godt af i dette projekt og det er jeg dig taknemmelig for. Jeg vil ligeledes sige mange tusinde tak til min projektvejleder Professor Carsten Heilmann, Rigshospitalets Juliane Marie Center. Carsten, jeg er dybt taknemmelig for din tro og støtte til mig gennem alle årene, således at jeg har kunnet udvikle mig både i forskerrollen men også som menneske. Du har en særlig evne til at stille skarpt på problemstillingerne, både i forskningen og i sproget. Du er ekspert i at opretholde enkelthed, overskuelighed og stringens i forskningen. Ligeledes går du hverken af banen for en golfbold eller Max Weber, hvilket er et udtryk for din alsidige styrke. Også mange tusinde tak til min bi-vejleder Professor Christoffer Johansen fra Kræftens Bekæmpelse. Christoffer, jeg er meget taknemmelig for den tid og energi du har brugt på mig i forbindelse med dette projekt. Du har en herlig evne til at tænke store tanker i forskningen, det er dejligt befriende. Tak for det. I skal alle have tak for jeres energi, store hjælpsomhed og ikke mindst tid, i forbindelse med dette projekt. Tak til de undervisere som har varetaget undervisningen til forældrene i forbindelse med projektet. I har været utrolig fleksible og har tilpasset tidspunkterne efter forældrenes behov. Først og fremmest vil jeg sige tak til pædagog Lise Auscher, for alt hvad du har lært mig om børn og forældre, og ikke mindst for at du har haft overskud til at formidle denne viden til forældrene i forbindelse med dette projekt. Dernæst vil jeg sige tak til de øvrige undervisere; sygeplejerske Helen Munk for utroligt mange gode tips og ideer til forældrene, psykolog Bo Snedker Boman for at introducere forældrene til kognitiv terapi på en anvendelig måde, og Tine Banke Høgsberg for at dele sin viden og tanker om, hvordan det er at være mor gennem et langt transplantationsforløb. I denne forbindelse vil jeg også sige en stor tak til Ronand McDonald huset på Rigshospitalet, og ikke mindst Karen Bjørløw Jacobsen, for at lægge lokaler til forældreundervisningen. Også Tak til sygeplejerskerne Anne Shaffer Lassen og Camilla Roepstorff, der har været stand ins for mig i forbindelse med varetagelse af den daglige intervention.

Projektet er udført både i Juliane Marie Centret og Finsencentret, hvorfor min tak også går til centerledelsen i Juliane Marie Centeret, centerdirektør Bent Ottesen og centerchefsygeplejerske Sanne Wilsdahl samt centerledelsen i Finsencentret, Centerdirektør Kurt Stig Jensen og centerchefsygeplejerske Jeanette Bech. Tak for jeres støtte til at skabe rammerne for projektudførelsen. Tak til Professor Kjeld Schmiegelow for husly. Desuden tak til sygeplejerskerne og lægerne i afdeling 5061, 4043 og 5002 for at tage godt i mod mig i forbindelse med udførelsen af projektet, for jeres støtte undervejs, og for det store engagement I har i det daglige arbejde med børn og forældre. Sheila Schmidt skylder jeg stor tak for hendes kommentarer og ikke mindst skarpe pen når det gælder det engelske sprog, og ass. Professor Anders Tolver, Institut for grundvidenskab og miljø, LIFE instituttet, for statistiske beregninger, tålmodighed, pædagogisk vejledning og ikke mindst hurtige analyser. Jeg vil også sige en kæmpe stor tak til mine kolleger på Rigshospitalet, sygeplejerskerne Sine Rasmussen, Jeanette Holder, Ann-Mari Bertelsen, Line Pedersen og Heidi Petersen, og sekretær Vivi Ljungberg for at have huset mig på Rigshospitalet i dagligdagen og ikke mindst for jeres engagement i projektet. I har lyttet tålmodigt på dagliglivets små finurligheder og samtidig haft en utrolig indsigt i hvordan problemer kan løses, hvilket jeg har draget stor nytte af. I er nogle uvurderlige ildsjæle. Tak! til alle mine kolleger på UCSF. Til forsker Mary Jarden, Tom Møller, Betina Lund Nielsen og Christina Andersen for at dele denne ph.d. proces med mig, al jeres hjælp, støtte og engagement undervejs og ikke mindst jeres glade grin og gode humør I er guld værd! Speciel tak til forsker Mary Jarden og forskningsfysioterapeut Kira Bloomquist for oversættelse af spørgeskemaer til projektet. Tak til seniorforsker Julie Midtgård for hjælp til projektbeskrivelsen, til Ingrid Egerod for et evigt godt humør og faglig indsigt og til forsker Dorte Overgaard for faglig gejst og gode snakke. I har alle bidraget med spændende perspektiver. Til alle øvrige medarbejdere i UCSF vil jeg sige tusind tak for mange hyggelige stunder: forskningsfysioterapeuterne Morten Quist, Jacob Uth og Christian Lillelund; ph.d. studerende Jesper Frank Christensen; forskningsassistenterne Pernille Cromhout, Maria Stage og Signe Risom; sygeplejerskerne Mette Leinø, Birgit Nielsen, Birgitte Rasmussen, Jørgen H. Laursen og servicemedarbejder Kjeld Jensen. En helt særlig tak vil jeg give til sekretær Ida Raun-Petersen. Ida du har været en stor del af dette projekt i alle dets faser, du har skrevet interviews ud, åbnet kuverter, sendt artikler, læst korrektur, sat dokumenter op, osv. Du har været en helt uvurderlig støtte, mange tak for dette og dit altid gode humør. Også en stor tak til sekretær Bente Kronborg for at du altid kan finde et par ord for meget, når det nu er det der skal til. Ligeledes tak til bibliotekar Anders Larsen, for assistance til litteratursøgning, referenceopsætning og redigering. Til sidst vil jeg sige mange tusinde tak til min mand Flemming for din tålmodighed, engagement, forståelse og kærlige opbakning gennem hele dette projekt forløb. Uden din hjælp var dette ikke lykkedes. Jeg vil også sige en stor tak til mine forældre Henning og Tove samt til min bror Jesper, min svigerinde Camilla og pigerne, Maja og Lea for jeres opbakning til mig undervejs. Hanne Bækgaard Larsen København, 27. juli 2011

ORIGINAL PAPERS This dissertation is based on the following papers: I. Larsen HB, Heilmann C, Johansen C, Adamsen L. (2011) An analysis of parental roles during haematopoietic stem cell transplantation of their offspring: a qualitative and participant observational study. Journal of Advanced Nursing. doi: 10.1111/j.1365-2648.2010.05587.x II. III. Larsen HB, Heilmann C, Johansen C, Adamsen L. Socially disadvantaged parents of children treated with allogeneic haematopoietic stem cell transplantation (HSCT): Report from a controlled intervention study. Submitted. Larsen HB, Adamsen L, Tolver A, Johansen C, Heilmann C. Supportive Intervention Program Targeting Parents to Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HSCT): a Controlled Study. Manuscript. The papers are referred to in the text by their Roman numerals.

DANSK RESUMÉ Et kontrolleret family navigator nurse ledet interventionsstudie hos medindlagte forældre til Allogen hæmatopoietisk stamcelletransplanterede (HSCT) børn. Baggrund Medindlagte forældrene er de primære omsorgsgivere hos børn med livstruende sygdomme under behandlingen med allogen hæmatopoietisk stamcelletransplantation (HSCT). Barnets HSCT behandling medfører omfattende fysiske og psykiske bivirkninger, risiko for komplikationer, samt en mortalitet på 22-50%. Litteraturen, egen pilotundersøgelse og kliniske erfaringer viste at forældrene er emotionelt og socialt svært belastede under barnets 4-6 ugers lange indlæggelse i isolation under transplantationsforløb. Der er udført få, ikke konklusive interventionsundersøgelser hvori et mindre antal deltagere (børn/forældre) er inkluderet. Formål, design og intervention Formålet var at undersøge effekten af et multifacetteret understøttende interventions program rettet mod omsorgskapacitet hos medindlagte forældres til børn behandlet med HSCT. Interventionsprogrammet indeholdt ni timers intervention/uge: a) daglig medicinsk information samt emotionelt og social understøttende intervention ved en Family Navigator Nurse (FNN); b) fem timers forældreudvisningsprogram; samt c) fysisk aktivitet for forældre. Teoretisk er undersøgelsen inspireret af et interaktionistisk perspektiv, Hochschild s teori om familie- og følelsernes sociologi samt kognitiv adfærdsterapi. Metoder og population Udbyttet af interventionsstudiet blev belyst i to kvalitative analyser: 1) ved convenient sampling blev 16 semistrukturerede interviews og otte deltagerobservationsstudier blandt medindlagte forældre inkluderet i en analyse af disses omsorgsroller, og 2) ved quota-sampling blev 21 semistrukturerede interviews og 25 deltagerobservationsstudier hos forældre i interventionsgruppen inkluderet i en analyse af forældrenes væsentligste problemstillinger under medindlæggelsen. Effekten af interventionen blev undersøgt med velvaliderede kvantitative spørgeskemaer (HADS, POMS, CHIP, BASES) ved at sammenligne en forældre interventionsgruppe (N=25) med: 1) en prospektiv forældrekontrolgruppe (N=8) der modtog afdelingens standardpleje, 2) en retrospektiv forældrekontrolgruppe (N=46) til børn behandlet i de foregående 3.5 år, der havde modtaget afdelingens standardpleje. De medindlagte forældre er 56 mødre (71%) og 23 fædre (29%) til 79 børn ( 46% piger og 54% drenge) i alderen 0-20 år ( median 8 år). Der udarbejdet 3 artikler baseret på resultaterne fra interventionsstudiet. Resultater Artikel 1: belyser, vha. kvalitative metoder, tre idealtyper for forælde og omsorg hhv. 1. ekspertise orienterede-, 2. dialog orienterede- og 3. socialt udfordrede forældre. De tre omsorgstyper afspejler forældrenes tilgang til barnets pleje og behandling samt influerer på samarbejdet og kommunikationen mellem barn, forældre og personale. Konflikter opstår når omgivelserne ikke agerer i overensstemmelse med forældrenes omsorgsrationalitet. For at kunne varetage omsorgsudøvelse udfører forældrene samtidig en følelsesmæssig bearbejdning af sig selv, hvilket socialt udfordrede forældre har vanskeligt ved. Artikel 2: viser, de tre problemområder som forældrene angiver som væsentligste at skulle forholde sig til under medindlæggelsen: 1. Den emotionelle belastning forbundet med barnets HSCT 2.

Reorganiseringen af familielivet for at kunne være medindlagt med barnet, og 3. Den økonomiske belastning forbundet med at skulle manøvrerer i det danske socialsystem. Det at have fire eller flere af følgende risikofaktorer: 1) enlig forældre, 2) lav indkomst, 3) lav uddannelsesniveau, 4) begrænset netværk, 5) arbejdsløs, 6) fysisk/psykisk sygdom, og 7) at være at nydansker, medførte, at forældrene befandt sig i en kompleks social, økonomisk og følelsesmæssig belastet situation, hvilket influerede på deres omsorgsevne og krævede omfattende og vedvarende FNN intervention. Artikel 3: afdækker, ved hjælp af spørgeskema HADS effekt af interventionen og udviklingen af forældrenes niveau for angst- og depressivsymptomer i forhold til barnets indlæggelsesforløb. Der fandtes ingen statistisk signifikans i forældrenes angst og depressionsniveau imellem grupperne.. Ved indlæggelsen havde 24% af forældrene en HADS score på over 10, hvilket indikerede et moderat til højt depressions symptomniveau og 39% have et moderat til højt angstsymptom niveau. Blandt forældre i interventionsgruppen blev angstniveauet signifikant reduceret ved følgende dage 0, +14, +21 og +100 fra baseline (dag 7). En tilsvarende reduktion i angstscore under indlæggelse kunne ikke påvises for kontrolgruppen, men på dag 100. Konklusion Allogen HSCT til børn er en kompleks invasiv behandling, som gennemgribende påvirker forældrenes emotionelle og sociale funktion samt forældreomsorgsevne. Dette er det første interventionsstudie rettet mod at understøtte medindlagte forældres omsorgskapacitet under barnets HSCT behandling. FNN interventionen understøttede forældrenes transition mellem hjem og hospitalsindlæggelse, og familiernes vej gennem det komplicerede behandlingsforløb. De tre identificerede idealtyper giver indsigt i forældrenes omsorgsrationalitet for barnet samt nye perspektiver på den komplekse interaktion mellem forældre, barn og sundhedsprofessionelle under HSCT behandlingen. Denne viden kan hjælpe personalet med at identificere gruppen af socialt udfordrede forældre, som har mest udtalt behov for støtte til at håndtere omsorgen for barnet. Samtidig har interventionsstudiet medvirket til at identificere nogle af de samfundsmæssig barrierer der negative påvirker forældrenes omsorgskapacitet.

ENGLISH ABSTRACT The Effects of a Controlled Family Navigator Nurse Directed Intervention Program for Parents Hospitalized with Children Undergoing Allogeneic Haematopoietic Stem Cell Transplantation (HSCT). Background Parents are the primary caregivers of children with a life-threatening disease and who undergo allogeneic haematopoietic stem cell transplantation (HSCT). A child s HSCT carries the risk of severe physical and emotional complications and a mortality risk of 22-50%. The literature, own pilot study and clinical experience describe these parents as being heavily emotional and socially burdened during the 4-6 weeks of the transplantation process in isolation. Very few inconclusive intervention studies with a small sample size (children/parents) have been carried out in this field. Aim, design and intervention The aim was to investigate the effect of a multifaceted intervention program targeting the care capacity of resident parents for children undergoing HSCT. The intervention program comprised nine hours/week: (a) daily medical information relay, emotional and social support with a Family Navigator Nurse (FNN), b) a five hour education program for parents, and c) physical activity for parents. Theoretically, the study was inspired by an interactive perspective, Hochschold s theory of family and emotional sociology and cognitive behavioral therapy. Methods and sample The benefits of the intervention study were explored in two qualitative analyses: 1) by convenient sampling; 16 semi-structured interviews and eight participant observation studies among the resident parents were included in an analysis of their caregiving roles, 2) by quota-sampling; 21 semi-structured interviews and 25 participant observation studies among parents in the intervention group were included in an analysis of the parents major problems during hospitalization. The effect of the intervention was examined by validated quantitative questionnaires (HADS, POMS, CHIP, BASES) by comparing the parental intervention group (N=25) to: 1) a prospective parental control group (N=8) receiving standard care, and 2) a retrospective parental control group (N=46) to children treated over the past 3.5 years and who received standard care. The residential parents were 56 mothers (72%) and 23 fathers (29%) to 79 children (46% girls and 54% boys) aged 0-20 years (median 8 years) Three papers were developed from the intervention study results. Results Paper 1: highlights, using qualitative methods, three types of parent care, i.e. 1) expertise minded; 2) dialogue minded, and 3) socially challenged parents. The three care types reflect the parents approach to their child s care and treatment as well as the influence of each approach on collaboration and communication between the child, the parents and the staff. Conflicts emerged when actions did not comply with the parents rationale for care. In order for the parents to provide childcare, they had to engage in emotional work which was difficult for the socially challenged parents. Paper 2: shows, on the backcloth of qualitative interviews, three major problem areas that the parents faced during hospitalization with their child: 1. the emotional burden associated with the child s HSCT; 2. the necessary reorganization of family life to accommodate hospitalization with the child; and 3. the economic burden associated with maneuvering within the Danish social welfare

system. Having four or more of the following risk factors: 1) being a single parent; 2) having a low income; 3) having a low education level; 4) having a limited social network; 5) being unemployed; 6) having a physical/psychological illness; and 7) being a new Danish citizen, all led to the parents feeling trapped in a complex socially, economically and emotionally burdensome situation that impacted their ability to care and they demanded continuous and comprehensive FNN intervention. Paper 3: uncovers, by means of the HADS questionnaire, the effect of the intervention process and the development in the parents levels of anxiety and depression in relation to the child s hospitalization process. There was no statistically significant difference between the prospective parental control group and the parental intervention group. At admission, 24% of the parents had HADS scores over 10, which indicates a moderate to severe level of depression and 39% of the parents had a moderate to severe level of anxiety. The anxiety level in the intervention group was reduced significantly on day: 0, +14, +21 and +100 following admission. A similar reduction in anxiety scores during hospitalization could not be seen in the control group, however, a significant reduction was observed on day 100. Conclusion Allogeneic HSCT for children is a complex invasive treatment that deeply affects their parents physical, emotional and social functions as well as their care abilities. This is the first intervention study targeting the resident parents caring abilities during the child s HSCT treatment. The FNN intervention supported the parents transition between home and hospital and supported the parents during the complex HSCT inpatient treatment course. The three identified ideal types provide an insight into the parents care rationale for the child and provide new perspectives on the complex interaction between parents, the child and the caregivers during HSCT treatment. This knowledge may assist staff to identify socially challenged parents who are in most need of assistance in caring for their child. In addition, the intervention study identified barriers within society that negatively affect the parents caregiving abilities.

ABBREVIATIONS ANC - Absolute Neutrophil Count BASES - Behavioural, Affective and Somatic Experience Scale CHIP - Coping Health Index for Parents CM - Case manager EORTC - European Organization for Research and Treatment of Cancer GvHD - Graft versus Host Disease FNN - Family Navigator nurse HADS - Hospital Anxiety and Depression Scale HLA-typing - Human Leukocyt Antigen - typing HSCT - Allogeneic Haematopoietic Stem Cell Transplantation I.V. fluid - Intravenous fluid LAF - Laminar Air Flow MD Medical Doctor PIG - Parental Intervention Group PN - Patient navigator POMS - Profile of Mood States-B PPCG - Prospective Parental Control Group RCT - Randomised control trials RN Registered Nurse RPCG - Retrospective Parental Control Group SEM - Standard Error of Means SD - Standard Deviation TBI - Total Body Irradiation UID Unique Identification Number

TABLE OF CONTENTS 1. INTRODUCTION... 1 2. HYPOTHESES AND AIMS... 1 3. BACKGROUND AND THEORETICAL INSPIRATION... 2 3.1 Allogeneic Hematopeietic Stem Cell Transplantation 3.2 The pre-hsct period 3.3 The HSCT inpatient course 3.4 The HSCT inpatient-setting and the parents care related tasks 3.5 Emotional distress during the isolation treatment 3.6 Clinical intervention studies of HSCT children 3.7 Clinical intervention studies among parents to HSCT children 3.8 Intervention studies aimed to reduce distress in parents to children with recent cancer diagnoses 3.9 Pilot study of Danish children previously treated with HSCT and their parents 3.10 Nurses performing the Case Manager/ Patient Navigator function 4. THEORETICAL FRAMEWORK... 6 4.1 A sociological approach to the family 4.2 Balancing work and home 4.3 Emotional management 4.4 Behavioural and cognitive behavioural therapy inspiration 4.5 Summary 5. MATERIALS AND METHODS... 8 5.1 Design 5.2 Sample 5.2.1 Excluded parents in the study 5.3 Baseline medical and socio-demographic characteristics of the children and parents 5.4 The supportive intervention 5.4.1 The author s background and function in the intervention program 5.5 Intervention program 5.6 Principles for the intervention 5.6.1 The daily FNN intervention schedule 5.6.2 The FNN intervention focused on three parent-targeted components 5.6.3 The daily rounds 5.6.4 The supervised, structured group-based education program 5.6.5 Physical activity 5.7 Standard care received by the control groups 5.8 Data collection 5.8.1 Qualitative data collection 5.8.1.1 Participant observation study 5.8.1.2 Semi-structured interviews 5.8.2 Quantitative data collection 5.8.2.1 Data collection schedule and procedures 5.8.2.2 Assessment instruments and questionnaires 1

6. DATA ANALYSES AND INTERPRETATION... 18 6.1 Qualitative data analysis 6.2 Quantitative data analysis 7. ETHICAL CONSIDERATIONS... 19 8. RESULTS... 20 8.1 Paper I 8.2 Paper II 8.3 Paper III 9. DISCUSSION... 23 9.1 Parental roles 9.2 The parental problem areas and risk factors 9.3 The parents level of anxiety and depression in relation to the intervention program 9.4 FNN role and dilemmas 9.5 Qualitative methodological considerations and limitations 9.5.1 Sampling in the participant observation study and qualitative interviews 9.5.2 Validation of the participant observational study and semi-structured interviews 9.5.3 Theoretical foundation of the qualitative findings 9.5.4 The researchers role in qualitative research 9.5.5 Transferability 9.6 Quantitative methods advantages and limitations 9.6.1 Advantages 9.6.2 Limitations and bias 10. CONCLUSION, IMPLICATIONS & RECOMMENDATIONS... 31 11. FUTURE RESEARCH... 33 REFERENCE LIST... 34 PAPERS I-III APPENDICES A. Qualitative and quantitative measueres B. Supplementary quantitative analyses C. Approvals 2

1. INTRODUCTION Allogeneic HSCT in children is a complex invasive and sometimes lethal treatment, which carries the risk of multiple physical side-effects and complications. During the 4-6 weeks of hospitalisation, the child must master the physical, emotional and social consequences of the HSCT. The child depends on the parents for around the clock care and support to cope with the treatment. Consequently, the parents are emotionally and socially affected by the child s HSCT, while they must continue with their responsibilities toward the healthy siblings. This dissertation is based on an intervention study that comprised medical information relay, emotional support and social counselling performed by a Family Navigator Nurse (FNN) and which targeted parents to children treated with allogeneic haematopoietic stem cell transplantation (HSCT). The present dissertation aims to explore the parental position during the child s HSCT, using qualitative and quantitative methods, and evaluates the benefits of a parent targeted support intervention program. Firstly, the parents caregiver role was explored in 16 parents by means of participant observation studies and semi-structured interviews (paper I). Secondly, the parents major problems and the benefits of the support intervention program were explored in 21 parents (paper II). Thirdly, to test the effect of the support intervention program, conducted by the FNN using validated questionnaires, a population based clinical controlled trial was conducted among 79 parents to children treated with HSCT. This part of the study compares a parental prospective intervention group (n=25) to 1) to a retrospective parental control group (n=46) and to 2) a prospective parental control group (n=8) (paper III). The study was performed at Finsen Centre and Juliane Marie Centre, Copenhagen University Hospital (Rigshospital) during the period from 2004 to 2009. 2. HYPOTHESES AND AIMS The aim of this dissertation is to investigate the qualitative and quantitative benefits of a support intervention program for resident parents during their child s 4-6 weeks inpatient treatment with myeloablative allogeneic HSCT. The FNN conducted parental intervention program comprised daily medical information relay, emotional support and social counselling as well as a supervised, structured education program for parents and the possibility for them to engage in physical activity (walking/biking). The hypotheses were, that the intervention would: support the parents ability to care for their child throughout the course of the HSCT. identify the parents major problems and test a support intervention program to meet these problems during the child s HSCT. reduce the parents level of anxiety and depression during their child s HSCT. The main objectives of each research focus (Papers I III) in this dissertation, include: investigating, from an interactionistic perspective, the parents experiences and reflections on their parental role while taking care of their child (paper I). exploring the major problems faced by parents to children treated with HSCT during the child s hospitalization and ascertaining how these problems affect the parents daily life and the FNN conducted intervention to assist them (Paper II). Determining the effect of the intervention program, through use of psychosocial questionnaires and investigating the parents levels of anxiety and depression during the child s HSCT (Paper III). 1

3. BACKGROUND AND THEORETICAL INSPIRATION The section will include a brief description of the allogeneic HSCT and of the families history leading up to the child s HSCT (1). 3.1 Allogeneic Hematopeietic Stem Cell Transplantation Allogeneic HSCT is a transplantation of haematopoietic stem cells from a living related or unrelated donor to a patient (2). HSCT is offered to children suffering from life threatening malignant (mainly leukaemia) and benign haematological diseases (e.g. severe aplastic anemia, immune deficiency and some genetic metabolic diseases) (3;4), where intensive treatment with e.g. chemo- and/or irradiation therapy is not sufficient to cure the child (3;5;6). Treatment with HSCT has an associated risk of developing Graft versus Host Disease (GvHD) and the advantage of achieving a Graft versus Tumour effect (7). HSCT was made known internationally in the late 1960s, and in 1971 the first transplant was performed in Denmark, at the Copenhagen University Hospital (Rigshospital). Rigshospital remains the only hospital in Denmark that offers HSCT to children. Initially the focus of the treatment was to understand the HSCT process biologically, reduce complication and infection rates and improve the survival rate. These areas are still important, however, the focus has expanded to treat a growing number of diseases, use of non-myeloablative conditioning regiments and the use of new sources of stem cells (6;7). Today, HSCT is a well-established treatment with more than 25.000 transplants performed worldwide each year; of these 20-25% are pediatric transplants (8-11). In Denmark approximately 100 HSCT are performed annually and 15 25 of these involve children. The overall survival rate has improved significantly and today the Danish 5-year survival rate for children is 78% while internationally it remains at 50-61% (10-12). The treatment related mortality, however, is still higher than 10% and the majority of deaths occur within the first year following HSCT, due mainly to malignant disease relapse, infections, GvHD and organ failure (10;11;13). Long-term sequelae following HSCT in childhood include physical complications such as chronic GvHD (32%), growth and reproductive impairment (33%- 51%) and an increased risk of secondary malignancy (14-17). Emotional and social complications affect 25-35% of long-term survivors and include increased levels of anxiety (18-21), impaired working abilities, financial problems and being single (18-20;20-25). Despite the significant improvement in the overall survival rate, allogeneic HSCT continues to be a treatment option exclusively for children suffering from life threatening diseases in the absence of any other treatment option to ensure long-term survival (7). Figure 1: Pre-HSCT Diagnosis Daily participant observation study, weekly questionnaires, Intervention period (daily FNN contact/weekly education program/exercise) HSCT in-patient course HSCT Isolation in LAF Isolation at home Questionnaire and qualitative interview Post- HSCT Disease treatment: e.g. chemoterapy 4 days: Preexamination 2-3 hours: Pre- HSCT information with MD & RN DAY: 0 Day -7: In-patient treatment with chemotherapy PARENTS TASKS Management of the child s: - emotional and physical adjustment to HSCT - side effects and complications Complications: GvHD, infections, organ toxicity Day: +30 Discharge Child: Side effects: nausea, vomiting, appetite loss, skin problems, mucositis, diarrhoea, anxiety, distress, withdrawal, outbursts DAY: + 100 2

Figure 1 illustrates the traditional breakdown of the HSCT course: 1) The pre-hsct period, leading up to the transplant, 2) The HSCT inpatient course, from day 7 to day +100, and 3) The post- HSCT period from day + 100. In addition, figure 1 provides a timeline for important medical events during the HSCT treatment course. The emphasis in this model is on the impact of the HSCT setting, the care related tasks performed by the parents and the impact of the medical treatment on the child s and the parents wellbeing. 3.2 The pre-hsct period The child s life threatening disease challenges the stability of the family and places multiple emotional, spiritual, social and organizational stressors on all of its members (26-28). The diagnosis process exposes the child to multiple invasive tests and procedures. To control malignant diseases requires months to yearlong treatment and often includes chemotherapy and/or irradiation. Consequently, the child and the parents must cope with related side-effects such as nausea, vomiting, weight loss or gain, loss of hair, infections, mucositis, pain, diarrhoea, fatigue, and toxic reactions, etc. (26;28). Prior to the HSCT, an eligible family (often sibling) or unrelated register donor must be identified by HLA-typing (29). Approximately four weeks prior to the HSCT, a senior HSCT physician, a transplant coordinator and a nurse inform the parents and the child about the medical rationale, potential side-effects and complications associated with the HSCT. Additionally, the child is hospitalized for four days for a comprehensive health examination. 3.3 The HSCT inpatient course During the first week of admission prior to the child s HSCT, the conditioning regimen of chemotherapy (in some cases combined with Total Body Irradiation (TBI)) is administered, followed by an infusion of stem cells from the donor. Consequently, the child experiences sideeffects and possible complications, including nausea, vomiting, loss of appetite, mucositis, pain, diarrhoea, fatigue and hair loss. The child may experience organ toxicity, GvHD and he/she is treated with immunosuppression to prevent GvHD, antibiotics to prevent infections as well as nutrition and I.V. fluid (3;30;31). When the marrow has engrafted (ANC>0.5 x 10 9 /l) and the child no longer displays acute medical or care related difficulties, then the family is discharged to isolation at home with weekly outpatient visits. 3.4 The HSCT inpatient-setting and the parents care related tasks The parents are the primary care givers and source of comfort for the child. Furthermore, they attempt to alleviate the child s distress during the HSCT course (32). To decrease the risk of infection, the child and one parent (the residential) are isolated behind double locked doors in a Laminar Air Flow (LAF) room from the time of the conditioning to engraftment. The average time spent in protective isolation is 3-4 weeks. If the child has two parents then they may alternate as the resident parent. During admission, the resident parent has comprehensive care responsibilities. This includes around the clock caring for the child s basic needs (nutrition, liquid, hygiene, activity, comfort etc.) oral care, toilet assistance and administration of oral medicine. These routine tasks must adhere to the hygienic standards of the isolation regime and the parents and the child must learn the standards before performing these basic care tasks themselves. Accordingly, parents mediate between the child and staff 24 hours/day for 4-6 weeks, during medical (invasive) procedures communicatively and by assisting the child to comply with the procedures (33;34). During the HSCT isolation period, the parents are expected to assist the child to comply with the increased basic care needs, the multiple side-effects to the treatment and the invasive medical procedures. In order for the parents to be continuously present at the hospital, they are granted leave 3

of absence from their work while retaining their regular salary which is subsidised by the social authorities (Law on social service 42 (35)). 3.5 Emotional distress during the isolation treatment At the time of admission to HSCT, 40% of children display anxiety (36), a significant increased level of somatic distress, mood disturbances and a lowered level of activity (30). Phipps et al. (30;37) showed that during the inpatient period, the child s distress symptoms peak one week following transplantation, and decrease to admission level by four-five weeks after HSCT. Common psychosocial reactions include depression, mood changes, anger, irritability, withdrawal and impaired interaction with others (33;37;38). At the time of admission, 20-66% of parents have a significantly elevated level of distress (39-42), and symptoms of depression and anxiety (18;40;43;44). One study suggested that a high parental level of distress and anxiety influence the parental caring ability, including responsiveness to their child needs and providing support and comfort during stressful situations (45). Parents find it especially stressful when they are unable to ease the child s fear, shield the child from pain and embrace the child s emotional reactions (32;34;46). The stress may affect the parents emotionally (e.g. cause secondary anxiety and depression), their parental role, the quality of the care they provide and their ability to make treatment related decisions (32;45). As such, the parents psychosocial well-being is interrelated with the child s adoption of HSCT (19;32;33;42;47). 3.6 Clinical intervention studies of HSCT children In the USA, 60% of the pediatric transplant centres (n=65) offer support groups and 49% provide art-in-medicine programs (e.g. art, play and musical therapy and relaxation) to the child aiming at reducing emotional distress and side-effects. However, the duration or what point in time during the HSCT these interventions are offered is not specified. Apart from two randomised control trials (RCT), the effect of these interventions has not been tested beyond the descriptive level (48-55). Studies have shown that the children like massages and writing/painting can be a method of expressing and processing the HSCT experience. Non of the studies were performed within a Danish or European context (48;53). The most comprehensive, complementary intervention RCT (n=178 families) compared 1) a child-targeted intervention of massage and humour therapy with 2) the child-targeted intervention supplemented by a parent-targeted intervention of massage and relaxation/imagery. The program included at least two hours of intervention per week for four weeks. However, the study did not show any significant effect on the child s level of somatic distress, on mood disturbance or on the use of analgetic and antiemetic medication (53;56). As such, HSCT child-targeted intervention programs are few in numbers (even less are RCT studies) and include a limited number of children. None of the studies have shown significant positive effects on the child s well-being. 3.7 Clinical intervention studies among parents to HSCT children The primary research focus on the parents has been an assessment of their levels of distress, anxiety and depression and on coping strategies and factors influencing the parents coping capacity (34;40;41). None of these studies were intervention studies. One RCT study aimed at lowering the parents (n=22) levels of distress by offering 90 minutes of education in stress management techniques (education, relaxation, communication) prior to the child s HSCT (57). The study showed that the intervention group used stress management techniques more frequently than the control group during the child s HSCT, however, no significant differences between the groups were found. 4

3.8 Intervention studies aimed to reduce distress in parents to children with recent cancer diagnoses Eight complementary intervention studies were identified that aimed to reduce the level of distress, anxiety or depression in parents to children newly diagnosed with cancer (58). The total duration of the intervention was 45 minutes to eight hours /week and included 8-217 parents (58). The studies show a decrease in the parents levels of distress and anxiety when they have access to a web-site with medical information (59), participated in discussion sessions (60), and enhancement of their problem solving skills by means of cognitive behavioural therapy (61;62). These studies indicate that interventions where parents could express emotions and enhance their problem solving skills may be effective in reducing parental distress. However, these findings require confirmation in other studies. 3.9 Pilot study of Danish children previously treated with HSCT and their parents As there is limited evidence in the literature for interventions aimed at the parents either to children undergoing treatment with HSCT or children newly diagnosed with cancer, it was decided to perform a pilot study among parents to Danish children treated with HSCT. The aim was to explore the families main needs and propose interventions that would diminish the strain on them during the HSCT inpatient period. This study included seven families and was conducted through qualitative semi-structured interviews by the author (HBL). The parents and children (3 months 3 years following treatment, in average 1 year) were recruited in the HSCT-unit s outpatient clinic. The parents and children described how complex chains of interrelated interactions between themselves and the staff affected the children s adjustment to treatment, the parents caring abilities and generated emotional responses. Discontinuity in interaction between the parents with the nursing staff resulted in inconsistent care and medical information relay, causing conflicts related to the care of the child. Parents and the staff s main priority was the child undergoing HSCT treatment and as such the needs of healthy siblings were disregarded, and parents experienced being isolated in resolving this dilemma. The child s LAF isolation resulted in the resident parent feeling socially isolated and physical inactive and generated emotional strains of insecurity, frustration and powerlessness. The parents requested that a small team of nurses be assigned to help meet the entire family s needs. The nurses should provide consistent care, medical information, and assistance in addressing problems on a day-to-day basis. The parents requested a broader perspective on the family s situation than just the child undergoing HSCT. This request inspired the inclusion of continuous nursing support and the provision of a case manager or patient navigator function. 3.10 Nurses performing the Case Manager/ Patient Navigator function Historically, the Case Manager (CM) and the Patient Navigator (PN) roles emerged from a need to assist patients during transition between and within the health care system and society (63). The CM provides assistance with discharge planning; housing arrangements, medical treatment, daily activities, finances, vocational training and navigation within the decentralized complex community care system (63-65). The role of the PN is to provide individualized assistance to cancer patients, families and caregivers to overcome health care system barriers, to navigate within the system, and to coordinate treatment plans (66). The PN supports the patient along the disease trajectory by streamlining the patients care, acting as a liaison between the patient and the medical staff, and advocating for the patients with the nurses and physicians (67;68) The expansion of the patient navigator role to include aspects of treatment options and compliance along the illness trajectory requires a person with an extensive nursing background in oncology care. The PN model has proven 5

a success in the early detection and treatment of breast cancer and in reducing the use of hospitals, cost of care and in family burden. The model also provides an increased stability with respect to housing, symptom control and quality of life for patients (66;67;69;70). The multifaceted functions described in the CM and PN models serve as inspiration for the introduction of a family navigator nurse to address the families needs during the child s HSCT. 4. THEORETICAL FRAMEWORK The sociology of the family inspired this dissertation, especially how childcare responsibility is divided between the parents and the state. The theoretical framework is also inspired by a symbolic interactionistic approach (71;72), founded by the Chicago School, and a cognitive behavioural approach (73-75). The Chicago School is characterised by being multidisciplinary, applying methodological diversity in their empirical research and attempting to provide means for people to improve their lives (76;77). Arlie Hochschild, a descendant from the Chicago School, inspired this study with her work on balancing home and work life within the family. Hochschild s contribution to the sociology of emotions also provides inspiration to the theoretical approach of the social context in emotional management. Behavioural and cognitive behavioural theories lent inspiration to the emotional support provided in the intervention study. 4.1 A sociological approach to the family The State expects the family to perform certain roles and functions while maintaining, transferring and establishing social order within the society. This includes an expectation that the family, as a social institution to care for offspring, also continues its caring role during treatment of life threatening diseases (78). Furthermore, the State has the authority to control the manner in which these care responsibilities are performed and can sanction any failures by e.g. constructing labels such as a problem family or ultimately removing the child from the parents custody. But, the State also provides the framework and resources for the family to comply with these expectations, e.g. in relation to the child s HSCT treatment the Danish social law ensures the parents economic compensation while caring for their child. In general, parents have the most enduring influence on the child s life and socialization. The most enduring influence on children s lives and socialization derives from the parents socio-economic status, child rearing practice, cultural background, religious beliefs and mode of communication (79). The importance of the parent s emotional well being and socio-economic status for the child s adaption to HSCT treatment is indicated in the literature on HSCT (41;42;80-83). However, what factors indirectly or directly influence the parents and the child remain unexplained as do the different patterns of parental adaptation to the caring task and how it is possible to intervene to strengthen the bond between parents and child (84;85). 4.2 Balancing work and home The books, The time bind (86) and The second shift (87), by sociologist Arlie Hochschild address the dilemma of balancing the expectations and relationship between work and home. She describes the competition that exists between work and family time and the problems related to being a serious player at work and a family man at home. Within the family, she highlights the relationship between power (actual or perceived) and the bonds of human caring. She studied the myths and strategies developed by couples to live up to inequalities in workloads and the economics of gratitude displayed. Hochschild s theory on the relationship between work and home provides an approach to the dilemma between the different rationalities that govern the work place and the home environment. The relationship between work and home, that Hoshschild describes, holds some resemblance to the relationship the parent describes when addressing the 6

association between the demands from the child s hospital inpatient treatment and home and as such economics of gratitude may be seen among the parents. 4.3 Emotional management Hochschild s sociology of emotions provides a framework for understanding how emotions are imbedded in the conflict between the body and society. Hochschild s interactionistic perspective is centred on notions like feeling rules, emotional work and altering of emotions by surface and deep acting. According to Hochschild, every society has a set of cultural rules that governs emotions that are possible to feel, which are appropriate to feel, which are expected to be displayed in a given situation, and how inappropriate emotions are sanctioned (88;89). Emotions are associated with images, ideas and thoughts and can be changed e.g. by changing the cognition, a process referred to as emotional work. Emotions are manipulated by surface acting or deep acting (88), the difference being the level of emotional work performed in the given situation. In surface acting, a person changes the outward expression to match a feeling rule, e.g. by smiling instead of showing anger where as in deep acting the cognition of the emotion is changed e.g. by transforming the emotion of anger into empathy (88). Hochchild s theory on emotions has inspired this dissertation in two ways, i.e. by providing an understanding of the emotions that the parents are expected to express during the HSCT course and by the way that the parents engage in emotional management by using surface and deep acting techniques while interacting with their child. 4.4 Behavioural and cognitive behavioural therapy inspiration In line with Hochschild s sociology of emotions, cognitive behavioural therapy emphasizes the importance of cognition of thoughts on the fringe of consciousness. These thoughts precede and influence the individual s emotional reactions and behaviour toward an event (73-75). Problemsolving strategies inspired by cognitive behavioural therapy are founded on a sense of optimism (a positive orientation) that problems can be solved (61). Solving problems requires accurate identification of the problem, the cause of the problem, implementation of a strategy for resolution, and evaluation of the solution (90). Mothers to children who were newly diagnosed with cancer (n=440) were offered an intervention of eight hours duration to learn problem-solving strategies. Compared with a group receiving standard care, their problems solving skills were significantly enhanced when measured at 3 months, e.g. the Social Problem-Solving Inventory (91) and Profile of Mood States (92), however, at 6 months following the intervention the standard care group reached the same lowered level as the intervention group, and at this point there was no significant effect noted from the intervention (61). In adults suffering from anxiety and depression, cognitive behavioural therapy techniques have proven effective in the treatment of emotional disorders within a limited time-frame (5 12 sessions) (74). In adults diagnosed with cancer the use of cognitive therapy has shown conflicting results (93-97). 4.5 Summary Only children with life threatening diseases are treated with HSCT. HSCT is a complex, invasive and lengthy treatment carried out in isolation, with high morbidity and mortality rates, and requiring comprehensive caregiving by the parents. The increased care needs during the HSCT treatment require a transition in the family s daily life and induces a high level of emotional and social distress in the parents and the child. During the 4-6 weeks HSCT isolation period, the parents are the primary caregivers around the clock to ensure the child s adjustment to increased basic care needs, side-effects and treatment complications. The few intervention studies performed among parents to children treated with HSCT have not shown positive significant effects. However, 7

intervention studies aimed at children with cancer and their parents have indicated promising results. Intervention programs have assisted parents in increasing their knowledge and sharing the cancer burden, and enhanced their problem-solving capacity. A Danish pilot study conducted by the author (HBL) indicated a need for a caregiver support intervention study, targeting the parents, by providing continuity in nursing care as well as nursing and medical guidance and by addressing the family s emotional and social circumstances. The multifaceted function and the continuity described in the CM and PN models inspired the implementation of a family navigator nursing function for families with multiple interrelated problems, such as those families of children treated with HSCT. 5. MATERIALS AND METHODS 5.1 Design This study is a retrospective and prospective controlled study of parents to children treated with HSCT in a population-based (5.5 million) and nationwide study in Denmark. To address the problem of the limited number (n=15-22) of children (aged 0-20 years) undergoing HSCT annually, it was decided to compare three groups of parents: Parental Intervention Group (PIG) was compared to 1) Prospective Parental Control Group (PPCG) receiving the HSCT unit s standard care, to 2) Retrospective Parental Control Group (RPCG) receiving the HSCT unit s standard care. The study is designed as a mixed method research using qualitative methods (in-dept semistructured interviews and participant observation) and quantitative methods (validated questionnaires). 5.2 Sample All resident parents to children (0-20 years) undergoing HSCT in Denmark were eligible for inclusion. The parents were approached during their child s medical pre-examination (figure 1, HSCT course) and were presented with oral and written study information. Exclusion criteria were: 1) parents to children with a medical prognosis of imminent death, 2) children without a resident parent as the primary caregiver, and 3) a resident parent who was unable to speak Danish. The parents were included in three different consecutive groups (figure 2: Parent flow chart). The retrospective parental control group (RPCG) was recruited in June 2007 among 62 children treated with HSCT from 1 January 2004 to 30 June 2007. Five (8%) children were classified as ineligible (four did not have a resident parent as caregiver and one was excluded due to intensive care treatment). Consequently, 57 parents were contacted by mailed questionnaire and 46 (81%) responded. The prospective parental control group (PPCG) was recruited from 1 July 2007 to 31 October 2007 among 10 children scheduled for HSCT treatment. Two children (20%) did not have a parental caregiver and were excluded. Parents to the remaining eight children were approached for participation and all consented. Two children died within the first 100 days and accordingly six parents (75%) completed the study. The parental intervention group (PIG) (n=25) was recruited from 1 November 2007 to 31 October 2009 among 31 children scheduled for HSCT treatment. Three did not have resident parents as caregivers, two were treated at the intensive care unit (ICU) and one child had parents who did not speak Danish. Consequently, six (19%) children were excluded. Parents to the remaining 25 children were approached for participation in the PIG and all consented. A total of four (19%) 8