The aim of this thesis was to develop and evaluate a complex intervention for major depression in patients with lung cancer. Major depression is a leading cause of disease burden worldwide and is particularly important in patients with lung cancer, not only because it is common in this poor prognosis cancer group but also because it substantially reduces the quality of the often short period of time that patients have left to live. The thesis describes a systematic review of the relevant research literature, the development of a complex intervention and a multi-centre randomised controlled trial. I found no trials, in my systematic review, that had evaluated the effectiveness of treatments for depression in patients with lung cancer. I did, however, find six trials of interventions intended to improve symptoms or quality of life in this patient group, the findings of which suggested that enhanced care approaches were more effective in reducing depressive symptoms than standard medical care. I developed the complex intervention ‘Depression Care for People with Lung Cancer’ (DCPLC) with 12 patients who had major depression and lung cancer. DCPLC was delivered by a team of cancer nurses and psychiatrists in collaboration with the patient’s GP. It included education about depression, antidepressant medication, psychological treatments (behavioural activation and problem solving therapy) and systematic progress monitoring. The trial comparing DCPLC with usual care included 142 patients. Patients who received DCPLC reported significantly lower average depression severity during their time in the trial, and better self-rated depression improvement, anxiety, quality of life, role functioning and perceived quality of depression care. The methodological limitations, relevant literature and implications of these findings for future research and for clinical practice are discussed.

No

<p>Effekter av utvidet slagbehandling og samarbeid på tvers av forvaltningsnivå.</p><p>Hjerneslag er en av de hyppigste årsaker til alvorlig funksjonshemming og død i Norge, i tillegg at sykdommen medfører betydelige samfunnsmessige kostnader. Forekomsten er ca. 14 000 hjerneslag pr. år, og antallet forventes å øke betraktelig i årene fremover da antall eldre over 65 år vil øke sterkt.</p><p>Det er en stor utfordring å organisere helsetjenesten slik at behandlingstilbudet for denne pasientgruppen blir best mulig. Akuttbehandling i slagenhet er i dag det best dokumenterte behandlingstiltak, men effekten av videre rehabilitering og oppfølging har vært et lite prioritert område for forskning.</p><p>Hovedhensikten med denne avhandlingen har vært å framskaffe mer kunnskap om hva som kan oppnås for slagpasienter ved en systematisk organisering og samarbeid mellom sykehus og primærhelsetjeneste når det gjelder behandling og rehabilitering etter akuttbehandling i slagenhet. Studien som ligger til grunn for avhandlingen ble gjennomført ved Seksjon for hjerneslag, Medisinsk avdeling, St. Olavs Hospital i perioden 1995-1998.</p><p>Intervensjonen var å konstruere en ny behandlingskjede for slagpasienter hvor fokus på bedre samarbeid med primærhelsetjenesten, oppfølging av et ambulerende team, tidlig utreise fra sykehus og rehabilitering med utgangspunkt i hjemmet ble sterkt vektlagt. Den konstruerte behandlingskjeden ble evaluert med tanke på helsegevinst for den enkelte og bedre ressursutnytting sammenlignet med det tradisjonelle behandlingstilbudet.</p><p>Studien ble gjennomført som en klinisk randomisert kontrollert studie der 320 pasienter med akutt hjerneslag ble inkludert. 160 pasienter fikk ordinær slagenhet behandling med videre institusjonsrehabilitering og/eller oppfølging av primærhelsetjenesten, mens de øvrige 160 pasienter fikk oppfølging av et ambulerende team i henhold til den nye og konstruerte behandlingskjeden.</p><p>I de fire arbeidene som inngår i avhandlingen er det sett på risiko for alvorlig funksjonshemning og død, endring i funksjonsnivå og livskvalitet, samt kostnadsanalyser og ressursforbruk av helsetjenester. Pasientene i de to gruppene ble undersøkt og sammenlignet 6 og 12 måneder etter sykdomsdebut.</p><p>Resultatene av studien viste at sammenlignet med tradisjonell behandling oppnådde pasientene i intervensjonsgruppen signifikant bedre funksjonsnivå (p=0.017) og redusert risiko for alvorlig funksjonshemning og død (p=0.044) etter ett år. De viste også tendens til bedret livskvalitet samtidig som initial liggetid i institusjon ble redusert med 40 % (p=0.032). Det var ingen økning i totalt ressursforbruk eller kostnader i intervensjonsgruppen.</p><p>Oppsummert viser avhandlingen at en slagbehandlingskjede med fokus på samarbeid på tvers av forvaltningsnivå, oppfølging av et ambulerende team og rehabilitering mens pasientene bor hjemme gir meget positiv effekt.</p><p>Den kliniske betydning av disse resultater er at en oppfølging i form av en slagbehandlingskjede i tillegg til akutt behandling i slagenhet bør inngå som en integrert del av behandlingstilbudet for denne pasientgruppen.</p><p>Arbeidene er utført ved INM og ISM, Det medisinske fakultet, NTNU. 1.amanuensis, dr.med Bent Indredavik har vært hovedveileder og Professor dr.med Roar Johnsen biveileder.</p> / <p>Extended Stroke Unit Service and Early Supported Discharge. Short and Long-term Effects.</p><p><i>Background and purpose</i></p><p>Stroke imposes a considerable burden for patients, their caregivers and the society worldwide. It is a challenge to organise the healthcare service that can provide effective management of patients who have suffered from stroke. Several trials have shown that stroke unit care improves the outcome for stroke patients. More limited information exists about the most effective way to organise the follow-up care after the acute care in a stroke unit. Stroke patients conventionally receive a substantial part of their rehabilitation in hospital or in other institutions that offer 24 hours-stay.</p><p>The primary aim of this thesis was to increase knowledge about the organising of follow-up care for stroke patients after the acute care in a stroke unit. To achieve this we performed a trial to evaluate the short and long-term effects of an extended stroke unit service (ESUS), with early supported discharge from hospital, co-operation with the primary health care, and more emphasize on rehabilitation at home as essential elements.</p><p><i>Methods</i></p><p>We performed a randomized controlled trial in which 320 acute stroke patients admitted to the Stroke Unit at St. Olavs Hospital, Trondheim University Hospital were included and allocated either to ordinary stroke unit care (OSUS) (160 patients) with further in-patient rehabilitation or follow-up from the primary healthcare service, or to stroke unit care with early supported discharge (160 patients). The ESUS consisted of a mobile team which co-ordinate early supported discharge and further rehabilitation.</p><p>Included in this thesis are 4 papers based on data from this study population of acute stroke patients followed in one year after the onset of stroke. We wanted to compare the groups in relation to independency, quality of life (QoL) and resource use and costs.</p><p>• Functional outcome were measured as the proportion of patients who were independent as assessed by modified Rankin Scale (RS)(RS<2 =global independence) and Barthel Index (BI)(BI>95 = independent in ADL) at 26 weeks and 52 weeks, the differences in final residence and analyses to identify patients who benefited most of an early supported discharge service (paper I and II). All assessments were blinded.</p><p>• The outcome of QoL was measured by the Nottingham Health Profile (NHP) at 52 weeks. Other outcomes measured at 52 weeks were differences between the groups according to social activity, depression, cognitive function and the burden for carers’. (paper III).</p><p>• The use of all health services during the first 52 weeks was recorded prospectively in both groups; its costs were measured as service costs and represent a combination of calculated average costs and tariffs. Hospital expenses were measured as costs per inpatient day. The secondary objectives were to explore differences in costs between the groups with respect to different types of services, time of service delivery and stroke severity (paper IV).</p><p><i>Results</i></p><p>• Extended stroke unit service with early supported discharge and co-ordination by a mobile team improves functional outcome 6 months and 12 months after stroke. The Odds Ratio for independence at one year was 1.56 (95% C.I, 1.01-to 2.44). It was most beneficial for patients with moderate stroke (papers I and II).</p><p>• Extended stroke unit service with early supported discharge can improve long-term quality of life measured by global NHP. The ESUS group had a significant better QoL after one year than the OSUS group (p = 0.048). There were no significant differences between the groups in the secondary outcomes social activity, depression and cognitive function. The caregivers who got their patients early at home did not report an increased burden compared to caregivers whose patients became ordinary stroke unit care (paper III).</p><p>• The length of initial institutional stay (hospital and rehab.clinic) were reduced with 40 % for the patients offered extended stroke unit service (18.6 days in the ESUS versus 31.1 days in the OSUS) (p=0.032). There was also a reduction in average number of total inpatient days during the first year in favour of the ESD group (p = 0.012) (paper IV).</p><p>• The total health services costs for ESUS was equal or less than costs for ordinary care during the first year after stroke. There was a non-significant reduction in total mean service costs in the ESUS group (EUR 18937 / EUR 21824). The service seemed to be most cost effective for patients with moderate severity of stroke (23% lower mean costs compared to OSUS). The important cost savings caused by reduced length of institutional stay did not lead to an increase in costs for home-based rehabilitation (paper IV).</p><p><i>Conclusion</i></p><p>An extended stroke unit service with early supported discharge improved functional outcome and reduced the length of stay in institutions compared to traditional stroke unit care. It also seems that this service can improve long-term quality of life. The costs are equal or less than costs for ordinary care.</p><p>An early, well organised discharge from hospital co-ordinated by a mobile team seems to be an important contribution in the treatment of stroke patients and should be considered, in addition to organised in-patient stroke unit care, as a part of a comprehensive stroke care.</p>

Effekter av utvidet slagbehandling og samarbeid på tvers av forvaltningsnivå. Hjerneslag er en av de hyppigste årsaker til alvorlig funksjonshemming og død i Norge, i tillegg at sykdommen medfører betydelige samfunnsmessige kostnader. Forekomsten er ca. 14 000 hjerneslag pr. år, og antallet forventes å øke betraktelig i årene fremover da antall eldre over 65 år vil øke sterkt. Det er en stor utfordring å organisere helsetjenesten slik at behandlingstilbudet for denne pasientgruppen blir best mulig. Akuttbehandling i slagenhet er i dag det best dokumenterte behandlingstiltak, men effekten av videre rehabilitering og oppfølging har vært et lite prioritert område for forskning. Hovedhensikten med denne avhandlingen har vært å framskaffe mer kunnskap om hva som kan oppnås for slagpasienter ved en systematisk organisering og samarbeid mellom sykehus og primærhelsetjeneste når det gjelder behandling og rehabilitering etter akuttbehandling i slagenhet. Studien som ligger til grunn for avhandlingen ble gjennomført ved Seksjon for hjerneslag, Medisinsk avdeling, St. Olavs Hospital i perioden 1995-1998. Intervensjonen var å konstruere en ny behandlingskjede for slagpasienter hvor fokus på bedre samarbeid med primærhelsetjenesten, oppfølging av et ambulerende team, tidlig utreise fra sykehus og rehabilitering med utgangspunkt i hjemmet ble sterkt vektlagt. Den konstruerte behandlingskjeden ble evaluert med tanke på helsegevinst for den enkelte og bedre ressursutnytting sammenlignet med det tradisjonelle behandlingstilbudet. Studien ble gjennomført som en klinisk randomisert kontrollert studie der 320 pasienter med akutt hjerneslag ble inkludert. 160 pasienter fikk ordinær slagenhet behandling med videre institusjonsrehabilitering og/eller oppfølging av primærhelsetjenesten, mens de øvrige 160 pasienter fikk oppfølging av et ambulerende team i henhold til den nye og konstruerte behandlingskjeden. I de fire arbeidene som inngår i avhandlingen er det sett på risiko for alvorlig funksjonshemning og død, endring i funksjonsnivå og livskvalitet, samt kostnadsanalyser og ressursforbruk av helsetjenester. Pasientene i de to gruppene ble undersøkt og sammenlignet 6 og 12 måneder etter sykdomsdebut. Resultatene av studien viste at sammenlignet med tradisjonell behandling oppnådde pasientene i intervensjonsgruppen signifikant bedre funksjonsnivå (p=0.017) og redusert risiko for alvorlig funksjonshemning og død (p=0.044) etter ett år. De viste også tendens til bedret livskvalitet samtidig som initial liggetid i institusjon ble redusert med 40 % (p=0.032). Det var ingen økning i totalt ressursforbruk eller kostnader i intervensjonsgruppen. Oppsummert viser avhandlingen at en slagbehandlingskjede med fokus på samarbeid på tvers av forvaltningsnivå, oppfølging av et ambulerende team og rehabilitering mens pasientene bor hjemme gir meget positiv effekt. Den kliniske betydning av disse resultater er at en oppfølging i form av en slagbehandlingskjede i tillegg til akutt behandling i slagenhet bør inngå som en integrert del av behandlingstilbudet for denne pasientgruppen. Arbeidene er utført ved INM og ISM, Det medisinske fakultet, NTNU. 1.amanuensis, dr.med Bent Indredavik har vært hovedveileder og Professor dr.med Roar Johnsen biveileder. / Extended Stroke Unit Service and Early Supported Discharge. Short and Long-term Effects. Background and purpose Stroke imposes a considerable burden for patients, their caregivers and the society worldwide. It is a challenge to organise the healthcare service that can provide effective management of patients who have suffered from stroke. Several trials have shown that stroke unit care improves the outcome for stroke patients. More limited information exists about the most effective way to organise the follow-up care after the acute care in a stroke unit. Stroke patients conventionally receive a substantial part of their rehabilitation in hospital or in other institutions that offer 24 hours-stay. The primary aim of this thesis was to increase knowledge about the organising of follow-up care for stroke patients after the acute care in a stroke unit. To achieve this we performed a trial to evaluate the short and long-term effects of an extended stroke unit service (ESUS), with early supported discharge from hospital, co-operation with the primary health care, and more emphasize on rehabilitation at home as essential elements. Methods We performed a randomized controlled trial in which 320 acute stroke patients admitted to the Stroke Unit at St. Olavs Hospital, Trondheim University Hospital were included and allocated either to ordinary stroke unit care (OSUS) (160 patients) with further in-patient rehabilitation or follow-up from the primary healthcare service, or to stroke unit care with early supported discharge (160 patients). The ESUS consisted of a mobile team which co-ordinate early supported discharge and further rehabilitation. Included in this thesis are 4 papers based on data from this study population of acute stroke patients followed in one year after the onset of stroke. We wanted to compare the groups in relation to independency, quality of life (QoL) and resource use and costs. • Functional outcome were measured as the proportion of patients who were independent as assessed by modified Rankin Scale (RS)(RS&lt;2 =global independence) and Barthel Index (BI)(BI&gt;95 = independent in ADL) at 26 weeks and 52 weeks, the differences in final residence and analyses to identify patients who benefited most of an early supported discharge service (paper I and II). All assessments were blinded. • The outcome of QoL was measured by the Nottingham Health Profile (NHP) at 52 weeks. Other outcomes measured at 52 weeks were differences between the groups according to social activity, depression, cognitive function and the burden for carers’. (paper III). • The use of all health services during the first 52 weeks was recorded prospectively in both groups; its costs were measured as service costs and represent a combination of calculated average costs and tariffs. Hospital expenses were measured as costs per inpatient day. The secondary objectives were to explore differences in costs between the groups with respect to different types of services, time of service delivery and stroke severity (paper IV). Results • Extended stroke unit service with early supported discharge and co-ordination by a mobile team improves functional outcome 6 months and 12 months after stroke. The Odds Ratio for independence at one year was 1.56 (95% C.I, 1.01-to 2.44). It was most beneficial for patients with moderate stroke (papers I and II). • Extended stroke unit service with early supported discharge can improve long-term quality of life measured by global NHP. The ESUS group had a significant better QoL after one year than the OSUS group (p = 0.048). There were no significant differences between the groups in the secondary outcomes social activity, depression and cognitive function. The caregivers who got their patients early at home did not report an increased burden compared to caregivers whose patients became ordinary stroke unit care (paper III). • The length of initial institutional stay (hospital and rehab.clinic) were reduced with 40 % for the patients offered extended stroke unit service (18.6 days in the ESUS versus 31.1 days in the OSUS) (p=0.032). There was also a reduction in average number of total inpatient days during the first year in favour of the ESD group (p = 0.012) (paper IV). • The total health services costs for ESUS was equal or less than costs for ordinary care during the first year after stroke. There was a non-significant reduction in total mean service costs in the ESUS group (EUR 18937 / EUR 21824). The service seemed to be most cost effective for patients with moderate severity of stroke (23% lower mean costs compared to OSUS). The important cost savings caused by reduced length of institutional stay did not lead to an increase in costs for home-based rehabilitation (paper IV). Conclusion An extended stroke unit service with early supported discharge improved functional outcome and reduced the length of stay in institutions compared to traditional stroke unit care. It also seems that this service can improve long-term quality of life. The costs are equal or less than costs for ordinary care. An early, well organised discharge from hospital co-ordinated by a mobile team seems to be an important contribution in the treatment of stroke patients and should be considered, in addition to organised in-patient stroke unit care, as a part of a comprehensive stroke care.

clanata@iin.sld.pe / Introduction: Pneumonia and diarrhoea are leading causes of death in children. There is a need to develop effective interventions. Objective: We present the design and baseline findings of a community-randomised controlled trial in rural Peru to evaluate the health impact of an Integrated Home-based Intervention Package in children aged 6 to 35 months. Methods: We randomised 51 communities. The intervention was developed through a community-participatory approach prior to the trial. They comprised the construction of improved stoves and kitchen sinks, the promotion of hand washing, and solar drinking water disinfection (SODIS). To reduce the potential impact of non-blinding bias, a psychomotor stimulation intervention was implemented in the control arm. The baseline survey included anthropometric and socio-economic characteristics. In a sub-sample we determined the level of faecal contamination of drinking water, hands and kitchen utensils and the prevalence of diarrhoegenic Escherichia coli in stool specimen. Results: We enrolled 534 children. At baseline all households used open fires and 77% had access to piped water supplies. E. coli was found in drinking water in 68% and 64% of the intervention and control households. Diarrhoegenic E. coli strains were isolated from 45/139 stool samples. The proportion of stunted children was 54%. Conclusions: Randomization resulted in comparable study arms. Recently, several critical reviews raised major concerns on the reliability of open health intervention trials, because of uncertain sustainability and non-blinding bias. In this regard, the presented trial featuring objective outcome measures, a simultaneous intervention in the control communities and a 12- month follow up period will provide valuable evidence. / This study received financial support of the UBS Optimus Foundation, through a grant given to the IIN and Swiss TPH. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. / Revisión por pares

Background: Currently, participation in the NHS Bowel Cancer Screening Programme (NHSBCSP) is poor, with around half of all people invited returning their (FOBT) kits. The research programme aimed to investigate whether a general practitioner’s (GP) letter encouraging participation and a detailed leaflet explaining how to complete the (FOBT) included with the invitation materials would improve uptake. Methods: The research programme was divided into three phases which were designed to sequentially develop and evaluate the two interventions. The initial and second phases developed and refined the two interventions and the trial outcome measures with previous participants and stakeholder representatives. The final phase was a randomised 2x2 factorial trial conducted with people invited to screening in October 2009. Participants were randomised to either a GP’s endorsement letter and/or a detailed procedural leaflet with their FOBT kit. The primary outcome was verified participation in the NHSBCSP. Questionnaires were also used to evaluate participant perceptions of CRC screening and GPs views on involvement with the NHSBCSP. Results: The factorial trial demonstrated both the GP’s endorsement letter and the detailed procedural leaflet increased participation in the NHSBCSP. In the intention-to-treat analysis, participation improved by 6% for the detailed procedural leaflet and 5.8% for the GP endorsement letter 20 weeks after receipt of the FOBT kit. The random effects logistic regression model confirmed that there was no important interaction between the two interventions, and estimated an adjusted rate ratio of 1.11 (P=0.038) for the GP’s letter and 1.12 (P=0.029) for the leaflet. The per protocol analysis indicated that the insertion of an electronic GP’s signature on the endorsement letter was associated with increased participation (P=0.039). Conclusions: Including both an endorsement letter from each patient’s GP and a detailed procedural leaflet could increase participation in the NHSBCSP by around 10%, a relative improvement of 20% on the current participation rate. Both interventions were well-received by participants and there was minimal impact on GP workload.

Background: Parent behaviours have a long-lasting impact on the health, education, and behaviour of the young people in their care. Group-based parenting interventions are a promising approach to improve parenting, as well as to prevent and reduce physical and emotional maltreatment of children. While a billion of adolescents live in low- and middle- income countries, few evaluations have examined parenting approaches for families with adolescents in these countries. Objectives: This study was nested within a randomised controlled trial of Sinovuyo Teen, a parenting programme for families with adolescents. The trial took place in rural South Africa in 2015-2016 with 552 families in 40 study clusters. Primary intervention outcomes included parenting and child maltreatment. This dissertation aims to: (1) describe the implementation (attendance, engagement, and fidelity) of the intervention delivered within the evaluation, (2) examine if participant characteristics affected attendance and engagement in the intervention, (3) examine if implementation characteristics affected programme results, and (4) examine if participant characteristics affected programme results. Methods: Programme implementation was assessed through observations of all programme group sessions and the records of the implementing organisation. The analyses also draw on participant self-report data from three time-points (baseline, immediate post-test, and follow-up). The data were analysed using a series of correlation and multilevel regression analyses, presented in three papers. Findings: Attendance levels in the intervention were somewhat lower than in previous similar studies, perhaps due to the role of home visits. Generally, more disadvantaged families participated at similar rates as families with more material and social resources. However, a number of factors affected attendance on individual and family levels, e.g. an overcrowded household, and at the community level, e.g. funeral and grant receipt days. Intervention fidelity was similar to the levels reported in high-income countries, thus suggesting that high implementation quality is feasible in a low-resource setting. There was no consistent impact of the variation in participation and implementation on participant outcomes. Baseline risks did not consistently affect variation in treatment effects, confirming recent findings that families at-risk can benefit from parenting support as much or more than less at-risk families.

The research in this thesis aimed to develop an algorithm to support midwives’ diagnosis of active labour in primiparous women and to compare the effectiveness of the algorithm with standard care in terms of maternal and neonatal outcomes. Four linked studies are presented following the template suggested by the Medical Research Council (MRC 2000) Framework for development and evaluation of randomised controlled trials (RCT) for complex interventions to improve health. Study one Aim: To develop an algorithm for diagnosis of active labour in primiparous women. Methods: An informal telephone survey was conducted with senior midwives to assess the need for a decision support tool for the diagnosis of active labour. A literature review identified the key cues for inclusion in the algorithm which was then drafted. Focus group interviews were conducted with midwives to ascertain the cues used by midwives in diagnosing active labour. Findings: Thirteen midwives took part in focus groups. They described using informational cues which could be separated into two categories: those arising from the woman (Physical signs, Distress and coping, Woman's expectations and Social factors) and those from the institution (Midwifery care, Organisational factors and Justifying actions). Study Two Aim: Preliminary testing of the algorithm Methods: Vignettes and questionnaires were used to test the consistency of midwives’ judgements (inter-rater reliability), the content of the algorithm and its acceptability to midwives (face and content validity). The study was conducted in two stages: the first stage (23 midwives) involved vignettes and questionnaires and the second stage (20 midwives) involved vignettes only. Findings: In the first stage a Kappa score of 0.45 indicated only moderate agreement between midwives using the algorithm. After modifying the algorithm, the Kappa score in stage two was 0.86, indicating a high level of agreement. While the majority of the midwives reported that the algorithm was easy to complete, most were able to identify snags or make suggestions for its improvement. Based on the findings of this study the algorithm was modified and the final version was developed. Study three Aim: To assess the feasibility of carrying out a cluster randomised trial (CRT) of the algorithm, in Scotland. Specifically, to identify maternity units potentially willing to participate in a CRT, to test the implementation strategy for the trial and to collect baseline data to inform the sample size calculation. Methods: A questionnaire and interviews were used. The CRT methods were piloted in two maternity units and the algorithm was used for a three-month period in order to test its acceptability and provide estimates of compliance and consent rates. Results: All maternity units surveyed expressed an interest in the proposed study. Midwives’ compliance with study protocol differed between units, although the consent rate of women was high (89% and 84%). Ultimately, one unit achieved 100% of the required sample and the other 60%. The midwives reported that the algorithm was acceptable and was a useful tool, particularly for teaching inexperienced midwives. Study four Aim: To compare the effectiveness of the algorithm for diagnosis of active labour in primiparous women with standard care in terms of maternal and neonatal outcomes. Method: A cluster randomised trial Participants: Fourteen maternity units in Scotland. Midwives in experimental sites used the algorithm to assist their diagnosis of active labour. Seven experimental units collected data from 1029 women at baseline and 896 post intervention. The seven control units had 1291 women at baseline and 1287 after study implementation. Outcomes: The primary outcome was the percentage use of oxytocin for augmentation of labour. Secondary outcomes were medical interventions in labour, labour admission management, unplanned out of hospital births and clinical outcomes for mothers and babies. Results: There was no significant difference between groups in percentage use of oxytocin for augmentation of labour or for the use of medical interventions in labour. Women in the algorithm group were more likely to be discharged from the labour suite following their first labour assessment and subsequently have more pre-labour admissions. Conclusion The studies presented in this thesis represent the full process of developing and testing a complex healthcare intervention (the algorithm). The final study, a national cluster randomised trial, demonstrated that the use of the algorithm did not result in a reduction in the number of women who received oxytocin for augmentation or the use of medical interventions in labour. The results suggest that misdiagnosis of labour is not the main reason for higher rates of intervention experienced by women admitted to labour wards while not yet in active labour. These studies contribute significantly to the debate on care of women in early labour, the organisation of maternity care and to maternity care research.

Contexte : Actuellement en France, le taux de participation au dépistage organisé du cancer colorectal (CCR) reste nettement inférieur aux recommandations européennes et ce, malgré l’implication des médecins généralistes.Objectifs : L’objectif général de ce travail de thèse était d’évaluer les pratiques des médecins généralistes en matière de dépistage organisé du CCR, de comprendre les freins au dépistage et d’évaluer les stratégies permettant d’améliorer la participation des patients à ce dépistage.Méthode : Nos travaux se sont appuyés sur les données du programme de dépistage organisé dans le Val-de-Marne. Nous avons reconstitué une cohorte historique de 157 979 patients suivis par 961 médecins généralistes, mené une recherche-action auprès de 21 médecins volontaires et réalisé un essai contrôlé randomisé en grappes incluant 144 médecins et 20 778 patients.Résultats : Une faible part de la variabilité de la probabilité de participation était attribuable à l’hétérogénéité entre médecins (coefficient de corrélation intra-classe, 5,5%). La participation au dépistage était moindre chez les hommes (odds ratio [OR], 0,79 ; IC 95%, 0,78–0,91), les jeunes (50–54 ans, OR, 0.61 ; IC 95%, 0.58–0.63 ; 55–59 ans, OR, 0.76 ; IC 95%, 0.73–0.80) ou les résidents des zones les plus défavorisées (OR, 0.82 ; IC 95%, 0.77–0.87).Nous avons identifiés 7 exigences essentielles pour l'activité de dépistage organisé du cancer colorectal par le médecin généraliste : Être proactif, Être un partenaire, Prendre en compte l’entourage, Se positionner comme expert du problème, Gérer le temps de manière efficiente, Expliquer la réalisation du test et Aider la réalisation du test. Pour chacune, nous avons pu identifier des techniques utilisables en situation de pratique clinique.Les rappels systématiques adressés par voie postale aux médecins généralistes comportant la liste mise à jour de leurs patients éligibles au dépistage n'ont pas augmenté de manière significative la participation des patients au dépistage après prise en compte de l’effet grappe (analyse multiniveau).Conclusions : Des actions ciblées vers les patients les plus jeunes, les hommes et les résidents des zones géographiques les plus défavorisées devraient être encouragées afin de réduire les disparités observées et améliorer l’efficacité globale du programme de dépistage. Des actions sur l'ensemble des médecins généralistes doivent être envisagées : mettre l'approche centrée sur le patient et la pratique réflexive au cœur du projet de formation initiale et continue, et proposer des recommandations de pratique basées sur les données issues de la pratique. / Background: Currently in France, participation rate in organised colorectal cancer (CRC) screening remains well below European guidelines, despite general practitioners involvement.Objectives: The overall objective of this thesis was to assess general practitioners practices in organized CRC screening, to understand barriers to screening participation and to assess strategies to improve patient participation to screening.Methods: Our work was based on data from the organised screening programme in the Val-de-Marne district. We conducted a retrospective cohort of 157 979 patients followed by 961 general practitioners, an action research among 21 volunteer general practitioners and a cluster-randomized controlled trial including 144 general practitioners and 20,778 patients.Results: A small part of the variability of the likelihood of participation was due to the heterogeneity among physicians (intraclass correlation coefficient, 5.5%). Screening participation was significantly lower in males (odds ratio [OR], 0.79; 95% CI, 0.78 to 0.91), the youngest age group (50-54 years, OR, 0.61; 95% CI, 0.58 -0.63; 55-59 years, OR, 0.76; 95% CI, 0.73-0.80) and patients living in socioeconomically deprived areas (OR, 0.82; 95% CI, 0.77-0.87).We have identified seven essential requirements for general practitioners when screening for CRC: Be proactive, Be partners in care, Take into consideration the patient's family and friends, Position themselves as the expert, Manage time efficiently, Explain the test procedure and Help carry out the test. We were able to identify techniques used for each requirement.Systematic reminders sent by post to general practitioners with the updated list of eligible patients for screening did not significantly improve patient participation to organised CRC screening after taking clustering into account (multilevel analysis).Conclusions: Targeted actions to improve CRC screening participation should focus on patients younger than 60 years, males, and individuals living in deprived areas. Actions to enhance the influence of general practitioners on patient participation should be directed to the overall population of general practitioners. Patient-centred care and reflective practice should be at the heart of initial and continuing medical education, and guidelines based on practice data should be proposed.

Yes / Abstract Objective Omega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22). Design A randomised, open-label, cross-over trial of 8 weeks’ treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week ‘washout’ period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing. Red blood cell (RBC) fatty acid analysis was performed by liquid chromatography tandem mass spectrometry. Results Both omega-3 PUFA formulations induced similar changes in RBC fatty acid content, except that drinks were associated with a larger, and more prolonged, decrease in omega-6 PUFA arachidonic acid than the capsule intervention (p=0.02). There were no significant changes in α or β diversity, or phyla composition, associated with omega-3 PUFA supplementation. However, a reversible increased abundance of several genera, including Bifidobacterium, Roseburia and Lactobacillus was observed with one or both omega-3 PUFA interventions. Microbiome changes did not correlate with RBC omega-3 PUFA incorporation or development of omega-3 PUFA-induced diarrhoea. There were no treatment order effects. Conclusion Omega-3 PUFA supplementation induces a reversible increase in several short-chain fatty acid-producing bacteria, independently of the method of administration. There is no simple relationship between the intestinal microbiome and systemic omega-3 PUFA exposure. / NIHR/EME Yorkshire Cancer Research (YCR)