« Je ne suis pas un numéro » Quand patients et professionnels souffrent de l'hôpital

Ce travail de thèse est structuré sur la base de trois recherches qui ont donné lieu à trois articles. Nous nous sommes intéressés, dans la partie introductive de ce document, aux éléments historiques et sociologiques qui permettent de rendre compte de la mue qui a fait passer le patient de plaintif à plaignant. Dans une première recherche (Article 1), nous avons cherché à comprendre quels sont les motifs d’insatisfaction qui conduisent les patients ou leurs proches à franchir le seuil d’un centre dédié à l’écoute des difficultés rencontrées durant la prise en charge hospitalière. Comment ces motifs se distribuent-ils, entre difficultés relationnelles entre patients, proches et professionnels de la santé, aspects techniques liées à la qualité des soins, et relations à l’institution médicale et sanitaire ? Dans une deuxième recherche (Article 2), nous avons eu pour but de mieux comprendre l’effet des doléances sur les professionnels et sur la façon dont ils vivent le processus de médiation. Il s’est agi en particulier d’étudier si et, le cas échéant, dans quelle mesure le processus lié au dépôt d’une doléance entraînait des effets comparables à ceux induits par le dépôt d’une plainte juridique. Dans une troisième recherche (Article 3), après avoir analysé successivement les doléances du point de vue du patient et de ses proches, puis leurs effets sur les professionnels, nous avons mis en perspective ces observations avec le concept émergent de « patient partenaire » souvent décrit, valorisé et parfois idéalisé dans la littérature médicale. Enfin, dans la partie « Discussion et perspectives », nous avons questionné de manière plus large les reconfigurations des relations entre le patient, ses proches, les professionnels et l’institution et avons abordé les perspectives de recherche et d’enseignement que nous souhaiterions développer au sein de l’hôpital. -- This thesis is based on three studies that led to three articles. In the introduction, we were interested in historical and sociological elements which provide an understanding of the change which encouraged the evolution of the patient from plaintive to complainant. In a first research (Article 1), we aimed to understand what are the reasons for dissatisfaction which prompt patients or their relatives to cross a complaint center’s threshold dedicated to the listening of difficulties met during the hospital care. How are these causes distributed among interpersonal problems between patients, their relatives and the health care professionals, technical aspect of care, and relations with the health care institution? In a second research (Article 2), we have tried to understand the effects of the complaint on the health care professionals, and specifically on the physicians and on their experience of the mediation process. We aimed in particular to understand to what extent the process linked to the filing of a complaint led to effects which were comparable to those induced by a legal process. In a third research (Article 3), after having analyzed successively the complaint from the patient’s/relatives’ point of view, and from the physicians’, we put into perspective their interpersonal dynamics under the aspect of the concept of « patient partnership » often described, valued and sometimes idealized in medical literature. Finally, in the part « Discussion and perspectives », we questioned in a broader way, the reconfiguration of the relations between the patient, relatives, health care professionals and the health care institution in this new context. We also addressed the research and teaching perspectives we would like to develop in the hospital

Patients : sujets avant d’être partenaires

Patients et professionnels de la santé souhaitent-ils devenir des partenaires dans la relation de soins ? Il est dans l’air du temps de le croire. Mais rien n’assure que ce soit le cas. L’analyse de données collectées auprès de l’Espace Patients & Proches, où les usagers du CHUV déposent leurs doléances liées à des difficultés rencontrées à l’hôpital, montre que les patients, leurs proches comme les professionnels de la santé souffrent d’un processus de dé-subjectivisation alimenté par la place grandissante des technologies et la standardisation des prises en charge. Ils éprouvent d’abord le besoin d’être reconnus comme des sujets avant de pouvoir envisager de devenir des partenaires. Ni les uns ni les autres ne formulent d’attentes quant à une relation égalitaire. Les tentatives allant dans ce sens sont parfois même vécues comme douloureuses

(in)hospitalités hospitalières - Conflit. Médiation.Réconciliation. Ouvrage collectif sous la direction de B.Schaad..

Les patients, leurs proches et les professionnels témoignent d'un environnement toujours plus complexe dans lequel ils peinent à trouver leur place, du sens, un rôle

Insulin and IGF1 receptors are essential for XX and XY gonadal differentiation and adrenal development in mice

Mouse sex determination provides an attractive model to study how regulatory genetic networks and signaling pathways control cell specification and cell fate decisions. This study characterizes in detail the essential role played by the insulin receptor (INSR) and the IGF type I receptor (IGF1R) in adrenogenital development and primary sex determination. Constitutive ablation of insulin/IGF signaling pathway led to reduced proliferation rate of somatic progenitor cells in both XX and XY gonads prior to sex determination together with the downregulation of hundreds of genes associated with the adrenal, testicular, and ovarian genetic programs. These findings indicate that prior to sex determination somatic progenitors in Insr;Igf1r mutant gonads are not lineage primed and thus incapable of upregulating/repressing the male and female genetic programs required for cell fate restriction. In consequence, embryos lacking functional insulin/IGF signaling exhibit (i) complete agenesis of the adrenal cortex, (ii) embryonic XY gonadal sex reversal, with a delay of Sry upregulation and the subsequent failure of the testicular genetic program, and (iii) a delay in ovarian differentiation so that Insr;Igf1r mutant gonads, irrespective of genetic sex, remained in an extended undifferentiated state, before the ovarian differentiation program ultimately is initiated at around E16.5

Absence of <i>Insr</i> and <i>Igf1r</i> negatively affects <i>SF1</i> gene expression and causes adrenal agenesis.

<p>Whole mount <i>in situ</i> hybridization on E10.5–E13.5 genital ridges (A), double IF with anti-SF1 (green) and anti-WT1 (red) at E11.5 (B) and qRT-PCR on genital ridges/mesonephroi at E11.5 and 12.5 (C) revealed that <i>Sf-1</i> is expressed at reduced levels both in XX and XY dko embryos during sex determination. Haematoxylin and eosin staining (D,H,L) as well as immunostaining for the adrenocortical markers SF1 (E,I,M) and 3βHSD (F,J,N) and chromaffin cell marker tyrosine hydroxylase, TH (G,K,O) from control (D–G) and dko (H–O) XY embryos at E16.5 revealed that adrenal glands are either massively reduced in size (H–K, 3 out of 27 embryos) or absent (L–O, 24 out of 27 embryos) in dko mutants. Fluorescence photomicrographs of XY genital ridges at E10.5 (P,T), E11.5 (Q,U), E12.5 (R,V) and E13.5 (S,W) from control (P–S) and dko (T–W) embryos expressing the <i>Sf1;eGFP</i> transgene. Note the absence of adrenal development (arrowhead) and gonadal primordium differentiation into testis (arrows) in dko animals. REL, relative expression levels. Values are expressed as means ± SEM, p*<0.05, ***p<0.001 vs control. Scale bar: 100 µm.</p

Delay in ovarian differentiation in the absence of insulin/IGF signaling, irrespective of the genetic sex.

<p>Expression of key ovarian genes (<i>Wnt4</i>, <i>Fst</i>, <i>Irx3</i>, <i>Lef1</i> and <i>Foxl2</i>) was assessed in XX or XY genital ridges/mesonephroi either by qRT-PCR (A–C), whole mount <i>in situ</i> hybridization (D–J), or with double immunofluorescence using the female marker FOXL2 (green) along with E–cadherin (red; K–V). We observed a significant reduction in levels of <i>Foxl2</i>, <i>Wnt4</i>, <i>Fst</i>, <i>Irx3</i> and <i>Lef1</i> in E12.5 and E13.5 dko gonads suggesting a delay in ovarian differentiation both in XX and XY dko embryos. REL, relative expression levels. Values are expressed as means ± SEM, *p<0.05, **p<0.01 versus control.</p

Testicular development is disrupted in the absence of insulin/IGF signaling.

<p>Expression of key testicular genes such as <i>Sry</i> (A–C), <i>Sox9</i> (D–F), <i>Fgf9</i> (G,H), <i>Amh</i> (I,J), <i>Insl3</i> and <i>p450scc</i> (K,L) was assessed in XY control and XY dko gonads at E11.5, E12.5 or E13.5 using qRT-PCR (A,D,G,I), whole mount <i>in situ</i> hybridization (B,E,H,J,K) or by double immunofluorescence (C,F,L) using sagittal sections, except for the first two panels in C, for which the embryos were cut transversally and arrows point toward genital ridges. XY control and XY dko gonads were immunostained for either SRY (C, in green), the Sertoli-cell marker SOX9 (F, in green), or the Leydig cell marker P450SCC (L, in green), along with E–cadherin (red), which labels germ cells and mesonephric tubules. Note the drastic reduction in <i>Sry</i>, <i>Sox9</i>, <i>Fgf9</i>, <i>Amh</i>, <i>Insl3</i> and <i>p450scc</i> expression and the absence of testis cords in XY dko gonads. REL, relative expression levels. Values are expressed as means ± SEM, **p<0.01, ***p<0.001 vs control.</p

Absence of <i>Insr</i> and <i>Igf1r</i> significantly reduces proliferation of somatic cell progenitors prior to sex determination.

<p>Photomicrographs of control and dko embryos at E10.5 (A, scale bar 2.5 mm), E11.5 (B, scale bar 4 mm) and E12.5 (C, scale bar 5 mm). (D) Body weights of control and dko animals at E10.5 (n≥9), E11.5 (n≥22) and E12.5 (n≥11). (E) Scanning electron microscopy pictures of control and dko genital ridges at E11.5 (scale bar 200 µm). A pink overlay marks the genital ridges. (F) FACS analysis was used to determine the number of SF1⁺ somatic progenitor cells in genital ridges of control and dko animals at E10.5 (n≥9), E11.5 (n≥12), E12.5 (n≥13) and E13.5 (n≥6). (G) Double IF using the gonadal progenitor marker GATA4 (red) along with proliferating marker Ki67 (green) in control and dko genital ridges at E11.5. Quantification of GATA4⁺/Ki67⁺ cells in XX and XY genital ridges of control and dko animals at E10.5 (H) and E11.5 (I) revealed a significant reduction in the proliferation rates of somatic gonadal precursors at E10.5 and E11.5 in dko genital ridges. Values are expressed as means ± SEM, *p<0.05, **p<0.01, ***p<0.001 vs control. Scale bar: 100 µm.</p

Expression profiles of key genes in adrenogonadal development and differentiation as determined by NanoString Multiplex Assays.

<p>Total RNAs were isolated from SF1⁺ cells isolated from XX and XY control or dko gonads between E10.5 and E13.5 control female mice (red); control male mice (blue); dko female mice (light red); dko male mice (light blue). Normalized counts for genes such as (A) <i>Sry</i>, (B) <i>Foxl2</i>, (C) <i>Follistatin</i> (<i>Fst</i>), (D) <i>Cerebellin 4</i> (<i>Cbln4</i>), (E) <i>Dmrt1</i>, (F) <i>Cyp26b1</i>, (G) <i>Dax1</i>, (H) <i>Runx1</i> and (I) <i>Sf1</i> were normalized with the geometric mean of the 6 reference genes. Bars represent the standard deviation.</p