How family caregivers' medical and moral assumptions influence decision making for patients in the vegetative state: a qualitative interview study.

Background Decisions on limiting life-sustaining treatment for patients in the vegetative state (VS) are emotionally and morally challenging. In Germany, doctors have to discuss, together with the legal surrogate (often a family member), whether the proposed treatment is in accordance with the patient's will. However, it is unknown whether family members of the patient in the VS actually base their decisions on the patient's wishes. Objective To examine the role of advance directives, orally expressed wishes, or the presumed will of patients in a VS for family caregivers' decisions on life-sustaining treatment. Methods and sample A qualitative interview study with 14 next of kin of patients in a VS in a long-term care setting was conducted; 13 participants were the patient's legal surrogates. Interviews were analysed according to qualitative content analysis. Results The majority of family caregivers said that they were aware of aforementioned wishes of the patient that could be applied to the VS condition, but did not base their decisions primarily on these wishes. They gave three reasons for this: (a) the expectation of clinical improvement, (b) the caregivers' definition of life-sustaining treatments and (c) the moral obligation not to harm the patient. If the patient's wishes were not known or not revealed, the caregivers interpreted a will to live into the patient's survival and non-verbal behaviour. Conclusions Whether or not prior treatment wishes of patients in a VS are respected depends on their applicability, and also on the medical assumptions and moral attitudes of the surrogates. We recommend repeated communication, support for the caregivers and advance care planning.

La médecine de famille en Suisse à l'horizon 2030: quelle place pour la délégation des tâches médicales. [Family practitioners in Switzerland by 2030: which roles for medical task delegation?]

Due to population aging, by 2030 Switzerland may face a demand of 24 million family practitioner visits, a growth of 13 percent from the 2005 level. This result is based on the assumption that the per capita demand for doctor visits remains what was observed in 2005 by age groups and sex. During the same period, the total number of practitioners may decrease by 14 percent whereas the female proportion of such practitioners may double. These changes may cause a 33 percent decrease in the supply of physician visits to reach only 14 millions. The comparison of the demand and supply of family doctor visits reveals that by 2030, 10 million visits may be unmet which represents 40 percent of the demand. On the supply side, a full scale implementation of task delegation may partially reduce that gap (minus 2 millions). On the demand side, improved health status may bring in a larger decrease in the needs for visits (minus 4 million).

Family physician involvement in cancer care and lung cancer patient emotional distress and quality of life.

PURPOSE: This study aims to describe emotional distress and quality of life (QoL) of patients at different phases of their lung cancer and the association with their family physician (FP) involvement. METHODS: A prospective study on patients with lung cancer was conducted in three regions of Quebec, Canada. Patients completed, at baseline, several validated questionnaires regarding their psychosocial characteristics and their perceived level of FP involvement. Emotional distress [profile of mood states (POMS)] and QoL [European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30)] were reassessed every 3-6 months, whether patients had metastasis or not, up to 18 months. Results were regrouped according to cancer phase. Mixed models with repeated measurements were performed to identify variation in distress and QoL. RESULTS: In this cohort of 395 patients, distress was low at diagnosis (0.79 ± 0.7 on a 0-4 scale), raising to 1.36 ± 0.8 at the advance phase (p < 0.0001). Patient's global QoL scores significantly decreased from the diagnosis to the advance phase (from 66 to 45 on a 0-100 scale; p < 0.0001). At all phases of cancer, FP involvement was significantly associated with patients' distress (p = 0.0004) and their global perception of QoL (p = 0.0080). These associations remained statistically significant even after controlling for age, gender, and presence of metastases. CONCLUSIONS: This study provides new knowledge on patients' emotional distress and QoL with cancer evolution and, particularly, their association with FP involvement. Other studies should be conducted to further explore FP role in cancer supportive care.

Delinquency in male adolescents: the role of alexithymia and family structure

The purpose of this study was to examine the linkages between alexithymia and delinquency in male adolescents (age ranging from 14 to 18 years), and to investigate whether alexithymia was a good discriminatory factor for juvenile delinquency. Thirty-six offender adolescents and 46 non-offender control adolescents participated in the study and completed the 20-item Toronto Alexithymia Scale (TAS-20) (alexithymia), the Revised Children's Manifest Anxiety Scale (R-CMAS) (anxiety), the Liste d'Adjectifs Bipolaires et en Echelles de Likert (LABEL) (personality-Big Five) and demographic data. Findings revealed that the adolescents of the offender group scored high on alexithymia and that proportion of disrupted family structure in the offender group is higher than in the control group. Logistic regressions confirmed that alexithymia and family structure are the strongest discriminatory factors for juvenile delinquency. Limitations and clinical implications are discussed, and recommendations for future research are provided

Inter-informant agreement and prevalence estimates for substance use disorders: direct interview versus family history method.

OBJECTIVES: Family studies typically use multiple sources of information on each individual including direct interviews and family history information. The aims of the present study were to: (1) assess agreement for diagnoses of specific substance use disorders between direct interviews and the family history method; (2) compare prevalence estimates according to the two methods; (3) test strategies to approximate prevalence estimates according to family history reports to those based on direct interviews; (4) determine covariates of inter-informant agreement; and (5) identify covariates that affect the likelihood of reporting disorders by informants. METHODS: Analyses were based on family study data which included 1621 distinct informant (first-degree relatives and spouses) - index subject pairs. RESULTS: Our main findings were: (1) inter-informant agreement was fair to good for all substance disorders, except for alcohol abuse; (2) the family history method underestimated the prevalence of drug but not alcohol use disorders; (3) lowering diagnostic thresholds for drug disorders and combining multiple family histories increased the accuracy of prevalence estimates for these disorders according to the family history method; (4) female sex of index subjects was associated with higher agreement for nearly all disorders; and (5) informants who themselves had a history of the same substance use disorder were more likely to report this disorder in their relatives, which entails the risk of overestimation of the size of familial aggregation. CONCLUSION: Our findings have important implications for the best-estimate procedure applied in family studies.

Efficacité du counseling d'orientation: impacts de l'alliance de travail et du contexte psychosocial

La problématique centrale de cette thèse de doctorat est l'efficacité de l'accompagnement à l'orientation. Elle renvoie en particulier à la multiplicité des types d'interventions ainsi qu'aux tensions entre les finalités de l'orientation qui rendent improbable une mesure univoque et objective de l'efficacité des pratiques. Le «mythe » de l'efficacité trouve notamment sa source dans le persistent monopole du modèle de l'appariement qui a largement influencé le développement de la discipline. Le manuscrit est basé sur deux études empiriques. Premièrement, « voies professionnelles » est une étude longitudinale visant l'évaluation de l'efficacité d'un service de counseling d'orientation au travers de mesures intraindividuelles. Les résultats immédiats (pre-post) indiquent une forte diminution de l'indécision vocationnelle des consultants ainsi qu'une augmentation de leur bien-être. Les résultats longitudinaux sur un an indiquent une évolution positive des difficultés plus ancrées ainsi qu'un fort taux d'implémentation des projets professionnels. La qualité de l'alliance de travail démontre un impact positif sur l'efficacité de la démarche. Deuxièmement, l'étude « orientation et genre » a permis de mettre en évidence un effet d'interaction entre le sexe et le niveau scolaire d'élèves en fin de scolarité sur leurs profils d'intérêts professionnels. Ce résultat affecte en particulier les jeunes filles dans une filière à exigences élémentaires car ces deux identités psychosociales semblent restreindre doublement les options professionnelles envisageables. Les deux études ont permis de soulever cinq implications centrales : (1) La distinction entre les aspects cognitifs et émotionnels de l'indécision vocationnelle est importante. En particulier, la préparation au choix est un construit qui nécessite clarification ; (2) Les processus de transitions professionnelles ainsi que leur accompagnement doivent être considérés dans leur dimension temporelle ; (3) L'interconnexion des différentes sphères de vie est centrale dans les processus d'orientation et leur accompagnement ; (4) L'efficacité du conseil en orientation est affectée par la qualité des aspects relationnels ; (5) La complexité des pratiques et de leurs finalités confronte l'orientation à son rôle envers des identités psychosociales fragilisées. - The central issue of this doctoral thesis is the effectiveness of career counseling and guidance. In particular, this refers to the many types of career interventions as well as the tensions between their objectives. Those aspects make it unlikely to get an unambiguous and objective measure of the effectiveness of career practices. The "myth of efficiency" is particularly rooted in the persistent monopoly of person-environment fit models, which greatly influenced the development of the discipline. This manuscript is based on two empirical studies. First, "career paths" is a longitudinal study looking at the effectiveness of a career counseling service through intraindividual measures. Pre-post impacts showed a significant decrease in clients' vocational indecision as well as a moderate increase in their well-being. The one year-longitudinal results highlighted significant decreases in more constant decision-making difficulties with a high proportion of clients having implemented their professional projects. The quality of the working alliance had a positive impact on the effectiveness of the intervention. The second study, "vocational development and gender" highlighted an interaction effect between late schoolchildren's gender and school level on their professional interests profile. This result particularly affected girls at a low school level, because these psychosocial identities were a double restraint in restricting career options. The two studies raised five central implications: (1) The distinction between cognitive and emotional aspects of vocational indecision is important. In particular, readiness to make a choice is a construct that requires clarification; (2) career transitions processes as well as supporting these transitions, should be considered in their temporal dimension (3) the interconnection of different spheres of life is central to vocational development and career guidance and counseling; (4) the effectiveness of career counseling is affected by the quality of the relational aspects in the intervention; (5) and the complexity of career interventions and their objectives forces practitioners to consider their role and responsibilities towards clients with marginalized psychosocial identities.

Mutation in the gene for connexin 30.3 in a family with erythrokeratodermia variabilis.

Erythrokeratodermia variabilis (EKV) is an autosomal dominant keratinization disorder characterized by migratory erythematous lesions and fixed keratotic plaques. All families with EKV show mapping to chromosome 1p34-p35, and mutations in the gene for connexin 31 (Cx31) have been reported in some but not all families. We studied eight affected and three healthy subjects in an Israeli family, of Kurdish origin, with EKV. After having mapped the disorder to chromosome 1p34-p35, we found no mutations in the genes for Cx31, Cx31.1, and Cx37. Further investigation revealed a heterozygous T-->C transition leading to the missense mutation (F137L) in the human gene for Cx30.3 that colocalizes on chromosome 1p34-p35. This nucleotide change cosegregated with the disease and was not found in 200 alleles from normal individuals. This mutation concerns a highly conserved phenylalanine, in the third transmembrane region of the Cx30.3 molecule, known to be implicated in the wall formation of the gap-junction pore. Our results show that mutations in the gene for Cx30.3 can be causally involved in EKV and point to genetic heterogeneity of this disorder. Furthermore, we suggest that our family presents a new type of EKV because of the hitherto unreported association with erythema gyratum repens.

A role for the src family kinase Fyn in NK cell activation and the formation of the repertoire of Ly49 receptors.

NK cell function is regulated by a dual receptor system, which integrates signals from triggering receptors and MHC class I-specific inhibitory receptors. We show here that the src family kinase Fyn is required for efficient, NK cell-mediated lysis of target cells, which lack both self-MHC class I molecules and ligands for NKG2D, an activating NK cell receptor. In contrast, NK cell inhibition by the MHC class I-specific receptor Ly49A was independent of Fyn, suggesting that Fyn is specifically required for NK cell activation via non-MHC receptor(s). Compared to wild type, significantly fewer Fyn-deficient NK cells expressed the inhibitory Ly49A receptor. The presence of a transgenic Ly49A receptor together with its H-2(d) ligand strongly reduced the usage of endogenous Ly49 receptors in Fyn-deficient mice. These data suggest a model in which the repertoire of inhibitory Ly49 receptors is formed under the influenced of Fyn-dependent NK cell activation as well as the respective MHC class I environment. NK cells may acquire Ly49 receptors until they generate sufficient inhibitory signals to balance their activation levels. Such a process would ensure the induction of NK cell self-tolerance.

Variable phenotypic expressivity in a Swiss family with autosomal dominant retinitis pigmentosa due to mutation T494m in the Prpf3 gene

Purpose:to describe the clinical features in a five generations family segregating autosomal dominant retinitis pigmentosa and to identify the causative gene Patient and Methods:Twenty five individuals of a large five-generation family originating from Western Switzerland were ascertained for phenotypic and genotypic characterization. Ophthalmologic evaluations included color vision testing, Goldman perimetry and digital fundus photography. Some patients had autofluorescence (AF) imaging, ocular coherence tomography (OCT) and ISCEV-standard full-field electroretinography (ERG). Blood samples were collected from 10 affected (4 to 70 years of age) and 15 unaffected members after informed consent. DNA was isolated and exons and intron-exons junctions of known adRP genes were sequenced using a Big Dye sequencing kit 1.1. Results:Age of onset of nightblindness and severity of progression of the disease was variable between members of the family. Some patients had early onset of nightblindess aged 3, others at mid-twenties. Most patients had visual acuity above 0.6 for the first 4 decades. Two older patients still had good vision (0.4) in their seventies. Myopia (range: -2 to -5) was noticed in most affected subjects. Fundus findings showed areas of atrophy along the arcades. The AF imaging showed a large high density ring bilaterally. A T494M change was found in exon 11 of PRPF3 gene. The change segregates with the disease in the family. Conclusion: A mutation in the PRPF3 gene is rare compared with other genes causing ADRP. Although a T494M change has been reported, our family is the first one with a variable expressivity. Mutations in PRPF3 gene can cause a variable phenotype of ADRP unlike the previously described Danish and English families. Our report gives a better understanding as to the phenotype/genotype description of ADRP due to PRPF3 mutation.

Maturation of marginal zone and follicular B cells requires B cell activating factor of the tumor necrosis factor family and is independent of B cell maturation antigen.

B cells undergo a complex series of maturation and selection steps in the bone marrow and spleen during differentiation into mature immune effector cells. The tumor necrosis factor (TNF) family member B cell activating factor of the TNF family (BAFF) (BLyS/TALL-1) plays an important role in B cell homeostasis. BAFF and its close homologue a proliferation-inducing ligand (APRIL) have both been shown to interact with at least two receptors, B cell maturation antigen (BCMA) and transmembrane activator and cyclophilin ligand interactor (TACI), however their relative contribution in transducing BAFF signals in vivo remains unclear. To functionally inactivate both BAFF and APRIL, mice transgenic for a soluble form of TACI were generated. They display a developmental block of B cell maturation in the periphery, leading to a severe depletion of marginal zone and follicular B2 B cells, but not of peritoneal B1 B cells. In contrast, mice transgenic for a soluble form of BCMA, which binds APRIL, have no detectable B cell phenotype. This demonstrates a crucial role for BAFF in B cell maturation and strongly suggests that it signals via a BCMA-independent pathway and in an APRIL-dispensable way.