Treatment motivation in adolescents with psychosis or at high risk: Determinants and impact on improvements in symptoms and cognitive functioning, preliminary results.

Abstract Low motivation is frequent in chronic disorders such as psychosis and may limit treatment efficacy. Although some evidence supports this view in adults, few studies so far have focused on adolescents. We assessed the impact of baseline symptoms, cognitive deficits and cognitive treatment characteristics on treatment motivation (TM), and examined whether TM affected treatment outcome. Twenty-eight adolescents with psychotic disorders participated in 16 sessions of computerized cognitive remediation or games. TM was assessed for each session. Lower TM was predicted by more severe symptoms at baseline, and was associated with smaller improvements in symptoms and both cognitive and psychosocial functioning at the end of the intervention. Experiencing success in the treatment exercises enhanced TM in all patients.

On problems of calculating energy expenditure and substrate utilization from respiratory exchange data.

Indirect calorimetry based on respiratory exchange measurement has been successfully used from the beginning of the century to obtain an estimate of heat production (energy expenditure) in human subjects and animals. The errors inherent to this classical technique can stem from various sources: 1) model of calculation and assumptions, 2) calorimetric factors used, 3) technical factors and 4) human factors. The physiological and biochemical factors influencing the interpretation of calorimetric data include a change in the size of the bicarbonate and urea pools and the accumulation or loss (via breath, urine or sweat) of intermediary metabolites (gluconeogenesis, ketogenesis). More recently, respiratory gas exchange data have been used to estimate substrate utilization rates in various physiological and metabolic situations (fasting, post-prandial state, etc.). It should be recalled that indirect calorimetry provides an index of overall substrate disappearance rates. This is incorrectly assumed to be equivalent to substrate "oxidation" rates. Unfortunately, there is no adequate golden standard to validate whole body substrate "oxidation" rates, and this contrasts to the "validation" of heat production by indirect calorimetry, through use of direct calorimetry under strict thermal equilibrium conditions. Tracer techniques using stable (or radioactive) isotopes, represent an independent way of assessing substrate utilization rates. When carbohydrate metabolism is measured with both techniques, indirect calorimetry generally provides consistent glucose "oxidation" rates as compared to isotopic tracers, but only when certain metabolic processes (such as gluconeogenesis and lipogenesis) are minimal or / and when the respiratory quotients are not at the extreme of the physiological range. However, it is believed that the tracer techniques underestimate true glucose "oxidation" rates due to the failure to account for glycogenolysis in the tissue storing glucose, since this escapes the systemic circulation. A major advantage of isotopic techniques is that they are able to estimate (given certain assumptions) various metabolic processes (such as gluconeogenesis) in a noninvasive way. Furthermore when, in addition to the 3 macronutrients, a fourth substrate is administered (such as ethanol), isotopic quantification of substrate "oxidation" allows one to eliminate the inherent assumptions made by indirect calorimetry. In conclusion, isotopic tracers techniques and indirect calorimetry should be considered as complementary techniques, in particular since the tracer techniques require the measurement of carbon dioxide production obtained by indirect calorimetry. However, it should be kept in mind that the assessment of substrate oxidation by indirect calorimetry may involve large errors in particular over a short period of time. By indirect calorimetry, energy expenditure (heat production) is calculated with substantially less error than substrate oxidation rates.

Determinants of generic drug substitution in Switzerland.

Background: Since generic drugs have the same therapeutic effect as the original formulation but at generally lower costs, their use should be more heavily promoted. However, a considerable number of barriers to their wider use have been observed in many countries. The present study examines the influence of patients, physicians and certain characteristics of the generics' market on generic substitution in Switzerland.Methods: We used reimbursement claims' data submitted to a large health insurer by insured individuals living in one of Switzerland's three linguistic regions during 2003. All dispensed drugs studied here were substitutable. The outcome (use of a generic or not) was modelled by logistic regression, adjusted for patients' characteristics (gender, age, treatment complexity, substitution groups) and with several variables describing reimbursement incentives (deductible, co-payments) and the generics' market (prices, packaging, co-branded original, number of available generics, etc.).Results: The overall generics' substitution rate for 173,212 dispensed prescriptions was 31%, though this varied considerably across cantons. Poor health status (older patients, complex treatments) was associated with lower generic use. Higher rates were associated with higher out-of-pocket costs, greater price differences between the original and the generic, and with the number of generics on the market, while reformulation and repackaging were associated with lower rates. The substitution rate was 13% lower among hospital physicians. The adoption of the prescribing practices of the canton with the highest substitution rate would increase substitution in other cantons to as much as 26%.Conclusions: Patient health status explained a part of the reluctance to substitute an original formulation by a generic. Economic incentives were efficient, but with a moderate global effect. The huge interregional differences indicated that prescribing behaviours and beliefs are probably the main determinant of generic substitution.

Inhabitants' and professionals' social representations of health determinants in a disadvantaged urban area in France: a qualitative analysis = représentations sociales des déterminants de santé dans une zone urbaine défavorisée en France : analyse qualitative auprès d'habitants et de professionnels

Background and objective. - Access to care in French disadvantaged urban areas remains an issue despite the implementation of local healthcare structures. To understand this contradiction, we investigated social representations held by inhabitants of such areas, as well as those of social and healthcare professionals, regarding events or behaviours that can impact low-income individuals' health. Method. - In the context of a health diagnosis, 288 inhabitants living in five disadvantaged districts of Aix-les-Bains, as well as 28 professionals working in these districts, completed an open-ended questionnaire. The two groups of respondents were asked to describe what could have an impact on health status from the inhabitants' point of view. The textual responses were analyzed using the Alceste method. Results. - We observed a number of differences in the way the inhabitants and professionals represented determinants of health in disadvantaged urban areas: the former proposed a representation mixing personal responsibility with physiological, social, familial, and professional aspects, whereas the latter associated health issues with marginalization (financial, drug, or alcohol problems) and personal responsibility. Both inhabitants and professionals mentioned control over events and lifestyle as determinants of health. Discussion. - The results are discussed regarding the consequences of these different representations on the beneficiary - healthcare-provider relationship in terms of communication and trust.

The Lausanne cohort Lc65+: a population-based prospective study of the manifestations, determinants and outcomes of frailty

BACKGROUND: Frailty is a relatively new geriatric concept referring to an increased vulnerability to stressors. Various definitions have been proposed, as well as a range of multidimensional instruments for its measurement. More recently, a frailty phenotype that predicts a range of adverse outcomes has been described. Understanding frailty is a particular challenge both from a clinical and a public health perspective because it may be a reversible precursor of functional dependence. The Lausanne cohort Lc65+ is a longitudinal study specifically designed to investigate the manifestations of frailty from its first signs in the youngest old, identify medical and psychosocial determinants, and describe its evolution and related outcomes. METHODS/DESIGN: The Lc65+ cohort was launched in 2004 with the random selection of 3054 eligible individuals aged 65 to 70 (birth year 1934-1938) in the non-institutionalized population of Lausanne (Switzerland). The baseline data collection was completed among 1422 participants in 2004-2005 through questionnaires, examination and performance tests. It comprised a wide range of medical and psychosocial dimensions, including a life course history of adverse events. Outcomes measures comprise subjective health, limitations in activities of daily living, mobility impairments, development of medical conditions or chronic health problems, falls, institutionalization, health services utilization, and death. Two additional random samples of 65-70 years old subjects will be surveyed in 2009 (birth year 1939-1943) and in 2014 (birth year 1944-1948). DISCUSSION: The Lc65+ study focuses on the sequence "Determinants --> Components --> Consequences" of frailty. It currently provides information on health in the youngest old and will allow comparisons to be made between the profiles of aging individuals born before, during and at the end of the Second World War.

Determinants of the effect of existential behavioral therapy for bereaved partners: a qualitative study.

BACKGROUND: Informal caregivers of palliative patients took part in existential behavioral therapy (EBT), a group intervention comprising mindfulness exercises to reduce psychological distress and improve quality of life. OBJECTIVES: This study examined what the participants perceived as helpful to cope with their loss during the first year of bereavement, particularly with regard to the EBT intervention. DESIGN: Sixteen problem-centered, semi-structured interviews were evaluated with content analysis. RESULTS: Two main categories were found: social support and self-regulation. Social support includes sense of belonging as well as emotional, cognitive, and practical help experienced from others. Mindfulness and acceptance, a clear focus on the positive, and orientation toward the future were helpful strategies of self-regulation; these were also part of the EBT intervention. Mindfulness was understood as permitting emotions and acceptance of one's inner processes, even if they were not pleasant, and was found to be helpful to stop ruminative thinking. CONCLUSIONS: The categories considered as being helpful parallel core elements of EBT and recent grief theories. The intervention was found to be supportive and met the needs of the participants. The interviewees appreciated the continuity of EBT support from palliative care into bereavement.

Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes.

MicroRNAs (miRNAs) have been shown to play important roles in both brain development and the regulation of adult neural cell functions. However, a systematic analysis of brain miRNA functions has been hindered by a lack of comprehensive information regarding the distribution of miRNAs in neuronal versus glial cells. To address this issue, we performed microarray analyses of miRNA expression in the four principal cell types of the CNS (neurons, astrocytes, oligodendrocytes, and microglia) using primary cultures from postnatal d 1 rat cortex. These analyses revealed that neural miRNA expression is highly cell-type specific, with 116 of the 351 miRNAs examined being differentially expressed fivefold or more across the four cell types. We also demonstrate that individual neuron-enriched or neuron-diminished RNAs had a significant impact on the specification of neuronal phenotype: overexpression of the neuron-enriched miRNAs miR-376a and miR-434 increased the differentiation of neural stem cells into neurons, whereas the opposite effect was observed for the glia-enriched miRNAs miR-223, miR-146a, miR-19, and miR-32. In addition, glia-enriched miRNAs were shown to inhibit aberrant glial expression of neuronal proteins and phenotypes, as exemplified by miR-146a, which inhibited neuroligin 1-dependent synaptogenesis. This study identifies new nervous system functions of specific miRNAs, reveals the global extent to which the brain may use differential miRNA expression to regulate neural cell-type-specific phenotypes, and provides an important data resource that defines the compartmentalization of brain miRNAs across different cell types.

Taxonomical and biogeographical problems in Mediterranean shrews of the genus Crocidura (Mammalia, Insectivora) with reference to a new karyotype from Sicily (Italy)

Shrews of the genus Crocidura from Sicily revealed a new karyotype from Europe: 2n = 36, NF = 56, NFa = 52. With reference to the revision of Vesmanis (1976), this shrew is provisionally attributed to C. caudata Miller, 1901 and it is proposed to call it the "Sicilian shrew". Its chromosome complement is similar to that of shrews from Canary Islands and a species from Burundi (Central Africa), suggesting that it might have split off from a line of Paleotropical origin. Following these findings, the modern concept of Mediterranean island colonization by shrews must be revised. The distinctive characteristics of Mediterranean shrews should also be revised.

Intervention précoce dans la phase initiale des troubles psychotiques à Lausanne: quels problèmes et quelles solutions [Early intervention for the initial phase of psychotic disorders in Lausanne: what problems and what solutions?]

Schizophrenia has long been considered with pessimism, but the recent interest in the early phase of psychotic disorders has modified this often unjustified perception. Literature has demonstrated the benefit of the development of programs specialised in the treatment of early psychosis, which tend to be developed in many countries. It is however important to match them to local needs as well as to the structure of local health services. This paper reviews elements that justify such a development in Lausanne, Switzerland, and describe its various elements.

Heritability, determinants and reference values of renal length: a family-based population study.

OBJECTIVES: In this population-based study, reference values were generated for renal length, and the heritability and factors associated with kidney length were assessed. METHODS: Anthropometric parameters and renal ultrasound measurements were assessed in randomly selected nuclear families of European ancestry (Switzerland). The adjusted narrow sense heritability of kidney size parameters was estimated by maximum likelihood assuming multivariate normality after power transformation. Gender-specific reference centiles were generated for renal length according to body height in the subset of non-diabetic non-obese participants with normal renal function. RESULTS: We included 374 men and 419 women (mean ± SD, age 47 ± 18 and 48 ± 17 years, BMI 26.2 ± 4 and 24.5 ± 5 kg/m(2), respectively) from 205 families. Renal length was 11.4 ± 0.8 cm in men and 10.7 ± 0.8 cm in women; there was no difference between right and left renal length. Body height, weight and estimated glomerular filtration rate (eGFR) were positively associated with renal length, kidney function negatively, age quadratically, whereas gender and hypertension were not. The adjusted heritability estimates of renal length and volume were 47.3 ± 8.5 % and 45.5 ± 8.8 %, respectively (P < 0.001). CONCLUSION: The significant heritability of renal length and volume highlights the familial aggregation of this trait, independently of age and body size. Population-based references for renal length provide a useful guide for clinicians. KEY POINTS: • Renal length and volume are heritable traits, independent of age and size. • Based on a European population, gender-specific reference values/percentiles are provided for renal length. • Renal length correlates positively with body length and weight. • There was no difference between right and left renal lengths in this study. • This negates general teaching that the left kidney is larger and longer.

The management of brain metastases

Brain metastases occur in 20-50% of NSCLC and 50-80% of SCLC. In this review, we will look at evidence-based medicine data and give some perspectives on the management of BM. We will address the problems of multiple BM, single BM and prophylactic cranial irradiation. Recursive Partitioning Analysis (RPA) is a powerful prognostic tool to facilitate treatment decisions. Dealing with multiple BM, the use of corticosteroids was established more than 40 years ago by a unique randomized trial (RCT). Palliative effect is high (_80%) as well as side-effects. Whole brain radiotherapy (WBRT) was evaluated in many RCTs with a high (60-90%) response rate; several RT regimes are equivalent, but very high dose per fraction should be avoided. In multiple BM from SCLC, the effect of WBRT is comparable to that in NSCLC but chemotherapy (CXT) although advocated is probably less effective than RT. Single BM from NSCLC occurs in 30% of all BM cases; several prognostic classifications including RPA are very useful. Several options are available in single BM: WBRT, surgery (SX), radiosurgery (RS) or any combination of these. All were studied in RCTs and will be reviewed: the addition of WBRT to SX or RS gives a better neurological tumour control, has little or no impact on survival, and may be more toxic. However omitting WBRT after SX alone gives a higher risk of cerebro-spinal fluid dissemination. Prophylactic cranial irradiation (PCI) has a major role in SCLC. In limited disease, meta-analyses have shown a positive impact of PCI in the decrease of brain relapse and in survival improvement, especially for patients in complete remission. Surprisingly, this has been recently confirmed also in extensive disease. Experience with PCI for NSCLC is still limited, but RCT suggest a reduction of BM with no impact on survival. Toxicity of PCI is a matter of debate, as neurological or neuro-cognitive impairment is already present prior to PCI in almost half of patients. However RT toxicity is probably related to total dose and dose per fraction. Perspectives : Future research should concentrate on : 1) combined modalities in multiple BM. 2) Exploration of treatments in oligo-metastases. 3) Further exploration of PCI in NSCLC. 4) Exploration of new, toxicity-sparing radiotherapy techniques (IMRT, Tomotherapy etc).

Contextual determinants of alcohol consumption changes and preventive alcohol policies: a 12-country European study in progress.

Beginning with France in the 1950s, alcohol consumption has decreased in Southern European countries with few or no preventive alcohol policy measures being implemented, while alcohol consumption has been increasing in Northern European countries where historically more restrictive alcohol control policies were in place, even though more recently they were loosened. At the same time, Central and Eastern Europe have shown an intermediate behavior. We propose that country-specific changes in alcohol consumption between 1960 and 2008 are explained by a combination of a number of factors: (1) preventive alcohol policies and (2) social, cultural, economic, and demographic determinants. This article describes the methodology of a research study designed to understand the complex interactions that have occurred throughout Europe over the past five decades. These include changes in alcohol consumption, drinking patterns and alcohol-related harm, and the actual determinants of such changes.