Genetic variation at CYP3A is associated with age at menarche and breast cancer risk : a case-control study

Abstract Introduction We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years. Methods We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics. Results We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P trend = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P trend = 0.005) but not cases (P trend = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P het = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (ORhet = 0.84, 95% CI 0.75, 0.94; ORhom = 0.81, 95% CI 0.51, 1.30; P trend = 0.002) but not for those who had their menarche age ≤11 years (ORhet = 1.06, 95% CI 0.95, 1.19, ORhom = 1.07, 95% CI 0.67, 1.72; P trend = 0.29). Conclusions To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels

La notion d'espace dans la prise en charge des psychoses en psychiatrie (approches historique, théorique et psychothérapeutique)

TOURS-BU Médecine (372612103) / SudocSudocFranceF

Hyperglycaemia upon onset of ICU-acquired bloodstream infection is associated with adverse outcome in a mixed ICU population

This study aimed to assess whether a relationship exists between hyperglycaemia and outcome in a mixed cohort of critically ill patients with nosocomial bloodstream infection (BSI), and to evaluate patterns of blood glucose levels between survivors and non-survivors. A historical observational cohort study was conducted in the intensive care unit (ICU) of a tertiary care referral centre. One-hundred-and-thirty patients with a microbiologically documented ICU-acquired BSI (period 2003 to 2004) were included. For the study, morning blood glucose levels were evaluated from one day prior until five days after onset of BSI. The contribution of hyperglycaemia, divided in three subgroups (>= 150 mg/dl, >= 175 mg/dl and >= 200 mg/dl), to in-hospital mortality was estimated by logistic regression. In-hospital mortality was 362%. Over the seven study days, no differences were found in daily morning blood glucose levels between survivors (n=83) and non-survivors (n=47). Nevertheless, the trend of blood glucose levels upon onset of BSI showed a remarkable increase in the non-survivors, whereas it decreased in the survivors. Hyperglycaemia (>= 175 mg/dl and >= 200 mg/dl) was observed more often among the non-survivors. Multivariate logistic regression showed that APACHE II (P=0.002), antibiotic resistance (P=0.004) and hyperglycaemia (>= 175 mg/dl) upon onset of BSI (P=0.017) were independently associated with in-hospital mortality, whereas a history of diabetes (P=0.041) was associated with better outcome. Hyperglycaemia (>= 175 mg/dl) upon onset of ICU-acquired BSI is associated with worse outcome in a heterogeneous ICU population. Patterns of morning blood glucose levels have only limited value in the prediction of the individual course

CBT program to reduce recidivism risk for road crashes among adolescents and young adults: Results of a randomized controlled study and prospects

International audienceRoad crashes are the first cause of mortality for young adults aged 18–25 years and the human factor contributes to 90–95% of events. The present study was carried out to determine the efficacity of the ECARR2 recurrence prevention program among adolescents and young adults at high risk of having a new traffic crash in the following months. A total of 288 participants having had a traffic crash that required going to the emergency room, at high risk of accident recurrence (ECARR≥5) were randomly allocated to either the intervention group (n = 144) or the control group (n = 144). Results: revealed that the risk of recurrence was highest during the first 6 months (66% of recurrences). In per-protocol analysis population, at 6 months after inclusion, the accident recurrence rate was 14.2% ± 3.3% in the intervention group, and 23.5% ± 4.0% in the control group. The intervention had an effect per se, independently of the other predictors (p = 0.020). This effect was mediated by the three interaction variables: BDI, Impulsive Behavior Scale lack of perseverance, and Orientation to Happiness engagement. It was therefore through these dimensions that the intervention had an effect. In conclusion, the ECARR score predicts the risk of recurrence, risk which is the highest during the first 6 months. Finally, results confirm the predictive validity of the ECARR scale. The ECARR score had an effect on the risk of recurrence regardless of group (p = 0.045) and was predictive of recurrence (p = 0.045). A brief psychological intervention such as ECARR2 program, offered to young people ar hight risk of having a new crash, just after the crash, seems to halve the risk of recurrence at 6 months. Future research should improve the brief psychological intervention and its access via a mobile application or few hours in high school or in a driving school given

Description of Various Factors Contributing to Traffic Accidents in Youth and Measures Proposed to Alleviate Recurrence

International audienceTraffic accidents are the leading cause of hospitalization in adolescence, with the 18-24-year-old age group accounting for 23% of deaths by traffic accidents. Recurrence rate is also high. One in four teenagers will have a relapse within the year following the first accident. Cognitive impairments known in adolescence could cause risky behaviors, defined as repetitive engagement in dangerous situations such as road accidents. Two categories of factors seem to be associated with traffic accidents: (1) factors specific to the traffic environment and (2) "human" factors, which seem to be the most influential. Moreover, the establishment of a stronger relation to high speed driving increases traffic accident risks and can also be intensified by sensation seeking. Other factors such as substance use (alcohol, drugs, and "binge drinking") are also identified as risk factors. Furthermore, cell phone use while driving and attention deficit disorder with or without hyperactivity also seem to be important risk factors for car accidents. The family environment strongly influences a young person's driving behavior. Some interventional driving strategies and preventive measures have reduced the risk of traffic accidents among young people, such as the graduated driver licensing program and advertising campaigns. So far, few therapeutic approaches have been implemented. Reason why, we decided to set up an innovative strategy consisting of a therapeutic postaccident group intervention, entitled the ECARR2 protoc

Homologous and Heterologous Prime-Boost Vaccination: Impact on Clinical Severity of SARS-CoV-2 Omicron Infection among Hospitalized COVID-19 Patients in Belgium

We investigated effectiveness of (1) mRNA booster vaccination versus primary vaccination only and (2) heterologous (viral vector–mRNA) versus homologous (mRNA–mRNA) prime-boost vaccination against severe outcomes of BA.1, BA.2, BA.4 or BA.5 Omicron infection (confirmed by whole genome sequencing) among hospitalized COVID-19 patients using observational data from national COVID-19 registries. In addition, it was investigated whether the difference between the heterologous and homologous prime-boost vaccination was homogenous across Omicron sub-lineages. Regression standardization (parametric g-formula) was used to estimate counterfactual risks for severe COVID-19 (combination of severity indicators), intensive care unit (ICU) admission, and in-hospital mortality under exposure to different vaccination schedules. The estimated risk for severe COVID-19 and in-hospital mortality was significantly lower with an mRNA booster vaccination as compared to only a primary vaccination schedule (RR = 0.59 [0.33; 0.85] and RR = 0.47 [0.15; 0.79], respectively). No significance difference was observed in the estimated risk for severe COVID-19, ICU admission and in-hospital mortality with a heterologous compared to a homologous prime-boost vaccination schedule, and this difference was not significantly modified by the Omicron sub-lineage. Our results support evidence that mRNA booster vaccination reduced the risk of severe COVID-19 disease during the Omicron-predominant period