Caroline Moreau

1H-NMR-Based Metabolomic Profiling of CSF in Early Amyotrophic Lateral Sclerosis

Background Pathophysiological mechanisms involved in amyotrophic lateral sclerosis (ALS) are complex and none has identified reliable markers useful in routine patient evaluation. The aim of this study was to analyze the CSF of patients with ALS by 1H NMR (Nuclear Magnetic Resonance) spectroscopy in order to identify biomarkers in the early stages of the disease, and to evaluate the biochemical factors involved in ALS. Methodology CSF samples were collected from patients with ALS at the time of diagnosis and from patients without neurodegenerative diseases. One and two-dimensional 1H NMR analyses were performed and metabolites were quantified by the ERETIC method. We compared the concentrations of CSF metabolites between both groups. Finally, we performed principal component (PCA) and discriminant analyses. Principal Findings Fifty CSF samples from ALS patients and 44 from controls were analyzed. We quantified 17 metabolites including amino-acids, organic acids, and ketone bodies. Quantitative analysis revealed significantly lower acetate concentrations (p = 0.0002) in ALS patients compared to controls. Concentration of acetone trended higher (p = 0.015), and those of pyruvate (p = 0.002) and ascorbate (p = 0.003) were higher in the ALS group. PCA demonstrated that the pattern of analyzed metabolites discriminated between groups. Discriminant analysis using an algorithm of 17 metabolites revealed that patients were accurately classified 81.6% of the time. Conclusion/Significance CSF screening by NMR spectroscopy could be a useful, simple and low cost tool to improve the early diagnosis of ALS. The results indicate a perturbation of glucose metabolism, and the need to further explore cerebral energetic metabolism.

Premenstrual syndrome prevalence and fluctuation over time: results from a French population-based survey.

OBJECTIVES To explore the experience of reproductive-age women in the French population with premenstrual syndrome (PMS) by estimating perceived symptom prevalence, identifying risk factors, and quantifying the burden of symptoms. This study also assesses the stability of the PMS diagnosis over a 1-year period of follow-up. METHODS The prevalence of reported PMS was estimated from a population-based cohort of 2863 French women interviewed in 2003 and 2004. Multivariate logistic regressions were used to identify risk factors associated with PMS. PMS fluctuation was studied by comparing womens responses in 2003 and 2004. RESULTS Results show that 4.1% of women qualified for severe PMS (six symptoms) and 8.1% qualified for moderate PMS (one to five symptoms), resulting in 12.2% of women who reported PMS symptoms that impacted their daily lives. Risk factors for PMS fell into three categories: hormonal, psychosocial, and physiological, with life stressors and exogenous hormonal exposure exerting the most substantial impact. Results also indicate a high level of intraindividual variation in PMS status over time; among women who qualified for PMS during 1 or both years of the study, 72% demonstrated fluctuation in their PMS status. CONCLUSIONS More women report suffering from distressing premenstrual symptoms than are captured by strict premenstrual dysphoric disorder (PMDD) diagnostic criteria. The impact of PMS symptoms on women appears to fluctuate over time, however, producing greater variability in the syndrome than previously recognized. Clinicians should be mindful of high intraindividual variability in the syndrome when advising patients about long-term management.

Rivastigmine in apathetic but dementia and depression-free patients with Parkinson's disease: a double-blind, placebo-controlled, randomised clinical trial

Background Even with optimal dopaminergic treatments, many patients with Parkinsons disease (PD) are frequently incapacitated by apathy prior to the development of dementia. We sought to establish whether rivastigmines ability to inhibit acetyl- and butyrylcholinesterases could relieve the symptoms of apathy in dementia-free, non-depressed patients with advanced PD. Methods We performed a multicentre, parallel, double-blind, placebo-controlled, randomised clinical trial (Protocol ID: 2008-002578-36; clinicaltrials.gov reference: NCT00767091) in patients with PD with moderate to severe apathy (despite optimised dopaminergic treatment) and without dementia. Patients from five French university hospitals were randomly assigned 1:1 to rivastigmine (transdermal patch of 9.5 mg/day) or placebo for 6 months. The primary efficacy criterion was the change over time in the Lille Apathy Rating Scale (LARS) score. Finding 101 consecutive patients were screened, 31 were eligible and 16 and 14 participants were randomised into the rivastigmine and placebo groups, respectively. Compared with placebo, rivastigmine improved the LARS score (from −11.5 (−15/−7) at baseline to −20 (−25/−12) after treatment; F(1, 25)=5.2; p=0.031; adjusted size effect: −0.9). Rivastigmine also improved the caregiver burden and instrumental activities of daily living but failed to improve quality of life. No severe adverse events occurred in the rivastigmine group. Interpretation Rivastigmine may represent a new therapeutic option for moderate to severe apathy in advanced PD patients with optimised dopaminergic treatment and without depression dementia. These findings require confirmation in a larger clinical trial. Our results also confirmed that the presence of apathy can herald a pre-dementia state in PD. Registration Clinicaltrials.gov reference: NCT00767091.

Role of Young Women's Depression and Stress Symptoms in Their Weekly Use and Nonuse of Contraceptive Methods

PURPOSE We prospectively examined the influence of young womens depression and psychological stress symptoms on their weekly contraceptive method use. METHODS We examined data from 689 women ages 18-20 years participating in a longitudinal cohort study. Women completed 8,877 weekly journals over the first year, which assessed reproductive, relationship, and health information. We focused on baseline depression (Center for Epidemiologic Studies-Depression Scale) and stress (Perceived Stress Scale) symptoms and weekly contraceptive method use. Analyses used multivariate random effects and multinomial logistic regression. RESULTS Approximately one quarter of women exhibited moderate/severe depression (27%) and stress (25%) symptoms at baseline. Contraception was not used in 10% of weekly journals, whereas coital and noncoital methods were used in 42% and 48% of weeks, respectively. In adjusted models, women with moderate/severe stress symptoms had more than twice the odds of contraception nonuse than women without stress (odds ratio [OR] 2.23, confidence interval [CI] 1.02-4.89, p = .04). Additionally, women with moderate/severe depression (RR .52, CI .40-.68, p < .001) and stress (relative risk [RR] .75, CI .58-.96, p = .02) symptoms had lower relative risks of using long-acting methods than oral contraceptives (OCs; reference category). Women with stress symptoms also had higher relative risks of using condoms (RR 1.17, CI 1.00-1.34, p = .02) and withdrawal (RR 1.29, CI 1.10-1.51, p = .001) than OCs. The relative risk of dual versus single method use was also lower for women with stress symptoms. CONCLUSION Womens psychological symptoms predicted their weekly contraceptive nonuse and use of less effective methods. Further research can determine the influence of dynamic psychological symptoms on contraceptive choices and failures over time.

Young women's consistency of contraceptive use - Does depression or stress matter?

BACKGROUND We prospectively examined the influence of young womens depression and stress symptoms on their weekly consistency of contraceptive method use. STUDY DESIGN Women ages 18-20 years (n = 689) participating in a longitudinal cohort study completed weekly journals assessing reproductive, relationship and health characteristics. We used data through 12 months of follow-up (n = 8877 journals) to examine relationships between baseline depression (CES-D) and stress (PSS-10) symptoms and consistency of contraceptive methods use with sexual activity each week. We analyzed data with random effects multivarible logistic regression. RESULTS Consistent contraceptive use (72% of weeks) was 10-15 percentage points lower among women with moderate/severe baseline depression and stress symptoms than those without symptoms (p < .001). Controlling for covariates, women with depression and stress symptoms had 47% and 69% reduced odds of contraceptive consistency each week than those without symptoms, respectively (OR 0.53, CI 0.31-0.91 and OR 0.31, CI 0.18-0.52). Stress predicted inconsistent use of oral contraceptives (OR 0.27, CI 0.12-0.58), condoms (OR 0.40, CI 0.23-0.69) and withdrawal (OR 0.12, CI 0.03-0.50). CONCLUSION Women with depression and stress symptoms appear to be at increased risk for user-related contraceptive failures, especially for the most commonly used methods. IMPLICATIONS Our study has shown that young women with elevated depression and stress symptoms appear to be at risk for inconsistent contraceptive use patterns, especially for the most common methods that require greater user effort and diligence. Based upon these findings, clinicians should consider womens psychological and emotional status when helping patients with contraceptive decision-making and management. User-dependent contraceptive method efficacy is important to address in education and counseling sessions, and women with stress or depression may be ideal candidates for long-acting reversible methods, which offer highly effective options with less user-related burden. Ongoing research will provide a greater understanding of how young womens dynamic mental health symptoms impact family planning behaviors and outcomes over time.

Terminations of pregnancy in the European Union

Please cite this paper as: Gissler M, Fronteira I, Jahn A, Karro H, Moreau C, Oliveira da Silva M, Olsen J, Savona‐Ventura C, Temmerman M, Hemminki E, the REPROSTAT group. Terminations of pregnancy in the European Union. BJOG 2011; DOI: 10.1111/j.1471‐0528.2011.03189.x.

Results from pooled Phase III studies of ulipristal acetate for emergency contraception

BACKGROUND Ulipristal acetate (UPA) is a new effective option to prevent unintended pregnancies up to 5 days after unprotected intercourse. We used pooled data from two Phase III studies to refine our understanding of the efficacy of UPA by time from unprotected intercourse and the effects of other factors on pregnancy rates. STUDY DESIGN Data from two Phase III studies were pooled to create a larger analysis population. Analyses were performed on the first participation of 2183 women. RESULTS A total of 41 women became pregnant despite the use of UPA, yielding an overall proportion pregnant of 1.9% (1.3%-2.5%). Proportions of pregnant women were higher among those with further acts of unprotected intercourse in the same cycle and among obese women. These varied from 1.3% (0.9%-2.0%) among nonobese women who had no further acts of unprotected intercourse (n=1704) to 8.3% (0.2%-38.5%) among obese women who had subsequent unprotected intercourse (n=12). CONCLUSIONS UPA is effective and safe in preventing pregnancy after unprotected intercourse. Its effectiveness is lower among women who have subsequent unprotected intercourse and among obese women.

Effect of prospectively measured pregnancy intentions on the consistency of contraceptive use among young women in Michigan

STUDY QUESTION What is the predictive value of pregnancy intentions on contraceptive behaviours among women aged 18-19? SUMMARY ANSWER Women aged 18-19 have high levels of inconsistent use of contraception, which mostly occur at times when women strongly wish to avoid a pregnancy. WHAT IS KNOWN ALREADY Pregnancy intentions provide an indication of how well individuals achieve their reproductive goals. However, retrospective accounts of pregnancy intentions using dichotomous indicators suffer temporal instability and fail to capture the wide range of attitudes towards pregnancy. STUDY DESIGN, SIZE, DURATION In this study, data are drawn from a population-based survey of 992 women of ages 18-19 years in Michigan, who completed weekly journals assessing contraceptive use, pregnancy intentions and reproductive outcomes during 2.5 years of follow-up. The response rate was 86% for the baseline interview and 65% after 2.5 years of follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS We examined 15 446 pairs of journal entries. We used logistic regression with random effects to assess the predictive effect of womens desire to become pregnant and to avoid a pregnancy, measured each week, on consistency of use of contraception the following week. MAIN RESULTS AND THE ROLE OF CHANCE Women reported inconsistent use of contraception in more than a quarter of weekly journals (28.3%). Consistent use of contraception increased from 22 to 78% as women s intentions to become pregnant decreased and increased from 23 to 78% as motivations to avoid pregnancy increased. The combination of scores of the pregnancy desire and avoidance scales shows indifferent or ambivalent pregnancy attitudes in 8.6% of weekly records. These women were more likely to report inconsistent contraceptive use compared with women who expressed anti-conception attitudes [OR = 2.8 (2.2-3.5)]. However, 23% of women who had unequivocal anti-conception feelings did not use contraception consistently, contributing to 72% of the weeks of inconsistent use in our population. LIMITATIONS, REASONS FOR CAUTION In this study, consistency of contraceptive use, based on the use of contraception at every act of intercourse, does not fully capture a womens risk of becoming pregnant. The 35% attrition after 2.5 years may have affected the internal validity of our results, although a reanalysis based on the first year of observation produced very similar results. WIDER IMPLICATIONS OF THE FINDINGS Because most instances of inconsistent use of contraception occur among women who are keen to avoid a pregnancy, our results suggest there is room for improving contraceptive behaviours by promoting use of methods which do not require user adherence. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Institute of Child Health and Human Development for grant #R01-HDHD050329 (P.I. Barber, University of Michigan) and grant #R24HD047879 (Center infrastructure of the Office of Population Research at Princeton University, JT and KSH). None of the authors have a competing interest.

Phenotypic variability in ARCA2 and identification of a core ataxic phenotype with slow progression

Autosomal recessive cerebellar ataxia 2 (ARCA2) is a recently identified recessive ataxia due to ubiquinone deficiency and biallelic mutations in the ADCK3 gene. The phenotype of the twenty-one patients reported worldwide varies greatly. Thus, it is difficult to decide which ataxic patients are good candidates for ADCK3 screening without evidence of ubiquinone deficiency. We report here the clinical and molecular data of 10 newly diagnosed patients from seven families and update the disease history of four additional patients reported in previous articles to delineate the clinical spectrum of ARCA2 phenotype and to provide a guide to the molecular diagnosis. First signs occurred before adulthood in all 14 patients. Cerebellar atrophy appeared in all instances. The progressivity and severity of ataxia varied greatly, but no patients had the typical inexorable ataxic course that characterizes other childhood-onset recessive ataxias. The ataxia was frequently associated with other neurological signs. Importantly, stroke-like episodes contributed to significant deterioration of the neurological status in two patients. Ubidecarenone therapy markedly improved the movement disorders, including ataxia, in two other patients. The 7 novel ADCK3 mutations found in the 10 new patients were two missense and five truncating mutations. There was no apparent correlation between the genotype and the phenotype. Our series reveals that the clinical spectrum of ARCA2 encompasses a range of ataxic phenotypes. On one end, it may manifest as a pure ataxia with very slow progressivity and, on the other end, as a severe infantile encephalopathy with cerebellar atrophy. The phenotype of most patients, however, lies in between. It is characterized by a very slowly progressive or apparently stable ataxia associated with other signs of central nervous system involvement. We suggest undergoing the molecular analysis of ADCK3 in patients with this phenotype and in those with cerebellar atrophy and a stroke-like episode. The diagnosis of patients with a severe ARCA2 phenotype may also be performed on the basis of biological data, i.e. low ubiquinone level or functional evidence of ubiquinone deficiency. This diagnosis is crucial since the neurological status of some patients may be improved by ubiquinone therapy.

Understanding Factors that Shape Gender Attitudes in Early Adolescence Globally: A Mixed-Methods Systematic Review

Background Early adolescence (ages 10–14) is a period of increased expectations for boys and girls to adhere to socially constructed and often stereotypical norms that perpetuate gender inequalities. The endorsement of such gender norms is closely linked to poor adolescent sexual and reproductive and other health-related outcomes yet little is known about the factors that influence young adolescents’ personal gender attitudes. Objectives To explore factors that shape gender attitudes in early adolescence across different cultural settings globally. Methods A mixed-methods systematic review was conducted of the peer-reviewed literature in 12 databases from 1984–2014. Four reviewers screened the titles and abstracts of articles and reviewed full text articles in duplicate. Data extraction and quality assessments were conducted using standardized templates by study design. Thematic analysis was used to synthesize quantitative and qualitative data organized by the social-ecological framework (individual, interpersonal and community/societal-level factors influencing gender attitudes). Results Eighty-two studies (46 quantitative, 31 qualitative, 5 mixed-methods) spanning 29 countries were included. Ninety percent of studies were from North America or Western Europe. The review findings indicate that young adolescents, across cultural settings, commonly express stereotypical or inequitable gender attitudes, and such attitudes appear to vary by individual sociodemographic characteristics (sex, race/ethnicity and immigration, social class, and age). Findings highlight that interpersonal influences (family and peers) are central influences on young adolescents’ construction of gender attitudes, and these gender socialization processes differ for boys and girls. The role of community factors (e.g. media) is less clear though there is some evidence that schools may reinforce stereotypical gender attitudes among young adolescents. Conclusions The findings from this review suggest that young adolescents in different cultural settings commonly endorse norms that perpetuate gender inequalities, and that parents and peers are especially central in shaping such attitudes. Programs to promote equitable gender attitudes thus need to move beyond a focus on individuals to target their interpersonal relationships and wider social environments. Such programs need to start early and be tailored to the unique needs of sub-populations of boys and girls. Longitudinal studies, particularly from low-and middle-income countries, are needed to better understand how gender attitudes unfold in adolescence and to identify the key points for intervention.