Prevalence of Autism Spectrum Disorder in 7-9-Year-Old Children in Denmark, Finland, France and Iceland: A Population-Based Registries Approach Within the ASDEU Project.

We estimated autism spectrum disorder (ASD) prevalence in 7-9 year-old children in 2015 using data from three nationwide health registry systems (Denmark, Finland, Iceland) and two French population-based regional registries. Prevalence ranged from 0.48% in South-East France to 3.13% in Iceland (South-West France: 0.73%, Finland: 0.77%, Denmark: 1.26%). Male/female ratios ranged from 3.3 in Finland to 5.4 in South-West France. Between 12% (Denmark) and 39% (South-West France) of cases were diagnosed with intellectual disability. The variations in population-based ASD prevalence across four European countries with universal health care practices likely reflect variation in detection, referral and diagnosis practices and autism awareness across these areas. Using established population-based data systems is an efficient approach to monitor ASD prevalence trends over time.

Hepatocellular carcinoma in patients with chronic hepatitis C and cirrhosis in Denmark: A nationwide cohort study.

Cirrhosis in patients with chronic hepatitis C increases the risk of hepatocellular carcinoma (HCC), and surveillance with ultrasound (US) and alpha-fetoprotein (AFP) is recommended. This study aimed to estimate changes in the HCC incidence rate (IR) over time, HCC stage and prognosis, and AFP and US performed in patients with hepatitis C and cirrhosis. Eligible patients were identified in the Danish Database for Hepatitis B and C, and data from national health registries and patient charts were obtained. Tumour stage was based on Barcelona-Clinic Liver Cancer stage, TNM classification and size and number of lesions combined into stages 0-3. We included 1075 patients with hepatitis C and cirrhosis, free of HCC and liver transplant at baseline. During 4988 person years (PY), 115 HCC cases were diagnosed. The HCC incidence rate increased from 0.8/100 PY [CI95% 0.4-1.5] in 2002-2003 to 2.9/100 PY [2.4-3.4] in 2012-2013. One-year cumulative incidence of at least one AFP or US was 53% among all patients. The positive predictive value of an AFP ≥ 20 ng mL-1 was 17%. Twenty-three (21%) patients were diagnosed with early-stage HCC (stage 0/1) and 84 (79%) with late stage. Median survival after HCC for early-stage HCC disease was 30.1 months and 7.4 months for advanced HCC (stage 2/3). The incidence rate of HCC increased over time among patients with hepatitis C and cirrhosis in Denmark. Application of AFP and US was suboptimal, and most patients were diagnosed with advanced HCC with a poor prognosis.

New interview and observation measures of the broader autism phenotype: impressions of interviewee measure.

A 20 item observational measure of social functioning, the Impression of Interviewee rating scale, is one of three measures devised to assess the broader autism phenotype. The sample studied included families containing at least two individuals with autism spectrum disorder; observations were undertaken by the researcher who interviewed the subject. An exploratory factor analysis suggested a single factor was most appropriate (Cronbach's α of 0.78). There was a modest but significant retest correlation of 0.42. Correlations between live ratings and blind consensus ratings of vignettes were high (0.93). Correlations with the interview measures were moderate but statistically significant. In conclusion, the observational scale provides a promising start but further work is required before general use can be recommended.

[A study on the abbreviated form of the Eysenck Personality Questionnaire Revised-Abbreviated (EPQR-A) in a student population]. / Étude du questionnaire de personnalité d'Eysenck révisé et abrégé (EPQR-A) dans une population d'étudiants.

The aim of this paper is to examine the short questionnaire of the Eysenck Personality Questionnaire Revised (the Eysenck Personality Questionnaire Revised-Abbreviated [EPQR-A]) among a student population. University students were invited, in groups, to fill in the forms proposed. Three sites were compared, representing a sample of 346 participants (Chambéry=118 subjects [44 males and 74 females]; Lille=110 subjects [50 males and 60 females] and Toulouse=118 subjects [60 males and 58 females]). The three groups of students have comparable scores on the EPQR-A wherever they live (Chambéry, Lille or Toulouse). Moreover, neither the age nor the gender allowed the detection of differences between subjects. Our sample of students is situated in the range of a "normal" group of students. Regarding the internal consistency coefficients, the French version we used of the neuroticism and the extraversion scales of the EPQR-A obtained a satisfactory result. The internal consistency coefficient of psychoticism was rather low (<70). This unsatisfactory level of internal reliability for the psychoticism is also found in the English version [7]. The four-factor model of the EPQR-A is judged to be an adequate explanation of the data. In the end, self-esteem correlated positively with extraversion and negatively with neuroticism. On the other hand, there is no link between psychoticism and self-esteem.

Combination of ammonia and xylanase pretreatments: impact on enzymatic xylan and cellulose recovery from wheat straw.

Soaking in aqueous ammonia (SSA) and/or xylanase pretreatments were developed on wheat straw. Both pretreatments were conducted at high-solids conditions: 15% and 20%, respectively, for SSA and xylanase pretreatments. SSA pretreatment led to the solubilisation of 38%, 12% and 11% of acid insoluble lignin, xylan and glucan, respectively. In case of xylanase pretreatment, 20% of xylan were removed from native wheat straw. When pretreatments were applied consecutively (SSA and xylanase) on straw, 56% of xylans were hydrolysed and a rapid reduction of media viscosity occurred. The enzymatic hydrolysis of cellulose with cellulases was evaluated from the different combinations of pretreated wheat straw. Cellulose hydrolysis was improved by 2.1, 2.2 and 2.9, respectively, for xylanase, SSA and SSA/xylanase pretreated straw. Xylans from untreated and pretreated wheat straws were also solubilised with cellulases. Chemical analysis of pretreated straw residues in connection with yields of cellulose hydrolysis highlighted the role of phenolic acids, acetyl content and cellulose crystallinity for cellulase efficiency.

[Clinical guidelines for the screening and the diagnosis of autism and pervasive developmental disorders]. / Recommandations pour la pratique clinique du dépistage et du diagnostic de l'autisme et des troubles envahissants du développement.

UNLABELLED: Autism is the best defined category among PDD. Its high prevalence, its onset in very young children and its persistence in adulthood arise many questions about early screening and early diagnosis. The aim of the study was to identify professional best practices about screening and diagnosis of autism in order to propose clinical guidelines and actions for the future. Scientific experts and parents take part to this procedure. Literature and previous guidelines were analyzed, experts in various fields were interviewed, a national study about the medical practices of the diagnosis of autism was made and questionnaires were send to 1600 psychiatrists and pediatricians. Guidelines built around 2 levels were proposed about screening and diagnosis. CONCLUSION: Diagnosis needs a multidisciplinary approach, validated instruments and more communication between professionals and parents. Finally one of the more important aims of the diagnosis of autism is to facilitate intervention program.

Resistance profiles and adherence at primary virological failure in three different highly active antiretroviral therapy regimens: analysis of failure rates in a randomized study.

OBJECTIVES: To investigate the interplay between resistance and adherence in the virological failure of three fundamentally different highly active antiretroviral therapy (HAART) regimens. METHODS: We retrospectively identified 56 verified primary virological failures (viral load >400 HIV-1 RNA copies/mL) among 293 patients randomized to two nucleoside reverse transcriptase inhibitors (NRTIs)+ritonavir+saquinavir (RS-arm) (n=115), two NRTIs+nevirapine+nelfinavir (NN-arm) (n=118), or abacavir+stavudine+didanosine (ASD-arm) (n=60) followed up for a median of 90 weeks. Data on adherence were collected from patient files, and genotyping was performed on plasma samples collected at time of failure. RESULTS: Treatment interruption or poor adherence was mainly caused by side effects and accounted for 74% of failures, and was associated with absence of resistance mutations. In the 30 failing patients not switched from randomized treatment, we found resistance in two of 12 patients in the RS-arm (M184 V only), four of six patients in the NN-arm [all four had non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations], and seven of 12 patients in the ASD-arm (NRTI mutations only). Two adherent patients on randomized treatment failed in the RS-arm, none in the NN-arm, and six in the ASD-arm. CONCLUSIONS: Primary virological failure was caused mainly by treatment interruption. No primary protease inhibitor (PI) mutations were found in patients failing on boosted saquinavir, whereas resistance to NNRTIs and NRTIs was prevalent in several patients failing on regimens based on these medications.

Drug resistance mutations and outcome of second-line treatment in patients with first-line protease inhibitor failure on nelfinavir-containing HAART.

OBJECTIVES: To determine resistance mutations emerging in HIV-1-infected patients experiencing their first protease inhibitor (PI)-failure on nelfinavir-containing highly active antiretroviral therapy (HAART), and to assess virological response to rescue regimens. METHODS: Plasma HIV-1 RNA from 24 patients failing nelfinavir-containing HAART was sequenced. Failure was defined as two consecutive measurements of viral load > 400 HIV-1 RNA copies/mL. Patients with previous failure on other PIs were excluded. Data on response to second-line treatment was extracted from patient files. RESULTS: At failure primary protease mutations were found in 14 patients (58%). Ten patients had D30N (38%), five patients had L90M (19%), two patients had V82A/F (8%) and two patients had M46I/L (8%). Two patients had both D30N and L90M. Pronounced increases of secondary protease mutations were seen at codon 88 (Delta: 33%), codon 36 (Delta: 30%) and codon 71 (Delta: 17%). Of eight patients with N88D, seven also harboured D30N (P < 0.01). Polymorphisms at codon 63 were detected at baseline in all patients who developed primary resistance mutations at failure (P < 0.01). On rescue regimens, 78% achieved viral loads below limit of detection (BLD). The presence of primary protease mutations was not associated with a higher risk of failure on second-line treatment. CONCLUSION: In patients failing nelfinavir-containing HAART, D30N was detected frequently and L90M occasionally. A pronounced accumulation of the secondary protease mutations N88D, M36I, and A71V/T was found, and D30N was strongly associated with N88D. A high proportion of patients became undetectable on second-line treatment and the presence of primary resistance mutations did not negatively affect the outcome of rescue regimens.

Virological and immunological profiles among patients with undetectable viral load followed prospectively for 24 months.

OBJECTIVE: To quantify HIV-RNA in plasma, in lymphoid tissue and proviral DNA in peripheral blood mononuclear cells and to relate these to immunological markers among patients with plasma viral load counts of /= 1 measurement with 21-200 and 25% had >/= 1 sample with plasma HIV-RNA > 200 copies/mL. Lymphoid tissue viral load was low at enrolment and declined further during follow-up. Baseline HIV-DNA and immunoglobulin (IgA) differed significantly between the plasma viral load rebound groups (P < 0.05). CONCLUSION: In this cohort, selected solely on the basis of having a plasma viral load of

Prevention and treatment of post-partum depression: a controlled randomized study on women at risk.

BACKGROUND: Research is needed to evaluate the efficacy of prevention and treatment for post-partum depression. METHOD: Subjects were screened with the Edinburgh Post-natal Depression Scale (EPDS) at the obstetric clinic. Mothers at risk (N = 258) (EPDS scores > or = 9) were randomly assigned to a prevention/treatment group or a control group. The prevention group received one cognitive-behavioural prevention session during hospitalization. At 4 to 6 weeks post-partum, subjects were screened again with the EPDS, after drop-out rates (refusals plus no return of the second EPDS) of 25.4% (33/130) in the intervention group and 10.9% (14/128) in the control group. Mothers with probable depression (EPDS scores > or = 11) were assessed using the Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory (BDI). Mothers with major depression continued in the treatment group (N = 18) or in the control group (N = 30). Treated subjects received a cognitive-behavioural programme of between five and eight weekly home-visits. RESULTS: Compared with the control group, women in the prevention group had significant reductions in the frequency of probable depression (30.2 % v. 48.2%). Recovery rates based on HDRS scores of < 7 and BDI scores of < 4 were also significantly greater in the treated group than in the control group. CONCLUSIONS: The study suggests that this programme for prevention and treatment of post-partum depression is reasonably well-accepted and efficacious.

[Detection, prevention and treatment of postpartum depression: a controlled study of 859 patients]. / Dépistage, prévention et traitement des dépressions du postpartum: une étude contrôlée chez 859 sujets.

This study evaluated the clinical effectiveness of a programme aimed at detecting, preventing and treating postpartum depression. The French version of the EPDS was used to measure the intensity of postpartum blues on a sample of 859 women, during their stay at the obstetrical clinic. Subjects under treatment for psychological problems were excluded from the study. Mothers scoring 9 or above on the EPDS, which is predictive of pospartum depression, were randomly assigned to a prevention and a control group. Written informed consent was obtained from the subjects after the study procedure had been explained. The prevention group received a counselling session integrating supportive, educational and cognitive-behavioral components. Therapists included five female Master's Degree level students in psychology. All therapists participated in didactic and clinical training as wells as weekly supervision from the first author. All subjects were given a second EPDS with written instructions to complete the questionnaire during the period 4 to 6 weeks postpartum and return it for analysis. At four to 6 weeks, women in the prevention group had significant reductions in the frequency of probable depression, as defined by a score of 11 or above on the EPDS (30.2% vs 48.2%, chi 2 = 7.36, dl = 1, p = 0.0067) and in the intensity of depressive symptoms measured by the mean score on the EPDS (8.5, SD = 4 vs 10.3, SD = 4.4, t = 3.06, dl = 209, p = 0.0024). Mothers with a probable depression were interviewed at home and assessed using the MINI (Mini Neuropsychiatric Interview, Lecrubier et al., 1997) to diagnose major depressive episode, the SIGH-D (Structured Interview Guide for the Hamilton Depression Rating Scale, Williams, 1988) and the BDI (Beck Depression Inventory, Beck et al., 1988). The baseline depression rating scores, EPDS (mean = 13.6, SD = 4), BDI (mean = 15.7, SD = 5.9), HDRS (mean = 14.8, SD = 6), were consistent with moderate depression. No significant differences in baseline scores were observed between the two groups on all the rating scales (p < 0.001). Mothers with probable depression in the prevention group were offered a program of 5 to 8 home visits. Most of the mothers in the prevention group (72%) agreed to participate in the program. On the contrary, most of the mothers (83.3%) who scored below 9 on the first EPDS and 11 or above on the second, who so did not received the preventive counselling session, declined to participate. This suggests the importance of the preventive session in establishing therapeutic alliance. The home visits program integrated four components, supportive, educational, cognitive-behavioral and psychodynamic centred on the mother-infant relationship in terms of the mother's personal history. Therapist participated in clinical training and weekly supervision. Fifteen women (71.4%) in the study group demonstrated complete symptom remission, as defined by HDRS score below 7 after the intervention, compared with 4 women (10.5%) in the control group (chi 2 = 23, p < 0.0001). A clearly therapeutic response to treatment was observed in the treated group with a mean reduction in HDRS score of 9.5 (DS = 6.7) from baseline. The improvement in the women in the treated group, as measured by the mean HDRS scores was statistically greater than that in the control group (m = 5.35, SD = 3.5 vs m = 15.8, SD = 4.6, t = 8.24, dl = 52, p < 0.0001). Our results indicate that a program based on an intervention at obstetrical clinics and on home visits is efficacious and well accepted for prevention, detection and treatment of postpartum depression.

Comparison of P-triglyceride levels among patients with human immunodeficiency virus on randomized treatment with ritonavir, indinavir or ritonavir/saquinavir.

This study compared the alterations in p-triglyceride (PT) in 111 protease inhibitor (PI)-naive patients on randomized treatment with either indinavir (800 mg 3 times daily), ritonavir (600 mg twice daily) or ritonavir/saquinavir (400 mg each twice daily) and 2 nucleoside reverse transcriptase inhibitors (NRTIs). PT (non-fasting) was measured at regular intervals until week 48. PT levels were evaluated in relation to PI regime, CD4 cell count and prior NRTI experience. The effect on PT levels of changing PI regime was analysed. For 24 patients fasting and non-fasting PT values were correlated. In the ritonavir-containing arms PT levels increased significantly (median PT at baseline: 1.80 mmol/l; week 36: 2.3 mmol/l; p < 0.001). In the indinavir arm no significant rise in PT levels was observed. Comparing the PI arms at week 48 showed significantly higher levels of PT in the ritonavir-containing arms than in the indinavir arm (p < 0.001). There was a high correlation between fasting and non-fasting PT values (p < 0.001, p = 0.88). A significant decline in PT values when changing PI treatment was observed (n = 13, p = 0.016). Ritonavir-containing regimens caused a rapid and sustained elevation of PT values, while indinavir did not significantly affect PT levels.

Influence of age on CD4 cell recovery in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy: evidence from the EuroSIDA study.

Influence of age on the CD4 cell response to highly active antiretroviral therapy (HAART) was examined in 1956 patients (median age, 37.2 years) in the EuroSIDA study. Median initial CD4 cell count was 192x106 cells/L, follow-up was 31 months, and time to maximum CD4 cell response was 20 months. Age groups were not different for baseline CD4 cell count, baseline human immunodeficiency virus RNA load, or treatment history. CD4 cell increase, stratified by age quartiles, differed during months 3-36 of HAART (P=.023). Maximum CD4 cell increase from start of HAART differed by age group (P=.0003), as did maximum CD4 cell count (P<10-4). Multivariate analysis confirmed the inverse relationship between age and maximum CD4 cell response (P=.023). Time to a CD4 increase of >200x106 cells/L was shorter for patients in the younger age groups (P=.0026), as confirmed by multivariate analysis (P<10-4). Younger age may favor CD4 cell restoration because of preserved thymic function.

The use of and response to second-line protease inhibitor regimens: results from the EuroSIDA study.

OBJECTIVE: To describe the use of second line protease-inhibitor (PI) regimens across Europe and to determine factors associated with virological and immunological response. DESIGN: Analysis of data from 984 patients with a median follow-up of 21 months enrolled in EuroSIDA. Patients started their second PI-containing regimen at least 16 weeks after starting the first PI-containing regimen and with viral load > 1000 copies/ml. METHODS: Virological response was defined as a viral load < 500 copies/ml and immunological response as an increase of 50 x 10(6)/l or more in CD4 lymphocyte count. RESULTS: The median CD4 cell count at starting the second PI was 171 x 10(6) cells/l; viral load was 4.45 log copies/ml. As a second PI regimen, 45% were using a dual PI, while of those on one PI, indinavir (42%) and nelfinavir (34%) were most common. In multivariate Cox models, a higher viral load at starting the second PI [relative hazard (RH), 0.67 per 1 log higher; 95% confidence interval (CI), 0.58-0.77; P < 0.0001) and a lower CD4 cell count (RH, 1.15 per 50% higher; 95% CI, 1.06-1.26; P = 0.0014) were associated with a reduced probability of virological response. Those who had achieved viral suppression on the first PI-regimen were more likely to respond to the second (RH, 1.65; 95% CI, 1.30-2.10; P < 0.0001) as were those who added one or two new nucleosides to their second PI. CONCLUSIONS: Patients who initiate a second PI regimen at lower viral load, higher CD4 cell count or who added new nucleosides tended to be more likely to achieve a viral load < 500 copies/ml. The roles of cross-resistance and adherence in response to second-line regimens needs further investigation.

Peripheral auditory asymmetry in infantile autism.

Difficulty in filtering relevant auditory information in background noise is one of the features of autism. Auditory filtering processes can be investigated at the peripheral level as they are hypothesized to involve active cochlear mechanisms which are regulated by the efferent activity of the medial olivocochlear (MOC) system. The aim of the present work was therefore to assess these peripheral auditory processes in 22 children and adolescents with autism compared with age- and gender-matched normal controls. Active cochlear mechanisms were evaluated with transiently evoked otoacoustic emissions (TEOAEs) and MOC system efficiency was assessed via TEOAEs which are decreased when stimulating the contralateral ear with noise. The MOC system evaluation was performed on 18 of the 22 children. In both studies, results were analysed according to age (from 4 to 10 years and from 11 to 20 years). The main result concerns the asymmetry of the efferent system which differs in individuals with autism. Several neural processes might be hypothesized as involved in the results obtained as the MOC system which originates in the brainstem received regulating controls from upper brain structures including auditory cortex. Lateralization abnormalities at the auditory periphery may reflect indirectly a problem at a higher level of auditory processing. A second important result shows a decrease in TEOAE amplitude with age, in patients, that may correspond to a decrease in hearing sensitivity.

Microcephaly and macrocephaly in autism.

Data from a series of 126 autistic children ages 2-16 years and referred to an Autism Diagnosis Unit in South-West France were examined. Macrocephaly (head circumference > 97th centile) was observed in 16.7% of the sample, a significantly higher proportion than that expected. Macrocephaly was more frequent among older subjects but was otherwise not associated with gender, developmental level, the presence of epilepsy or of medical disorders, or severity of autistic symptomatology. Microcephaly (head circumference < 3rd centile) was also significantly raised and found in 15.1% of the sample. Microcephaly was significantly associated with the presence of medical disorders. Results support those from recent studies suggesting a raised rate of macrocephaly in autism which, pooling published data, can be estimated to be 20%. It is argued that the raised incidence of microcephaly among low-functioning autistic subjects with medical disorders might have contributed to delay the recognition of an increased head circumference among a minority of subjects with idiopathic autism.

[Psychopharmacology of autism]. / Psychopharmacologie de l'autisme.

Results of recent studies in pharmacotherapy in autism are presented. Haloperidol, fenfluramine and naltrexone have been the most extensively studied drugs in systematic research. Haloperidol appeared to decrease levels of hyperactivity, stereotypies, emotional lability but also abnormal object relations and social withdrawal. However, the therapeutic effect was generally modest and long term administration was associated with dyskinesias in autistic children. The frequent hyperserotonemia in autism has suggested the use of fenfluramine, an antiserotoninergic agent. Although the initial reports were optimistic, more recent carefully designed studies often failed to show that fenfluramine was superior to placebo. Naltrexone, a potent opiate antagonist, was explored following the opioid hypothesis based on the similarity between autistic symptomatology and abnormal behaviors observed in opiate addicts and in laboratory animals administered opiates and on the abnormalities of endogenous opioids that exit in a subgroup of autistic children. However, the current studies do not concur and no definite conclusions can be made of the efficacy of naltrexone at present time. Low doses of amisulpride which have been shown to improve negative symptoms in schizophrenia and serotoninergic antidepressants, which have proven effective in repetitive and ritualized behaviors, have recently began to be evaluated in controlled studies. At present time, no medication has shown to alter the course or the symptoms of autism, but some seem to be effective in reducing severe aberrant behaviors.

School achievement in children with hypothyroidism detected at birth and search for predictive factors.

Neonatal screening of hypothyroidism started in 1975, and now sufficient hindsight is gained to assess school results in children with hypothyroidism and compare them to IQ tests. From the 85 cases of hypothyroidism detected in the Midi-Pyrénées area, 40 have enrolled in or finished primary school and 18 started secondary school. School achievement was assessed by school test results in French and mathematics using specific grids for each class and by retention rates. These results were compared to control groups. The hypothyroid group obtained identical results in French to those of the control groups but scored lower in mathematics. Grade retention rated higher in hypothyroid children (20%) than in the control groups (12.5%), especially in the first primary school grade. The search for predictive severity factors revealed significant differences between the grade repeater group and the nonrepeater group: more cases of athyrosis (75 vs. 25% for ectopia), lower T4 levels at birth, lower bone surface, lower IQ at 4 and 7 years, neurological troubles of fine motricity and coordination, and lower socioeconomic level. These results should shortly be taken into consideration in order to isolate a group at risk and undertake specialized care to improve school results in this group.