Measured moisture in buildings and adverse health effects: A review.

It has not yet been possible to quantify dose-related health risks attributable to indoor dampness or mold (D/M), to support setting specific health-related limits for D/M. An overlooked target for assessing D/M is moisture in building materials, the critical factor allowing microbial growth. A search for studies of quantified building moisture and occupant health effects identified 3 eligible studies. Two studies assessed associations between measured wall moisture content and respiratory health in the UK. Both reported dose-related increases in asthma exacerbation with higher measured moisture, with 1 study reporting an adjusted odds ratio of 7.0 for night-time asthma symptoms with higher bedroom moisture. The third study assessed relationships between infrared camera-determined wall moisture and atopic dermatitis in South Korea, reporting an adjusted odds ratio of 14.5 for water-damaged homes and moderate or severe atopic dermatitis. Measuring building moisture has, despite extremely limited available findings, potential promise for detecting unhealthy D/M in homes and merits more research attention. Further research to validate these findings should include measured "water activity," which directly assesses moisture availability for microbial growth. Ultimately, evidence-based, health-related thresholds for building moisture, across specific materials and measurement devices, could better guide assessment and remediation of D/M in buildings.

Utilisation d'une solution polyamphotère lors de lésions et brûlures chimiques oculaires cutanées et buccales. effet sur la douleur de la diphotérine®.

Polyamphoteric washing solutions (PWS) have been used for several years, mainly in industries, for cases of chemical ocular or cutaneous splashes by acid or alkali. We collected 37 cases reporting the use of PWS for ocular and cutaneous chemical splashes from several centres. Among the 37 cases, 55.26% resulted from occupational exposure. Among ocular exposures, initial clinical symptoms included pain (20 cases), blepharospasm (4 cases), hyperaemia (15 cases), palpebral oedema (2 cases) and blurred vision (7 cases). Among cutaneous exposures, 2 injuries were classified as deep, and 11 as superficial. Mean (SD) pain (VAS) before PWS was 6,29 +/- 2,74; mean (SD) pain after PWS was 1,47 +/- 1,73. Early application of PWS to the eye or skin reduces the intensity of pain that is associated with chemical damage. Early application of amphoteric solution appears to reduce the incidence of sequelae, provided its pre-hospital and hospital use is early. However, further studies are needed.

Development of a method to relate the moisture content of a building material to its water activity.

Subjective indicators of building dampness consistently have been linked to health, but they are, at best, semi-quantitative, and objective and quantitative assessments of dampness are also needed to study dampness-related health effects. Investigators can readily and non-destructively measure the "moisture content" (MC) of building materials with hand-held moisture meters. However, MC does not indicate the amount of the water in a material that is available to microorganisms for growth, that is, the "water activity" (Aw ). Unfortunately, Aw has not been readily measurable in the field and is not relatable to MC unless previously determined experimentally, because for the same moisture meter reading, Aw can differ across materials as well as during moisture adsorption vs desorption. To determine the Aw s that correspond to MC levels, stable air relative humidities were generated in a glove box above saturated, aqueous salt solutions, and the Aw of gypsum board and the relative humidity of the chamber air were tracked until they reached equilibrium. Strong correlations were observed between meter readings and gravimetrically determined MC (r=.91-1.00), among readings with three moisture meters (r=.87-.98), and between meter readings and gypsum board Aw (r=.77-.99).

Preoperative Staphylococcus aureus Carriage and Risk of Surgical Site Infection After Cardiac Surgery in Children Younger than 1 year: A Pilot Cohort Study.

Surgical site infections (SSI) increase length of stay, morbidity, mortality and cost of hospitalization. Staphylococcus aureus (SA) carriage is a known risk factor of SSI in adults, but its role in pediatrics remains uncertain. The main objective of this pilot prospective monocentric cohort study was to describe the prevalence of SA colonization in children under 1 year old before cardiac surgery. The secondary objectives were to compare the incidence of SSI and other nosocomial infections (NI) between preoperative carriers and non-carriers. From May 2012 to November 2013, all children <1 year old undergoing cardiac surgery under cardiopulmonary bypass underwent preoperative methicillin-resistant (MRSA) and methicillin-sensitive SA (MSSA) screening using real-time PCR. The only exclusion criterion was invalid PCR. All patients were followed up to 1 year after the surgery regarding SSI and other nosocomial infections. Among the 68 studied patients, SA colonization prevalence was 26.5%, comprising 23.5% MSSA and 2.9% MRSA. There was no significant difference between colonized and non-colonized children regarding SSI rate (16.7 vs 20%; p = 0.53), but ventilator-associated pneumonia rate was significantly higher among the SA carriers (22.2 vs 2%; p < 0.05). The colonization rate was different depending on the age of the patients (p < 0.05). This pilot study highlights that colonization with MSSA is frequent whereas MRSA prevalence is low in our population. In this cohort, there was no association between SA colonization and SSI incidence but further studies are needed to analyze this association.

Higher measured moisture in California homes with qualitative evidence of dampness.

Relationships between measured moisture and qualitative dampness indicators (mold odor, visible mold, visible water damage, or peeling paint) were evaluated using data collected from California homes in a prospective birth cohort study when the infants were 6 or 12 months of age (737 home visits). For repeated visits, agreement between observation of the presence/absence of each qualitative indicator at both visits was high (71-87%, P < 0.0001). Among individual indicators, musty odor and visible mold were most strongly correlated with elevated moisture readings. Measured moisture differed significantly between repeated visits in opposite seasons (P < 0.0001), and dampness increased with the number of indicators in a home. Linear mixed-effect models showed that 10-unit increases in maximum measured moisture were associated with the presence of 0.5 additional dampness indicators (P < 0.001). Bedroom (BR) walls were damper than living room (LR) walls in the same homes (P < 0.0001), although both average and maximum readings were positively correlated across room type (r = 0.75 and 0.67, respectively, both P < 0.0001). Exterior walls were significantly damper than interior walls (P < 0.0001 in both LRs and BRs), but no differences were observed between maximum wall readings and measurements at either window corners or sites of suspected dampness.

[Not Available]. / Épidémiologie descriptive de la brûlure dans un territoire de santé exemple du « territoire nord franche-comté ¼ durant l'année 2014.

This is an epidemiologic study of the need for Health Services for burns in the northern part of Franche Comté (north-east of France) along year 2014 (114 patients). Mean age was 26 years (8 month-81 years), one third of burns occurred in children below 15. Most burns take part in summer, around mealtime, in "school-free" days, at home and are scalds. Their surface is low (4,81%) and they are usually partial thickness ones. Patients are consulted in Emergency Department in 88,59% of the cases, and hospitalised thereafter in a Burns Unit (in Lyon more than Nancy or Metz) in 12,28%.

Next-generation DNA sequencing reveals that low fungal diversity in house dust is associated with childhood asthma development.

UNLABELLED: Dampness and visible mold in homes are associated with asthma development, but causal mechanisms remain unclear. The goal of this research was to explore associations among measured dampness, fungal exposure, and childhood asthma development without the bias of culture-based microbial analysis. In the low-income, Latino CHAMACOS birth cohort, house dust was collected at age 12 months, and asthma status was determined at age 7 years.The current analysis included 13 asthma cases and 28 controls. Next-generation DNA sequencing methods quantified fungal taxa and diversity. Lower fungal diversity (number of fungal operational taxonomic units) was significantly associated with increased risk of asthma development: unadjusted odds ratio(OR) 4.80 (95% confidence interval (CI) 1.04­22.1). Control for potential confounders strengthened this relationship. Decreased diversity within the genus Cryptococcus was significantly associated with increased asthma risk (OR 21.0, 95% CI 2.16­204). No fungal taxon (species, genus, class) was significantly positively associated with asthma development, and one was significantly negatively associated. Elevated moisture was associated with increased fungal diversity, and moisture/mold indicators were associated with four fungal taxa. Next-generation DNA sequencing provided comprehensive estimates of fungal identity and diversity, demonstrating significant associations between low fungal diversity and childhood asthma development in this community. PRACTICAL IMPLICATIONS: Early life exposure to low fungal diversity in house dust was associated with increased risk for later asthma developmen tin this low-income, immigrant community. No individual fungal taxon (species, genus, or class) was associated with asthma development, although exposure to low diversity within the genus Cryptococcus was associated with asthma development. Future asthma development studies should incorporate fungal diversity measurements, in addition to measuring individual fungal taxa. These results represent a step toward identifying the aspect(s) of indoor microbial populations that are associated with asthma development and suggest that understanding the factors that control diversity in the indoor environment may lead to public health recommendations for asthma prevention in the future.

Fungi and pollen exposure in the first months of life and risk of early childhood wheezing.

BACKGROUND: Many studies have found that the risk of childhood asthma varies by month of birth, but few have examined ambient aeroallergens as an explanatory factor. A study was undertaken to examine whether birth during seasons of elevated ambient fungal spore or pollen concentrations is associated with risk of early wheezing or blood levels of Th1 and Th2 type cells at 24 months of age. METHODS: 514 children were enrolled before birth and followed to 24 months of age. Early wheezing was determined from medical records, and Th1 and Th2 type cells were measured in peripheral blood using flow cytometry. Ambient aeroallergen concentrations were measured throughout the study period and discrete seasons of high spore and pollen concentrations were defined. RESULTS: A seasonal pattern was observed, with birth in autumn to winter (the spore season) associated with increased odds of early wheezing (adjusted odds ratio 3.1; 95% confidence interval 1.3 to 7.4). Increasing mean daily concentrations of basidiospores and ascospores in the first 3 months of life were associated with increased odds of wheeze, as were increasing mean daily concentrations of total and specific pollen types. Levels of Th1 cells at age 24 months were positively associated with mean spore concentrations and negatively associated with mean pollen concentrations in the first 3 months of life. CONCLUSIONS: Children with higher exposure to spores and pollen in the first 3 months of life are at increased risk of early wheezing. This association is independent of other seasonal factors including ambient levels of particulate matter of aerodynamic diameter

A positron emission tomography (PET) study of cerebral dopamine D2 and serotonine 5-HT2A receptor occupancy in patients treated with cyamemazine (Tercian).

RATIONALE: Cyamemazine (Tercian) is an antipsychotic drug with anxiolytic properties. Recently, an in vitro study showed that cyamemazine possesses high affinity for serotonin 5-HT(2A) receptors, which was fourfold higher than its affinity for dopamine D(2) receptors (Hameg et al. 2003). OBJECTIVES: The aim of this study is to confirm these previous data in vivo in patients treated with clinically relevant doses of Tercian. METHODS: Eight patients received 37.5, 75, 150 or 300 mg/day of Tercian depending on their symptomatology. Dopamine D(2) and serotonin 5-HT(2A) receptor occupancies (RO) were assessed at steady-state plasma levels of cyamemazine with positron emission tomography (PET), using [(11)C]raclopride and [(11)C]N-methyl-spiperone, respectively. The effective plasma level of the drug leading to 50% of receptor occupancy was estimated by fitting RO with plasma levels of cyamemazine at the time of the PET scan. RESULTS: Cyamemazine induced near saturation of 5-HT(2A) receptors (RO=62.1-98.2%) in the frontal cortex even at low plasma levels of the drug. On the contrary, occupancy of striatal D(2) receptors increased with plasma levels, and no saturation was obtained even at high plasma levels (RO=25.2-74.9%). The effective plasma level of cyamemazine leading to 50% of D(2) receptor occupancy was fourfold higher than that for 5-HT(2A) receptors. Accordingly, individual 5-HT(2A)/D(2) RO ratios ranged from 1.26 to 2.68. No patients presented relevant increased prolactin levels, and only mild extrapyramidal side effects were noticed on Simpson and Angus Scale. CONCLUSION: This in vivo binding study conducted in patients confirms previous in vitro findings indicating that cyamemazine has a higher affinity for serotonin 5-HT(2A) receptors compared to dopamine D(2) receptors. In the dose range 37.5-300 mg, levels of dopamine D(2) occupancy remained below the level for motor side effects observed with typical antipsychotics and is likely to explain the low propensity of the drug to induce extrapyramidal side effects.

Restless legs syndrome and low brain iron levels in patients with haemochromatosis.

Regional brain iron levels of two patients with haemochromatosis and severe restless legs syndrome (RLS) were assessed using R2' magnetic resonance imaging (MRI) sequences in both patients and in nine healthy controls. R2' relaxation rates in the patients were decreased in the substantia nigra, red nucleus, and pallidum when compared with the controls. These results indicate that local brain iron deficiency may occur in patients with haemochromatosis and suggest a role for brain iron metabolism in the pathophysiology of RLS.

Concentrations of airborne culturable bacteria in 100 large US office buildings from the BASE study.

UNLABELLED: This paper presents summary statistics of airborne culturable bacteria from the US Environmental Protection Agency Building Assessment Survey and Evaluation (BASE) study. Air samples were collected with single-stage, multiple-hole, agar impactors in 100 large office buildings in 1994-1998 to obtain normative data on indoor environmental quality. Bacterial concentrations were compared by incubation temperature, location, season, and climate zone. Forty-one percent of the samples were below the 2- or 5-min detection limits (18 or 7 CFU/m3, respectively) but less than 1% were overgrown. Mesophilic bacteria (30 degrees C) accounted for >95% of culturable bacteria, both indoors and outdoors. Average concentrations were higher outdoors, except for Gram-positive cocci, which were the only group that were significantly higher indoors (39 vs. 24 CFU/m3), and Gram-negative cocci, for which both concentrations were low and the difference were not significant. Outdoor concentrations of culturable bacteria were somewhat higher in winter (194 vs.165 CFU/m3), and the two dominant outdoor groups were unknown bacteria and Gram-positive rods. Conversely, indoor concentrations were significantly higher in summer (116 vs. 87 CFU/m3), consisting primarily of unknown bacteria and Gram-positive cocci. Bacterial concentrations were within the ranges reported in previous studies of non-problem buildings, and the extreme aggregated indoor concentrations (e.g. the 90th percentile, 175 CFU/m3) of these 100 representative buildings may serve as upper bounds to develop interpretation guidelines for office environments and similar non-manufacturing workplaces in various climate zones. PRACTICAL IMPLICATIONS: The Building Assessment Survey and Evaluation (BASE) study was one of the most comprehensive investigations of indoor environmental quality in which a standardized protocol was used to measure bioaerosols in 100 typical US office buildings. The information on the indoor and outdoor concentrations of airborne bacteria in different climate zones during the heating and cooling seasons has expanded the baseline data available for interpretation of measurements from building investigations. With suggested refinements, the BASE protocol may serve as a guide for future studies of bioaerosol concentrations, building characteristics, and occupant perceptions of the indoor environment.

Concentrations of cat and dust-mite allergens in dust samples from 92 large US office buildings from the BASE Study.

UNLABELLED: The concentrations of cat (Fel d1) and dust-mite (Der f1 and Der p1) allergens were measured in 92 large office buildings in the US Environmental Protection Agency's Building Assessment Survey and Evaluation (BASE) Study (251 dust samples; one to four samples per building). Fel d1 was detected in almost all buildings and samples (91 buildings, 99%; 235 samples, 94%; range: <0.01-19 microg/g; median: 0.3 microg/g). Cat allergen exceeded 1 microg/g (a lower symptom threshold) in 56 samples (22%) from 45 buildings, but exceeded 8 microg/g (a sensitization threshold) in only two samples (1%) from two buildings. Der f1 or Der p1 was found in approximately half of all buildings and samples (63 and 70% of buildings; 45 and 51% of samples; range: <0.01-53 microg/g and <0.01-25 microg/g; median: <0.02 and 0.03 microg/g, respectively). Mite allergen exceeded 2 microg/g (a sensitization threshold) in seven samples (3%) from five buildings and exceeded 10 microg/g (a symptom threshold) in three samples (1%) from three buildings. Fel d1 concentration was significantly higher in samples collected in summer (June to September, 48 buildings), but cat allergen was not correlated with either mite allergen. Der f1, but not Der p1, concentration tended to be higher in samples collected in winter (December to April, 44 buildings), and the two mite allergens were significantly correlated only in winter. Cat and mite allergens were detected in 78% of representative US office buildings, but the concentrations seldom exceeded levels associated with sensitization or symptom provocation. PRACTICAL IMPLICATIONS: The information on the concentrations of cat and dust-mite allergens in representative large US offices has expanded the baseline data available for interpretation of measurements from other building investigations. With suggested refinements, the BASE protocol for measurement of allergen concentrations in dust samples may serve as a guide to future studies of building characteristics, bioaerosol concentrations, and occupant perceptions of the indoor environment.

Long-term sequestration of fluorinated compounds in tissues after fluvoxamine or fluoxetine treatment: a fluorine magnetic resonance spectroscopy study in vivo.

Fluorine magnetic resonance spectroscopy (19F MRS), spectroscopic imaging (MRSI) and proton anatomical magnetic resonance imaging (1H MRI) were performed on brains and lower extremities of six subjects in vivo concurrently with HPLC of serum to investigate tissue and plasma drug localization and withdrawal kinetics in humans treated with fluvoxamine or fluoxetine. 19F MRS signal was unexpectedly detected in the lower extremities months after complete disappearance of signal from plasma and brain. MRSI suggested that the lower extremity fluvoxamine signal originated mainly from bone marrow. Results suggest long-term sequestration of these drugs or their metabolites mainly in bone marrow and possibly in surrounding tissue and demonstrate the usefulness of MRS to reveal drug-trapping compartments in the body.

[Development of compounds active in insomnia: recent developments and methodological aspects]. / Développement de molécules actives dans l'insomnie: actualités et aspects méthodologiques.

Most pharmacotherapeutic treatments designed to treat insomnia target GABAergic activity globally in the brain. Development of new molecules having a more specific activity pathway should improve treatment efficacy and acceptance. Both subjective and objective criteria are needed to study drug efficacy. Data regarding drug effects on polysomnographic recordings are mandatory for the development of hypnotics. Whether the drug-induced sleep is comparable to normal sleep is tackled with the spectral analysis of the sleep EEG. Residual drug effects are assessed with a package of psychomotor and neurocognitive tests, and with the driving simulator test Clinical studies investigating drug efficacy and tolerability have to be conducted on large groups of patients carefully selected using polysomnographic recordings. Our knowledge about sleep will undoubtedly soon become available for treatment of insomnia.

[Personality changes in opioid-dependent subjects in a methadone maintenance treatment program]. / Changements psychologiques au cours d'un traitement de substitution de méthadone, mesurés par l'Inventaire de Personnalité d'Eysenck.

Personality disorders and particularly antisocial personality disorders (APD) are quite frequent in opioid-dependent subjects. They show various personality traits: high neuroticism, high impulsivity, higher extraversion than the general population. Previous studies have reported that some but not all personality traits improved with treatment. In a previous study, we found a low rate of APD in a French population of opioid-dependent subjects. For this reason, we evaluated personality traits at intake and during maintenance treatment with methadone. Methods - The form A of the Eysenck Personality Inventory (EPI) was given to opioid addicts at intake and after 6 and 12 months of methadone treatment. Results - 134 subjects (96 males and 38 females) took the test at intake, 60 completed 12 months of treatment. After 12 months, the EPI Neuroticism (N) and the Extraversion-introversion (E) scale scores decreased significantly. The N score improved in the first 6 months, while the E score improved only during the second 6 months of treatment. Compared to a reference group of French normal controls, male and female opioid addicts showed high N and E scores. Demographic data and EPI scores of patients who stayed in treatment for 12 months did not differ significantly from those of dropouts (n=23). Patients with a history of suicide attempts (SA) started to use heroin at an earlier age and they showed a higher E score and a tendency for a higher N score at intake. Discussion - The two personality dimensions of the EPI changed during MMT, and the N score converged towards the score of normal controls. Opioid addicts differ from normal controls mostly in their N score. The EPI did not help to differentiate 12-month completers from dropouts. Higher E scores in patients with an SA history might reflect a higher impulsivity, which has been linked to suicidality in other patient groups.

[Pilot study comparing in blind the therapeutic effect of two doses of agomelatine, melatonin- agonist and selective 5HT2c receptors antagonist, in the treatment of major depressive disorders]. / Etude pilote comparant en aveugle l'effet thérapeutique de deux doses d'agomélatine, agoniste des récepteurs de la mélatonine et antagoniste des récepteurs 5HT2C, chez 30 patients présentant un épisode dépressif majeur.

RATIONALE AND METHOD: Two doses of agomelatine (S-20098), a novel potential antidepressant drug with a new pharmacological profile (melatonin agonist and selective 5HT2C antagonist), were compared in a double-blind, randomised, pilot study in order to estimate the antidepressant activity shown in preclinical data. Inpatients suffering from major depressive disorder (DSM III-R criteria) and presenting a minimal score of 25 for MADRS were selected at D-7. After one week of run-in placebo treatment, included patients received one evening dose of agomelatine (either 5 or 100 mg) for 4 to 8 weeks. Hospitalization was required at least for the first 3 weeks. Patients presenting a satisfying response to treatment (MADRS total score < 15 or decrease > or = 40% from inclusion score) could be treated as outpatients. A follow up of 2 weeks was performed after stopping the treatment. The total duration of the treatment period could vary, according to investigator's decision, between 7 and 11 weeks. Evaluation criteria included MADRS, HAMD-17, HAM-A, CGI and AMDP 5 at D0, D7, D14 and D28, and, when applicable, at D35, D42, D49 and D56. Safety evaluations included recording of adverse events, ECG monitoring and biology. RESULTS: Thirty inpatients were selected and 28 included (14 per group). There was no major difference between groups at inclusion, neither for demographic nor evaluation criteria. One patient of each group was excluded of the ITT analysis; 19 patients completed the mandatory period up to D28: 10 in the 5 mg group and 9 in the 100 mg group; 10 patients (5 in each group) carried on the study during the optional period, up to D56 for 7 out of them (4 in the 5 mg group, 3 in the 100 mg group). Efficacy criteria showed a significant improvement in both groups, with highly significant within group evolutions (p < 0.001 whatever the criteria) and without significant difference between groups. However, better results were observed in the 5 mg group compared to the 100 mg group. Total MADRS scores then decreased from 30.7 +/- 3.5 to 14.8 +/- 6.4 in the 5 mg group vs a decrease from 31.6 +/- 4.7 to 18.6 +/- 14.8 in the 100 mg group. Furthermore, significant improvement between D14 and D28 visits were only seen in the 5 mg group. Analysis of somatic complaints (AMDP 5) showed with both treatments a strong decrease of symptoms during the study, especially for items related to sleep disorders (difficulties in falling asleep, interrupted sleep, shortened sleep, early wakening and drowsiness). Acceptability was good for both doses of agomelatine. However, there were slightly more emergent adverse events and severe treatment-related adverse events in the 100 mg group. No modifications of cardio-vascular parameters nor biological abnormalities were observed in both groups. CONCLUSION: Preliminary clinical data with agomelatine confirm the potential antidepressant effect in accordance with positive preclinical results. There was no significant difference between 5 and 100 mg, both for efficacy and for safety. However, the data suggest that 5 mg could be a dose at least as effective and slightly better tolerated than 100 mg. Further double-blind controlled studies versus active comparators and placebo are required in order to confirm these results.

Characterization of the CNS effects of naftidrofuryl (Praxilène) by quantitative EEG and functional MRI: a study in healthy elderly subjects.

In the present study, we investigated the effects of a single and a repeated (5 days) administration of naftidrofuryl, a serotonin 5-HT2 receptor inhibitor having neuroprotective properties, on functional brain physiology in male healthy elderly subjects, using quantitative electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Twelve subjects aged 60 +/- 3.8 years completed the quantitative EEG study, where the effects of 400 and 600 mg were assessed, and 12 other subjects (aged 56 +/- 4.7 years) completed the fMRI study, where the effect of 400 mg was assessed on the brain activation induced by the continuous performance test (CPT). Naftidrofuryl induced a transient reduction in alpha activity followed by a specific synchronisation of the 9.5- to 11-Hz EEG activity most pronounced after repeated administration. Such regimen also increased the CPT-induced brain activation visualized by way of fMRI. The results of the present study can be interpreted at the functional level that naftidrofuryl induced an improved level of vigilance or an increased capacity of alertness in healthy elderly subjects.

Disturbances in hypothalamo pituitary adrenal and thyroid axis identify different sleep EEG patterns in major depressed patients.

This study was aimed at investigating the relationships between sleep EEG abnormalities and hypothalamo pituitary adrenal (HPA) and hypothalamo pituitary thyroid (HPT) disturbances in major depressive disorder. Post dexamethasone (DXM) cortisol levels and the dual TSH response to 08:00 h and 23:00 h TRH administration were determined after a 2 weeks wash-out period in a group of 113 DSM-IV major depressed patients (72 females aged 44.3+/-13.0 and 41 males aged 45.7+/-11) who were consecutively admitted to undergo sleep EEG recordings. Post-DXM cortisolemia, 08:00 and 23:00 post-TRH TSH values, time spent in rapid eye movement sleep (REMS), in slow wave sleep (SWS), and in stage 2 as well as time awake after sleep onset were introduced in a principal component (PC) analysis. The four 3 PC scores explaining up to 74% of the data set were further calculated for each patients and used in a cluster analysis. A three-cluster solution was retained. Controlling for the effects of age and gender, patients belonging to these three clusters could clearly be differentiated on the basis of their neuroendocrine responses and on their sleep EEG profiles. Compared to the two other clusters, cluster I (n=26) patients showed the most severe sleep continuity disturbances. Post-DXM cortisol escape and sleep architecture disturbances (consisting of a shortening of REMS latency and a decreased SWS) identified patients belonging to cluster II (n=39). Patients in cluster III (n=48) had the lowest TSH response to TRH and the less marked sleep EEG alteration. Clinical or demographic variables were unable to differentiate the three clusters. Our results suggest that different biological dysfunctions could each underlie particular neuroendocrine and sleep EEG disturbances in major depression.

[The impact of substitution treatment by methadone among opiate-dependent subjects evaluated by Addiction Severity Index and by urine tests]. / Impact d'un traitement de substitution par méthadone sur des sujets dépendants aux opiacés évalué par l'Addiction Severity Index et des contrôles urinaires.

Methadone maintenance treatment (MMT) has been evaluated in the United States and in a few other countries. MMT has been developed in France since 1995, and over 5 000 patients receive this treatment. However no French study has yet been published on the efficacy of MMT as assessed by a validated scale. Retention in treatment for one year has been considered as a threshold to define maintenance of treatment benefits after discharge from a methadone program; determination of retention predictors is important. Over a three year period, we evaluated patients at admission and during treatment using the Addiction Severity Index (ASI), and urine drug screening was performed weekly; 95 patients (66 males and 29 females) were evaluated at intake. Their mean age was 30.2 5.5, and they had used opioids for a mean of 10.6 5.7 years. Their ASI severity scores for drugs were over 5, showing a clear need for treatment. Female patients differed from males only in the employment-finances ASI score; 43 patients completed at least one year of treatment, after which their drug and legal composite scores significantly improved. No significant changes in their consumption of cocaine, alcohol, benzodiazepines or cannabis were found, but they smoked fewer cigarettes at 12 months. Demographics, ASI severity scores, and history of suicide attempts did not differentiate one-year completers from dropouts (n=16). However, dropouts had used more buprenorphine and less methadone in the 30 days preceding their admission, and they received a lower dose of methadone during treatment. Our population is comparable to other French MMT populations; they enter treatment after a long history of opioid dependence. The improvement found on the ASI composite scores is also similar to the improvement described in other international studies. Dropouts in our study seem to be more treatment-resistant patients, in the sense that they had used more buprenorphine before intake and were not stabilized with it; and they may have had a more negative attitude towards methadone.

[Pilot study comparing in blind the therapeutic effect of two doses of agomelatine, melatoninergic agonist and selective 5HT2C receptors antagonist, in the treatment of major depressive disorders]. / Etude pilote comparant en aveugle l'effet thérapeutique de deux doses d'agomélatine - agoniste des récepteurs de la mélatonine et antagoniste des récepteurs 5HT2c - chez 30 patients.

Rational and method - Two doses of agomelatine (S-20098), a novel potential antidepressant drug with a new pharmacological profile (melatonin agonist and selective 5HT2C antagonist -MASSA), were compared in a double-blind, randomised, pilot study in order to estimate the antidepressant activity shown in preclinical data. Inpatients suffering from major depressive disorder (DSM III-R criteria) and presenting a minimal score of 25 for MADRS were selected at D -7. After one week of run-in placebo treatment, included patients received one evening dose of agomelatine (either 5 or 100 mg) for 4 to 8 weeks. Hospitalization was required at least for the first 3 weeks. Patients presenting a satisfying response to treatment (MADRS total score<15 or decrease 40% from inclusion score) could be treated as outpatients. A follow up of 2 weeks was performed after stopping the treatment. The total duration of the treatment period could vary, according to investigator's decision, between 7 and 11 weeks. Evaluation criteria included MADRS, HAMD-17, HAM-A, CGI and AMDP 5 at D0, D7, D14 and D28, and, when applicable, at D35, D42, D49 and D56. Safety evaluations included recording of adverse events, ECG monitoring and biology. Results - Thirty inpatients were selected and 28 included (14 per group). There was no major difference between groups at inclusion, neither for demographic nor evaluation criteria. One patient of each group was excluded of the ITT analysis; 19 patients completed the mandatory period up to D28: 10 in the 5 mg group and 9 in the 100 mg group; 10 patients (5 in each group) carried on the study during the optional period, up to D56 for 7 out of them (4 in the 5 mg group, 3 in the 100 mg group). Efficacy criteria showed a significant improvement in both groups, with highly significant within group evolutions (p<0.001 whatever the criteria) and without significant difference between groups. However, better results were observed in the 5 mg group compared to the 100 mg group. Total MADRS scores then decreased from 30.7 3.5 to 14.8 6.4 in the 5 mg group vs a decrease from 31.6 4.7 to 18.6 14.8 in the 100 mg group. Furthermore, significant improvement between D14 and D28 visits were only seen in the 5 mg group. Analysis of somatic complaints (AMDP 5) showed with both treatment a strong decrease of symptoms during the study, especially for items related to sleep disorders (difficulties for falling asleep, interrupted sleep, shortened sleep, early wakening and drowsiness). Acceptability was good for both doses of agomelatine. However, there were slightly more emergent adverse events and severe treatment-related adverse event in the 100 mg group. No modifications of cardio-vascular parameters nor biological abnormalities were observed in both groups. Conclusion - Preliminary clinical data with agomelatine confirm the potential antidepressant effect in accordance with positive preclinical results. There was no significant difference between 5 and 100 mg, both for efficacy and for safety. However, the data suggest that 5 mg could be a at least as effective and slightly better tolerated dose than 100 mg. Further double-blind controlled studies versus active comparators and placebo are required in order to confirm these results.