Prediction of lithium response using clinical data.

OBJECTIVE: Promptly establishing maintenance therapy could reduce morbidity and mortality in patients with bipolar disorder. Using a machine learning approach, we sought to evaluate whether lithium responsiveness (LR) is predictable using clinical markers. METHOD: Our data are the largest existing sample of direct interview-based clinical data from lithium-treated patients (n = 1266, 34.7% responders), collected across seven sites, internationally. We trained a random forest model to classify LR-as defined by the previously validated Alda scale-against 180 clinical predictors. RESULTS: Under appropriate cross-validation procedures, LR was predictable in the pooled sample with an area under the receiver operating characteristic curve of 0.80 (95% CI 0.78-0.82) and a Cohen kappa of 0.46 (0.4-0.51). The model demonstrated a particularly low false-positive rate (specificity 0.91 [0.88-0.92]). Features related to clinical course and the absence of rapid cycling appeared consistently informative. CONCLUSION: Clinical data can inform out-of-sample LR prediction to a potentially clinically relevant degree. Despite the relevance of clinical course and the absence of rapid cycling, there was substantial between-site heterogeneity with respect to feature importance. Future work must focus on improving classification of true positives, better characterizing between- and within-site heterogeneity, and further testing such models on new external datasets.

Quality of life in bipolar disorder: towards a dynamic understanding.

BACKGROUND: Although quality of life (QoL) is receiving increasing attention in bipolar disorder (BD) research and practice, little is known about its naturalistic trajectory. The dual aims of this study were to prospectively investigate: (a) the trajectory of QoL under guideline-driven treatment and (b) the dynamic relationship between mood symptoms and QoL. METHODS: In total, 362 patients with BD receiving guideline-driven treatment were prospectively followed at 3-month intervals for up to 5 years. Mental (Mental Component Score - MCS) and physical (Physical Component Score - PCS) QoL were measured using the self-report SF-36. Clinician-rated symptom data were recorded for mania and depression. Multilevel modelling was used to analyse MCS and PCS over time, QoL trajectories predicted by time-lagged symptoms, and symptom trajectories predicted by time-lagged QoL. RESULTS: MCS exhibited a positive trajectory, while PCS worsened over time. Investigation of temporal relationships between QoL and symptoms suggested bidirectional effects: earlier depressive symptoms were negatively associated with mental QoL, and earlier manic symptoms were negatively associated with physical QoL. Importantly, earlier MCS and PCS were both negatively associated with downstream symptoms of mania and depression. CONCLUSIONS: The present investigation illustrates real-world outcomes for QoL under guideline-driven BD treatment: improvements in mental QoL and decrements in physical QoL were observed. The data permitted investigation of dynamic interactions between QoL and symptoms, generating novel evidence for bidirectional effects and encouraging further research into this important interplay. Investigation of relevant time-varying covariates (e.g. medications) was beyond scope. Future research should investigate possible determinants of QoL and the interplay between symptoms and wellbeing/satisfaction-centric measures of QoL.

Vulnerability of CMOS image sensors in Megajoule Class Laser harsh environment.

CMOS image sensors (CIS) are promising candidates as part of optical imagers for the plasma diagnostics devoted to the study of fusion by inertial confinement. However, the harsh radiative environment of Megajoule Class Lasers threatens the performances of these optical sensors. In this paper, the vulnerability of CIS to the transient and mixed pulsed radiation environment associated with such facilities is investigated during an experiment at the OMEGA facility at the Laboratory for Laser Energetics (LLE), Rochester, NY, USA. The transient and permanent effects of the 14 MeV neutron pulse on CIS are presented. The behavior of the tested CIS shows that active pixel sensors (APS) exhibit a better hardness to this harsh environment than a CCD. A first order extrapolation of the reported results to the higher level of radiation expected for Megajoule Class Laser facilities (Laser Megajoule in France or National Ignition Facility in the USA) shows that temporarily saturated pixels due to transient neutron-induced single event effects will be the major issue for the development of radiation-tolerant plasma diagnostic instruments whereas the permanent degradation of the CIS related to displacement damage or total ionizing dose effects could be reduced by applying well known mitigation techniques.

Experimental strength of restorations with fibre posts at different stages, with and without using a simulated ligament.

The aim of this study was to analyse the strength and failure mode of teeth restored with fibre posts under retention and flexural-compressive loads at different stages of the restoration and to analyse whether including a simulated ligament in the experimental setup has any effect on the strength or the failure mode. Thirty human maxillary central incisors were distributed in three different groups to be restored with simulation of different restoration stages (1: only post, 2: post and core, 3: post-core and crown), using Rebilda fibre posts. The specimens were inserted in resin blocks and loaded by means of a universal testing machine until failure under tension (stage 1) and 50º flexion (stages 2-3). Half the specimens in each group were restored using a simulated ligament between root dentine and resin block and the other half did not use this element. Failure in stage 1 always occurred at the post-dentine interface, with a mean failure load of 191·2 N. Failure in stage 2 was located mainly in the core or coronal dentine (mean failure load of 505·9 N). Failure in stage 3 was observed in the coronal dentine (mean failure load 397·4 N). Failure loads registered were greater than expected masticatory loads. Fracture modes were mostly reparable, thus indicating that this post is clinically valid at the different stages of restoration studied. The inclusion of the simulated ligament in the experimental system did not show a statistically significant effect on the failure load or the failure mode.

Influence of material and diameter of pre-fabricated posts on maxillary central incisors restored with crown.

Numerous research works have studied the effect of post-design parameters on the mechanical behaviour of restored teeth without reaching any clear conclusions. Previous works by the authors ascertained the effect of material and post-dimensions for non-crowned restored teeth. The aim of this work was to study the effect of post-material and diameter for crowned teeth. First, an experimental fracture strength test was performed on eighteen extracted human maxillary central incisors. Teeth were decoronated, treated endodontically and restored (nine with glass fibre posts and nine with stainless steel posts). Several post-diameters were used. The final crown restoration was carried out using a reinforced glass-ceramic material. Failure loads were recorded and results were compared using the one-way anova. Secondly, the finite element technique was used to model the restored teeth and to compare the estimated stress distributions. The addition of the crown did not affect the strength of the restoration to any significant extent and post-diameter did not influence the biomechanical performance of either of the post-systems. The crown acts as a protector, thus eliminating the influence of the post-diameter that was found previously when using stainless steel posts, but it does not completely rule out the possibility of a root fracture. Significantly, lower failure loads were found experimentally for teeth restored with stainless steel posts. The stress distributions predicted by the model corroborated these findings and allowed the authors to propose the use of glass fibre posts as a more robust restorative technique.

Kinematics reduction applied to the comparison of highly-pronated, normal and highly-supinated feet during walking.

BACKGROUND: Kinematic analysis could help to study how variations in the static foot posture affect lower limb biomechanical function. The analysis of foot kinematics is complex because it involves managing the time-dependent joint angles in different joints and in all three planes of motion. But it could be simplified if joint angles are coordinated. METHODS: The kinematics of the ankle, midtarsal and metatarsophalangeal joints were registered in 20 highly-pronated, 30 normal and 20 highly-supinated subjects (assessed by the Foot Posture Index - FPI) as they walked barefoot. Coordination for each sample was analysed through principal component analysis applied to the dorsiflexion, abduction and inversion angles measured. Finally, a systematic comparison among the samples was performed through a set of ANOVAs applied to the reduced variables corresponding to the factors found. RESULTS: Three principal components (coordination patterns) accounted for about 70% of the variance of the joint angles, and were affected by the FPI. The main coordination in normal feet was the supination movement, while in highly-supinated and highly-pronated feet it was the flexion coordination of all foot joints, which could work against adaptation in cases of varying terrain. The original joint angles were reduced to three factors, and the ANOVAs applied to them showed that highly-pronated feet presented a delayed propulsion peak and smaller ranges of motion during propulsion regarding all factors, and that highly-supinated feet require more pronation time to fully support the foot during walking. SIGNIFICANCE: The coordination patterns of normal feet might be considered the normal patterns used for an efficient gait, and may help in planning surgical procedures and designing foot prostheses or orthotics. Dimensional reduction makes it possible to perform more systematic kinematic analyses, which have revealed that highly-pronated feet are in poorer propulsive condition, and this in turn may make them more prone to injury.

[Cohort of patients initiated to home ventilation. Observational and prospective study]. / Cohorte de patients nouvellement traités par ventilation non invasive à domicile. Étude observationnelle, prospective et multicentrique.

Cohort of patients initiated to home ventilation. Observational and prospective study. The effectiveness of home noninvasive ventilation (NIV) for chronic respiratory failure (CRF) is well established. However, few data are available about home NIV prescription and utilization according to the different etiologies of respiratory failure. The ANTADIR Federation, in partnership with the Ventilatory Support Group of the French Speaking Pulmonary Society, has set up a national, observational and multicenter cohort study. The main goal of this study is to analyze the clinical data justifying home NIV prescription in patients with chronic respiratory insufficiency. The secondary objectives will be to assess: the evolution of comorbidities or their occurrence, hospitalizations, NIV compliance, dropout and survival. The population includes patients with chronic respiratory failure newly initiated onto NIV, both in a stable state and following an acute exacerbation who qualify for long-term NIV. Data collected include: diagnosis and comorbidities, age, sex, BMI, biomarkers (hematocrit, arterial blood gases, total CO2) and functional data (FEV1, VC, TLC), nocturnal results (SaO2, PtcCO2), type of ventilator used, ventilator parameters and mask type. Follow-up data will be collected at 4 months, 1 year and 2 years and will include: hospitalizations, changes in prescription, adherence, dropouts and deaths. This work will make it possible to obtain new scientific information on long-term NIV use in France.

Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia.

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10-7) and PKP4 (P=8.67 × 10-7); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, PFDR=0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [P=2.99 × 10-3]), SCZ (rg=0.34 [P=4.37 × 10-5]) and MDD (rg=0.57 [P=1.04 × 10-3]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.

Influence of prefabricated post material on restored teeth: fracture strength and stress distribution.

AIMS: This work studied how prefabricated intraradicular post material affects the mechanical performance of restored teeth. The effect of using two different materials (glass fiber and stainless steel) with significantly different elastic moduli was studied. METHODS: A combined theoretical and experimental method was used: first, an experimental fracture strength test was performed on 60 extracted human maxillary central incisors. The teeth were decoronated, treated endodontically and restored, 30 with glass fiber posts and 30 with stainless steel posts. The data were recorded and the results compared using an ANOVA test. Then, the finite element technique was used to develop a model of the restored tooth. For both post systems, the model allowed for the study of stress distribution patterns on the restored tooth under external loads. RESULTS: For teeth restored with stainless steel posts, a significantly lower failure load was found, as compared with those teeth restored with glass fiber posts (520 N versus 803 N). The estimated distributions confirmed a worse mechanical performance on teeth restored using stainless steel posts, with a high stress concentration due to the significant difference between the elastic moduli of the steel and the surrounding materials. CONCLUSION: Within the limitations of this study, post systems, where the elastic modulus of the post is similar to that of dentin and core, have a better biomechanical performance.

Vitamin B12 and folate levels and lithium administration in patients with affective disorders.

BACKGROUND: It is unclear whether there is a relationship between lithium administration and vitamin B12 metabolism. METHODS: We compared serum B12, serum folate, and red blood cell folate concentrations in patients receiving and not receiving lithium at two Mood Disorders Clinics. As the two centers differed in vitamin assay methods, data were first analyzed separately and then combined. To rule out an in vitro effect of lithium on the assays, we also added varying amounts of lithium to lithium-free blood samples and measured vitamin concentrations. RESULTS: Mean serum B12 concentrations were approximately 20% lower in the lithium than in the nonlithium group at each center. This difference was statistically significant for each center and on combination (two-tailed p = .017, .021, and .0009). The parametric effect size for each center and the combined weighted mean effect size were moderate in magnitude (.605, .523, and .565). There was a nonsignificant trend toward an increased prevalence of assay-defined B12 deficiency in the lithium group at one center only, with no cases in either group at the other center and a nonsignificant combined relative risk. CONCLUSIONS: Our data may represent a lithium-associated decrease in serum B12 concentration. The clinical significance of these findings is not yet clear.

Effects of clinical audit on the quality of care in patients with type 2 diabetes: results of the DIABEST pilot study.

OBJECTIVE: To improve the quality of diabetes care in general practice by the use of audit. MATERIAL AND METHODS: A prospective multicenter pilot study. Thirty-five groups of ten general practitioners (GPs) have been set up throughout France on a voluntary basis. These groups were led by a steering committee that includes a diabetologist and a GP. Each group established a consensus on healthcare standards and carried out 2 data collections over a 12-month period, with adoption of corrective measures between these 2 collections. RESULTS: 309 (90.4%) of the 342 practitioners completed the first data collection, assessing the management of 3,125 patients over a year. Less than half the groups have reached the 80% reference threshold for quality of care with regard to foot examination, microalbuminuria, ECG, fundoscopy and assessment of diet. The audit also found no intervention within one year in case of poor glucose control for 47% of patients, unsatisfactory quality of HbA(1c) measurement and insufficient resources for diet and education. 226 (66.1%) practitioners completed the second data collection assessing the management of 2,248 patients. Comparison between the two phases of the audit showed significant improvements for all the indicators of the process of care (p<0.001). Quality of HbA(1c) measurement and diet assessment by GPs progressed (p<0.01). Outcomes of care also improved with respect to the proportion of patients with HbA(1c)<=8% (p=0.007), fasting glycaemia<1.40 g/l (p=0.05) and SBP<140 mmHg (p=0.02). CONCLUSIONS: This pilot study confirms the feasibility of using clinical audit at the national level. It seems to be an effective measure to improve the management of patients with type 2 diabetes in primary care. It is intended that the large-scale DIABEST study will address this issue.

[Value of plethysmography in the respiratory function evaluation of coal miners in Lorraine]. / Intérêt de la phéthysmographie dans le bilan fonctionnel respiratoire du mineur de charbon lorrain.

The results of body plethysmography in 607 coalminers from Lorraine, France, are analysed. The relationship between radiological aspects and tobacco consumption are discussed. When progressive massive fibrosis (PMF) is absent, total lung capacity (TLC) and slow vital capacity (VC) are related with profusion, but remain independant of X-ray type and tobacco consumption. Tobacco alters flows and FEV1/VC results. A 20% incidence of residual volume (RV) inflation is observed unrelated to X-ray aspect. When PMF is present, TLC results are more contrasted (8.9% restrictive defects, 5.7% hyperinflation) and obstructive pattern follows X-ray progression. Tobacco consumption induces more RV and functional residual capacity inflation. These results strongly support the fact that the effects of dust exposure vary with smoking. Consequently, the interactions between pneumoconiotic fibrosis and distension appear to be reflected by plethysmography. This method is useful for determining each functional pattern. It may also be of pronostic value but this needs to be confirmed by further studies.

[Secretion of growth hormone in men and women during the reproductive age, in aged men and menopausal women with or without estrogens or progesterone]. / Secreción de hormona del crecimiento en hombres y mujeres en edad fértil, hombres seniles y mujeres postmenopáusicas con y sin estrógenos o progesterona.

PIP: Apomorphine hydrochloride 0.75 mcg subcutaneously was given to 39 men and 36 women, 18-66 years of age, and the seric concentration of growth hormone was measured. All the men showed a maximal concentration over 6 mcg/l in a total of 61 tests; while in 16 of 58 tests in women, maximal concentration was less than 6 mcg/1. Senile men had a significantly greater response of growth hormone than premenopausal and postmenopausal women. There was no significant correlation between maximal concentration and the age in men and women. There was no significant difference in maximal growth hormone concentration for men ages 24-42 and men 45-66 years of age. However, there was a trend for high levels in young men and a significantly greater concentration 60 minutes after apomorphine administration (but not at 30 and 45 minutes) in young men as compared with older men. There was no difference in secretory response to apomorphine in premenopausal and postmenopausal women. After mestranol administration (0.08 mcg orally, 3 times/day for 3 days) to 6 postmenopausal women, there was a significant increase in the secretory response of growth hormone to apomorphine. Progesterone (250 mg intramuscularly for 3 days) does not antagonize growth hormone secretion induced by apomorphine in postmenopausal women. (author's)^ieng

[Nontumoral nervous complications of bronchial cancer]. / Les complications nerveuses non tumorales du cancer bronchique.

The authors present 52 cases of neurological complications of bronchial cancer including 35 cases of non-tumoral manifestations. They stress the frequency and the severity of these complications which are dominated by cerebral vascular accidents and describe the pathogenic features of this particular complication. They define the complications accessible to treatment: iatrogenic pathology, deficiency disorders and certain paraneoplasic syndromes.

Influence of prefabricated post dimensions on restored maxillary central incisors.

The aim of this study was to test the following hypothesis: biomechanical performance (fracture strength and stress distribution) of restored teeth is less sensitive to post diameter and post length when using glass fibre posts than when using stainless steel posts. First, an experimental fracture strength test was performed on 80 extracted human maxillary central incisors. Teeth were decoronated, treated endodontically and restored (40 with glass fibre posts and 40 with stainless steel posts), and the length and diameter of the posts varied uniformly. Failure loads were recorded and results were compared using an ancova analysis. Secondly, the finite element technique was used to develop a model of the restored tooth. The post diameter had a significant effect on the biomechanical performance of teeth restored with stainless steel posts. Lower failure loads were found as post diameter increased. However, the post diameter of those teeth restored with glass fibre posts, and the post length for both post systems under consideration, did not affect the biomechanical performance of restored teeth to a significant degree. The stress distributions predicted by the developed model corroborated these findings, confirmed the assumed hypothesis, and permitted the proposal of the use of glass fibre posts to achieve a restorative technique that is less sensitive to post dimensions, and thus more robust.

Upper airway artifact in respiratory impedance measurements.

When studying respiratory impedance by forced oscillations, part of the flow measured at the mouth is lost in upper airway wall motion and does not enter the trachea. The corresponding error was studied in 10 normal subjects and 8 patients with chronic obstructive pulmonary disease (COPD) by measuring respiratory impedance with the cheeks unsupported, with the cheeks supported, and when upper airway wall motion was simultaneously measured with a head plethysmograph, and corrected for. In normal subjects, wall motion had little influence on respiratory resistance but, whether the cheeks were supported or not, increased the resonant frequency (p less than 0.05) and respiratory compliance (p less than 0.001) and decreased respiratory inertance (p less than 0.001). In patients with COPD, average resistance from 4 to 30 Hz was significantly lower when the cheeks were not supported (3.32 +/- 0.57 cm/H2O X L-1 X s; m +/- SD) than when they were (4.59 +/- 0.73, p less than 0.01) and when the data were corrected (5.41 +/- 1.14, p less than 0.001). Moreover, resistance increased with increasing frequency when wall motion was corrected for and decreased when it was not. Upper airway wall motion also tended to increase resonant frequency and decrease inertance in patients. The data show that supporting the cheeks does not prevent large errors on respiratory impedance and derived parameters, especially in obstructive patients; accurate measurements require that airway wall motion be evaluated and corrected for.