Neural correlates of consciousness and related disorders: From phenotypic descriptors of behavioral and relative consciousness to cortico-subcortical circuitry.

We report a review of medical aspects of the consciousness. The behavioral dimension, phenotypic descriptors, relative consciousness and neural correlates of consciousness and related disorders were addressed successively in a holistic and chronological approach. Consciousness is relative, specific to each individual across time and space. Historically defined as the perception of the self and the environment, it cannot be separated from behaviors, entailing an idea of conscious behavior with metapractic and metagnostic aspects. Observation of spontaneous and evoked overt behavior distinguishes three main types of disorder of consciousness (DoC): coma, vegetative state or unresponsive wakefulness, and minimally conscious or relationally impoverished state. Modern functional exploration techniques, such as imaging, increase the understanding of DoCs and consciousness. Whether consciousness is a superior function and/or an instrumental function is discussed. Neural correlates can be subdivided into two wakefulness pathways (superior thalamic cholinergic and inferior extra-thalamic), and cortico-subcortical circuitry. The deep brain structures are those described in the well-known sensorimotor, associative and limbic loops, as illustrated in the mesolimbic model of DoC. The cortices can be segregated into several overlapping networks: (1) a global workspace including thalamo-cortical loops; (2) the default mode network (DMN) and related intrinsic connectivity networks (i.e., central executive, medial DMN and salience networks); (3) a 3-fold network comprising the fronto-parietal control system and its dorsal and ventral attentional sub-networks, the fronto-parietal executive control network, and the cingulo-opercular salience network; (4) the internal and external cortices, respectively medial, turned toward the self, and lateral, turned toward the environment. The network dynamics is the reflection of consciousness, notably anticorrelations such as the decrease in activity of the posterior cingulate-precuneus regions during attentional tasks. Thanks to recent advances in DoC pathophysiology, further significative therapeutic progress is expected, taking into account the societal context. This depends notably on the dissemination of medical knowledge and its transfer to a wider public.

Fibromyalgia in the workplace: risk factors for sick leave are related to professional context rather than fibromyalgia characteristics- a French national survey of 955 patients.

BACKGROUND: Work and workplace factors are important in fibromyalgia management. We investigated factors associated with sick leave in professionally active women living with fibromyalgia. METHODS: A questionnaire for fibromyalgia patients in employment was developed by pain and occupational physicians and patients' organizations. Women in full-time work, screened for fibromyalgia with the FiRST questionnaire, were recruited for a national online survey. Sick leave over the preceding year was analyzed. RESULTS: In 5 months, we recruited 955 women, with a mean of 37 days of sick leave in the previous year: no sick leave (36%), up to 1 month (38%), 1 to 2 months (14%), more than 2 months (12%). In the groups displayed no differences in demographic characteristics, fibromyalgia symptoms, functional severity and psychological distress were observed. However, they differed in workplace characteristics, commute time, stress and difficulties at work, repetitive work, noisy conditions, career progression problems and lack of recognition, which were strong independent risk factors for longer sick leave. Sedentary positions, an extended sitting position, heavy loads, exposure to thermal disturbances and the use of vibrating tools did not increase the risk of sick leave. CONCLUSIONS: Women with fibromyalgia frequently take sick leave, the risk factors for which are related to the workplace rather than fibromyalgia characteristics. PERSPECTIVE: This is the first study to assess the impact of occupational and clinical factors on sick leave in women living with fibromyalgia. Risk factors were found to be related to the workplace rather than fibromyalgia and personal characteristics. Workplace interventions should be developed for women with fibromyalgia.

Persistence of treatment with biologics for patients with psoriasis: a real-world analysis of 16 545 biologic-naïve patients from the French National Health Insurance database (SNIIRAM).

BACKGROUND: Long-term clinical effectiveness of biologics in psoriasis is needed. OBJECTIVES: We aimed to assess the long-term persistence of biologics used to treat psoriasis in a real-life setting. METHODS: All adults with psoriasis having been registered in the French National Health Insurance database (SNIIRAM) between 2008 and 2016 were eligible for inclusion. Psoriasis was defined as the fulfilment of at least two prescriptions for topical formulations of a vitamin D derivative within a 2-year period. The study population comprised biologic-naïve patients, i.e. those with a first prescription of etanercept, infliximab, adalimumab or ustekinumab. Persistence of treatment with a biologic was defined as the time interval between initiation and discontinuation. RESULTS: In this nationwide population-based cohort, 16 545 out of 874 549 patients with psoriasis were biologic-naïve (mean age 48·6 years; males 57·3%, mean follow-up 3·6 years). The mean ± SD length of follow-up for biologic-naïve patients was 3·6 ± 2·4 years. There were 9988 treatment discontinuations. Kaplan-Meier survival analyses revealed a persistence rate of 61·9% for the first, 33·3% for the third and 22·6% for the fifth year. Ustekinumab had a higher persistence rate than the other biologics. This finding should be interpreted with caution, in view of differences in administration between the biologics. About 85% of patients, having discontinued their first biologic, resumed systemic treatment of some type in the following year (biologics in 85% of cases). CONCLUSIONS: Our data suggest that biologics are less effective than physicians have been led to believe in a real-life, nonselected population. Further, long-term disease control requires several courses of different biologics.

The French PROMIS-29. Psychometric validation and population reference values.

BACKGROUND: PROMIS-29 is a new generic standardized questionnaire measuring self-reported health status. It was developed as part of the Patient Reported Outcome Measurement Information System (PROMIS) in the United States. The objective of this study was to carry out the psychometric validation of a French-language version of PROMIS-29 and to establish general population reference values for France. METHODS: Quota sampling was conducted by an independent polling company (Ipsos) to obtain a general population sample (n=1,501) representative with regards to: gender, age, occupation, region, and population density of the place of residence. Data collected included the results of the questionnaires PROMIS-29 and Short Form Health Survey (SF-36), the presence of selected chronic diseases, and socio-demographic information. RESULTS: The French PROMIS-29 demonstrated excellent factorial validity, confirming the 7-factor model of the original PROMIS-29. The use of modern measurement methods indicated that the PROMIS-29 scales satisfy the important characteristics of unidimensionality and, for five of the seven composite scales, invariance across age, educational level and gender. Gender and age specific (10-year intervals) reference values were generated for PROMIS-29 use in France. CONCLUSION: The French version of PROMIS-29 is a valid and reliable measure of self-reported health status in the French population. The instrument's sensitivity to change needs to be evaluated before its use in longitudinal studies can be recommended.

Thromboembolic risk after lumbar spine surgery: a cohort study on 325 000 French patients.

Essentials The risk of venous thromboembolism (VTE) after lumbar spine surgery (LBS) is not precisely known. More than 320 000 patients who underwent LBS in France between 2009 and 2014 were followed-up. The overall risk of VTE after LBS is less than 1% but modulated by patient and procedural factors. Surgical device implantation, anterior approach and complex surgery increase the risk of VTE. SUMMARY: Background Postoperative venous thromboembolism (VTE) is a severe complication, the risk of which after lumbar spine surgery (LBS) is not precisely known. Objective To estimate the incidence of VTE after LBS, and to identify individual and surgical risk factors. Methods All patients aged >18 years who underwent LBS in France between 2009 and 2014 were identified. Among 477 024 patients screened, exclusions concerned recent VTE or surgery, and multiple surgeries during the same hospital stay. Results In 323 737 patients (mean age 52.9 years, 51.4% male), we observed 2911 events (0.91%) after a median time of 12 days (Q1-Q3: 5-72 days). The multivariate adjusted Cox model showed increased risks associated with age (4% per year of age; 95% confidence interval [CI] 3.8-4.3), obesity (hazard ratio [HR] 1.32, 95% CI 1.18-1.46), active cancer (HR 1.65, 95% CI 1.5-1.82), previous thromboembolism (HR 5.41, 95% CI 4.74-6.17), severe paralysis (HR 1.47, 95% CI 1.17-1.84), renal disease (HR 1.28, 95% CI 1.04-1.6), psychiatric disease (HR 1.21, 95% CI 1.1-1.32), use of antidepressants (HR 1.13, 95% CI 1.03-1.24), use of contraceptives (HR 1.56, 95% CI 1.19-2.03), extended surgery for scoliosis (HR 3.61, 95% CI 2.96-4.4), implantation of pedicular screws with a 'dose-effect' association, and an anterior approach (HR 1.97, 95% CI 1.6-2.43) or a combined approach (HR 2.03, 95% CI 1.44-2.84). Conclusions The overall VTE risk after LBS is moderate (< 1%) but is widely modulated by several easily identifiable risk factors. The surgical community should be aware of this heterogeneity, adapt prevention according to patients and to the procedure, and use drug prophylaxis in the event of a high risk being present.

Value of a national administrative database to guide public decisions: From the système national d'information interrégimes de l'Assurance Maladie (SNIIRAM) to the système national des données de santé (SNDS) in France.

In 1999, French legislators asked health insurance funds to develop a système national d'information interrégimes de l'Assurance Maladie (SNIIRAM) [national health insurance information system] in order to more precisely determine and evaluate health care utilization and health care expenditure of beneficiaries. These data, based on almost 66 million inhabitants in 2015, have already been the subject of numerous international publications on various topics: prevalence and incidence of diseases, patient care pathways, health status and health care utilization of specific populations, real-life use of drugs, assessment of adverse effects of drugs or other health care procedures, monitoring of national health insurance expenditure, etc. SNIIRAM comprises individual information on the sociodemographic and medical characteristics of beneficiaries and all hospital care and office medicine reimbursements, coded according to various systems. Access to data is controlled by permissions dependent on the type of data requested or used, their temporality and the researcher's status. In general, data can be analyzed by accredited agencies over a period covering the last three years plus the current year, and specific requests can be submitted to extract data over longer periods. A 1/97th random sample of SNIIRAM, the échantillon généraliste des bénéficiaires (EGB), representative of the national population of health insurance beneficiaries, was composed in 2005 to allow 20-year follow-up with facilitated access for medical research. The EGB is an open cohort, which includes new beneficiaries and newborn infants. SNIIRAM has continued to grow and extend to become, in 2016, the cornerstone of the future système national des données de santé (SNDS) [national health data system], which will gradually integrate new information (causes of death, social and medical data and complementary health insurance). In parallel, the modalities of data access and protection systems have also evolved. This article describes the SNIIRAM data warehouse and its transformation into SNDS, the data collected, the tools developed in order to facilitate data analysis, the limitations encountered, and changing access permissions.

Microbial flora on cell-phones in an orthopedic surgery room before and after decontamination.

INTRODUCTION: Cell-phones are the typical kind of object brought into the operating room from outside by hospital staff. A great effort is made to reduce the level of potentially contaminating bacteria in the operating room, and introducing these devices may run counter to good practice. The study hypothesis was that cell-phones are colonized by several strains of bacteria and may constitute a source of nosocomial contamination. The main study objective was to screen for bacterial colonies on the surfaces of cell-phones introduced in an orthopedic surgery room. The secondary objective was to assess the efficacy of decontamination. MATERIAL AND METHOD: Samples were taken from the cell-phones of hospital staff (surgeons, anaesthetists, nurses, radiology operators, and external medical representatives) entering the operating room of the university hospital center orthopedic surgery department, Toulouse (France). Sampling used Count Tact® contact gel, without wiping the phone down in advance. Both sides of the phone were sampled, before and after decontamination with a pad imbibed with 0.25% Surfanios® Premium disinfectant. A nasal sample was also taken to investigate the correlation between Staphylococcus aureus in the nasal cavities and on the cell-phone. RESULTS: Fifty-two cell-phones were sampled. Before decontamination, the mean number of colony-forming units (CFU) was 258 per phone (range, 0-1,664). After decontamination, it was 127 (range, 0-800) (P=0.0001). Forty-nine cell-phones bore CFUs before decontamination (94%), and 39 after (75%) (P=0.02). DISCUSSION: Cell-phones are CFU carriers and may thus lead to contamination. Guidelines should be drawn up to encourage cleaning phones regularly and to reduce levels of use within the operating room.

Personalized mapping of the deep brain with a white matter attenuated inversion recovery (WAIR) sequence at 1.5-tesla: Experience based on a series of 156 patients.

OBJECTIVE: Deep brain mapping has been proposed for direct targeting in stereotactic functional surgery, aiming to personalize electrode implantation according to individual MRI anatomy without atlas or statistical template. We report our clinical experience of direct targeting in a series of 156 patients operated on using a dedicated Inversion Recovery Turbo Spin Echo sequence at 1.5-tesla, called White Matter Attenuated Inversion Recovery (WAIR). METHODS: After manual contouring of all pertinent structures and 3D planning of trajectories, 312 DBS electrodes were implanted. Detailed anatomy of close neighbouring structures, whether gray nuclei or white matter regions, was identified during each planning procedure. We gathered the experience of these 312 deep brain mappings and elaborated consistent procedures of anatomical MRI mapping for pallidal, subthalamic and ventral thalamic regions. We studied the number of times the central track anatomically optimized was selected for implantation of definitive electrodes. RESULTS: WAIR sequence provided high-quality images of most common functional targets, successfully used for pure direct stereotactic targeting: the central track corresponding to the optimized primary anatomical trajectory was chosen for implantation of definitive electrodes in 90.38%. CONCLUSION: WAIR sequence is anatomically reliable, enabling precise deep brain mapping and direct stereotactic targeting under routine clinical conditions.

High-sensitivity C-reactive protein does not improve the differential diagnosis of HNF1A-MODY and familial young-onset type 2 diabetes: A grey zone analysis.

AIM: Low plasma levels of high-sensitivity C-reactive protein (hs-CRP) have been suggested to differentiate hepatocyte nuclear factor 1 alpha-maturity-onset diabetes of the young (HNF1A-MODY) from type 2 diabetes (T2D). Yet, differential diagnosis of HNF1A-MODY and familial young-onset type 2 diabetes (F-YT2D) remains a difficult challenge. Thus, this study assessed the added value of hs-CRP to distinguish between the two conditions. METHODS: This prospective multicentre study included 143 HNF1A-MODY patients, 310 patients with a clinical history suggestive of HNF1A-MODY, but not confirmed genetically (F-YT2D), and 215 patients with T2D. The ability of models, including clinical characteristics and hs-CRP to predict HNF1A-MODY was analyzed, using the area of the receiver operating characteristic (AUROC) curve, and a grey zone approach was used to evaluate these models in clinical practice. RESULTS: Median hs-CRP values were lower in HNF1A-MODY (0.25mg/L) than in F-YT2D (1.14mg/L) and T2D (1.70mg/L) patients. Clinical parameters were sufficient to differentiate HNF1A-MODY from classical T2D (AUROC: 0.99). AUROC analyses to distinguish HNF1A-MODY from F-YT2D were 0.82 for clinical features and 0.87 after including hs-CRP. For the grey zone analysis, the lower boundary was set to miss<1.5% of true positives in non-tested subjects, while the upper boundary was set to perform 50% of genetic tests in individuals with no HNF1A mutation. On comparing HNF1A-MODY with F-YT2D, 65% of patients were classified in between these categories - in the zone of diagnostic uncertainty - even after adding hs-CRP to clinical parameters. CONCLUSION: hs-CRP does not improve the differential diagnosis of HNF1A-MODY and F-YT2D.

[Medico-economic analysis of a neurosurgery department at a university hospital]. / Analyse médico-économique d'un service de neurochirurgie en centre hospitalier et universitaire.

OBJECTIVE: Economic and societal constraints require to take into account the economic dimension and medical performance of hospital departments. We carried out a self-assessment study, which we thought could be useful to share with the neurosurgical community. MATERIAL AND METHODS: Care and research activities were assessed from 2009 to 2013. We used institutional and assessment-body parameters in order to describe activities and perform a financial evaluation. It was a retrospective descriptive study based on the guidelines of the DHOS/O4 circular No. 2007/390 of October 29, 2007. RESULTS: The average annual, analytic income statement was +1.39 millions euros, for 63 beds with a 92% occupancy rate, including 6.7 full-time equivalent neurosurgeons (and assistants), for 2553 patients and 1975 surgeries. The average mortality rate was 2.74%. The annual mean length of stay was 6.82 days. Per year, on average 15.6% of patients were admitted in emergency and 76.9% returned home. The annual, act-related-pricing and publication-related incomes represented 77% and 0.6%, respectively of the total funding. Difficulties to find downstream beds for the most severe patients induced 1401 "waiting days" in 2012. CONCLUSION: Medico-economic analysis of a neurosurgery department at a university hospital was useful in order to take into account the care, teaching and research activities, as well as its related financial value.

Electrical modulation of neuronal networks in brain-injured patients with disorders of consciousness: a systematic review.

Six clinical studies of chronic electrical modulation of deep brain circuits published between 1968 and 2010 have reported effects in 55 vegetative or minimally conscious patients. The rationale stimulation was to activate the cortex through the reticular-thalamic complex, comprising the tegmental ascending reticular activating system and its thalamic targets. The most frequent intended target was the central intralaminar zone and adjacent nuclei. Hassler et al. also proposed to modulate the pallidum as part of the arousal and wakefulness system. Stimulation frequency varied from 8Hz to 250Hz. Most patients improved, although in a limited way. Schiff et al. found correlations between central thalamus stimulation and arousal and conscious behaviours. Other treatments that have offered some clinical benefit include drugs, repetitive magnetic transcranial stimulation, median nerve stimulation, stimulation of dorsal column of the upper cervical spinal cord, and stimulation of the fronto-parietal cortex. No one treatment has emerged as a gold standard for practice, which is why clinical trials are still on-going. Further clinical studies are needed to decipher the altered dynamics of neuronal network circuits in patients suffering from severe disorders of consciousness as a step towards novel therapeutic strategies.

An overview of the diagnostic tools.

Prions are unconventional infectious agents that cause fatal neurological illnesses such as Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy, and scrapie. Variant CJD can occur via blood transfusions. However, as no screening assay is available, uncertainties remain over the prevalence of vCJD in asymptomatic blood donors. Development of a diagnostic assay is therefore a primary objective. Little is known about the nature, distribution and level of infectivity in human blood and we have to rely on assumptions made from animal models. Ideally, two types of assays are required: a rapid high-throughput assay to routinely screen all blood donations and a confirmatory assay to ensure that all positive results from initial screening are true positives. Key event in prion disease is thought to be the conversion of normal cellular prion protein PrPc to a misfolded aggregated form termed PrP(TSE). This specific characteristic has been exploited to develop some tests.