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.

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.

[Unusual location of a brain abscess due to Listeria monocytogenes]. / Abcès cérébral à Listeria monocytogenes de localisation inhabituelle.

Here we report a case of sustentorial brain abscess due to Listeria monocytogenes. Blood culture and procalcitonine blood measurement were negative. L. monocytogenes was isolated from CSF after inoculation in Castañeda medium.

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.

Prevalence of symptomatic hip and knee osteoarthritis: a two-phase population-based survey.

OBJECTIVE: Osteoarthritis (OA) epidemiologic data are scarce in Europe. To estimate the prevalence of symptomatic knee and hip OA in a multiregional sample in France. DESIGN: A two-phase population-based survey was conducted in six regions in 2007-2009. On initial phone contact using random-digit dialing, subjects 40-75 years old were screened with a validated questionnaire. Subjects screened positive were invited for ascertainment: physical examination and hip and/or knee radiography (Kellgren-Lawrence grade≥2). Multiple imputation for data missing not-at-random was used to account for refusals. RESULTS: Of 63,232 homes contacted, 27,632 were eligible, 9621 subjects screened positive, 3707 participated fully in the ascertainment phase, and 1010 had symptomatic OA: 317 hip, 756 knee. Hip OA prevalence according to age class ranged from 0.9% to 3.9% for men and 0.7-5.1% for women. Knee OA ranged from 2.1% to 10.1% for men and 1.6-14.9% for women. Both differed by geographical region. The hip and knee standardized prevalence was 1.9% and 4.7% for men and 2.5% and 6.6% for women, respectively. CONCLUSIONS: This confirmed the feasibility of using a screening questionnaire for eliciting population-based estimates of OA. In France, it increases with age and is greater among women above the age of 50. The geographical disparity of hip and knee OA parallels the distribution of obesity. Study registration ID number 906297 at http://www.clinicaltrials.gov/.

Advances in transfusion medicine in the first decade of the 21st century: Advances in miniaturized technologies.

Several miniaturized high throughput technologies have been developed in the last decade, primarily to study genomic structures and gene expression patterns under various conditions. At the same time, the microarrays, biosensors, integrated microfluidic lab-on-a-chip devices, next generation sequencing or digital PCR are gradually finding their diagnostic applications, although their suitability for specialised diagnostic fields has still to be assessed. In this review we discuss the potential applications of the new technologies to blood testing.

New electrophysiological mapping combined with MRI in parkinsonian's subthalamic region.

The subthalamic nucleus (STN) is the main target for deep brain stimulation in Parkinson's disease. We analysed the relationships between magnetic resonance imaging (MRI) anatomy and spontaneous neuronal activity to confirm the potential of microelectrode recordings to assist in determining the optimal surgical target. Ten bilateral surgeries were performed after 1.5-T (T2-weighted) anatomical MRI identification of the STN, zona incerta (ZI), Forel's field H2 (H2) and substantia nigra (SN). Spontaneous neuronal activity was recorded simultaneously along the distal 10 mm on a central track (optimally covering the STN) and a 2-mm anterior track. We calculated off-line mean firing rate and burst frequency on 248 neurons clustered according to anatomical structure. Subjective visual analysis of signal was also realized on-line, during surgery, to classify patterns of activity. Mean firing rate and burst frequency increased from H2-ZI to SN. The mean firing rate was higher in SN only using paired comparison (SN vs. its neighbours). The burst frequency was lower in H2 than in SN; using comparison with neighbours, it was lower in H2 and ZI. An irregular high activity (type 2C) was more often detected in STN and SN than in H2 and ZI. Anatomical boundaries and unitary recordings appear to be linked, supporting the ability of MRI to provide a detailed anatomy. Electrophysiological mapping combined with MRI is a useful tool for precise targeting in the subthalamic region.

A report on transmissible spongiform encephalopathies and transfusion safety.

The incidence of BSE in Europe is in continued decline. At present, iatrogenic transmission from person to person is considered a serious threat to public health. This report of the International Society of Blood Transfusion Working Party on Transmissible Spongiform Encephalopathy will focus on the state of the art in relation to blood components and plasma safety. Latest information on the pathogenicity of the infectious agent, the frequency and dynamics of infection in blood and transfusion transmissibility will be documented. Preventive measures including donor deferral policies, technologies for prion removal from labile blood components and for prion detection in plasma, the absence of a sensitive and rapid reference assay able to confirm the positive results from any putative blood screening assay will be updated. At last, as many uncertainties remain and a number of assumptions await confirmation, the areas to continue to explore are listed.

Diagnostic value of exhaled nitric oxide to detect interstitial lung disease in systemic sclerosis.

BACKGROUND AND AIM: Increased alveolar concentration of nitric oxide (CA(NO)) is related to the severity of interstitial lung disease (ILD) in systemic sclerosis (SSc). However, cut-off levels of CA(NO) to rule out, or to rule in, the presence of ILD in individual patients are unknown. We aimed to assess the validity of CA(NO) for the diagnosis of ILD in SSc and to determine the thresholds of CA(NO) that can be used in clinical practice to predict the likelihood of ILD in SSc. METHODS: Lung HRCT scan, PFTs and partitioned exhaled NO measurements were performed in 65 consecutive SSc patients. ILD was diagnosed on pulmonary HRCT according to the presence of ground glass or reticular opacities. Diagnostic performance of CANo for ILD diagnosis was assessed using ROC curves. RESULTS: 38 out of 65 SSc patients had ILD. CA(NO), at a cut-off level of 4.3 ppb, had a sensitivity and specificity for the diagnosis of ILD of 87% (95% CI: 77 to 99) and 59% (95% CI: 41 to 78), respectively. The same cut-off level of CA(NO) could detect impairment of gas exchange with a sensitivity and specificity of 78% (95% CI: 67 to 90) and 73% (95% CI: 46 to 99), respectively. Moreover, ILD could be ruled in (positive predictive value > 95%) when CA(NO) > or = 10.8 ppb, and ruled out C(ANO) values < or = 3.8 ppb (negative predictive value > 95%). CONCLUSION: CA(NO) could be a valid non-invasive biological marker of ILD in SSc, and be of use in clinical practice.

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.

The leucotriene receptor antagonist montelukast and the risk of Churg-Strauss syndrome: a case-crossover study.

BACKGROUND: There has been some concern that leucotriene receptor antagonists might precipitate the onset of Churg-Strauss syndrome (CSS). A study was undertaken to investigate the relationship between the leucotriene receptor antagonist montelukast and the onset of CSS. METHODS: Medication histories of 78 patients with CSS from France and Germany were retraced by questioning the patients, treating physicians and dispensing pharmacists, and from medical records. Using a case-crossover research design, exposures to montelukast and other asthma medications during the 3-month "index" period immediately preceding the onset of CSS were compared with those of four previous 3-month "control" periods. Odds ratios (ORs) were computed by conditional logistic regression. RESULTS: The ORs for CSS onset were 4.5 (95% CI 1.5 to 13.9) for montelukast, 3.0 (95% CI 0.8 to 10.5) for inhaled long-acting beta(2) agonists, 1.7 (95% CI 0.5 to 5.4) for inhaled corticosteroids and 4.0 (95% CI 1.3 to 12.5) for oral corticosteroids. Montelukast exposure during control periods increased temporally over three consecutive calendar periods of CSS onset from 1999 to 2003 (p(trend) <0.0001). CONCLUSION: Montelukast use was associated with a 4.5-fold higher risk of CSS onset within 3 months. However, the positive estimates obtained for other long-term asthma control medications suggest that this link might be confounded by a general escalation of asthma therapy before CSS onset. The association between montelukast and CSS observed in this study is probably also explained by the increasing use of this medication over time.

Screening for hip and knee osteoarthritis in the general population: predictive value of a questionnaire and prevalence estimates.

OBJECTIVE: To study the feasibility and validity of a two-step telephone screening procedure for symptomatic knee and hip osteoarthritis (OA) in the general population. METHOD: The screening questionnaire was based on signs and symptoms, previous diagnosis of OA and validated OA criteria. A random sample of telephone numbers was obtained and, at each number, one person aged 40-75 years was included. A physical examination and knee or hip radiographs were offered when the screen was positive. A sample of subjects with negative screens was also examined. The diagnosis of hip/knee OA was based on the American College of Rheumatology criteria for signs and symptoms and Kellgren-Lawrence radiographic stage 2 or greater. Prevalence rates were estimated with correction for the performance of the screening procedure. RESULTS: Of 1380 subjects, 479 had positive screens, among whom 109 were evaluated; symptomatic radiographic OA was found in 50 subjects, at the knee (n = 35) or hip (n = 20). Corrected prevalence estimates of symptomatic OA were 7.6% (6.4%-8.8%) for the knee and 5% (3.9%-6.1%) for the hip. The screening procedure had 87% (95% CI 79% to 95%) sensitivity and 92% (95% CI 91% to 93%) specificity for detecting knee OA and respectively 93% (95% CI 86% to 100%) and 93% (95% CI 92% to 94%) for hip OA. CONCLUSION: This study establishes the feasibility of telephone screening for symptomatic knee/hip OA, which could be used for a nationwide prevalence study. Pain and previous OA diagnosis were the best items for detecting symptomatic OA.

A role for wind-up in trigeminal sensory processing: intensity coding of nociceptive stimuli in the rat.

Wind-up is a progressive, frequency-dependent increase in the excitability of trigeminal and spinal dorsal horn wide dynamic range (WDR) nociceptive neurons evoked by repetitive stimulation of primary afferent nociceptive C-fibres. The correlate of wind-up in humans is temporal summation, which is an increase in pain perception to repetitive constant nociceptive stimulation. Although wind-up is widely used as a tool for studying the processing of nociceptive information, including central sensitization, its actual role is still unknown. Here, we recorded from trigeminal WDR neurons using in vivo electrophysiological techniques in rats and assessed the wind-up phenomenon in response to stimuli of different intensities and frequencies. First, we found that the amplitude of C-evoked responses of WDR neurons to repetitive stimulation increased progressively to reach a peak, then consistently showed a stable or slightly decreasing plateau phase. Only the first phase of this time course fitted in with the wind-up description. Therefore, to assess wind-up, we measured a limited number of initial responses. Second, we showed that wind-up, i.e. the slope of the frequency-dependent increase in the response to C-fibre stimulation, was linearly correlated to the stimulus intensity. Intensities of brief C-fibre inputs were thus coded into frequencies of action potentials by second-order neurons through frequency-dependent potentiation of the evoked responses. Third, wind-up also occurred at stimulation intensities below the threshold for C-evoked responses in WDR neurons, suggesting that wind-up can amplify subthreshold C-fibre inputs to WDR neurons. This might account for the observation that sparse, subliminal, neuronal activity in nociceptors can become painful via central integration of neural responses. Altogether, the present results show that wind-up can provide trigeminal WDR neurons with the capability to encode the intensity of short-duration orofacial nociceptive stimuli and to detect subthreshold nociceptive input. Thus, not only may wind-up play a physiological role in trigeminal sensory processing, but its enhancement may also underlie the pathophysiology of chronic orofacial pain conditions.

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.

Fitting new technologies into the safety paradigm: use of microarrays in transfusion.

Until the late 1990s, mandatory blood screening for transmissible infectious agents depended entirely on antigen/antibody-based detection assays. The recent emergence of Nucleic acid Amplification Technologies (NAT) has revolutionised viral diagnosis, not only by increasing the level of sensitivity but also by facilitating the detection of several viruses in parallel by multiplexing specific primers. In more complex biological situations, when a broad spectrum of pathogens must be screened, the limitations of these first generation technologies became apparent. High throughput systems, such as DNA Arrays, permit a conceptually new approach. These miniaturised micro systems allow the detection of hundreds of different targets simultaneously, inducing a dramatic decrease in reagent consumption, a reduction in the number of confirmation tests and a simplification of data interpretation. However, the systems currently available require additional instrumentation and reagents for sample preparation and target amplification prior to detection on the DNA array. A major challenge in the area of DNA detection is the development of methods that do not rely on target amplification systems. Likewise, the advances of protein microarrays have lagged because of poor stability of proteins, complex coupling chemistry and weak detection signals. Emerging technologies like Biosensors and nano-particle based DNA or Protein Bio-Barcode Amplification Assays are promising diagnostic tools for a wide range of clinical applications, including blood donation screening.