Mismatch negativity to predict subsequent awakening in deeply sedated critically ill patients.

BACKGROUND: Mismatch negativity (MMN) is the neurophysiological correlate of cognitive integration of novel stimuli. Although MMN is a well-established predictor of awakening in non-sedated comatose patients, its prognostic value in deeply sedated critically ill patients remains unknown. The aim of this prospective, observational pilot study was to investigate the prognostic value of MMN for subsequent awakening in deeply sedated critically ill patients. METHODS: MMN was recorded in 43 deeply sedated critically ill patients on Day 3 of ICU admission using a classical 'odd-ball' paradigm that delivers rare deviant sounds in a train of frequent standard sounds. Individual visual analyses and a group level analysis of recordings were performed. MMN amplitudes were then analysed according to the neurological status (awake vs not awake) at Day 28. RESULTS: Median (inter-quartile range) Richmond Assessment Sedation Scale (RASS) at the time of recording was -5 (range, from -5 to -4.5). Visual detection of MMN revealed a poor inter-rater agreement [kappa=0.17, 95% confidence interval (0.07-0.26)]. On Day 28, 30 (70%) patients had regained consciousness while 13 (30%) had not. Quantitative group level analysis revealed a significantly greater MMN amplitude for patients who awakened compared with those who had not [mean (standard deviation) = -0.65 (1.4) vs 0.08 (0.17) µV, respectively; P=0.003). CONCLUSIONS: MMN can be observed in deeply sedated critically ill patients and could help predict subsequent awakening. However, visual analysis alone is unreliable and should be systematically completed with individual level statistics.

Clinical benefit, price and approval characteristics of FDA-approved new drugs for treating advanced solid cancer, 2000-2015.

Background: Prices of anti-cancer drugs are skyrocking. We aimed to assess the clinical benefit of new drugs for treating advanced solid tumors at the time of their approval by the US Food and Drug Administration (FDA) and to search for a relation between price and clinical benefit of drugs. Materials and methods: We included all new molecular entities and new biologics for treating advanced solid cancer that were approved by the FDA between 2000 and 2015. The clinical benefit of drugs was graded based on FDA medical review of pivotal clinical trials using the 2016-updated of the American Society of Clinical Oncology Value Framework (ASCO-VF) and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Characteristics of drugs and approvals were obtained from publicly available FDA documents and price was evaluated according to US Medicare, US Veterans Health Administration and United Kingdom market systems. Results: The FDA approved 51 new drugs for advanced solid cancer from 2000 to 2015; we could evaluate the value of 37 drugs (73%). By the ESMO-MCBS, five drugs (14%) were grade one (the lowest), nine (24%) grade two, 10 (27%) grade three, 11 (30%) grade four and two (5%) grade five (the highest). Thus, 13 drugs (35%) showed a meaningful clinical benefit (scale levels 4 and 5). By the ASCO-VF which had a range of 3.4-67, the median drug value was 37 (interquartile range 20-52). We found no relationship between clinical benefit and drug price (P = 0.9). No characteristic of drugs and of approval was significantly associated with clinical benefit. Conclusion: Many recently FDA-approved new cancer drugs did not have high clinical benefit as measured by current scales. We found no relation between the price of drugs and benefit to society and patients.

Magnetic resonance imaging for abnormally invasive placenta: the added value of intravenous gadolinium injection.

OBJECTIVES: To assess the added value of intravenous gadolinium injection to magnetic resonance imaging (MRI) -based diagnosis of abnormally invasive placenta (AIP) and to examine this in relation to the radiologist's experience. DESIGN: Retrospective study. SETTING: Between March 2009 and October 2012, 31 pregnant women who had previous caesarean delivery together with a placenta praevia and suspected placenta accreta on ultrasound in the third trimester of pregnancy. POPULATION: All were offered MRI examination, and made aware of the limited (but so far reassuring) data regarding fetal safety of gadolinium. Twenty pregnant women agreed to undergo prenatal MRI (1.5 T), with and without gadolinium injection. METHODS: Two sets of MRI examinations without and with gadolinium were reviewed independently 2 months apart by two senior and two junior radiologists; all were blinded to the outcome (known in all cases). Histopathological findings and clinical signs of AIP were considered as the defining criteria of diagnosis. MAIN OUTCOME MEASURE: accuracy of MRI with and without gadolinium was assessed. RESULTS: Eight of the 20 women had confirmed abnormal placental invasion. The overall performance of both sets of readers in detecting AIP increased with gadolinium-sensitivity and specificity of 75.0% (42.0-100%) and 47.9% (19.9-75.9%) increasing to 87.5% (57.1-100%) and 60.4% (33.9-86.9%), respectively (P = 0.04). The added value of gadolinium remained irrespective of radiologist's experience, although senior radiologists performed better overall (sensitivity and specificity of 87.5% and 62.5% versus 62.5% and 33.3%, respectively, increasing with injection to 93.8% and 70.8% versus 81.3% and 50%, respectively; P < 10-4 ). CONCLUSION: There was an association between gadolinium use and improvement in MRI-based diagnostic accuracy for the diagnosis of AIP, for both junior and senior radiologists. TWEETABLE ABSTRACT: Gadolinium injection improves MRI performance of radiologists for the diagnosis of placenta accreta.

Influence of ultrasound determination of fetal head position on mode of delivery: a pragmatic randomized trial.

OBJECTIVE: To evaluate the influence of ultrasound determination of fetal head position on mode of delivery. METHODS: This was a pragmatic open-label randomized controlled trial that included women with a singleton pregnancy in the vertex presentation at ≥ 37 weeks' gestation, cervical dilation ≥ 8 cm and who received epidural anesthesia. Women were assigned randomly to undergo either digital vaginal examination (VE group) or both digital vaginal and ultrasound examinations (VE+US group) to determine fetal head position. When the ultrasound and digital vaginal findings were inconsistent in the VE+US group, the ultrasound result was used for clinical management. The primary outcome assessed was operative delivery (Cesarean or instrumental vaginal delivery), and maternal and fetal morbidity were also assessed. RESULTS: The VE and VE+US groups included 959 and 944 women, respectively. The overall rate of operative delivery was significantly higher in the VE+US group than in the VE group: 33.7% vs 27.1%, respectively (relative risk (RR), 1.24 (95% CI, 1.08-1.43)), as was the rate of Cesarean delivery: 7.8% vs 4.9%, respectively (RR, 1.60 (95% CI, 1.12-2.28)). The rate of instrumental vaginal delivery was also higher, albeit not significantly: 25.8% in the VE+US group vs 22.2% in the VE group (RR, 1.16 (95% CI, 0.99-1.37)). Neonatal outcomes did not differ between the two groups. When analysis was restricted to instrumental vaginal deliveries only, maternal and neonatal morbidity outcomes were similar in both groups. CONCLUSION: Correction of fetal occiput position, determined initially by digital vaginal examination, using systematic ultrasound examination did not improve management of labor and increased the rate of operative delivery without decreasing maternal and neonatal morbidity.

Long-term survival of advanced triple-negative breast cancers with a dose-intense cyclophosphamide/anthracycline neoadjuvant regimen.

BACKGROUND: Triple-negative (TN) breast cancers exhibit major initial responses to neoadjuvant chemotherapy, but generally have a poor outcome. Because of the lack of validated drug targets, chemotherapy remains an important therapeutic tool in these cancers. METHODS: We report the survival of two consecutive series of 267 locally advanced breast cancers (LABC) treated with two different neoadjuvant regimens, either a dose-dense and dose-intense cyclophosphamide-anthracycline (AC) association (historically called SIM) or a conventional sequential association of cyclophosphamide and anthracycline, followed by taxanes (EC-T). We compared pathological responses and survival rates of these two groups and studied their association with tumours features. RESULTS: Although the two regimens showed equivalent pathological complete response (pCR) in the whole population (16 and 12%), the SIM regimen yielded a non-statistically higher pCR rate than EC-T (48% vs 24%, P=0.087) in TN tumours. In the SIM protocol, DFS was statistically higher for TN than for non-TN patients (P=0.019), although we showed that the TN status was associated with an increased initial risk of recurrence in both regimens. This effect gradually decreased and after 2 years, TN was associated with a significantly decreased likelihood of relapse in SIM-treated LABC (hazard ratio (HR)=0.25 (95% CI: 0.07-0.86), P=0.028). CONCLUSIONS: AC dose intensification treatment is associated with a very favourable long-term survival rate in TN breast cancers. These observations call for a prospective assessment of such dose-intense AC-based regimens in locally advanced TN tumours.

Permutation tests for centre effect on survival endpoints with application in an acute myeloid leukaemia multicentre study.

When analysing multicentre data, it may be of interest to test whether the distribution of the endpoint varies among centres. In a mixed-effect model, testing for such a centre effect consists in testing to zero a random centre effect variance component. It has been shown that the usual asymptotic χ(2) distribution of the likelihood ratio and score statistics under the null does not necessarily hold. In the case of censored data, mixed-effects Cox models have been used to account for random effects, but few works have concentrated on testing to zero the variance component of the random effects. We propose a permutation test, using random permutation of the cluster indices, to test for a centre effect in multilevel censored data. Results from a simulation study indicate that the permutation tests have correct type I error rates, contrary to standard likelihood ratio tests, and are more powerful. The proposed tests are illustrated using data of a multicentre clinical trial of induction therapy in acute myeloid leukaemia patients.

Increased incidence of Campylobacter jejuni-associated Guillain-Barré syndromes in the Greater Paris area.

The role of Campylobacter jejuni as the triggering agent of Guillain-Barré syndrome (GBS) has not been reassessed since the end of the 1990s in France. We report that the number of C. jejuni-related GBS cases increased continuously between 1996 and 2007 in the Paris region (mean annual increment: 7%, P = 0·007).

Human herpesvirus 8 (HHV8) transmission and related morbidity in organ recipients.

The aims of the study were to assess the risk of HHV8 transmission resulting from organ transplantation, and related morbidity in liver, heart and kidney transplant recipients. Donor and recipient serologies were screened between January 1, 2004 and January 1, 2005 using HHV8 indirect immunofluorescence latent assay (latent IFA) and indirect immunofluorescent lytic assay (lytic IFA). Recipients negative for latent IFA with a donor positive for at least one test were sequentially monitored for HHV8 viremia and underwent serological tests over a period of 2 years. The results showed that among 2354 donors, HHV8 seroprevalence was 9.9% (lytic IFA) and 4.4% (latent IFA). A total of 454 organ recipients (281 renal, 116 liver and 57 heart) were monitored over a 2-year period. Seroconversion was observed in 12 patients (cumulative incidence 28%) whose donor had positive latent IFA and in 36 patients (cumulative incidence 29%) whose donors were positive only for lytic IFA, without differences across types of transplants. Positive HHV8 viremia was detected in only 4 out of 89 liver transplant recipients during follow-up and not in recipients of other types of transplant. Two liver transplant recipients and one kidney transplant recipient developed KS. In conclusion, although HHV8 transmission is a frequent event after organ transplantation, HHV8-related morbidity is rather rare but can be life threatening. Donor screening is advisable for monitoring HHV8 seronegative liver transplant recipients.

Polylactic acid vs. polyacrylamide hydrogel for treatment of facial lipoatrophy: a randomized controlled trial [Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (ANRS) 132 SMILE].

OBJECTIVES: The aim of the study was to demonstrate the noninferiority of polyacrylamide hydrogel (PH) vs. polylactic acid (PLA) for the treatment of facial lipoatrophy in HIV-infected adults. METHODS: A randomized, blinded, multicentre, noninferiority 96-week study was carried out. Patients with facial lipoatrophy were randomly assigned to receive intradermal injections with PH or PLA, and were blinded to the filler. The primary efficacy endpoint was patient satisfaction at week 48 assessed using a visual analogue scale score (VAS). Secondary efficacy end-points included cheek thickness and skin-fold, lipoatrophy grading and quality of life. Safety was assessed by the reporting of adverse events. RESULTS: A total of 148 patients were included in the study; 93% were men, the median age was 47 years, the median CD4 count was 528 cells/µL, and the median duration of antiretroviral therapy was 12 years. Mean VAS increased from 2.8 at baseline to 7.1 and 7.5 in the PLA and PH arms, respectively, at week 48 (P=0.0002 for noninferiority) and was sustained at week 96 (6.7 and 7.9 in the PLA and PH arms, respectively; P=0.003 for noninferiority). Cheek thickness and skin-fold increases and lipoatrophy improvement were similar in the two arms. Quality of life remained unchanged or improved depending on the questionnaire used. In injected patients, subcutaneous nodules emerged in 28 (41%) and 26 (37%) patients in the PLA and PH arms, respectively (P=0.73). Four patients in the PH arm developed severe inflammatory nodules, a median of 17 months after the last injection. CONCLUSIONS: PH and PLA have similar efficacies in the treatment of facial lipoatrophy, but PH may be associated with more delayed inflammatory nodules.

Invasive pneumococcal disease in HIV-infected adults in France from 2000 to 2011: antimicrobial susceptibility and implication of serotypes for vaccination.

PURPOSE: Invasive pneumococcal diseases (IPD) remain frequent and severe events in human immunodeficiency virus (HIV)-infected subjects despite the use of antiretroviral therapy and the availability of vaccines. Our aim was to assess the antibiotic susceptibilities and serotypes of strains responsible for IPD in HIV-infected patients. METHODS: We retrospectively analyzed all Streptococcus pneumoniae strains isolated from normally sterile sites between 2000 and 2011 in HIV-infected patients from a single reference center in Paris. The minimum inhibitory concentrations were determined by the E-test, and serotyping was performed by the antiserum agglutination method. RESULTS: Among our study group, 41 HIV-infected adults presented 43 IPD during the study period. Of these 41 patients, 78 % were men, and the median age was 43 (range 23-62) years. the median CD4 cell count was 184/mm(3) (6-1,090/mm(3)), 51 % were receiving antiretroviral therapy, and 24 % had plasma HIV-RNA levels of <400 copies/mL. Only two patients had received the pneumococcal polysaccharide 23-valent vaccine (PPV23). Isolates were susceptible to penicillin G, amoxicillin, and cotrimoxazole in 44, 70, and 59 % of cases, respectively, and were significantly less susceptible to these antibiotics than isolates in the French general population during the same period. Among the 27 strains serotyped, 18 different serotypes were observed, of which 19A, 14, 7F, and 6A were the most frequent. Serotype distribution was similar to that in the French general population. The PPV23 vaccine and the 13-valent conjugate vaccine (PCV13) would have theoretically covered 78 and 70 % of cases, respectively. CONCLUSIONS: In our HIV-infected patient cohort, S. pneumoniae isolates demonstrated higher levels of resistance to beta-lactamines and cotrimoxazole than in the French general population. HIV-infected patients should benefit from the herd protection effect expected from the large-scale vaccination of children by PCV13.

Repeat measurements of nuchal translucency at 11-14 weeks of gestation: when do we need them?

OBJECTIVE: Previous studies have recommended that several repeat measurements of nuchal translucency (NT) be obtained to optimize sensitivity of the screening process. However, truncation is applied within the risk calculation for small NT measurements; therefore, repeating NT measurements in the lower range may be unnecessary. The aim of this study was to determine the optimal number of NT measurements and whether this is dependent on the initial value obtained. METHODS: We simulated the expected distribution of sets of five repeat NT measurements and their corresponding likelihood ratios (LR) for a variety of crown-rump length (CRL) values at 11-14 weeks' gestation, based on the published mixture model for first-trimester NT measurements and on published data regarding NT measurement variability. The ratio between LR obtained from the highest and the initial measurement in each set were computed, with a ratio of 1 indicating that repeat measurements would have no effect on risk estimation. We calculated NT cut-offs below which a change in estimated LR would occur in fewer than 10% of cases if repeat measurements were obtained, and we tested this approach on a real first-trimester screening dataset. RESULTS: The simulations performed indicated that repeating NT measurements when the first NT obtained ranged between ≤ 0.9 and ≤ 1.6 mm at CRLs of 45 and 84 mm, respectively, is not useful. When applied to a real dataset, our approach allowed avoiding repetition of measurements in 47/165 cases (28%). CONCLUSIONS: Although there is some variability in NT measurements, repeat assessment is not useful to optimize screening performance for the smallest NT measurements due to lower truncation limits that are applied in risk calculation. Our study provides NT cut-off values, in relation to CRL, below which it appears that there is no need to repeat measurements once a good quality image has been obtained.

Long-term functional stability of sacrospinous ligament-fixation repair of pelvic organ prolapse.

The objective of this study was to evaluate the variation over 5 years of functional discomfort associated with pelvic organ prolapse (POP) repaired by sacrospinous ligament fixation (SLF). A total of 178 women who had undergone SLF from 1992 to 2001. In 2002 and 2008, patients were sent a questionnaire including the pelvic floor distress inventory (PFDI-20); 79 responded and comparison of those data served to evaluate subjective signs at 5 years. This population was divided into two groups: ≤60 and >60 years old, and their 2002-2008 differences were compared. The outcomes were satisfaction, functional results and sexuality. Mean follow-up was 115 (72-173) months. Our results showed the long-term stability of SLF functional outcomes for women >60 years. However, for those≤60 years, functional outcomes and satisfaction had declined at 5 years.

[Radiation-induced neuropathies: collateral damage of improved cancer prognosis]. / Neuropathies post-radiques: un dommage collatéral chez les patients cancéreux long-survivants.

INTRODUCTION: Because of the improvement of cancer prognosis, long-term damages of treatments become a medical and public health problem. Among the iatrogenic complications, neurological impairment is crucial to consider since motor disability and pain have a considerable impact on quality of life of long cancer survivors. However, radiation-induced neuropathies have not been the focus of great attention. The objective of this paper is to provide an updated review about the radiation-induced lesions of the peripheral nerve system. STATE OF THE ART: Radiation-induced neuropathies are characterized by their heterogeneity in both symptoms and disease course. Signs and symptoms depend on the affected structures of the peripheral nerve system (nerve roots, nerve plexus or nerve trunks). Early-onset complications are often transient and late complications are usually progressive and associated with a poor prognosis. The most frequent and well known is delayed radiation-induced brachial plexopathy, which may follow breast cancer irradiation. Radiation-induced lumbosacral radiculoplexopathy is characterized by pure or predominant lower motor neuron signs. They can be misdiagnosed, confused with amyotrophic lateral sclerosis (ALS) or with leptomeningeal metastases since nodular MRI enhancement of the nerve roots of the cauda equina and increased cerebrospinal fluid protein content can be observed. In the absence of specific markers of the link with radiotherapy, the diagnosis of post-radiation neuropathy may be difficult. Recently, a posteriori conformal radiotherapy with 3D dosimetric reconstitution has been developed to link a precise anatomical site to unexpected excess irradiation. PERSPECTIVES AND CONCLUSION: The importance of early diagnosis of radiation-induced neuropathies is underscored by the emergence of new disease-modifying treatments. Although the pathophysiology is not fully understood, it is already possible to target radiation-induced fibrosis but also associated factors such as ischemia, oxidative stress and inflammation. A phase III trial evaluating the association of pentoxifylline, tocopherol and clodronate (PENTOCLO, NCT01291433) in radiation-induced neuropathies is now recruiting.

Cerebral aspergillosis in the era of new antifungals: The CEREALS national cohort study Nationwide CEREbral Aspergillosis Lesional study (CEREALS).

BACKGROUND: Cerebral aspergillosis (CA) is a life-threatening disease for which diagnosis and management remain challenging. Detailed analyses from large cohorts are lacking. METHODS: We included 119 cases of proven (n = 54) or probable (n = 65) CA diagnosed between 2006 and 2018 at 20 French hospitals. Data were collected at baseline and during follow-up. Cerebral imaging was reviewed centrally by two neuroradiologists. RESULTS: The most frequent underlying conditions were hematological malignancy (40%) and solid organ transplantation (29%). Galactomannan was detected in the serum of 64% of patients. In 75% of cases, at least one of galactomannan, Aspergillus PCR, and ß-d-glucan was positive in the cerebrospinal fluid. Six-week mortality was 45%. Two distinct patterns of disease were identified according to presumed route of dissemination. Presumed haematogenous dissemination (n = 88) was associated with a higher frequency of impaired consciousness (64%), shorter time to diagnosis, the presence of multiple abscesses (70%), microangiopathy (52%), detection of serum galactomannan (69%) and Aspergillus PCR (68%), and higher six-week mortality (54%). By contrast, contiguous dissemination from the paranasal sinuses (n = 31) was associated with a higher frequency of cranial nerve palsy (65%), evidence of meningitis on cerebral imaging (83%), macrovascular lesions (61%), delayed diagnosis, and lower six-week mortality (30%). In multivariate analysis and in a risk prediction model, haematogenous dissemination, hematological malignancy and the detection of serum galactomannan were associated with higher six-week mortality. CONCLUSION: Distinguishing between hematogenous and contiguous dissemination patterns appears to be critical in the workup for CA, as they are associated with significant differences in clinical presentation and outcome.

Likelihood ratio-based quality control for nuchal translucency measurements at 11-14 weeks of gestation.

OBJECTIVE: To develop a quantitative quality control process of nuchal translucency (NT) measurement at 11-14 weeks of gestation based on the mixture model, characterized by analysis of the corresponding distribution of the likelihood ratio (LR). METHODS: Based on the published mixture model for NT measurement in the first trimester, we simulated the expected distribution of NT and the corresponding LR. This approach was then tested for the quality control of 15 048 NT measurements performed by four operators trained and certified by The Fetal Medicine Foundation. The new quality control approach based on LR was compared with existing processes based on NT plots, multiples of the median (MoMs) and analysis of the 95(th) centile. RESULTS: Each operator contributed 2176-4730 examinations. Median, 5(th) and 95(th) centile of NT values ranged from 1.4 to 1.6, 1.0 to 1.0 and 2.2 to 2.6 mm, respectively. Median of NT-MoM values ranged from 0.83 to 0.95. Analysis of the distribution of NT measurements confirmed departure from the assumptions of the delta-NT and NT-MoM models. Analysis of LR distributions demonstrated a significant difference between observed and expected distributions for all operators (P < 10(-4) ). CONCLUSION: An LR-based quality control process is feasible at 11-14 weeks of gestation. Because it is more sensitive to measurement bias around the critical area of the 95(th) centile, its use should be encouraged.

Home-based exercise in autoimmune myasthenia gravis: A randomized controlled trial.

The tolerance of exercise and its effects on quality of life in myasthenia gravis are not currently backed up by strong evidence. The aim of this study was to determine whether exercise as an adjunct therapy is well tolerated and can improve health-related quality of life (HRQoL) in stabilized, generalized autoimmune myasthenia gravis (gMG). We conducted a parallel-group, multi-center prospective RCT using computer-generated block randomization. Adults with stabilized, gMG, and no contra-indication to exercise, were eligible. Participants received usual care alone or usual care and exercise. The exercise intervention consisted of 3-weekly 40 min sessions of an unsupervised, moderate-intensity home rowing program over 3 months. The primary endpoint was the change in HRQoL from randomization to post-intervention. Assessor-blinded secondary endpoints were exercise tolerance and effects on clinical, psychological and immunological status. Of 138 patients screened between October 2014 and July 2017, 45 were randomly assigned to exercise (n = 23) or usual care (n = 20). Although exercise was well tolerated, the intention-to-treat analysis revealed no evidence of improved HRQoL compared to usual care (MGQOL-15-F; mean adjusted between-groups difference of -0.8 points, 95%CI -5.4 to 3.7). Two patients hospitalized for MG exacerbation were from the usual care group.

Location of lacunar infarcts correlates with cognition in a sample of non-disabled subjects with age-related white-matter changes: the LADIS study.

OBJECTIVES: In cerebral small vessel disease, white-matter hyperintensities (WMH) and lacunes are both related to cognition. Still, their respective contribution in older people remains unclear. The purpose of this study is to assess the topographic distribution of lacunes and determine whether it has an impact on cognitive functions in a sample of non-disabled patients with age-related white-matter changes. METHODS: Data were drawn from the baseline evaluation of the LADIS (Leucoaraioisis and Disability study) cohort of non-disabled subjects beyond 65 years of age. The neuropsychological evaluation was based on the Mini Mental Status Examination (MMSE), a modified Alzheimer Diseases Assessment Scale for global cognitive functions, and compound Z scores for memory, executive functions, speed and motor control. WMH were rated according to the Fazekas scale; the number of lacunes was assessed in the following areas: lobar white matter, putamen/pallidum, thalamus, caudate nucleus, internal/external capsule, infratentorial areas. An analysis of covariance was performed after adjustment for possible confounders. RESULTS: Among 633 subjects, 47% had at least one lacune (31% at least one within basal ganglia). The presence of lacunes in the thalamus was associated with lower scores of MMSE (beta = -0.61; p = 0.043), and worse compound scores for speed and motor control (beta = -0.25; p = 0.006), executive functions (beta = -0.19; p = 0.022) independently of the cognitive impact of WMH. There was also a significant negative association between the presence of lacunes in putamen/pallidum and the memory compound Z score (beta = -0.13; p = 0.038). By contrast, no significant negative association was found between cognitive parameters and the presence of lacunes in internal capsule, lobar white matter and caudate nucleus. CONCLUSION: In non-disabled elderly subjects with leucoaraisosis, the location of lacunes within subcortical grey matter is a determinant of cognitive impairment, independently of the extent of WMH.

IFNgamma and antibody responses among French nurses during a tuberculosis contact tracing investigation.

STUDY: A comparative study which compared PPD skin testing inserted according to the French Society of Pneumology's recommendations and interferon gamma release assay (IGRA) (QuantiFERON((R)) TB Gold In-tube, QF-TB-IT, Cellestis, Carnegie, Australia) was performed during a tuberculosis contact investigation in our hospital. PATIENTS: Nineteen French health-care workers (HCWs) volunteered to participate. All of the HCW enrolled were BCG vaccinated and had a normal chest X-ray at entry. RESULTS: Among the HCW, 68.4% were TST positive. By comparison, only 31.6% had a positive QF-TB-IT result. We took advantage of the negative tube and the corresponding plasma for antibody detection by ELISA. None were ELISA positive. Fourteen HCWs were followed up. None of the HCWs accepted a course of antiTB chemoprophylaxis. Despite the difficulty in establishing a trend in kinetics, we saw the complexity of interpretation of a dynamic T-cell response after contact with an index case. CONCLUSION: This initial and first French picture provides us with the observation that only 44% of TST-positive HCW were IGRA positive, and the IGRA test allowed the detection of LTBI in two TST negative HCWs.