Study of choroidal thickness variations after ingestion of a taurine and caffeine-containing energy drink.

BACKGROUND & AIMS: Choroidal thickness can undergo considerable variations in response to different substances. The aim of this study was to assess the change in choroidal thickness after the ingestion of taurine and caffeine contained in the Red Bull energy drink. METHODS: Enhanced Depth Imaging - Spectral Domain Optical Coherence Tomography was used to measure subfoveal choroidal thickness (SFCT) variations in healthy volunteers at several time points after drinking a Red Bull can (25 cl). RESULTS: Forty eyes of 20 volunteers were enrolled. A significant reduction in SFCT (-14 µm, p < 0.0001) occurred at 1 h after the Red Bull intake, and was even more important (-20.14 µm, p < 0.0001) in eyes with particularly thick choroids (≥ 395 µm). SFCT measurements at 4 h were comparable to baseline. CONCLUSIONS: A concomitant ingestion of caffeine and taurine can induce a transient choroidal thinning that is more marked in eyes with thick choroids. REGISTRATION NUMBER OF CLINICAL TRIAL: NCT02856256.

Influence of the clindamycin administration route on the magnitude of clindamycin-rifampicin interaction: a prospective pharmacokinetic study.

OBJECTIVES: An important clindamycin-rifampicin pharmacokinetic (PK) interaction has been reported, but the potential influence of the clindamycin administration route on that interaction is unknown. This prospective, observational, comparative PK study was undertaken to characterize and analyse the impact of the route, comparing the rifampicin enzyme-inductor effects on clindamycin clearance (CLclin) for oral versus intravenous (IV) administration. METHODS: Patients with bone-and-joint infections (BJIs) were treated with clindamycin monotherapy (n = 20) or clindamycin-rifampicin combination therapy (n = 19). Patients received continuous IV clindamycin infusion for 2-6 weeks, followed by an oral regimen. Liquid chromatography-mass spectrometry was used to measure plasma clindamycin concentrations at the end of IV and after 2 weeks of oral treatment. The ratios of the mean CLclin for the combination and monotherapy groups were calculated for IV (Riv) and oral (Rpo) routes, with the final ratio, Rf = Rpo/Riv, representing the fold change of the rifampicin-inducing effect from the IV to the oral route. RESULTS: Comparing monotherapy with combination-therapy groups, the former's median steady-state concentration was two-fold higher after IV administration (8.49 versus 3.82 mg/L, p < 0.001) and its median AUC0-8h was 12 times higher after oral intake (37.7 versus 3.1 mg.h/L, p < 0.001). Riv, Rpo and Rf were 2.68, 18.8 and 7.0 respectively. CONCLUSION: The magnitude of this interaction was markedly increased by oral intake, questioning the use of oral treatment for difficult-to-treat infections like BJIs. Nevertheless, the clindamycin-rifampicin combination seems possible provided that clindamycin is administered by continuous IV infusion.

Echocardiography in Confirmed and Highly Suspected Symptomatic COVID-19 Patients and Its Impact on Treatment Change.

BACKGROUND: COVID-19 interacts at multiple levels with the cardiovascular system. The prognosis of COVID-19 infection is known to be worse for patients with underlying cardiovascular diseases. Furthermore, the virus is responsible for many cardiovascular complications. Myocardial injury may affect up to 20% of the critically ill patients. However, echocardiography's impact on the management of patients affected by COVID-19 remains unknown. OBJECTIVES: To explore echocardiography's impact on the management of COVID-19 patients. METHODS: This study was conducted from March 24th to April 14th, 2020, in a single center at Adolphe de Rothschild Foundation Hospital, Paris, France. All consecutive inpatients with laboratory and/or CT COVID-19 diagnosis were included in this study. Patients' characteristics (clinical, biological, and imaging) and treatment change induced by echocardiography were collected and analyzed. Patients with and without treatment change induced by echocardiography were compared. RESULTS: A total of 56 echocardiographies in 42 patients with highly suspected or confirmed COVID-19 were included in the final analyses. The median age was 66 (IQR 60.5-74). Echocardiography induced a treatment change in 9 cases (16%). The analyzed clinical data were not associated with any treatment change induced by echocardiography. D-dimer and Troponin levels were the only biological predictors of the induced treatment change. On echocardiography, higher systolic pulmonary arterial pressure and documented cardiac thrombi were associated with treatment changes in these patients. CONCLUSIONS: Echocardiography may be useful for the management of selected COVID-19 patients, especially those with elevated D-Dimer and Troponin levels, in up to 16% of patients.

Blood Pressure Target in Acute Stroke to Reduce HemorrhaGe After Endovascular Therapy: The Randomized BP TARGET Study Protocol.

Background: High systolic blood pressure (BP) is associated with an increased risk of intracranial hemorrhage (ICH) in patients undergoing reperfusion therapy. However, there are no data from randomized trials to guide BP management after reperfusion following endovascular therapy (EVT) for patients with acute ischemic stroke (AIS) with large vessel occlusion (LVO). The objective is to evaluate if BP control with a target of 100-129 mmHg systolic BP ("tight" SBP control) can reduce ICH as compared to 130-185 mmHg ("usual" SBP control) in AIS participants after reperfusion by EVT. Methods: The BP TARGET trial is a multicenter, prospective, randomized, controlled, open-label, blinded endpoint clinical trial. AIS participants with LVO experiencing successful reperfusion are randomly assigned, in a 1:1 ratio, to have a "tight" SBP control (100-129 mmHg) or a conservative SBP control (130-185 mmHg) during the following 24-36 h. The primary outcome is the rate of ICH (either symptomatic or asymptomatic) on follow-up CT scan at 24-36 h. Secondary outcomes include the rate of the symptomatic ICH, the overall distribution of the modified Rankin Scale (mRS) at 90 days, favorable outcome (90-day mRs 0-2), infarct volume at follow-up CT scan at 24-36 h, change in National Institute of Health Stroke Scale at 24 h, and all-cause mortality at 90 days. Conclusion: This is the first randomized trial directly comparing the efficacy of different SBP targets after EVT reperfusion. This prospective trial aims to determine whether a "tight" SBP control after EVT reperfusion can reduce the risk of ICH.

Correction: Absence of peripapillary retinal nerve-fiber-layer thinning in combined antiretroviral therapy-treated, well-sustained aviremic persons living with HIV.

[This corrects the article DOI: 10.1371/journal.pone.0229977.].

Left Ventricular End Diastolic Volume and Ejection Fraction Calculation: Correlation between Three Echocardiographic Methods.

BACKGROUND: Left ventricular ejection fraction (LVEF) and end diastolic volume (EDV) are measured using Simpson's biplane (SB), 3-dimensional method (3DE), and speckle tracking (STE). Comparisons between methods in routine practice are limited. Our purpose was to compare and to determine the correlations between these three methods in clinical setting. METHODS: LVEF and EDV were measured by three methods in 474 consecutive patients and compared using multiple Bland-Altman (BA) plots. The correlations (R) between methods were calculated. RESULTS: Median (IQR) LVEF_SB, LVEF_STE, and LVEF_3DE were 63.0% (60-69)%, 61% (57-65)%, and 62% (57-68)%. Median (IQR) EDV_SB, EDV_STE, and EDV_3DE were 85 ml (71-106) ml, 82 ml (69-100) ml, and 73 ml (59-89) ml. R between LVEF_SB and LVEF_3DE was 0.65 when echogenicity was good and 0.43 when poor. R for EDV_SB and EDV_3DE was 0.75 when echogenicity was good and 0.45 when poor. On BA analysis, biases were acceptable (<3.5% for LVEF) but limits of agreement (LOA) were large: 95% of the differences were between -15.4% and +18.8% for LVEF as evaluated by SB in comparison with 3DE, with a bias of 1.7%. In the comparison EDV_SB and EDV_3DE, the bias was 14 ml and the LOA were between -24 ml and +53 ml. On linear regressions, LVEF_3DE = 17.92 + 0.69 LVEF_SB and EDV_3DE = 18.94 + 0.63 EDV_SB. CONCLUSIONS: The three methods were feasible and led to acceptable bias but large LOA. Although these methods are not interchangeable, our results allow 3DE value prediction from SB, the most commonly used method.

Absence of peripapillary retinal nerve-fiber-layer thinning in combined antiretroviral therapy-treated, well-sustained aviremic persons living with HIV.

PURPOSE: To compare peripapillary retinal nerve-fiber-layer (pRNFL) thickness, total retina macular volume, and ganglion-cell-layer (GCL) macular volume and thickness between persons living with HIV (PLHIVs) with well-controlled infections and good immune recovery, and sex- and age-matched HIV-uninfected controls (HUCs). METHODS: This prospective cross-sectional study (www.clinicaltrials.gov identifier: NCT02003989) included 56 PLHIVs, infected for ≥10 [median 20.2] years and with sustained plasma HIV-load suppression on combined antiretroviral therapy (cART) for ≥5 years, and 56 matched HUCs. Participants underwent spectral-domain optical coherence tomography (SD-OCT) with thorough ophthalmological examinations and brain magnetic resonance imaging (MRI). Their overall and quadrant pRNFL thicknesses, total macular volumes, and GCL macular volumes and thicknesses were compared. Cerebral small-vessel diseases (CSVD) complied with STRIVE criteria. RESULTS: Median [interquartile range, IQR] ages of PLHIVs and HUCs, respectively, were 52 [46-60] and 52 [44-60] years. Median [IQR] PLHIVs' nadir CD4+ T-cell count and current CD4/CD8 T-cell ratio were 249/µL [158-350] and 0.95 [0.67-1.10], respectively; HIV-seropositivity duration was 20.2 [15.9-24.5] years; cART duration was 16.8 [12.6-18.6] years; and aviremia duration was 11.4 [7.8-13.6] years. No significant between-group pRNFL thickness, total macular volume, macular GCL-volume and -thickness differences were found. MRI-detected CSVD in 21 (38%) PLHIVs and 14 (25%) HUCs was associated with overall thinner pRNFLs, and smaller total retina and GCL macular volumes, independently of HIV status. CONCLUSIONS: SD-OCT could not detect pRNFL thinning or macular GCL-volume reduction in well-sustained, aviremic, cART-treated PLHIVs who achieved good immune recovery. However, CSVD was associated with thinner pRNFLs and GCLs, independently of HIV status.

Microalbuminuria: a sentinel of neurocognitive impairment in HIV-infected individuals?

BACKGROUND: According to population-based studies, microalbuminuria is associated with subsequent cognitive decline over a 4-6-year period, because of cerebral small-vessel disease (CSVD). This prospective cross-sectional study (NCT02852772) was designed to evaluate whether a history of microalbuminuria is associated with subsequent cognitive decline in combined antiretroviral therapy (cART)-treated persons living with human immunodeficiency virus (PLHIVs). METHODS: From our computerized medical database, we identified 30 PLHIVs (median age 52 years), immunovirologically controlled on cART, who had microalbuminuria in 2008 and had undergone, between 2013 and 2015, a comprehensive neuropsychological assessment (NPA) including seven domains (cases): information-processing speed, motor skills, executive functions, attention/working memory, learning/memory, reasoning and verbal fluency. Forty-nine PLHIVs matched for age (median age 48 years; p = 0.19), sex, and year of first HIV-seropositivity without microalbuminuria in 2008 were identified and underwent the same NPA between 2013 and 2015 (controls). RESULTS: Cases performed less well than controls for information-processing speed (p = 0.01) and motor skills (p = 0.02), but no differences were found for the other cognitive domains and global z-scores. A multivariable linear-regression model adjusted for confounding factors confirmed the microalbuminuria effect for the information-processing-speed z score. CONCLUSION: cART-treated PLHIVs with a history of microalbuminuria subsequently had worse cognitive performances for the information-processing-speed domain, possibly because of CSVD. Our observations should be considered preliminary findings of a temporal link between microalbuminuria, CSVD, and subsequent cognitive impairment.

Comparison of Laser Platform Estimation and Objective Measurement of Maximum Ablation Depth Using Scheimpflug Pachymetry in Myopic Femtosecond Laser In Situ Keratomileusis.

PURPOSE: To compare the preoperative estimation of maximum ablation depth provided by the laser platform with objective measurement using Scheimpflug pachymetry in myopic femtosecond laser-assisted in situ keratomileusis (FS-LASIK). METHODS: This is a prospective study carried out at the Rothschild Foundation, Paris, France. In 89 consecutive myopic eyes (45 patients) treated with FS-LASIK, the maximum ablation depth was calculated by measuring the difference between preoperative and 3-month postoperative measurements in central corneal thickness using Scheimpflug pachymetry (Pentacam HR; Oculus Optikgeräte, Wetzlar, Germany). These values were compared with the preoperative estimation of the maximum ablation depth provided by the laser platform, without nomogram adjustment. RESULTS: We found a strong linear correlation between laser platform estimation of maximum ablation depth and Scheimpflug pachymetry (P < 0.00001). The mean ablation depth measured using Scheimpflug pachymetry was greater than that predicted by the laser platform, with a mean overall difference of 2.15 µm (P < 0.05). Subgroup analysis revealed a difference in ablation depth measurements of 7.1 µm in the high myopia subgroup, which was the only subgroup where the difference remained statistically significant. CONCLUSIONS: In myopic FS-LASIK, laser platform estimation of maximum ablation depth correlates well with measurement of maximum ablation depth using Scheimpflug pachymetry and therefore can be used safely.

Brief Report: Impact of ART Classes on the Increasing Risk of Cerebral Small-Vessel Disease in Middle-Aged, Well-Controlled, cART-Treated, HIV-Infected Individuals.

BACKGROUND: Cerebral small-vessel disease (CSVD) is a chronic disease accounting for one-third of strokes and the second etiology of dementia. Despite sustained immunovirological control, CSVD prevalence is doubled in middle-aged persons living with HIV (PLHIVs), even after adjustment for traditional cardiovascular risk factors. We aimed to investigate whether exposure to any antiretroviral drug class could be associated with an increasing risk of CSVD. METHODS: The MicroBREAK-2 case-control study (NCT02210130) enrolled PLHIVs aged 50 years and older, treated with combined antiretroviral therapy for ≥5 years, with plasma HIV load controlled for ≥12 months. Cases were PLHIVs with radiologically defined CSVD, and controls were CSVD-free PLHIVs matched for age (±5 years), sex, and year of HIV diagnosis (±5 years). Multivariable conditional logistic regression analyses focused on cumulative exposure to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and/or exposure to integrase inhibitors (yes or no), adjusted for hypertension, CD4 nadir, current CD4/CD8 ratio, and HIV transmission group. RESULTS: Between May 2014 and April 2017, 77 cases and 77 controls (85.7% males) were recruited. PLHIVs' median age was 57.6 years, and median HIV diagnosis year was 1992. The increasing risk of CSVD was not associated with exposure to any ART class. CONCLUSION: No deleterious effect of ART class exposure on the risk of CSVD was found for middle-aged treated PLHIVs.

A new association: acute macular neuroretinopathy in acute optic neuritis.

BACKGROUND: Acute optic neuritis (AON) is a common optic nerve disease leading to retrograde degeneration of optic nerve axons, reflected by thinning of the inner retinal layers on optical coherence tomography. On the contrary, acute macular neuroretinopathy (AMN) type 2 is a rare outer retinal disorder that leads to thinning of the outer nuclear layers and is diagnosed by multimodal imaging. The aim of this study was to report a new association between these two diseases. METHODS: Patients with a first episode of optic neuritis were invited to participate in a study that involved optical coherence tomography evaluation at baseline and the following 1, 3, 6 and 12 months. All the study patients underwent ophthalmologic evaluation that comprised of visual acuity, visual field and multimodal imaging as well as orbital and brain Magnetic Resonance Imaging. A diagnosis of multiple sclerosis was made according to the 2010 McDonald criteria. RESULTS: Six of the 114 patients with acute optic neuritis also had acute macular neuroretinopathy, of whom three were positive for myelin oligodendrocyte glycoprotein antibodies (MOG-Abs), two had relapsing-remitting multiple sclerosis and one had clinical isolated syndrome. CONCLUSION: Our study suggests that it is imperative to check for associated AMN in cases of AON, especially those associated with MOG-Abs.

Platelet Functions are Decreased in Obesity and Restored after Weight Loss: Evidence for a Role of the SERCA3-Dependent ADP Secretion Pathway.

In obesity, platelets are described as hyperactive, mainly based on increased platelet size and presence of pro-thrombotic plasmatic molecules. We explored platelet functions, including calcium signalling in obesity, and the effect of weight loss. We included 40 obese patients (women with body mass index [BMI] of ≥ 35 kg/m2) who were to undergo gastric bypass surgery and 40 healthy lean subjects (women with BMI of < 25 kg/m2) as a control group. Approximately 1 year after surgery, the obese patients lost weight (75% had a BMI < 35 kg/m2). They were explored a second time with the same healthy control for the same platelet experiments. Compared with controls, obese patients' platelets displayed reduced sensitivity to thrombin (aggregation EC50 increased by 1.9 ± 0.3-fold, p = 0.005) and a lower Ca2+ response (70 ± 7% decrease, p < 10-4). In 17 pairs of patients, we performed additional experiments: in obese patients' platelets, thrombin-induced αIIbß3 activation was significantly lower (p = 0.003) and sarco-endoplasmic reticulum Ca2+ATPase (SERCA3) expression was decreased (48 ± 6% decrease, p < 10-4). These differences were abolished after weight loss. Interestingly, pharmacological inhibition of SERCA3 activity in control group's platelets mimicked similar alterations than in obese patients' platelets and was associated with defective adenosine diphosphate (ADP) secretion. Addition of ADP to agonist restored platelet functions in obese patients and in SERCA3-inhibited control platelets (five experiments) confirming the direct involvement of the SERCA3-dependent ADP secretion pathway. This is the first study demonstrating that platelets from obese patients are hypo-reactive, due to a deficiency of SERCA3-dependent ADP secretion. Weight loss restores SERCA3 activity and subsequent calcium signalling, αIIbß3 activation, platelet aggregation and ADP secretion.

A novel method of inducing endogenous pupil oscillations to detect patients with unilateral optic neuritis.

PURPOSE: To use and test a new method of inducing endogenously generated pupillary oscillations (POs) in patients with unilateral optic neuritis (ON), to describe a signal analysis approach quantifying pupil activity and to evaluate the extent to which POs permit to discriminate patients from control participants. METHOD: Pupil size was recorded with an eye-tracker and converted in real time to modulate the luminance of a stimulus (a 20° disk) presented in front of participants. With this biofeedback setting, an increasing pupil size transforms into a high luminance, entraining a pupil constriction that in turn decreases the stimulus luminance, and so on, resulting in endogenously generated POs. POs were recorded for 30 seconds in the affected eye, in the fellow eye and in binocular conditions with 22 patients having a history of unilateral ON within a period of 5 years, and with 22 control participants. Different signal analysis methods were used to quantify the power and frequency of POs. RESULTS: On average, pupil size oscillated at around 1 Hz. The amplitude of POs appears not to be a reliable marker of ON. In contrast, the frequency of POs was significantly lower, and was more variable over time, in the patients' affected eye, as compared to their fellow eye and to the binocular condition. No such differences were found in control participants. Receiver operating characteristic analyses based on the frequency and the variability of POs to classify patients and control participants gave an area under the curve of 0.82, a sensitivity of 82% (95%CI: 60%-95%) and a specificity of 77% (95%CI: 55%-92%). CONCLUSIONS: The new method used to induce POs allowed characterizing the visual afferent pathway defect in ON patients with encouraging accuracy. The method was fast, easy to use, only requiring that participants look ahead, and allows testing many stimulus parameters (e.g. color, stimulus location, size, etc).

Aflibercept Treatment in Polypoidal Choroidal Vasculopathy: Results of a Prospective Study in a Caucasian Population.

INTRODUCTION: Polypoidal choroidal vasculopathy (PCV) is a choroidal pathology characterized by frequent occurrences of subretinal hemorrhages and resistance to monotherapies such as ranibizumab or bevacizumab intravitreal injections (IVT). The purpose of this study is to evaluate both the anatomical and functional efficacy of aflibercept IVT as a monotherapy in PCV in a Caucasian population. METHODS: We conducted a prospective multicenter study in either treatment-naïve patients with PCV or PVC patients who had not been treated with anti-VEGF within the previous 3 months or with photodynamic therapy (PDT) within the previous 6 months. All patients had been treated with 3 initial monthly loading doses of aflibercept followed by a Q8 regimen for 28 weeks in total. All patients underwent a complete ophthalmic examination including the measurement of best-corrected visual acuity (BCVA) before each IVT and after 28 weeks as well as an optical coherent tomography (OCT) of the macula. At baseline and 28 weeks, the polypoidal dilations were analyzed with indocyanine green angiography. RESULTS: Thirty-four eyes of 34 patients were included in this study. All patients were followed for 28 weeks and received 5 aflibercept IVT. The mean baseline BCVA was 55 letters. After 28 weeks, significant +13 letters in BCVA and a regression of exudative signs on OCT in all patients were observed. In 62% of the cases, polyp disappearance was observed on indocyanine green angiography. DISCUSSION: In this study on a Caucasian population, we showed that aflibercept as a monotherapy provided both a significant visual gain and the regression of polypoidal dilations. Aflibercept use in monotherapy may contribute to reduce the hemorrhagic risk and atrophy linked to PDT.

Thrombus Neutrophil Extracellular Traps Content Impair tPA-Induced Thrombolysis in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Neutrophil Extracellular Traps (NETs) are DNA extracellular networks decorated with histones and granular proteins produced by activated neutrophils. NETs have been identified as major triggers and structural factors of thrombosis. A recent study designated extracellular DNA threads from NETs as a potential therapeutic target for improving tissue-type plasminogen activator (tPA)-induced thrombolysis in acute coronary syndrome. The aim of this study was to assess the presence of NETs in thrombi retrieved during endovascular therapy in patients with acute ischemic stroke (AIS) and their impact on tPA-induced thrombolysis. METHODS: We analyzed thrombi from 108 AIS patients treated with endovascular therapy. Thrombi were characterized by hematoxylin/eosin staining, immunostaining, and ex vivo enzymatic assay. Additionally, we assessed ex vivo the impact of deoxyribonuclease 1 (DNAse 1) on thrombolysis of AIS thrombi. RESULTS: Histological analysis revealed that NETs contributed to the composition of all AIS thrombi especially in their outer layers. Quantitative measurement of thrombus NETs content was not associated with clinical outcome or AIS pathogenesis but correlated significantly with endovascular therapy procedure length and device number of passes. Ex vivo, recombinant DNAse 1 accelerated tPA-induced thrombolysis, whereas DNAse 1 alone was ineffective. CONCLUSIONS: This study suggests that thrombus NETs content may be responsible for reperfusion resistance, including mechanical or pharmacological approaches with intravenous tPA, irrespectively of their etiology. The efficacy of a strategy involving an administration of DNAse 1 in addition to tPA should be explored in the setting of AIS. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02907736.

Implications of a paediatrician-psychologist tandem for sickle cell disease care and impact on cognitive functioning.

Sickle cell disease (SCD), a life-threatening chronic disease, necessitates a paediatric treatment plan that considers the influence of psychological, family and intercultural factors. At the Louis-Mourier Hospital (APHP) in Colombes, France, we introduced an original paediatric-psychological partnership where a clinical psychologist accompanies the paediatrician at programmed consultations. We evaluated children and their parents treated in Colombes and in two other paediatric units using standardized culture-free tools and clinical interviews to evaluate the psychological repercussions of SCD. We first present a global view of the different ways that SCD affects both children and their families. We then discuss findings from a study evaluating the overall efficacy of an integrated psycho-medical treatment model as compared to the usual medical care model. Children in the integrated care model improved their cognitive functioning assessed using the Rey-Osterrieth complex figure test compared to treatment as usual. CONCLUSION: Findings suggest that the concept of a "partnership practice" can improve children's ability to grapple with SCD and is a promising approach for long-term care of SCD. What is Known: • Painful crises of sickle cell disease are unpredictable and appear in early childhood • Stress as well as the complex psychological and intercultural issues associated with SCD may aggravate the children's symptoms • Standard pediatric care and research deal primarily with medical issues What is New: • Evidence-based research examining the psychological repercussions of SCD in pediatric treatment as well as the parental distress • First study using standardized culture-free tools • Cognitive functioning improves under an innovative "partnership" model.

Silent Cerebral Small-Vessel Disease Is Twice as Prevalent in Middle-Aged Individuals With Well-Controlled, Combination Antiretroviral Therapy-Treated Human Immunodeficiency Virus (HIV) Than in HIV-Uninfected Individuals.

Background: Silent cerebral small-vessel disease (CSVD) is defined as white matter hyperintensities, silent brain infarction, or microbleeds. CSVD is responsible for future vascular events, cognitive impairment, frailty, and shorter survival. CSVD prevalence among middle-aged people living with well-controlled human immunodeficiency virus (HIV) infection (PLHIV) is unknown. Methods: The French National Agency for Research on AIDS and Viral Hepatitis (ANRS) EP51 Microvascular Brain Retina and Kidney Study (MicroBREAK; NCT02082574) is a cross-sectional study with prospective enrollment of treated PLHIV, ≥50 years old with viral load controlled for ≥12 months, and frequency age- and sex-matched HIV-uninfected controls (HUCs). It was designed to estimate CSVD prevalence on 3T magnetic resonance imaging (3D fluid-attenuated inversion recovery, transversal T2-weighted gradient-echo imaging and diffusion-weighted imaging), as diagnosed by 2 blinded neuroradiologists. A logistic regression model was used to assess the impact of HIV on CSVD after adjustment for traditional risk factors. Results: Between June 2013 and May 2016, 456 PLHIV and 154 HUCs were recruited. Median age was 56 and 58 years, respectively (P = .001), among whom 84.9% and 77.3%, respectively (P = .030), were men. CSVD was detected in 51.5% of PLHIV and 36.4% of HUCs with an adjusted odds ratio (aOR) of 2.3. The HIV impact differed according to age, with aOR values of 5.3, 3.7, and 1.0 for age groups <54, 54-60, and >60 years, respectively (P = .022). Older age, hypertension, and lower CD4 cell count nadir were independently associated with a higher risk of CSVD among PLHIV. Conclusions: HIV is an independent risk factor for CSVD. Despite sustained immunovirological control, the CSVD prevalence was twice as high among middle-aged PLHIV than HUCs. Clinical Trials Registration: NCT02082574.

Loxapine to control agitation during weaning from mechanical ventilation.

BACKGROUND: Weaning from mechanical ventilation (MV) may be impeded by the occurrence of agitation. Loxapine has the ability to control agitation without affecting spontaneous ventilation. The aim of this study was to establish whether loxapine would reduce MV weaning duration in agitated patients. METHODS: We performed a multicentre, double-blind, placebo-controlled, parallel group, randomised trial. Patients who were potential candidates for weaning but exhibited agitation (Richmond Agitation-Sedation Scale score ≥ 2) after sedation withdrawal were randomly assigned to receive either loxapine or placebo. In case of severe agitation, conventional sedation was immediately resumed. The primary endpoint was the time between first administration of loxapine or placebo and successful extubation. RESULTS: The trial was discontinued after 102 patients were enrolled because of an insufficient inclusion rate. Median times to successful extubation were 3.2 days in the loxapine group and 5 days in the placebo group (relative risk 1.2, 95% CI 0.75-1.88, p = 0.45). During the first 24 h, sedation was more frequently resumed in the placebo group (44% vs 17%, p = 0.01). CONCLUSIONS: In this prematurely stopped trial, loxapine did not significantly shorten weaning from MV. However, loxapine reduced the need for resuming sedation. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01193816 . Registered on 26 August 2010.

End of life in the intensive care unit: should French law be adapted?

BACKGROUND: Longstanding concerns regarding end of life in the ICU led in France to the publication of guidelines, updated in 2009, that take into account the insights provided by a recent law (Leonetti's law) regarding patients' rights. After the French President asked a specific expert to review end of life issues, the French Intensive Care Society (SRLF) surveyed their members (doctors and paramedics) about various aspects of end of life in the ICU. METHODS: SRLF members were invited to respond to a questionnaire, sent by Email, designed to assess their knowledge of Leonetti's law and to determine how many caregivers would agree with the authorization of lethal drug administration in selected end of life situations. RESULTS: Questionnaires returned by 616 (23%) of 2,700 members were analyzed. Most members (82.5%) reported that they had a good knowledge of Leonetti's law, which most (88%) said they have often applied. One third of respondents had received 'assisted death' requests from patients and more than 50% from patients' relatives. One quarter of respondents had experienced the wish to give lethal drugs to end of life patients. Assuming that palliative care in the ICU is well-managed, 25.7% of the respondents would approve a law authorizing euthanasia, while 26.5% would not. Answers were influenced by the fear of a possible risk of abuse. Doctors and nurses answered differently. CONCLUSION: ICU caregivers appear to be well acquainted with Leonetti's law. Nevertheless, in selected clinical situations with suitable palliative care, one quarter of respondents were in favor of a law authorizing administration of lethal drugs to patients.