Voltammetric Investigation of Ferulic Acid at Disposable Pencil Graphite Electrode.

Ferulic acid (FA), a monohydroxycinnamic acid, is an antioxidant with multiple beneficial effects on human health, presenting also importance in the food and cosmetics industry. Its electrochemical behavior was investigated at the disposable and cost-effective pencil graphite electrode (PGE). Cyclic voltammetry emphasized its pH-dependent, diffusion-controlled oxidation. Using the optimized conditions (HB type PGE, Britton Robinson buffer pH 4.56) differential pulse and square-wave voltammetric techniques were applied for its quantitative determination in the range 4.00 × 10-7-1.00 × 10-3 mol/L FA. The developed methods were employed for the rapid and simple assessment of the FA content from a commercially available powder designed for cosmetic use.

Risk of Multidrug Resistant Bacteria Acquisition in Patients with Declared ß-Lactam Allergy during Hospitalization in Intensive Care Unit: A Retrospective Cohort Study (2007-2018).

INTRODUCTION: The risk of extended spectrum ß-lactamase (ESBL) bacterial acquisition in patients with ß-lactam allergy has been poorly investigated. In a previous study conducted over a 6-year long period (2007-2012), we found that patients with declared ß-lactam allergy had a higher risk of ESBL bacterial carriage at admission in intensive care unit (ICU), but they had not a higher risk of ESBL bacterial acquisition. We present the final results of the study which was eventually conducted over a 12-year long period (2007-2018). MATERIALS AND METHODS: The study included all patients admitted in ICU and receiving antibiotic treatment from January 2007 to December 2018. ESBL bacterial acquisition was the main clinical outcome. Mortality in ICU, multidrug resistant bacterial carriage at admission and discharge were the secondary outcomes. RESULTS: Overall, 3332 patients were included, 132/3332 (3.9%) were labelled ß-lactam allergic, while 3200/3332 (96.1%) did not presented ß-lactam allergy. No significant difference in rates of ESBL acquisition was detected (4/132, 3% vs. 78/3200, 2.4%; p = 0.17). Patients with ß-lactam allergy had higher rates of ESBL bacterial carriage at admission (19/132, 14.4% vs. 248/3200, 7.8%, p = 0.01) and at discharge (22/132, 16.7% vs. 351/3200, 11%, p = 0.04) than nonallergic patients. No differences in mortality, duration of hospitalization, and carriage of methicillin resistant Staphylococcus aureus were reported. Female gender was the only factor associated with ß-lactam allergy at the multivariate analysis. CONCLUSIONS: This study confirms that patients with declared ß-lactam allergy had not a higher risk of ESBL bacterial acquisition during hospitalization in ICU. However, they had a higher ESBL bacterial carriage at admission.

ß-Lactam allergy and risk of multidrug-resistant bacteria in the intensive care unit: A cohort study.

Patients identified as allergic to ß-lactams are frequently exposed to treatment with broad-spectrum antibiotics. However, the risk of carriage of extended-spectrum ß-lactamase (ESBL)-producing isolates in this population has been poorly investigated. The aim of this study was to evaluate the characteristics and clinical outcomes of patients admitted to the intensive care unit (ICU) with and without declared ß-lactam allergy at admission. A retrospective monocentric study was performed including adult patients admitted to the ICU between 2007 and 2012. The presence of multidrug-resistant bacteria was documented in rectal and nasal swabs at admission and discharge. Patients labelled allergic to ß-lactams and unlabelled patients were compared. Patients labelled allergic had significantly higher rates of ESBL at admission (13.3% vs. 4.3%; P = 0.0220) and discharge (20.0% vs. 9.0%; P = 0.0460) compared with unlabelled patients, but no significant difference in rates of ESBL acquisition in the ICU was detected. No differences in mortality, duration of hospitalisation or typical risk factors for ESBL acquisition (intubation, central venous catheter and duration of hospitalisation) were reported. No differences in carriage of methicillin-resistant Staphylococcus aureus were detected. This study showed that patients with declared ß-lactam allergy had a higher risk of ESBL carriage at ICU admission and discharge.

Clinical and microbiological characteristics of the infections in patients treated with rituximab for autoimmune and/or malignant hematological disorders.

INTRODUCTION: Rituximab is commonly used for the treatment of hematological malignancies and autoimmune diseases. Despite a reputation for good tolerance, case-series and registries reported rituximab-related infections of variable severity including opportunistic infections. We aimed at describing the natural history of infectious events (IE) after treatment by rituximab providing clinical and microbiological features and outcome. PATIENTS AND METHODS: We retrospectively analyzed the medical records of patients treated with rituximab in an internal medicine department of a tertiary hospital between 2007 and 2015, and identified all IE after this therapy. Events' severity was assessed using the Common Terminological Criteria of Adverse Events (version 4.3) definitions. RESULTS: Among 101 patients treated with rituximab, we identified 228 IE in 74 (73.3%) of these patients (median follow-up 30.4months). Indication for rituximab was either autoimmune disease (AID) (52.5% of patients), or monoclonal hematological disease (MHD) (47.5%). Patients received an overall median number of 5 rituximab infusions [interquartile range: 4-8], representing a cumulative dose of 4340mg [2620-6160]. After last rituximab infusion, IE occurred after 3.1months [0.7-9.4]. Respectively, IE were severe in 28.1% of cases in patients treated for AID vs 58.0% in patients treated for MHD (p<0.001), due to opportunistic pathogens in 7.8% vs 11.0% (p=0.49) and fatal in 4.7% vs 13.0% (p=0.044). Factor associated with mortality were polymicrobial infection (p<0.001), monoclonal hematological disease (p=0.035), use of steroids over 10mg/d within the last two weeks (p=0.003), and rituximab cumulative dose (p<0.001). We identified a group of 10 patients (9.9%) showing life-threatening, polymicrobial, and opportunistic infections constituting a 'catastrophic infectious syndrome', which was lethal in 7 cases. CONCLUSION: IE after treatment by rituximab can be extremely severe, especially in patients immunocompromised by several other drugs. Further studies should focus on the group with life-threatening polymicrobial infections.

Nonorgan-specific autoantibodies in HIV-infected patients in the HAART era.

Nonorgan-specific autoantibodies (AAbs) are used for diagnosing autoimmune diseases but can also be detected in other conditions. We carried out a cross-sectional study with the aim to screen HIV1-infected patients in the era of highly active antiretroviral therapy (HAART) for AAbs and to analyze the association of their presence with hypergammaglobulinemia and immunovirological status.Blood samples from HIV1-infected patients without major concomitant illnesses followed in 2 hospitals in Paris, France were tested for immunovirological status, serum immunoglobulin G (IgG) level, antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), anti-extractable nuclear antigens (anti-ENAs), anticardiolipin (aCL), anti-ß2glycoprotein1 (anti-ß2GP1), and antineutrophil cytoplasmic antibodies (ANCAs). Clinically relevant AAbs were defined as ANAs with titers ≥1:160, anti-dsDNA or anti-ENA antibodies; aCL or anti-ß2GP1 antibodies with a level ≥40 U/ml; and ANCAs reacting with proteinase 3 or myeloperoxidase.We included 92 patients (mean age 47 years, men 55%, sub-Saharan African background 55%, HAART 85%, mean CD4 lymphocyte count 611/mm, viral load < 40 copies/mL 74%). At least 1 AAb was detected in 45% of patients, mostly ANAs (33%) and ANCAs (13%); 12% had ≥1 clinically relevant AAb. Above-normal IgG levels were found in 71% of patients. We found an inverse association between the presence of ≥1 AAb and CD4 lymphocyte count (P = 0.03) and between above-normal IgG levels and duration of virological control (P = 0.02) and non-sub-Saharan African background (P = 0.001).In sum, in HIV1-infected patients without any major concomitant illness in the HAART era, the prevalence of AAbs remains high but AAb patterns leading to high suspicion of autoimmune diseases are rather uncommon. AAb presence is associated with reduced CD4 lymphocyte count but not hypergammaglobulinemia.

Types, frequencies, and burden of nonspecific adverse events of drugs: analysis of randomized placebo-controlled clinical trials.

PURPOSE: Scarce studies analyzing adverse event (AE) data from randomized placebo-controlled clinical trials (RPCCTs) of selected illnesses suggested that a substantial proportion of collected AEs are unrelated to the drug taken. This study analyzed the nonspecific AEs occurring with active-drug exposure in RPCCTs for a large range of medical conditions. METHODS: Randomized placebo-controlled clinical trials published in five prominent medical journals during 2006-2012 were searched. Only trials that evaluated orally or parenterally administered active drugs versus placebo in a head-to-head setting were selected. For AEs reported from ≥10 RPCCTs, Pearson's correlation coefficients (r) were calculated to determine the relationship between AE rates in placebo and active-drug recipients. Random-effects meta-analyses were used to compute proportions of nonspecific AEs, which were truncated at a maximum of 100%, in active-drug recipients. RESULTS: We included 231 trials addressing various medical domains or healthy participants. For the 88 analyzed AE variables, AE rates for placebo and active-drug recipients were in general strongly correlated (r > 0.50) or very strongly correlated (r > 0.80). The pooled proportions of nonspecific AEs for the active-drug recipients were 96.8% (95%CI: 95.5-98.1) for any AEs, 100% (97.9-100) for serious AEs, and 77.7% (72.7-83.2) for drug-related AEs. Results were similar for individual medical domains and healthy participants. The pooled proportion of nonspecificity of 82 system organ class and individual AE types ranged from 38% to 100%. CONCLUSION: The large proportion of nonspecific AEs reported in active-drug recipients of RPCCTs, including serious and drug-related AEs, highlights the limitations of clinical trial data to determine the tolerability of drugs. Copyright © 2017 John Wiley & Sons, Ltd.

Autoimmune diseases in HIV-infected patients: 52 cases and literature review.

OBJECTIVES: 1) To describe autoimmune diseases (AD) in HIV-infected people; and 2) to perform a literature review concerning this issue. DESIGN: 52 HIV-infected patients that presented an AD in 14 medical departments in Paris and Ile-de-France area were retrospectively included in this study. RESULTS: The ADs were vasculitis (11), immune cytopenias (8), rheumatic diseases (8), lupus (7), sarcoidosis (7), thyroid diseases (6), hepatic diseases (5), and antiphospholipid syndrome (4). Four patients presented 2 ADs. In 5 patients the AD preceded HIV infection, in 14 HIV infection was diagnosed at the same time as the AD and 34 were HIV-infected when they developed an AD. 40 ADs (80%) occurred in patients with a CD4 T lymphocyte count of more than 200/mm(3). Cases of autoimmune hemolytic anemia occurred only in patients severely immunodepressed. In five patients (a vasculitis case, a sarcoidosis case, three thyroid disease cases) the AD presented as a form of immune restoration inflammatory syndrome (IRIS). Some ADs allowed HIV-infection diagnosis at a stage of moderate immune deficiency (vasculitis, antiphospholipid syndrome, immune thrombocytopenia). 37 patients received immunosuppressant treatments with good tolerance. These results confirm in a large series of patients previous data concerning autoimmune diseases occurrence in HIV-infected people. CONCLUSION: In the HAART era, when HIV-infected people are treated more and more early, autoimmune diseases can occur, mainly at the phase of immunological recovery. HIV infection should not limit immunosuppressant treatment use.

Safety and immunogenicity of yellow fever 17D vaccine in adults receiving systemic corticosteroid therapy: an observational cohort study.

OBJECTIVE: To assess the safety and immunogenicity of live attenuated yellow fever (YF) 17D vaccine in adults receiving systemic corticosteroid therapy. METHODS: All adult travelers on systemic corticosteroid therapy who had received the YF17D vaccine in 24 French vaccination centers were prospectively enrolled and matched with healthy controls (1:2) on age and history of YF17D immunization. Safety was assessed in a self-administered standardized questionnaire within 10 days after immunization. YF-specific neutralizing antibody titers were measured 6 months after vaccination in patients receiving corticosteroids. RESULTS: Between July 2008 and February 2011, 102 vaccine recipients completed the safety study (34 receiving corticosteroids and 68 controls). The median age was 54.9 years (interquartile range [IQR] 45.1-60.3 years) and 45 participants had a history of previous YF17D immunization. The median time receiving corticosteroid therapy was 10 months (IQR 1-67 months) and the prednisone or equivalent dosage was 7 mg/day (IQR 5-20). Main indications were autoimmune diseases (n = 14), rheumatoid arthritis (n = 9), and upper respiratory tract infections (n = 8). No serious adverse event was reported; however, patients receiving corticosteroids reported more frequent moderate/severe local reactions than controls (12% and 2%, respectively; relative risk 8.0, 95% confidence interval 1.4-45.9). All subjects receiving corticosteroids who were tested (n = 20) had neutralizing antibody titers >10 after vaccination. CONCLUSION: After YF17D immunization, moderate/severe local reactions may be more frequent in patients receiving systemic corticosteroid therapy. Immunogenicity seems satisfactory. Large-scale studies are needed to confirm these results.

Long-term evolution and determinants of renal function in HIV-infected patients who began receiving combination antiretroviral therapy in 1997-1999, ANRS CO8 APROCO-COPILOTE.

Among 1121 patients (90% Caucasian) infected by the human immunodeficiency virus (HIV), the glomerular filtration rate increased (+0.72 mL/min/1.73 m(2)/month) from treatment initiation to month 16 (the rate increase was lower among men and those with low body mass index, AIDS, or receipt of indinavir), then remained stable up to 7 years. Kidney function should be monitored in patients previously exposed to indinavir.