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BACKGROUND: Women with HIV are globally underrepresented in clinical research. Existing studies often focus on reproductive outcomes, seldom focus on older women, and are often underpowered to assess sex/gender differences. We describe CD4, HIV viral load (VL), clinical characteristics, comorbidity burden, and use of antiretroviral therapy (ART) among women with HIV in the RESPOND study and compare them with those of the men in RESPOND. METHODS: RESPOND is a prospective, multi-cohort collaboration including over 34 000 people with HIV from across Europe and Australia. Demographic and clinical characteristics, including CD4/VL, comorbidity burden, and ART are presented at baseline, defined as the latter of 1 January 2012 or enrolment into the local cohort, stratified by age and sex/gender. We further stratify men by reported mode of HIV acquisition, men who have sex with men (MSM) and non-MSM. RESULTS: Women account for 26.0% (n = 9019) of the cohort, with a median age of 42.2 years (interquartile range [IQR] 34.7-49.1). The majority (59.3%) of women were white, followed by 30.3% Black. Most women (75.8%) had acquired HIV heterosexually and 15.9% via injecting drug use. Nearly half (44.8%) were receiving a boosted protease inhibitor, 31.4% a non-nucleoside reverse transcriptase inhibitor, and 7.8% an integrase strand transfer inhibitor. The baseline year was 2012 for 73.2% of women and >2019 for 4.2%. Median CD4 was 523 (IQR 350-722) cells/µl, and 73.6% of women had a VL <200 copies/mL. Among the ART-naïve population, women were more likely than MSM but less likely than non-MSM (p < 0.001) to have CD4 <200 cells/µL and less likely than both MSM and non-MSM (p < 0.001) to have VL ≥100 000 copies/mL. Women were also more likely to be free of comorbidity than were both MSM and non-MSM (p < 0.0001). CONCLUSION: RESPOND women are diverse in age, ethnicity/race, CD4/VL, and comorbidity burden, with important differences relative to men. This work highlights the importance of stratification by sex/gender for future research that may help improve screening and management guidelines specifically for women with HIV.
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INTRODUCTION: Faced with the first wave of Covid-19 pandemic, guidelines for surgical triage were developed to free up healthcare resources. The aim of our study was to assess clinical characteristics and surgical outcomes of triaged patients during the first Covid-19 crisis. METHOD: We conducted a cohort-controlled, non-randomized, study in a University Hospital of south-eastern France. Data were collected prospectively from consecutive patients after triage during the period from March 15th to May 1st and compared with control data from outside pandemic period. Primary endpoint was intensive care unit (ICU) admissions for surgery-related complications. Rates of surgery-specific death, postponed operations, positive PCR testing and Clavien-Dindo complications and data from cancer and non- cancer subgroups were assessed. RESULTS: After triage, 96 of 142 elective surgeries were postponed. Altogether, 71 patients, median age 68 y.o (IQR: 56-75 y.o), sex ratio M/F of 4/1, had surgery, among whom, 48 (68%) had uro-oncological surgery. No patients developed Covid-19 pneumonia in the post-surgery period. Three (4%) were admitted to the ICU, one of whom died from multi-organ failure due to septic shock caused by klebsiella pneumonia following a delay in treatment. Three Covid-19 RT-PCR were done and all were negative. There was no difference in mortality rates or ICU admission rates between control and Covid- era patients. CONCLUSIONS: Surgery after triage during the first Covid-19 pandemic was not associated with worse short-term outcomes. Urological cancers could be operated on safely in our context but delays in care for aggressive genitourinary diseases could be life threatening. LEVEL OF EVIDENCE: 3.
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COVID-19/epidemiologia , Pandemias , Triagem/organização & administração , Doenças Urológicas/cirurgia , Neoplasias Urológicas/cirurgia , Idoso , Teste para COVID-19 , Estudos de Coortes , Feminino , França/epidemiologia , Hospitalização , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Doenças Urológicas/epidemiologia , Neoplasias Urológicas/epidemiologiaRESUMO
The EuroSIDA study was initiated in 1994 and follows adult people living with HIV (PLHIV) in 100 collaborating clinics across 35 countries covering all European regions, Israel and Argentina. The study aims to study the long-term virological, immunological and clinical outcomes of PLHIV and to monitor temporal changes and regional differences in outcomes across Europe. Annually collected data include basic demographic characteristics, information on AIDS- and non-AIDS-related clinical events, and details about antiretroviral therapy (ART), hepatitis C treatment and other medications, in addition to a range of laboratory values. The summer 2016 data set held data from a total of 23 071 individuals contributing 174 481 person-years of follow-up, while EuroSIDA's unique plasma repository held over 160 000 samples. Over the past 25 years, close to 300 articles have been published in peer-reviewed journals (h-index 52), covering a range of scientific focus areas, including monitoring of clinical and virological outcomes, ART uptake, efficacy and adverse events, the influence of hepatitis virus coinfection, variation in the quality of HIV care and management across settings and regions, and biomarker research. Recognizing that there remain unresolved issues in the clinical care and management of PLHIV in Europe, EuroSIDA was one of the cohorts to found The International Cohort Consortium of Infectious Disease (RESPOND) cohort consortium on infectious diseases in 2017. In celebration of the EuroSIDA study's 25th anniversary, this article aims to summarize key scientific findings and outline current and future scientific focus areas.
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Infecções por HIV/tratamento farmacológico , HIV/imunologia , Hepatite C/tratamento farmacológico , RNA Viral/genética , Argentina , Contagem de Linfócito CD4 , Coinfecção , Europa (Continente) , Feminino , HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Israel , Perda de Seguimento , Masculino , Estudos Multicêntricos como Assunto , Resultado do Tratamento , Carga ViralRESUMO
OBJECTIVES: Although outcomes of antiretroviral therapy (ART) have been evaluated in randomized controlled trials, experiences from subpopulations defined by age, CD4 count or viral load (VL) in heterogeneous real-world settings are limited. METHODS: The study design was an international multicohort collaboration. Logistic regression was used to compare virological and immunological outcomes at 12 ± 3 months after starting ART with an integrase strand transfer inhibitor (INSTI), contemporary nonnucleoside reverse transcriptase inhibitor (NNRTI) or boosted protease inhibitor (PI/b) with two nucleos(t)ides after 1 January 2012. The composite treatment outcome (cTO) defined success as VL < 200 HIV-1 RNA copies/mL with no regimen change and no AIDS/death events. Immunological success was defined as a CD4 count > 750 cells/µL or a 33% increase where the baseline CD4 count was ≥ 500 cells/µL. Poisson regression compared clinical failures (AIDS/death ≥ 14 days after starting ART). Interactions between ART class and age, CD4 count, and VL were determined for each endpoint. RESULTS: Of 5198 ART-naïve persons in the International Cohort Consortium of Infectious Diseases (RESPOND), 45.4% started INSTIs, 26.0% PI/b and 28.7% NNRTIs; 880 (17.4%) were aged > 50 years, 2539 (49.4%) had CD4 counts < 350 cells/µL and 1891 (36.8%) had VL > 100 000 copies/mL. Differences in virological and immunological success and clinical failure among ART classes were similar across age groups (≤ 40, 40-50 and > 50 years), CD4 count categories (≤ 350 vs. > 350 cells/µL) and VL categories at ART initiation (≤ 100 000 vs. > 100 000 copies/mL), with all investigated interactions being nonsignificant (P > 0.05). CONCLUSIONS: Differences among ART classes in virological, immunological and clinical outcomes in ART-naïve participants were consistent irrespective of age, immune suppression or VL at ART initiation. While confounding by indication cannot be excluded, this provides reassuring evidence that such subpopulations will equally benefit from contemporary ART.
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Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/genética , Inibidores de Proteases/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , Inibidores de Integrase de HIV/farmacologia , HIV-1/efeitos dos fármacos , Humanos , Cooperação Internacional , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inibidores de Proteases/farmacologia , RNA Viral/efeitos dos fármacos , Inibidores da Transcriptase Reversa/farmacologia , Resultado do Tratamento , Carga ViralRESUMO
OBJECTIVES: We examined trends in the incidence rates of invasive cervical cancer (ICC) and in the rate of survival after ICC among women living with HIV (WLHIV) in France and compared them to those of the general population. METHODS: Histologically validated incident cases of ICC in the period 1992-2009 from the French Hospital Database on HIV (FHDH-ANRS CO4) were included in the study. Age-standardized incidence rates were estimated for FHDH and the general population in France for 1992-1996 [pre-combination antiretroviral therapy (cART) period], 1997-2000 (early cART period), 2001-2004 (intermediate cART period), and 2005-2009 (late cART period). Age-standardized incidence ratios (SIRs) were calculated. Five-year survival was compared with that of the general population for ICC diagnosed in 2005-2009 after standardization for age. RESULTS: Among 28 977 WLHIV, 60 incident ICCs were histologically validated. There was a nonsignificant decreasing trend for the incidence across the cART periods (P = 0.07), from 60 to 36/100 000 person-years. The risk of ICC was consistently significantly higher in WLHIV than in the general population; the SIR was 5.4 [95% confidence interval (CI) 3.0-8.9] during the pre-cART period and 3.3 (95% CI 2.2-4.7) in 2005-2009. Survival after ICC did not improve across periods (log-rank P = 0.14), with overall estimated 5-year survival of 78% (95% CI 0.67-0.89%). Five-year survival was similar for WLHIV and the general population for women diagnosed with ICC in 2005-2009, after standardization (P = 0.45). CONCLUSIONS: ICC risk is still more than three times higher in WLHIV than in the general population. Survival after ICC did not improve over time and was similar to that of the general population during the most recent period. Such results call for promotion of the uptake of screening in WLHIV.
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Antirretrovirais/administração & dosagem , Infecções por HIV/tratamento farmacológico , Neoplasias do Colo do Útero/epidemiologia , Adulto , Antirretrovirais/uso terapêutico , Estudos de Coortes , Feminino , França/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/mortalidade , Humanos , Incidência , Pessoa de Meia-Idade , Medição de Risco , Análise de Sobrevida , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/mortalidadeRESUMO
OBJECTIVES: There are currently few data on the long-term risk of cancer and death in individuals taking raltegravir (RAL). The aim of this analysis was to evaluate whether there is evidence for an association. METHODS: The EuroSIDA cohort was divided into three groups: those starting RAL-based combination antiretroviral therapy (cART) on or after 21 December 2007 (RAL); a historical cohort (HIST) of individuals adding a new antiretroviral (ARV) drug (not RAL) to their cART between 1 January 2005 and 20 December 2007, and a concurrent cohort (CONC) of individuals adding a new ARV drug (not RAL) to their cART on or after 21 December 2007. Baseline characteristics were compared using logistic regression. The incidences of newly diagnosed malignancies and death were compared using Poisson regression. RESULTS: The RAL cohort included 1470 individuals [with 4058 person-years of follow-up (PYFU)] compared with 3787 (4472 PYFU) and 4467 (10 691 PYFU) in the HIST and CONC cohorts, respectively. The prevalence of non-AIDS-related malignancies prior to baseline tended to be higher in the RAL cohort vs. the HIST cohort [adjusted odds ratio (aOR) 1.31; 95% confidence interval (CI) 0.95-1.80] and vs. the CONC cohort (aOR 1.89; 95% CI 1.37-2.61). In intention-to-treat (ITT) analysis (events: RAL, 50; HIST, 45; CONC, 127), the incidence of all new malignancies was 1.11 (95% CI 0.84-1.46) per 100 PYFU in the RAL cohort vs. 1.20 (95% CI 0.90-1.61) and 0.83 (95% CI 0.70-0.99) in the HIST and CONC cohorts, respectively. After adjustment, there was no evidence for a difference in the risk of malignancies [adjusted rate ratio (RR) 0.73; 95% CI 0.47-1.14 for RALvs. HIST; RR 0.95; 95% CI 0.65-1.39 for RALvs. CONC] or mortality (adjusted RR 0.87; 95% CI 0.53-1.43 for RALvs. HIST; RR 1.14; 95% CI 0.76-1.72 for RALvs. CONC). CONCLUSIONS: We found no evidence for an oncogenic risk or poorer survival associated with using RAL compared with control groups.
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Antirretrovirais/administração & dosagem , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Neoplasias/epidemiologia , Neoplasias/mortalidade , Raltegravir Potássico/administração & dosagem , Adulto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Análise de SobrevidaRESUMO
Among European countries, prevalence rates of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are particularly high in those bordering the Mediterranean. This is the case for Italy, with 26% of Escherichia coli displaying resistance to the 3rd generation cephalosporins in 2013. An ESBL-E toolkit designed to assist clinicians in managing patients harboring ESBL-E was favorably implemented in Southern France. In a context of lack of specific Italian recommendations, its extension to an adjacent region of Italy was made possible through a cross-border EU cooperation program. Italian infectious disease (ID) specialists, microbiologists, and community-based general practitioners from three districts in Liguria were offered a toolkit consisting in a warning system and detailed procedures for the management of patients harboring ESBL-E, including seeking advice from an ID specialist, and were trained during 52 video conferences by an experienced French team. Indications and trends in antimicrobial prescription were studied following implementation of the toolkit. Between November 2013 and November 2014, 476 patients were identified as harboring ESBL-E and expert advice was sought for 364 of these; all patients and/or their caregivers were advised on appropriate hygiene measures and 209/341 with documented management received antimicrobial treatment, while asymptomatic carriers (39%) were not prescribed antibiotics. The ESBL-E toolkit was well received by the healthcare staff. A specific, simple tool consisting in a care-bundle approach to manage ESBL-E carriers can restrict antimicrobial prescription to symptomatic patients while raising awareness among caregivers of the importance of seeking expert advice and implementing appropriate hygiene measures.
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Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/genética , beta-Lactamases/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Criança , Pré-Escolar , Gerenciamento Clínico , Enterobacteriaceae/efeitos dos fármacos , Infecções por Enterobacteriaceae/prevenção & controle , Feminino , Humanos , Lactente , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Adulto Jovem , Resistência beta-LactâmicaRESUMO
BACKGROUND: Physical activity can slow the ageing process and preserve autonomy in the elderly. The aim of this study was to assess the combined impact of an organized urban walking circuit and individual coaching on women senior citizens' physical well-being and quality of life. METHODS: Insufficiently physically active women >65 years were included in a quasi-experimental trial. Active arm: District with improved urban environment (IUE). Control arm: District without improved urban environment (WIUE). In each district, subjects were randomly allocated to receive coaching (C+ vs. C-). The main outcome measures were endurance, physical activity score, flexibility, quality of life, physical self-esteem, ageing exercise stereotypes, functional health and perceived health at baseline, three (M3) and six (M6) months. RESULTS: Fifty-two insufficiently physically active women were included, 23 in IUE and 29 in WIUE. Groups were comparable at baseline. At M3, endurance and physical activity score significantly improved compared with baseline in the IUE group and in the C+ group while no statistically significant change was observed for the WIUE group and the C- group. Moreover, endurance score was higher in the IUE group, whether coupled with coaching or not. After the coaching was removed, the IUE group regresses to baseline overall and the WIUE shows a decrement in endurance. CONCLUSION: Our study highlights the positive impact of an improved environment and of individual coaching on the level of physical activity and quality of life of insufficiently physically active elderly women.
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BACKGROUND: Child and adolescent psychiatrists are frequently confronted with suicide attempts and comorbid mood disorders. Diagnoses of juvenile bipolar disorders (BD) are rare and controversial and standardized assessment is helpful for a reliable diagnosis. The main objective of this study was to identify the number of juvenile bipolar disorder diagnoses according to DSM-5 criteria in a population of children and adolescents hospitalized for suicide attempts. Secondary objectives were the assessment of a patient's characteristics and the comparison of suicide attempt recurrence during 12 months of follow-up. METHODS: This current practice study consecutively included children and adolescents aged 6 to 18 years and hospitalized for a suicide attempt in a French University Pediatric Hospital over a 4-month period. Patients were assessed at baseline, at 3 months and at 12 months. The standardized assessment was realized by the investigator using semi-structured interview K-SADS-PL (2013) to diagnose juvenile bipolar disorders based on DSM-5 criteria. Clinical diagnoses based on medical charts and according to ICD-10 criteria were also collected at 12-month follow-up. Standardized assessment was completed by the French validated K-SADS-PL (2004) for comorbidities (DSM-IV), dimensional assessment by MADRS-YMRS-ARI-C-SSR, and C-GAS at inclusion. Patients were divided into two groups: (1) those presenting juvenile bipolar disorder according to DSM 5 (BD+) and (2) those without criteria for bipolar disorder (BD-). Suicide risk factors and suicide attempt relapse were assessed at 3 and 12 months of follow-up. RESULTS: Twenty-six inpatients (22 female and 4 male) aged 14.5 years (SD 1,5) were consecutively included. Twenty patients were followed up during the 12-month period. At baseline, 5 patients (19.2 %) presented a diagnosis of BD (DSM-5): 1 BD type 2, 2 non specified BD, 2 cyclothymic disorders. According to the medical charts (ICD-10), none of the patients had been diagnosed with BD but had diagnoses of dysthymia, of borderline personality disorder and of conduct disorder corresponding to DMDD in 3, 2 and 1 patient respectively. During the 12-month follow-up, 9 patients of the BD- group and none of the BD+ presented recurrence of suicide attempt with 67 % during the first 3 months and 3 patients with multi-relapses. These 3 patients were female adolescents out of care and carrying at least three suicide risk factors. Six patients have been lost to follow-up (1 BD+, 5 BD-). In the BD+ group, 3 patients out of 4 had a persistent diagnosis (DSM-5) of BD at 12 months. CONCLUSION: In our adolescent population hospitalized for suicidal attempt, 19,2 % present BD using DSM-5 criteria. Diagnoses are stable during 12 months of follow-up, but under diagnosed in current clinical practice. DSM-5 standardized assessment appears to be very important to diagnose juvenile BD, mandatory for medium and long-term psychiatric follow-up, especially for suicide prevention and psychopharmacologic therapeutics. Nevertheless, no recurrence of suicide attempts has been observed in our BP+ group, contrary to BP-, possibly due the absence of BP 1 disorder.
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Transtorno Bipolar/psicologia , Tentativa de Suicídio/psicologia , Adolescente , Transtorno Bipolar/epidemiologia , Criança , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Seguimentos , França/epidemiologia , Hospitalização , Humanos , Classificação Internacional de Doenças , Entrevista Psicológica , Masculino , Recidiva , Fatores de Risco , Tentativa de Suicídio/estatística & dados numéricosRESUMO
Persistent immune activation is one of the suspected causes of HIV-associated neurocognitive disorders (HAND) in cART era. The CD4/CD8 ratio has been recently showed as a marker of immune activation and HAND. Our aim was to analyze if a decrease in the CD4/CD8 ratio over time could have an impact on neurocognitive deterioration. Randomly selected HIV-infected patients were followed for neuropsychological (NP) testing during a period of almost 2 years. Tests were adjusted for age, gender, and education. Patients were divided into 5 groups: normal tests (NT), neuropsychological deficit (ND, one impaired cognitive domain), asymptomatic neurocognitive disorders (ANI), mild neurocognitive disorders (MND), and HIV-associated dementia (HAD). Risk factors for neurocognitive deterioration were analyzed. Two hundred fifty-six patients underwent NP tests and 94 participated in the follow-up. The groups were comparable. Upon neuropsychological re-testing, six patients showed clinical improvement, 30 had worsened, and 58 were stable, resulting in 42 patients presenting with HAND (45 %). The majority of HAND cases consisted of ANI (26 %) and MND (16 %). In patients whose NP performance worsened, CPE 2010 score was lower at inclusion (7.13 vs 8.00, p = 0.003) and CD4/CD8 decrease more frequent (60 vs 31 %, p = 0.008) than in those who were stable or improved. Multivariate analysis confirmed these results. A decreasing CD4/CD8 ratio during a longitudinal follow-up of randomly selected HIV-infected patients and lower CSF-penetrating regimens were independently associated with cognitive decline. Monitoring trends in CD4/CD8 ratio could contribute to identifying patients at higher risk of neurocognitive deterioration.
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Complexo AIDS Demência/imunologia , Antivirais/farmacocinética , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Disfunção Cognitiva/imunologia , HIV/fisiologia , Complexo AIDS Demência/diagnóstico , Complexo AIDS Demência/patologia , Complexo AIDS Demência/virologia , Adulto , Terapia Antirretroviral de Alta Atividade , Antivirais/administração & dosagem , Biomarcadores/análise , Contagem de Linfócito CD4 , Relação CD4-CD8 , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/virologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/patologia , Disfunção Cognitiva/virologia , Feminino , HIV/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Testes Neuropsicológicos , Permeabilidade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Replicação ViralRESUMO
Adsorption of the Glycine-Proline (Gly-Pro) dipeptide has been investigated using surface science complementary techniques on Au(110) and Ag(110), showing some interesting differences both in the chemical form and surface organization of the adsorbed peptide. On Au(110), Gly-Pro mainly adsorbs in neutral form (COOH/NH2), at low coverage or for a short interaction time; the surface species become zwitterionic at a higher coverage or longer interaction time. These changes are accompanied by a complete reorganization of the molecules at the surface. On Ag(110), only anionic molecules (COO-/NH2) were detected on the surface and only one type of arrangement was observed. These results will be compared to some previously obtained on Cu(110), thus providing a unique comparison of the adsorption of the same di-peptide on three different metal surfaces; the great influence of the substrate on both the chemical form and the arrangement of adsorbed di-peptides was made clear.
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Dipeptídeos/química , Ouro/química , Prata/química , Adsorção , Íons/química , Modelos Moleculares , Espectroscopia Fotoeletrônica , Propriedades de SuperfícieRESUMO
France has remained among the top five European countries for ambulatory antibiotic consumption since such monitoring began in 1998. Young children are major antibiotic consumers, in spite of the viral origin of most infections in this population. Recommendations were updated in 2011 to limit prescriptions. In order to assess their impact, diagnoses and prescriptions were compared in a population of children attending daycare centres in southeastern France in 2008 and 2012. Trends in the reimbursement of paediatric antibiotic prescriptions by the national health insurance (NHI) for the whole area were also studied. Distribution of diagnoses accounting for antibiotic treatment and type of antibiotic prescribed over the previous 3 months to children below 4 years of age attending daycare centres in the Alpes-Maritimes area in southeastern France were compared between 2008 and 2012 prior to and following the availability of these new recommendations. Trends in reimbursed ambulatory antibiotic prescriptions by general practitioners and paediatricians in the area were studied for this age group from 2008 to 2012 and in 2013. The majority of recorded diagnoses concerned upper respiratory tract infections (URTI). Inappropriate antibiotic prescription persisted for colds and bronchitis in similar proportions during both surveys. Improvement in the choice of antibiotic with fewer prescriptions for third-generation cephalosporins was observed both in daycare centres and according to NHI data; however, this was mainly recorded among paediatricians. The management of paediatric URTI still needs improvement, pointing to the need to investigate and adequately address the reasons for inappropriate antibiotic prescription.
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Antibacterianos/uso terapêutico , Uso de Medicamentos , Padrões de Prática Médica , Atenção Primária à Saúde/métodos , Pré-Escolar , Estudos Transversais , Feminino , França , Humanos , Lactente , Recém-Nascido , Masculino , Guias de Prática Clínica como Assunto , Prescrições/estatística & dados numéricosRESUMO
OBJECTIVES: Inversion of the CD4:CD8 ratio is a marker of immune activation and age-associated disease. We measured the CD4:CD8 ratio as a marker of cognitive impairment in HIV-infected patients and explored differences according to clinical severity. METHODS: Post hoc analysis of data from two prospective cohorts of HIV-infected patients randomly selected to undergo neuropsychological tests was performed. Test scores were adjusted for age, gender and education. Inclusion criteria were undetectable viral load and stable treatment for at least 6 months. Subjects with HIV-associated dementia were excluded. Patients were divided into an unimpaired group, a group with asymptomatic neurocognitive disorder (ANI) and a group with symptomatic HIV-associated neurocognitive disorder (sHAND), represented by mild neurocognitive disorder (MND). Demographic and background parameters, immune activation markers and the CD4:CD8 ratio were recorded. RESULTS: Two hundred patients were included in the study. The mean age was 52 years, 78% were male, the mean CD4 count was 624 cells/µL, the mean nadir CD4 count was 240 cells/µL, 27% were hepatitis C virus (HCV)-coinfected, the mean duration of HIV infection was 16 years, and the mean time on current combination antiretroviral therapy (cART) was 2.9 years. Twenty-nine per cent of subjects had HAND (21% had ANI and 8% had MND). In multivariate analysis, a CD4:CD8 ratio < 1 was associated with a nadir CD4 count < 200 cells/µL [odds ratio (OR) 3.68] and with the presence of CD4(+) CD38(+) HLA(+) cells (OR 1.23). Multinominal logistic regression showed that, in comparison with the unimpaired group, diagnosis of sHAND was associated with a CD4:CD8 ratio < 1 (OR 10.62), longer HIV infection (OR 1.15) and longer current cART (OR 1.34), while the ANI group differed from the unimpaired group only for education level. CONCLUSIONS: Aviraemic patients with sHAND did not display the same pattern of immune activation as subjects with ANI, suggesting that the underlying pathophysiological mechanisms could be different.
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Complexo AIDS Demência/imunologia , Transtornos Cognitivos/imunologia , Ativação Linfocitária/imunologia , Complexo AIDS Demência/tratamento farmacológico , Complexo AIDS Demência/fisiopatologia , Relação CD4-CD8 , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/fisiopatologia , Estudos Transversais , Feminino , França/epidemiologia , Humanos , Modelos Logísticos , Ativação Linfocitária/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Carga ViralRESUMO
In this paper, we describe the successful construction, characteristics and interaction with proteins of stimuli-responsive thin nanostructured films prepared by layer-by-layer (LbL) sequential assembly of PNIPAM-containing polyelectrolytes and PAH. PAA-b-PNIPAM block copolymers were synthesized in order to benefit from (i) the ionizable properties of PAA, to be involved in the LbL assembly, and (ii) the sensitivity of PNIPAM to temperature stimulus. The impact of parameters related to the structure and size of the macromolecules (their molecular weight and the relative degree of polymerization of PAA and PNIPAM), and the interaction with proteins under physico-chemical stimuli, such as pH and temperature, are carefully investigated. The incorporation of PAA-b-PNIPAM into multilayered films is shown to be successful whatever the block copolymer used, resulting in slightly thicker films than the corresponding (PAA/PAH)n film. Importantly, the protein adsorption studies demonstrate that it is possible to alter the adsorption behavior of proteins on (PAA-b-PNIPAM/PAH)n surfaces by varying the temperature and/or the pH of the medium, which seems to be intimately related to two key factors: (i) the ability of PNIPAM units to undergo conformational changes and (ii) the structural changes of the film made of weak polyelectrolytes. The simplicity of construction of these PNIPAM block copolymer-based LbL coatings on a large range of substrates, combined with their highly tunable features, make them ideal candidates to be employed for various biomedical applications requiring the control of protein adsorption.
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Polímeros/química , Proteínas/química , Resinas Acrílicas/química , Adsorção , Concentração de Íons de Hidrogênio , Ovalbumina/química , Ovalbumina/metabolismo , Polímeros/síntese química , Proteínas/metabolismo , Técnicas de Microbalança de Cristal de Quartzo , TemperaturaRESUMO
OBJECTIVES: The aim of the study was to statistically model the relative increased risk of cardiovascular disease (CVD) per year older in Data collection on Adverse events of anti-HIV Drugs (D:A:D) and to compare this with the relative increased risk of CVD per year older in general population risk equations. METHODS: We analysed three endpoints: myocardial infarction (MI), coronary heart disease (CHD: MI or invasive coronary procedure) and CVD (CHD or stroke). We fitted a number of parametric age effects, adjusting for known risk factors and antiretroviral therapy (ART) use. The best-fitting age effect was determined using the Akaike information criterion. We compared the ageing effect from D:A:D with that from the general population risk equations: the Framingham Heart Study, CUORE and ASSIGN risk scores. RESULTS: A total of 24 323 men were included in analyses. Crude MI, CHD and CVD event rates per 1000 person-years increased from 2.29, 3.11 and 3.65 in those aged 40-45 years to 6.53, 11.91 and 15.89 in those aged 60-65 years, respectively. The best-fitting models included inverse age for MI and age + age(2) for CHD and CVD. In D:A:D there was a slowly accelerating increased risk of CHD and CVD per year older, which appeared to be only modest yet was consistently raised compared with the risk in the general population. The relative risk of MI with age was not different between D:A:D and the general population. CONCLUSIONS: We found only limited evidence of accelerating increased risk of CVD with age in D:A:D compared with the general population. The absolute risk of CVD associated with HIV infection remains uncertain.
Assuntos
Doença das Coronárias/etiologia , Infecções por HIV/complicações , Infarto do Miocárdio/etiologia , Acidente Vascular Cerebral/etiologia , Adulto , Fatores Etários , Idoso , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Regressão , Fatores de RiscoRESUMO
Although preliminary studies showed that preexposure prophylaxis (PrEP) lowers the HIV transmission in individuals with HIV, confirmative trials are ongoing and PrEP is not routinely recommended. The aim of this study was to assess whether individuals with HIV share antiretroviral (ARV) drugs for PrEP and to describe awareness and discussion on PrEP in this population. A cross-sectional survey was conducted in France in 23 representative departments of infectious diseases and internal medicine. Physicians administered an anonymous standardized questionnaire to all individuals with HIV receiving ARVs and followed between 24 and 31 October 2011. The questionnaire included items regarding PrEP (awareness; discussion with their close circle, physician or patients' association; experience), personal sociodemographic characteristics, risk behaviors and HIV status of the participants. Five hundred and ninety three participants were recruited: male 74.2% (men who have sex with men 52.4%, heterosexuals 21.6%), member of patient's association 9.8%. Half of them (50.6%) lived with a stable partner and 35.2% with an HIV-negative partner. Almost half (41.8%) were aware and 29.5% had had discussion about PrEP. In logistic regression, awareness and discussion on PrEP were more frequent: (1) among males, in patients' association members (p< 0.001 for both) and in nonheterosexuals (p=0.023 and 0.057, respectively); (2) among women, in those not living with a stable partner (p=0.035 and p=0.03, respectively) or living with an HIV-negative partner (p=0.049 and p=0.083, respectively). One percent of the participants declared having shared ARVs with someone and 8.3% reported PrEP in their close circle. Men reporting PrEP in their close circle shared ARVs more frequently than those who did not (10.3% vs. 0.2%, p < 0.001). Today, individuals with HIV do not seem to widely share personal ARVs for PrEP with seronegative people. A significant number of individuals with HIV are aware of and commonly discuss PrEP.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/prevenção & controle , Comportamento Sexual/estatística & dados numéricos , Parceiros Sexuais , Administração Oral , Estudos Transversais , Feminino , França/epidemiologia , Infecções por HIV/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Educação de Pacientes como Assunto , Vigilância de Evento Sentinela , Inquéritos e QuestionáriosRESUMO
Aromatic self-assembled monolayers (SAMs) can be used as negative tone electron resists in functional surface lithographic fabrication. A dense and resistant molecular network is obtained under electron irradiation through the formation of a cross-linked network. The elementary processes and possible mechanisms involved were investigated through the response of a model aromatic SAM, p-terphenylthiol SAM, to low-energy electron (0-10 eV) irradiation. Energy loss spectra as well as vibrational excitation functions were measured using High Resolution Electron Energy Loss Spectroscopy (HREELS). A resonant electron attachment process was identified around 6 eV through associated enhanced excitation probability of the CH stretching modes ν(CH)(ph) at 378 meV. Electron irradiation at 6 eV was observed to induce a peak around 367 meV in the energy loss spectra, attributed to the formation of sp(3)-hybridized CHx groups within the SAM. This partial loss of aromaticity is interpreted to be the result of resonance formation, which relaxes by reorganization and/or CH bond dissociation mechanisms followed by radical chain reactions. These processes may also account for cross-linking induced by electron irradiation of aromatic SAMs in general.
RESUMO
OBJECTIVES: All HIV/hepatitis C virus (HCV)-coinfected patients with chronic HCV infection and ≥ F2 fibrosis should be considered for HCV therapy. This study aimed to determine the rate of HCV treatment uptake among coinfected patients in Europe. METHODS: EuroSIDA patients with viraemic HCV infection were included in the study. Poisson regression was used to identify temporal changes and regional differences in HCV treatment uptake. RESULTS: A total of 1984 patients were included in the study, with a median follow-up time of 168 months [interquartile range (IQR) 121-204 months]. To date, 501 (25.3%) HIV/HCV-coinfected patients have received HCV therapy. Treatment incidence rose from 0.33 [95% confidence interval (CI) 0.16-0.50] per 100 person-years of follow-up (PYFU) in 1998 to 5.93 (95% CI 4.49-7.38) in 2007, falling to 3.78 (95% CI 2.50-5.07) in 2009. After adjustment, CD4 cell count > 350 cells/µL [incidence rate ratio (IRR) 1.33 (95% CI 1.06-1.67) vs.â CD4 count 200-350 cells/µL] and ≥F2 liver fibrosis [IRR 1.60 (95% CI 1.14-2.25; P = 0.0065) vs. < F2 fibrosis] were predictors of anti-HCV treatment initiation. However, 22% of patients who remain untreated for HCV, with fibrosis data available, had ≥F2 fibrosis and should have been considered for treatment, while only 36% of treated patients had ≥F2 fibrosis. CONCLUSIONS: Although treatment incidence for HCV has increased, there remain a large proportion of patients indicated for treatment who have yet to be treated.
Assuntos
Antivirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adulto , Contagem de Linfócito CD4/estatística & dados numéricos , Estudos de Coortes , Coinfecção , Quimioterapia Combinada , Europa (Continente)/epidemiologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/virologia , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Interferon-alfa/uso terapêutico , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Distribuição de Poisson , Estudos Prospectivos , Ribavirina/uso terapêuticoRESUMO
The purpose of this investigation was to assess the impact of selective reporting of antibiotic susceptibility data on the appropriateness of intended documented antibiotic prescriptions in urinary tract infections (UTIs) among residents training in general practice. We conducted a randomised-controlled case-vignette study in three French universities using a questionnaire with four UTI vignettes. In each university, residents were randomly allocated to two groups: a control group with usual full-length reporting of antibiotic susceptibility data (25 antibiotics) and an intervention group with selective reporting of antibiotic susceptibility data (2 to 4 antibiotics only). 326/611 residents (53 %) participated in the survey, 157/305 (52 %) in the intervention group and 169/306 (55 %) in the control group. For all four UTI scenarios, selective reporting of antibiotic susceptibility data significantly improved the appropriateness of antibiotic prescriptions (absolute increase ranging from 7 to 41 %, depending on the vignette). The variety of antibiotic prescriptions was reduced in the intervention group, and cephalosporins and fluoroquinolones were less often prescribed. Among 325 respondents, 124 (38 %) declared being either not really or not at all at ease with antibiotic susceptibility data, whereas 112/157 (71 %) of the residents in the intervention group declared that selective reporting of antibiotic susceptibility data made their antibiotic choice easier. Selective reporting of antibiotic susceptibility data could be a promising strategy to improve antibiotic use in UTIs, as part of a multi-faceted antibiotic stewardship programme. Microbiology laboratories should be aware that they can have a significant influence on antibiotic use.
Assuntos
Antibacterianos/administração & dosagem , Testes de Sensibilidade Microbiana/métodos , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Prescrições de Medicamentos/normas , Feminino , França , Humanos , Internato e Residência , Masculino , Médicos , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
Low-energy electron induced degradation of a model self-assembled monolayer (SAM) of acid terminated alkanethiol was studied under ultra-high vacuum (UHV) conditions at room and low (~40 K) temperatures. Low-energy electron induced chemical modifications of 11-mercaptoundecanoic acid (MUA, HS-(CH2)10-COOH) SAMs deposited on gold were probed in situ as a function of the irradiation energy (<11 eV) by combining two complementary techniques: High Resolution Electron Energy Loss Spectroscopy (HREELS), a surface sensitive vibrational spectroscopy technique, and Electron Stimulated Desorption (ESD) analysis of neutral fragments. The SAM's terminal functions were observed to be selectively damaged at around 1 eV by a resonant electron attachment mechanism, observed to decay by CO, CO2 and H2O formation and desorption. CO2 and H2O were also directly identified at low temperature by vibrational analysis of the irradiated SAMs. At higher irradiation energy, both terminal functions and spacer alkyl chains are damaged upon electron irradiation, by resonant and non-resonant processes.