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1.
Tech Coloproctol ; 28(1): 23, 2024 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-38198036

RESUMEN

In France, about 2000 new cases of anal cancer are diagnosed annually. Squamous cell carcinoma is the most common histological type, mostly occurring secondary to persistent HPV16 infection. Invasive cancer is preceded by precancerous lesions. In addition to patients with a personal history of precancerous lesions and anal cancer, three groups are at very high risk of anal cancer: (i) men who have sex with men and are living with HIV, (ii) women with a history of high-grade squamous intraepithelial lesions (HSILs) or vulvar HPV cancer, and (iii) women who received a solid organ transplant more than 10 years ago. The purpose of screening is to detect HSILs so that they can be treated, thereby reducing the risk of progression to cancer. All patients with symptoms should undergo a proctological examination including standard anoscopy. For asymptomatic patients at risk, an initial HPV16 test makes it possible to target patients at risk of HSILs likely to progress to cancer. Anal cytology is a sensitive test for HSIL detection. Its sensitivity is greater than 80% and exceeds that of proctological examination with standard anoscopy. It is indicated in the event of a positive HPV16 test. In the presence of cytological abnormalities and/or lesions and a suspicion of dysplasia on clinical examination, high-resolution anoscopy is indicated. Performance is superior to that of proctological examination with standard anoscopy. However, this technique is not widely available, which limits its use. If high-resolution anoscopy is not possible, screening by a standard proctological examination is an alternative. There is a need to develop high-resolution anoscopy and triage tests and to evaluate screening strategies.


Asunto(s)
Neoplasias del Ano , Lesiones Precancerosas , Minorías Sexuales y de Género , Masculino , Humanos , Femenino , Virus del Papiloma Humano , Homosexualidad Masculina , Lesiones Precancerosas/diagnóstico , Neoplasias del Ano/diagnóstico
3.
Sci Total Environ ; 810: 152213, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-34896511

RESUMEN

SARS-CoV-2 is a coronavirus causing a globalized outbreak called COVID-19. SARS-CoV-2 transmission is associated with inhalation of contaminated respiratory droplets and could causes severe complications. Until today several "waves" of infections have been observed despite implementation of strict health policies. Decisions for such sanitary measures are based on population health monitoring. Unfortunately, for COVID-19, a significant proportion of individuals are asymptomatic but play a role in the virus transmission. To overcome these limitations, several strategies were developed including genome quantification in wastewater that could allow monitoring of the health status of population, since shedding of SARS-CoV-2 in patient stool is frequent. Wastewater-based epidemiology (WBE) was established and several countries implemented this approach to allow COVID-19 outbreak monitoring. In France, the OBEPINE project performed a quantitative analysis of SARS-CoV-2 in raw wastewater samples collected from major wastewater treatment plants (WWTP) since March 2020. In the greater Paris area 1101 samples (507 for five WWTP and 594 for sewer) were collected. This 16 months monitoring allows us to observe the outbreak dynamics. Comparison of WBE indicators with health data lead to several important observation; the good level of correlation with incidence rates, the average 3 days lead time, and the sensitivity (WBE change when incidence is > to 7/100000 inhabitants). We also compared the local monitoring (city level) with the regional monitoring, to help cluster identification. Moreover, variants of concern (VOC) emerged due to the selection pressure. We developed a specific RT-qPCR method targeting the deletion H69-V70 in the spike protein, using this deletion as a proxy of the B.1.1.7 presence in the wastewater. With this data we demonstrate the predominant role played by this strain in the third wave. All these results allow a better description and understanding of the pandemic and highlight the role of such WBE indicators.


Asunto(s)
COVID-19 , SARS-CoV-2 , Brotes de Enfermedades , Humanos , Aerosoles y Gotitas Respiratorias , Aguas Residuales
4.
Rev Med Interne ; 42(7): 509-512, 2021 Jul.
Artículo en Francés | MEDLINE | ID: mdl-33846035

RESUMEN

INTRODUCTION: Propylthiouracil (PTU) is a synthetic antithyroid drug that can induce ANCA-associated vasculitis. OBSERVATION: A 27-year-old woman diagnosed with Graves' disease was on PTU for the past 10 years. She developed purpuric lesions of the legs and on the tip of the nose diagnosed as vasculitis. ANCAs were positive, with anti-MPO and anti-PR3 on blood ELISA. After discontinuation of PTU, she was able to fully recover. CONCLUSION: All synthetic antithyroid drugs can induce ANCA-associated vasculitis, more often PTU. In most cases, antibodies are directed against MPO. Dual anti-MPO and anti-PR3 positivity is possible, but rare. The mechanism could be through an accumulation of PTU in neutrophils, altering the structure of MPO and making it immunogenic. PTU can also induce ANCA-free or lupus vasculitis, maculopapular rashes or urticaria. Many other drugs can induce ANCA-associated vasculitis.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Hipertiroidismo , Púrpura , Adulto , Anticuerpos Anticitoplasma de Neutrófilos , Antitiroideos/efectos adversos , Femenino , Humanos , Hipertiroidismo/inducido químicamente , Hipertiroidismo/complicaciones , Hipertiroidismo/diagnóstico , Propiltiouracilo/efectos adversos
6.
Clin Microbiol Infect ; 25(12): 1560.e1-1560.e7, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31051265

RESUMEN

OBJECTIVES: Sub-Saharan Africa is a region with high incidence of both human immunodeficiency virus (HIV) and cervical cancer. We conducted the first national study in Togo to assess prevalence of human papillomavirus (HPV), HIV and other sexually transmitted infections (STIs) among female sex workers (FSW). METHODS: A multicentric cross-sectional study was conducted among FSW recruited in hot spots (clubs, streets) in four Togolese cities. HPV and STIs were tested from cervical and anal swabs. HIV and syphilis were screened with rapid tests. RESULTS: In all, 310 FSW were recruited; HIV and cervical high-risk HPV (hrHPV) prevalence were 10.6% (33/310) and 32.9% (102/310), respectively. The most frequent hrHPV types were HPV58 (13.6%, 19/140), HPV35 (12.9%, 18/140), HPV31 (12.1%, 17/140) and HPV16 (10.7%, 15/140). Prevalence of hrHPV and multiple hrHPV infections showed higher rates in HIV-positive than in HIV-negative FSW (48.5% versus 31.0%, p 0.04 and 21.2% versus 9.0%, p 0.03; respectively). Prevalence of hrHPV was higher in cervical than anal swabs (34.1% versus 20.7%, p 0.0004). High-risk HPV anal infections were more frequent among HIV-positive than HIV-negative FSW (51.9% versus 17.3%, p 2 × 10-5). Concomitant anal and cervical hrHPV infections were present in 43.2% (41/95) of hrHPV-positive FSW. Overall prevalence in the cervix of Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium and Trichomonas vaginalis were 4.2%, 6.1%, 5.5% and 6.5%, respectively. CONCLUSIONS: This first African study on paired cervical and anal samples showed a high prevalence of genital HPV infections with a rather high rate of concomitant HPV infections but low type concordance. We report an unusual distribution of hrHPV types. These findings highlight the critical need for implementation of a national HPV vaccination strategy.


Asunto(s)
VIH/aislamiento & purificación , Papillomaviridae/aislamiento & purificación , Trabajadores Sexuales , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/epidemiología , Adulto , Canal Anal/microbiología , Canal Anal/parasitología , Canal Anal/virología , Cuello del Útero/microbiología , Cuello del Útero/parasitología , Cuello del Útero/virología , Coinfección/diagnóstico , Coinfección/epidemiología , Estudios Transversales , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Humanos , Papillomaviridae/clasificación , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Prevalencia , Pruebas Serológicas , Togo/epidemiología , Adulto Joven
7.
HIV Med ; 19(10): 698-707, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30062761

RESUMEN

OBJECTIVES: The aim of the study was to assess the interest to combine cytological examination and human papillomavirus (HPV) typing of anal and cervical Papanicolaou (Pap) smears of HIV-infected patients on combination antiretroviral therapy (cART), to evaluate whether differences in prevalence exist between anal and cervical squamous intraepithelial lesions in patients with high-risk oncogenic HPV infection. METHODS: Anal and/or cervical Pap smears were obtained by anoscopy and/or colposcopy in 238 subjects recruited consecutively in 2015: anal smears were obtained from 48 male and female patients [42 men; 35 men who have sex with men (MSM)] and cervical smears from 190 female patients. Cytological Bethesda classification was coupled with HPV typing. HPV typing was performed, on the same smears, using the Xpert® HPV Assay, which detects only high-risk HPV (hrHPV), and the Anyplex® II HPV28 Detection assay, which detects hrHPV and low-risk (lr) HPV. RESULTS: Our data showed clear-cut differences between the anal and cervical samples. Compared with the cervical samples, the anal samples exhibited (1) more numerous cytological lesions, which were histologically proven; (2) a higher hrHPV infection prevalence; (3) a higher prevalence of multiple hrHPV coinfections whatever HPV typing kit was used; (4) a predominance of HPV16 and HPV18/45 types. Overall, there was an almost perfect agreement between the two HPV typing assays (absolute agreement = 90.3%). CONCLUSIONS: Co-testing consisting of cytology and HPV typing is a useful screening tool in the HIV-infected population on cART. It allows detection of prevalence differences between anal and cervical HPV-related lesions. As recently recommended, anal examination should be regularly performed especially in HIV-infected MSM but also in HIV-infected women with genital hrHPV lesions.


Asunto(s)
Antirretrovirales/uso terapéutico , Coinfección/diagnóstico , Técnicas Citológicas/métodos , Infecciones por VIH/complicaciones , Técnicas de Diagnóstico Molecular/métodos , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Adulto , Anciano , Canal Anal/patología , Canal Anal/virología , Cuello del Útero/patología , Cuello del Útero/virología , Coinfección/virología , Femenino , Genotipo , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Papillomaviridae/clasificación , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Prevalencia , Estudios Prospectivos , Adulto Joven
8.
J Antimicrob Chemother ; 73(9): 2485-2492, 2018 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-29873733

RESUMEN

Background: Integrase strand transfer inhibitors (INSTIs) are recommended by international guidelines as first-line therapy in antiretroviral-naive and -experienced HIV-1-infected patients. Objectives: This study aimed at evaluating the prevalence at failure of INSTI-resistant variants and the impact of baseline minority resistant variants (MiRVs) on the virological response to an INSTI-based regimen. Methods: Samples at failure of 134 patients failing a raltegravir-containing (n = 65), an elvitegravir-containing (n = 20) or a dolutegravir-containing (n = 49) regimen were sequenced by Sanger sequencing and ultra-deep sequencing (UDS). Baseline samples of patients with virological failure (VF) (n = 34) and of those with virological success (VS) (n = 31) under INSTI treatment were sequenced by UDS. Data were analysed using the SmartGene platform, and resistance was interpreted according to the ANRS algorithm version 27. Results: At failure, the prevalence of at least one INSTI-resistant variant was 39.6% by Sanger sequencing and 57.5% by UDS, changing the interpretation of resistance in 17/134 (13%) patients. Among 53 patients harbouring at least one resistance mutation detected by both techniques, the most dominant INSTI resistance mutations were N155H (45%), Q148H/K/R (23%), T97A (19%) and Y143C (11%). There was no difference in prevalence of baseline MiRVs between patients with VF and those with VS. MiRVs found at baseline in patients with VF were not detected at failure either in majority or minority mutations. Conclusions: UDS is more sensitive than Sanger sequencing at detecting INSTI MiRVs at treatment failure. The presence of MiRVs at failure could be important to the decision to switch to other INSTIs. However, there was no association between the presence of baseline MiRVs and the response to INSTI-based therapies in our study.


Asunto(s)
Terapia Antirretroviral Altamente Activa/métodos , Farmacorresistencia Viral , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Inhibidores de Integrasa VIH/farmacología , Inhibidores de Integrasa VIH/uso terapéutico , VIH-1/efectos de los fármacos , Adulto , Femenino , Técnicas de Genotipaje , Infecciones por VIH/epidemiología , VIH-1/genética , VIH-1/aislamiento & purificación , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Paris/epidemiología , Prevalencia , Insuficiencia del Tratamiento
10.
Aliment Pharmacol Ther ; 47(12): 1652-1660, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29737553

RESUMEN

BACKGROUND: IBD diagnosed after the age of 60 is increasing. Data on post-operative complications in elderly onset IBD are scarce. AIM: To describe the incidence of and factors associated with post-operative complications in elderly onset IBD, diagnosed after the age of 60. METHODS: Using EPIMAD Cohort (1988-2006), among 841 incident IBD patients, 139 (17%) underwent intestinal surgery, including 100 Crohn's disease (CD) and 39 ulcerative colitis (UC). RESULTS: After a median post-operative follow-up of 6 years (2-10), 50 (36%) patients experienced at least 1 complication with a total of 69. During the first 30 post-operative days, the mortality rate was 4%. Thirty-two early complications (<30 days) were observed in 23 patients (17%), with 15 infectious, without significant difference between CD and UC. More than half early post-operative complications (n = 19, 59%) were severe (>grade 2) without significant difference between CD and UC (P = 0.28). Thirty-seven long-term adverse effects of surgical therapy (≥30 days) were observed in 33 patients (24%). Multivariate analysis found (1) acute severe colitis (OR = 7.84 [2.15-28.52]) and emergency surgery (OR = 4.46 [1.75-11.36]) were associated with early post-operative complications, and (2) Female gender (HR = 2.10 [1.01-4.37]) and delay before surgery >3 months (HR = 2.09 [1.01-4.31]) with long-term adverse effects of surgical therapy. CONCLUSIONS: One-third of elderly IBD patients experienced at least 1 post-operative complication. Half of the early complications were severe, and infectious. Emergency surgery was the key driver for post-operative complication.


Asunto(s)
Colitis Ulcerosa/cirugía , Enfermedad de Crohn/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Complicaciones Posoperatorias/epidemiología , Anciano , Estudios de Cohortes , Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/epidemiología , Femenino , Humanos , Incidencia , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo
11.
J Antimicrob Chemother ; 73(8): 2147-2151, 2018 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-29718247

RESUMEN

Background: Atazanavir is a PI widely used as a third agent in combination ART. We aimed to determine the prevalence and the patterns of resistance in PI-naive patients failing on an atazanavir-based regimen. Methods: We analysed patients failing on an atazanavir-containing regimen used as a first line of PI therapy. We compared the sequences of reverse transcriptase and protease before the introduction of atazanavir and at failure [two consecutive viral loads (VLs) >50 copies/mL]. Resistance was defined according to the 2014 Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) algorithm. Results: Among the 113 patients, atazanavir was used in the first regimen in 71 (62.8%) patients and in the first line of a PI-based regimen in 42 (37.2%). Atazanavir was boosted with ritonavir in 95 (84.1%) patients and combined with tenofovir/emtricitabine or lamivudine (n = 81) and abacavir/lamivudine or emtricitabine (n = 22). At failure, median VL was 3.05 log10 copies/mL and the median CD4+ T cell count was 436 cells/mm3. The median time on atazanavir was 21.2 months. At failure, viruses were considered resistant to atazanavir in four patients (3.5%) with the selection of the following major atazanavir-associated mutations: I50L (n = 1), I84V (n = 2) and N88S (n = 1). Other emergent PI mutations were L10V, G16E, K20I/R, L33F, M36I/L, M46I/L, G48V, F53L, I54L, D60E, I62V, A71T/V, V82I/T, L90M and I93L/M. Emergent NRTI substitutions were detected in 21 patients: M41L (n = 2), D67N (n = 3), K70R (n = 1), L74I/V (n = 3), M184V/I (n = 16), L210W (n = 1), T215Y/F (n = 3) and K219Q/E (n = 2). Conclusions: Resistance to atazanavir is rare in patients failing the first line of an atazanavir-based regimen according to the ANRS. Emergent NRTI resistance-associated mutations were reported in 18% of patients.


Asunto(s)
Sulfato de Atazanavir/uso terapéutico , Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1/genética , Adulto , Didesoxinucleósidos , Combinación de Medicamentos , Emtricitabina/uso terapéutico , VIH-1/efectos de los fármacos , Humanos , Lamivudine , Masculino , Persona de Mediana Edad , Mutación , Estudios Retrospectivos , Tenofovir/uso terapéutico , Insuficiencia del Tratamiento , Carga Viral
12.
J Clin Virol ; 99-100: 57-60, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29331843

RESUMEN

OBJECTIVES: There is no consensus about the performances of genotypic rules for predicting HIV-1 non-B subtype tropism. Three genotypic methods were compared for CRF01_AE HIV-1 tropism determination. METHODS: The V3 env region of 207 HIV-1 CRF01_AE and 178 B subtypes from 17 centers in France and 1 center in Switzerland was sequenced. Tropism was determined by Geno2Pheno algorithm with false positive rate (FPR) 5% or 10%, the 11/25 rule or the combined criteria of the 11/25, net charge rule and NXT/S mutations. RESULTS: Overall, 72.5%, 59.4%, 86.0%, 90.8% of the 207 HIV-1 CRF01_AE were R5-tropic viruses determined by Geno2pheno FPR5%, Geno2pheno FPR10%, the combined criteria and the 11/25 rule, respectively. A concordance of 82.6% was observed between Geno2pheno FPR5% and the combined criteria for CRF01_AE. The results were nearly similar for the comparison between Geno2pheno FPR5% and the 11/25 rule. More mismatches were observed when Geno2pheno was used with the FPR10%. Neither HIV viral load, nor current or nadir CD4 was associated with the discordance rate between the different algorithms. CONCLUSION: Geno2pheno predicted more X4-tropic viruses for this set of CRF01_AE sequences than the combined criteria or the 11/25 rule alone. For a conservative approach, Geno2pheno FPR5% seems to be a good compromise to predict CRF01_AE tropism.


Asunto(s)
Algoritmos , Técnicas de Genotipaje/métodos , Infecciones por VIH/virología , VIH-1/fisiología , Tropismo Viral , Recuento de Linfocito CD4 , Reacciones Falso Positivas , Francia , Genotipo , Proteína gp120 de Envoltorio del VIH/genética , VIH-1/clasificación , VIH-1/genética , Humanos , ARN Viral/sangre , Suiza , Carga Viral
14.
Neurogastroenterol Motil ; 30(6): e13291, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29345097

RESUMEN

BACKGROUND: The functional lumen imaging probe (EndoFLIP® ) is a new technology that measures the distensibility of the anal canal represented by the anal distensibility index. The aims of this study were (i) to compare the anal distensibility index to anal pressure in a cohort of patients with fecal incontinence (FI) and (ii) to compare the diagnostic value of the EndoFLIP® to that of high-resolution anorectal manometry (HRAM) in the same cohort of patients. METHODS: Eighty-three consecutive patients with FI who underwent EndoFLIP® and HRAM assessments were enrolled. The diagnostic value of the EndoFLIP® was compared to that of HRAM and agreement between EndoFLIP® and HRAM data was assessed. KEY RESULTS: More than 70% of the patients diagnosed with anal deficiency at rest and/or during voluntary contractions by HRAM had the same diagnosis using the EndoFLIP® . Two patients with higher distensibility indexes at rest had normal anal resting pressures. Sixteen patients with a normal EndoFLIP® index (ie, normal distensibility index at rest and during voluntary contractions) had an abnormal HRAM result. Seven of these 16 patients (44%) had no sphincter lesion or neuropathic disorder that could explain an abnormal anal sphincter function. CONCLUSIONS & INFERENCES: We demonstrated that the anal distensibility index and HRAM results are largely in agreement. We did, however, identify several discrepancies between the two techniques, indicating that they may be complementary.


Asunto(s)
Canal Anal/fisiopatología , Impedancia Eléctrica , Incontinencia Fecal/diagnóstico , Incontinencia Fecal/fisiopatología , Manometría/métodos , Recto/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Canal Anal/patología , Estudios de Cohortes , Electrodos , Femenino , Humanos , Masculino , Manometría/instrumentación , Persona de Mediana Edad , Estudios Prospectivos , Recto/patología , Estudios Retrospectivos
15.
J Antimicrob Chemother ; 72(9): 2431-2437, 2017 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-28859447

RESUMEN

Objectives: To determine natural phenotypic susceptibility of non-group M HIV-1 to integrase strand transfer inhibitors (INSTIs) in a large panel of 39 clinical strains from groups O, N and P and to identify genotypic polymorphisms according to susceptibility levels. Methods: Susceptibility to raltegravir, elvitegravir and dolutegravir was evaluated in 36 HIV-1/O, 2 HIV-1/N and 1 HIV-1/P strains plus an HIV-1/M reference strain. IC50 values were determined after 3 days, and fold changes (FCs) were calculated relative to the HIV-1/M strain. Genotypic polymorphism was determined by amplification of codons 19-263 of the integrase; the natural occurrence of resistance-associated mutations was analysed using the main resistance algorithms and the IAS-USA list. VESPA analysis of the strain sequences was used to determine a signature pattern associated with higher FC. Results: Similar IC50 results were observed for the three drugs. Based on the value for the HIV-1/M reference strain, the data showed FC values <2.5 for raltegravir and dolutegravir, whereas the distribution for elvitegravir was heterogeneous, with FC > 10 for six strains (15%). Analysis of the non-M integrase sequences showed a high level of polymorphism without a major genotypic impact; it also revealed mutations that may be associated with the highest FC values obtained for elvitegravir. Conclusions: Our phenotypic data showed that non-M strains are globally susceptible to the three currently used INSTIs, but the impact of the high FC values observed for some strains with elvitegravir needs to be explored. Clinical data are now needed to confirm these phenotypic results.


Asunto(s)
Infecciones por VIH/virología , Inhibidores de Integrasa VIH/farmacología , VIH-1/efectos de los fármacos , Sustitución de Aminoácidos , Farmacorresistencia Viral/genética , Genotipo , Infecciones por VIH/tratamiento farmacológico , Integrasa de VIH/genética , VIH-1/clasificación , VIH-1/genética , VIH-1/fisiología , Compuestos Heterocíclicos con 3 Anillos/farmacología , Humanos , Concentración 50 Inhibidora , Mutación , Oxazinas , Fenotipo , Filogenia , Piperazinas , Polimorfismo Genético/efectos de los fármacos , Piridonas , Quinolonas/farmacología , Raltegravir Potásico/farmacología
16.
Neuroimage ; 156: 119-127, 2017 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-28506872

RESUMEN

There is considerable need to develop tailored approaches to psychiatric treatment. Numerous researchers have proposed using functional magnetic resonance imaging (fMRI) biomarkers to predict therapeutic response, in particular by measuring task-evoked subgenual anterior cingulate (sgACC) and amygdala activation in mood and anxiety disorders. Translating this to the clinic relies on the assumption that blood-oxygen-level dependent (BOLD) responses in these regions are stable within individuals. To test this assumption, we scanned a group of 29 volunteers twice (mean test-retest interval=14.3 days) and calculated the within-subject reliability of the amplitude of the amygdalae and sgACC BOLD responses to emotional faces using three paradigms: emotion identification; emotion matching; and gender classification. We also calculated the reliability of activation in a control region, the right fusiform face area (FFA). All three tasks elicited robust group activations in the amygdalae and sgACC (which changed little on average over scanning sessions), but within-subject reliability was surprisingly low, despite excellent reliability in the control right FFA region. Our findings demonstrate low statistical reliability of two important putative treatment biomarkers in mood and anxiety disorders.


Asunto(s)
Mapeo Encefálico/métodos , Encéfalo/diagnóstico por imagen , Reconocimiento Facial/fisiología , Imagen por Resonancia Magnética/métodos , Adulto , Emociones/fisiología , Femenino , Humanos , Masculino , Trastornos Mentales/diagnóstico , Reproducibilidad de los Resultados , Adulto Joven
17.
HIV Med ; 18(9): 696-700, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28444829

RESUMEN

OBJECTIVES: Transmitted drug resistance (TDR) can impair the response to first-line antiretroviral therapy. In treatment-naïve patients chronically infected with HIV type 1 (HIV-1), it was previously shown through Sanger sequencing that TDR was more common in men who have sex with men (MSM) than in other transmission risk groups. We aimed to compare two HIV-1 transmission groups in terms of the presence of TDR mutations. METHODS: We investigated, through Sanger sequencing and ultradeep sequencing (UDS), the presence of resistance mutations, both in majority (> 20%) and in minority (1-20%) proportions, in 70 treatment-naïve MSM and 70 treatment-naïve heterosexual patients who recently screened positive for HIV-1. RESULTS: The global prevalence of TDR was not significantly different between the two groups, either by Sanger or by UDS. Nevertheless, a higher frequency of nucleoside reverse transcriptase inhibitor TDR was observed among heterosexual patients (P = 0.04). There was also a trend for a higher frequency of TDR among MSM infected with HIV-1 subtype B compared with MSM infected with HIV-1 non-B subtypes (P = 0.06). CONCLUSIONS: Ultradeep sequencing UDS allowed sensitive monitoring of TDR, and highlighted some disparities between transmission groups.


Asunto(s)
Farmacorresistencia Viral , Infecciones por VIH/virología , VIH-1/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Análisis de Secuencia de ARN/métodos , Adulto , Fármacos Anti-VIH/farmacología , Femenino , VIH-1/clasificación , VIH-1/efectos de los fármacos , Heterosexualidad , Homosexualidad Masculina , Humanos , Masculino , Mutación , Inhibidores de la Transcriptasa Inversa/farmacología
18.
J Antimicrob Chemother ; 72(6): 1769-1773, 2017 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-28333232

RESUMEN

Background: Surveillance of HIV-1 resistance in treated patients with a detectable viral load (VL) is important to monitor, in order to assess the risk of spread of resistant viruses and to determine the proportion of patients who need new antiretroviral drugs with minimal cross-resistance. Methods: The HIV-1 protease and reverse transcriptase (RT) and integrase genes were sequenced in plasma samples from 782 consecutive patients on failing antiretroviral regimens, seen in 37 specialized centres in 2014. The genotyping results were interpreted using the ANRS v24 algorithm. Prevalence rates were compared with those obtained during a similar survey conducted in 2009. Results: The protease and RT sequences were obtained in 566 patients, and the integrase sequence in 382 patients. Sequencing was successful in 60%, 78%, 78% and 87% of patients with VLs of 51-200, 201-500, 501-1000 and >1000 copies/mL, respectively. Resistance to at least one antiretroviral drug was detected in 56.3% of samples. Respectively, 3.9%, 8.7%, 1.5% and 3.4% of patients harboured viruses that were resistant to any NRTI, NNRTI, PI and integrase inhibitor (INI). Resistance rates were lower in 2014 than in 2009. Resistance was detected in 48.5% of samples from patients with a VL between 51 and 200 copies/mL. Conclusion: In France in 2014, 90.0% of patients in AIDS care centres were receiving antiretroviral drugs and 12.0% of them had VLs >50 copies/mL. Therefore, this study suggests that 6.7% of treated patients in France might transmit resistant strains. Resistance testing may be warranted in all treated patients with VL > 50 copies/mL.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Viral Múltiple , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Carga Viral , Adulto , Terapia Antirretroviral Altamente Activa , Femenino , Francia , Genes Virales , Genotipo , Infecciones por VIH/sangre , Integrasa de VIH/sangre , Integrasa de VIH/genética , Proteasa del VIH/sangre , Proteasa del VIH/genética , Transcriptasa Inversa del VIH/sangre , Transcriptasa Inversa del VIH/genética , VIH-1/genética , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Análisis de Secuencia de ADN , Insuficiencia del Tratamiento
19.
Int J Tuberc Lung Dis ; 21(12): 1272-1279, 2017 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-29297448

RESUMEN

OBJECTIVES: To develop a diagnostic predictive model for the identification of patients with presumptive pulmonary tuberculosis (PTB) at high risk for active disease and those requiring nucleic acid amplification (NAAT) testing and/or preventive respiratory isolation in low-incidence, high-income countries. DESIGN: A 1:1 case-control study was conducted in consecutive immunocompetent patients with presumed PTB hospitalised between 2009 and 2012 in Paris, France. Cases were defined as individuals with culture-confirmed PTB, regardless of smear result. Those with presumed PTB and three smear- and culture-negative samples were selected as controls. A score was derived using conditional logistic regression. Internal validity of the score was assessed using the bootstrap method. RESULTS: A total of 354 patients were included in the analysis (177 cases, 177 controls). Among the 177 cases, 74 (42%) were smear-negative but culture-positive. Factors independently associated with PTB were age <50 years (adjusted OR [aOR] 4.7, 95%CI 1.8-12), diabetes (aOR 3.2, 95%CI 1.1-9.8), absence of cough with or without sputum (aOR 3.7, 95%CI 1.7-8.3), fever >15 days (aOR 3.5, 95%CI 1.3-9.5), apical infiltration without cavity (aOR 3.4, 95%CI 1.4-8.5) and cavitation or miliary pattern (aOR 19.7, 95%CI 7.6-51.1). Score C-index was 0.84 (95%CI 0.79-0.88). Calibration for the overall population (P = 0.770) and in smear-negative patients (P = 0.980) was appropriate. A score of 3.3 had 90% sensitivity, 50% specificity and 79% (IQR 28-95) median probability of PTB. CONCLUSIONS: This score could be used to build an algorithm to determine the need for respiratory isolation and/or NAAT use in PTB disease.


Asunto(s)
Modelos Estadísticos , Técnicas de Amplificación de Ácido Nucleico/métodos , Esputo/microbiología , Tuberculosis Pulmonar/diagnóstico , Adulto , Anciano , Estudios de Casos y Controles , Tos/epidemiología , Tos/etiología , Femenino , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Paris/epidemiología , Prevalencia , Probabilidad , Sensibilidad y Especificidad , Tuberculosis Pulmonar/epidemiología
20.
J Antimicrob Chemother ; 71(9): 2651-3, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27234463

RESUMEN

OBJECTIVES: There are few data on clinical and virological factors associated with maraviroc virological response (VR) in clinical practice. This study aimed to identify factors associated with VR in 94 treatment-experienced, but CCR5 inhibitor-naive, HIV-1 patients switched to maraviroc-containing regimens. METHODS: Patients with HIV-1 RNA viral load (VL) <50 copies/mL switching to an antiretroviral treatment containing maraviroc were followed. VR was defined at month 3 as VL <50 copies/mL. The impact of age, baseline tropism, zenith VL, nadir CD4 cell count and CD4 cell count, HIV subtype (B versus non-B), genotypic susceptibility score of treatment, once- or twice-daily treatment and presence of raltegravir in optimized background therapy on VR was investigated. RESULTS: Baseline characteristics were: median age 49 years (range 25-73 years), median CD4 cell count 481 cells/mm(3) (range 57-1830 cells/mm(3)) and median nadir CD4 cell count 99 cells/mm(3) (range 3-585). Maraviroc was administered twice daily in 88 of 94 patients and once daily in 6 of 94 patients (300 mg/day for 4 of 6 and 150 mg/day for 2 of 6). At month 3, 89.4% of patients were responders. A better VR to a switch regimen containing maraviroc was associated with the B subtype (P = 0.0216) and a lower zenith VL (median of 5.24 and 5.70 log10 copies/mL for patients in success or in failure, respectively) in univariate analysis. Only B subtype was associated with a better VR in multivariate analysis. CONCLUSIONS: This study evidenced the efficacy of a switch regimen containing maraviroc in clinical practice. VR was better for patients with a lower zenith VL and B subtype.


Asunto(s)
Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa/métodos , Antagonistas de los Receptores CCR5/uso terapéutico , Ciclohexanos/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/aislamiento & purificación , Triazoles/uso terapéutico , Carga Viral , Adulto , Anciano , Femenino , Humanos , Masculino , Maraviroc , Persona de Mediana Edad , Resultado del Tratamiento
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