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1.
Asia Pac J Ophthalmol (Phila) ; 12(6): 537-564, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38079242

RESUMO

The development of minimally invasive glaucoma surgeries (MIGSs) was intended to provide safe and modestly efficacious modalities for early intervention of mild-to-moderate glaucoma, with minimal trauma and rapid recovery. They were mainly ab interno procedures that reduce intraocular pressure by facilitating the aqueous outflow by bypassing the trabecular meshwork resistance, reinforcing the uveoscleral flow via the supraciliary space, and reducing aqueous production by the ciliary body. While the cumulating evidence helps shape the role of the available MIGS, the exponential new development and advancement in this field has expanded the territory of MIGS. Apart from developing subconjunctival MIGS filtration devices (Xen gel stent and PRESERFLO MicroShunt), there is a tendency to revisit the "traditional" MIGS for alternative use and to modify the procedures with consideration of the fundamental aqueous outflow physiology. Combined MIGS has also been suggested, based on the theory that their different mechanisms may provide additive or synergistic effects. The advancement of laser procedures is also promising and could supplement unmet needs along the glaucoma treatment algorithm. This review examines the broad array of MIGS, updates the recent findings, discusses their potential alternative applications, and explores future challenges.


Assuntos
Cirurgia Filtrante , Implantes para Drenagem de Glaucoma , Glaucoma , Humanos , Glaucoma/cirurgia , Pressão Intraocular , Cirurgia Filtrante/métodos , Tonometria Ocular
2.
J Cataract Refract Surg ; 49(1): 108-113, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36573765

RESUMO

A 50-year-old ophthalmic technician was referred by her retina specialist for urgent consultation due to markedly elevated intraocular pressure (IOP) unresponsive to medical therapy. Her history included chronic polyarticular juvenile rheumatoid arthritis and chronic uveitis requiring ongoing topical steroid therapy. She had a sub-Tenon injection of Kenalog (triamcinolone) 18 months prior to referral. Chronic topical anti-inflammatory therapy included nepafenac (Ilevro) and prednisolone acetate 2 times a day. Attempts to discontinue topical steroid resulted in worsening inflammation. The patient was referred when the IOP measured 44 mm Hg in the left eye despite aggressive medical therapy, including acetazolamide. The IOP improved slightly when loteprednol was substituted for prednisolone acetate. Current medications in the left eye include brimonidine 3 times a day, loteprednol 2 times a day, nepafenac 2 times a day, and fixed combination latanoprost + netarsudil at bedtime. Her only medication in the right eye was travoprost. She is intolerant to dorzolamide. She was also taking acetazolamide 500 mg 2 times a day. She was not taking any anticoagulants. Past surgical history included cataract surgery in each eye. She has not had laser trabeculoplasty in either eye. Examination revealed uncorrected visual acuity of J1+ in the right eye (near) and 20/30 in the left eye (mini-monovision). There was no afferent pupillary defect. There was mild band keratopathy in each eye while the central cornea was clear in both eyes without keratic precipitates. Here angles were open to gonioscopy without peripheral anterior synechia. There was mild to moderate flare in each eye with trace cells. The IOP was 17 mm Hg in the right eye and 31 mm Hg in the left. Central corneal thickness measured 560 µm and 559 µm in the right and left eye respectively. There was a well-positioned intraocular lens within each capsule with a patent posterior capsulotomy. There was mild vitreous syneresis but no vitreous cell. The cup to disc ratio was 0.5 in each eye with a symmetrical neural rim. The retina was flat without macular edema. Visual field was normal in both eyes (Figures 1 and 2). Optical coherence tomography of retinal nerve fiber layer (RNFL) is shown in Figure 3 and retinal ganglion cell layer is shown in Supplemental Figure 1 (http://links.lww.com/JRS/A756).JOURNAL/jcrs/04.03/02158034-202301000-00020/figure1/v/2022-12-26T045736Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202301000-00020/figure2/v/2022-12-26T045736Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202301000-00020/figure3/v/2022-12-26T045736Z/r/image-tiff Please comment on your management of this patient's left eye.


Assuntos
Pressão Intraocular , Irite , Humanos , Feminino , Pessoa de Meia-Idade , Acetazolamida , Etabonato de Loteprednol , Triancinolona Acetonida , Latanoprosta
4.
Emerg Infect Dis ; 26(4): 769-772, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32186500

RESUMO

From November 2018 through July 2019, an outbreak of Rift Valley fever in humans occurred in Mayotte, France; 142 cases were confirmed. Exposure to animals or their biological fluid was reported by 73% of patients. Health authorities have been implementing control measures, including veterinary surveys, vector control interventions, and prevention measures.


Assuntos
Febre do Vale de Rift , Vírus da Febre do Vale do Rift , Animais , Comores/epidemiologia , Surtos de Doenças , França/epidemiologia , Humanos , Febre do Vale de Rift/epidemiologia , Vírus da Febre do Vale do Rift/genética
5.
BMC Infect Dis ; 19(1): 896, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31660879

RESUMO

BACKGROUND: The advent of effective direct-acting antivirals (DAAs), has prompted an assessment of the French Hepatitis C virus (HCV) screening strategy, which historically targeted high-risk groups. One of the options put forward is the implementation of combined (i.e., simultaneous) HCV, Hepatitis B virus (HBV) and HIV screening for all adults at least once during their lifetime ("universal combined screening"). However, recent national survey-based data are lacking to guide decision-making regarding which new strategy to implement. Accordingly, we aimed to provide updated data for both chronic hepatitis C (CHC) and B (CHB) prevalence and for HCV and HBV screening history, using data from the BaroTest and 2016 Health Barometer (2016-HB) studies, respectively. METHODS: 2016-HB was a national cross-sectional phone based health survey conducted in 2016 among 20,032 randomly selected individuals from the general population in mainland France. BaroTest was a virological sub-study nested in 2016-HB. Data collected for BaroTest were based on home blood self-sampling on dried blood spots (DBS). RESULTS: From 6945 analyzed DBS, chronic hepatitis C (CHC) and B (CHB) prevalence was estimated at 0.30% (95% Confidence Interval (CI): 0.13-0.70) and 0.30% (95% CI: 0.13-0.70), respectively. The proportion of individuals aware of their status was estimated at 80.6% (95% CI: 44.2-95.6) for CHC and 17.5% (95% CI: 4.9-46.4) for CHB. Universal combined screening would involve testing between 32.6 and 85.3% of 15-75 year olds according to whether we consider only individuals not previously tested for any of the three viruses, or also those already tested for one or two of the viruses. CONCLUSIONS: Our data are essential to guide decision-making regarding which new HCV screening recommendation to implement in France. They also highlight that efforts are still needed to achieve the WHO's targets for eliminating these diseases. Home blood self-sampling may prove to be a useful tool for screening and epidemiological studies.


Assuntos
Teste em Amostras de Sangue Seco , Hepatite B/sangue , Hepatite B/epidemiologia , Hepatite C Crônica/sangue , Hepatite C Crônica/epidemiologia , Programas de Rastreamento/métodos , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Conscientização , Estudos Transversais , Feminino , França/epidemiologia , Infecções por HIV/epidemiologia , Hepacivirus/imunologia , Hepatite B/psicologia , Vírus da Hepatite B/imunologia , Hepatite C Crônica/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
6.
J Viral Hepat ; 26(2): 278-286, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30339311

RESUMO

Nucleoside and nucleotide analogues (NUCs) targeting hepatitis B virus are capable of selecting resistant viruses upon long-term administration as monotherapies. The prevalence of resistance-associated substitutions (RASs) and fitness-associated substitutions at baseline of NUC therapy and their impact on treatment responses remain unknown. A total of 232 treatment-naïve patients chronically infected with hepatitis B virus (HBV) consecutively referred for the first time to one of French reference centres were included. The nearly full-length HBV reverse transcriptase was sequenced by means of deep sequencing, and the sequences were analysed. RASs were detected in 25% of treatment-naïve patients, generally representing low proportions of the viral quasispecies. All amino acid positions known to be associated with HBV resistance to currently approved NUCs or with increased fitness of resistant variants were affected, except position 80. RASs at positions involved in lamivudine, telbivudine and adefovir resistance were the most frequently detected. All patients with RASs detectable by next-generation sequencing at baseline who were treatment-eligible and treated with currently recommended drugs achieved a virological response. The presence of pre-existing HBV RASs has no impact on the outcome of therapy if potent drugs with a high barrier to resistance are used.


Assuntos
Antivirais/uso terapêutico , Farmacorresistência Viral Múltipla/genética , Vírus da Hepatite B/efeitos dos fármacos , Nucleosídeos/uso terapêutico , Nucleotídeos/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Aptidão Genética , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , DNA Polimerase Dirigida por RNA/genética
7.
JMIR Res Protoc ; 7(10): e180, 2018 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-30314963

RESUMO

BACKGROUND: Despite substantial screening for HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) infections in France, a great number of infected persons remain undiagnosed. In this context, Santé publique France experimented with a new screening approach for HBV, HCV, and HIV infection, based on home self-sampling using dried blood spot (DBS) for blood collection. OBJECTIVE: The objectives of the BaroTest study were to assess the acceptability and feasibility of this approach and to update the prevalence estimates of HBV, HCV, and HIV infections in the general population. METHODS: Participants were enrolled using the 2016 Health Barometer, a national cross-sectional telephone survey based on a large representative sample of the general population aged 15 to 75 years (N=15,000). Upon completion of the questionnaire, any participant in the Health Barometer aged 18 to 75 years, having medical health insurance, and not under guardianship was invited to receive a self-sampling kit delivered by standard postal mail and to return the DBS card to the laboratory. The laboratory was then responsible for reporting the results to the participants. Acceptability of the protocol was based on the percentage of eligible individuals agreeing to receive the self-sampling kit, on the proportion of people returning the DBS card, and on the proportion of participants out of the total eligible population. The feasibility of the approach was based on the number of participants with adequately filled blood spots and the number of participants with blood spots for which at least one virological analysis could be performed. A complex system of reminders was implemented to increase the participation rate. Accordingly, we assumed that 35.00% (4900/14,000) of eligible persons would accept and return their DBS card. As the highest expected prevalence was for HBV infection, estimated at 0.65% in 2004, 5000 persons would make it possible to estimate this prevalence with an accuracy of approximately 0.22%. All indicators can be analyzed according to the characteristics of the participants collected in the Health Barometer questionnaire. BaroTest was approved by the French Ethics Committee (November 11, 2015) and the Commission on Information Technology and Liberties (December 24, 2015). The study has been registered by the French medical authority under number 2015-A01252-47 on November 10, 2015. RESULTS: The results on acceptability and feasibility are expected in the last quarter of 2018 and those on the prevalence estimates in the first semester of 2019. CONCLUSIONS: The BaroTest results will help to inform new strategies for HIV, HBV, and HCV screening, and the Health Barometer provides a reliable updated assessment of the burden of HBV, HCV, and HIV infections in the general population in France while reducing the costs typically associated with this type of research. REGISTERED REPORT IDENTIFIER: RR1-10.2196/9797.

8.
Psychiatr Serv ; 69(6): 620-622, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29540115

RESUMO

In 2010, the Regional Council of the Capital Region of Denmark endorsed a vision of mental health services based on personal recovery, rehabilitation, and the involvement of caregivers. Programs to achieve this vision include hiring peer support workers, a Recovery College, and service user participation at the organizational level. This column describes a cornerstone of these initiatives-an education program in the recovery model for mental health professionals. In 2013-2014, the Capital Region implemented 148 workshops on recovery-oriented services for all practitioner staff in mental health services in the region. The workshops featured a coteaching model, with both a mental health professional and an individual with lived experience serving as trainers. This model showed promise and should be expanded, including more targeted training for specific services. Such an expansion could be included in a national strategy for user involvement and recovery-oriented practice set to launch in 2018.


Assuntos
Pessoal de Educação , Pessoal de Saúde/educação , Transtornos Mentais/reabilitação , Serviços de Saúde Mental , Reabilitação Psiquiátrica/métodos , Dinamarca , Educação/métodos , Humanos , Desenvolvimento de Programas
9.
Euro Surveill ; 22(30)2017 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-28797326

RESUMO

Given recent profound improvements in the effectiveness of antiviral treatment for chronic Hepatitis C virus (HCV) infection, we aimed to describe the characteristics of patients referred to hepatology expert centres in France from 2000 to 2007 and from 2010 to 2014, and to identify factors associated with severe liver disease at their first visit for evaluation. We analysed data from two sources covering all of France: the former hepatitis C surveillance network, which included patients between 2000 and 2007, and the ANRS CO22 HEPATHER multi-centre cohort, which included patients between 2012 and 2014. Severe liver disease (SLD) was defined as the presence of either cirrhosis (histological, biochemical or clinical) or hepatocellular carcinoma. Multivariable Poisson regression models were used to identify the factors associated with SLD in complete-case analysis and after multiple imputation. Overall, 16,851 patients were included in the analysis and SLD was diagnosed in 11.6%. SLD at first visit was significantly associated with known risk factors (male sex, history of excessive alcohol intake, HCV genotype 3), late referral to hepatologists after diagnosis and HCV diagnosis at an older age. Providing earlier specialised care and treatment may be an important target for public health action.


Assuntos
Hepacivirus/genética , Hepatite C Crônica/virologia , Cirrose Hepática/epidemiologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/virologia , Adulto , Fatores Etários , Biópsia , Feminino , França/epidemiologia , Hepatite C Crônica/epidemiologia , Humanos , Fígado/patologia , Fígado/virologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais
10.
Surv Ophthalmol ; 62(5): 706-711, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27217122

RESUMO

The iStent is an intraocular implant that resides within Schlemm canal and allows for direct bypass of the trabecular meshwork by aqueous fluid. It is one of several procedures termed microinvasive glaucoma surgery. The prominence of microinvasive glaucoma surgery is growing because of its role in lowering intraocular pressure in mild to moderate glaucoma combined with its favorable safety profile. With transcleral glaucoma filtering surgery, there is an increased potential for significant complications including hypotony, suprachoroidal hemorrhage, and long-term risk of endophthalmitis. In comparison, the iStent minimizes this risk and has been shown to be similar to cataract surgery in terms of associated complications. As will be discussed, multiple publications have addressed both the safety and efficacy of the implant. This review additionally presents an overview of implantation technique as well as what to expect postoperatively. Looking forward, the second-generation models may ease implantation and the use of multiple stents may potentially play a role in more advanced disease.


Assuntos
Extração de Catarata/métodos , Catarata/complicações , Cirurgia Filtrante/instrumentação , Implantes para Drenagem de Glaucoma , Glaucoma/cirurgia , Stents , Desenho de Equipamento , Glaucoma/complicações , Humanos , Acuidade Visual
11.
J Cataract Refract Surg ; 42(7): 1103, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27669089
12.
PLoS One ; 10(5): e0126920, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25961575

RESUMO

BACKGROUND: Recent HCV therapeutic advances make effective screening crucial for potential HCV eradication. To identify the target population for a possible population-based screening strategy to complement current risk-based testing in France, we aimed to estimate the number of adults with undiagnosed chronic HCV infection and age and gender distribution at two time points: 2004 and 2014. METHODS: A model taking into account mortality, HCV incidence and diagnosis rates was applied to the 2004 national seroprevalence survey. RESULTS: In 2014, an estimated 74,102 individuals aged 18 to 80 were undiagnosed for chronic HCV infection (plausible interval: 64,920-83,283) compared with 100,868 [95%CI: 58,534-143,202] in 2004. Men aged 18-59 represented approximately half of the undiagnosed population in 2014. The proportion of undiagnosed individuals in 2004 (43%) varied from 21.9% to 74.1% in the 1945-1965 and 1924-1944 birth cohorts. Consequently, age and gender distributions between the chronically-infected (diagnosed and undiagnosed) and undiagnosed HCV populations were different, the 1945-1965 birth cohort representing 48.9% and 24.7%, respectively. CONCLUSIONS: Many individuals were still undiagnosed in 2014 despite a marked reduction with respect to 2004. The present work contributed to the 2014 recommendation of a new French complementary screening strategy, consisting in one-time simultaneous HCV, HBV and HIV testing in men aged 18-60. Further studies are needed to assess the cost-effectiveness and feasibility of such a strategy. We also demonstrated that data on the undiagnosed HCV population are crucial to help adapt testing strategies, as the features of the chronically-infected HCV population are very distinct.


Assuntos
Análise Custo-Benefício/estatística & dados numéricos , Hepacivirus/isolamento & purificação , Hepatite C Crônica/epidemiologia , Programas de Rastreamento/economia , Modelos Estatísticos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , França/epidemiologia , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/economia , Hepatite C Crônica/virologia , Humanos , Incidência , Masculino , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade
13.
J Ocul Pharmacol Ther ; 30(2-3): 277-82, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24512297

RESUMO

PURPOSE: Schlemm's canal (SC) inner wall is adjacent to the juxtacanalicular trabecular meshwork (TM) over their entire circumference. We seek to transfer reporter and therapeutic genes to these outflow-modulating tissues via canaloplasty surgery in live monkeys. METHODS: A standard canaloplasty surgical approach was performed in cynomolgus monkeys using flexible canaloplasty catheters, modified for monkey eyes with a 175-µm outer diameter and an LED-lighted tip. A 6-0 prolene suture was used for the exact localization of SC. Trypan blue was injected during catheter withdrawal to document catheter placement within SC and to determine ease of injecting fluid into SC. Before, during, and after the injection, the position of the catheter and the anatomic details were video-captured with an externally positioned noncontact endoscopic imaging system and 50 mHz ultrasound biomicroscopy (UBM). RESULTS: A 360° catheterization and injection of dye into SC was achieved. Suture, catheter, and trypan blue were imaged with the endoscope camera system and the catheter was also visualized with UBM. Trypan blue was seen in the SC over 5 clock hours after a 1 clock-hour insertion of the catheter. CONCLUSIONS: A modified canaloplasty catheter device might be used for gene delivery to the SC/TM area without circumferential catheterization. Further studies comparing different delivery methods of the vector/transgene into the SC using canaloplasty are needed.


Assuntos
Cateterismo/métodos , Terapia Genética/métodos , Glaucoma/terapia , Esclera/cirurgia , Animais , Endoscopia , Macaca fascicularis , Malha Trabecular
14.
Am J Med Genet A ; 161A(5): 1019-27, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23532960

RESUMO

Polyalanine repeat expansion diseases are hypothesized to result from unequal chromosomal recombination, yet mechanistic studies are lacking. We identified two de novo cases of hand-foot-genital syndrome (HFGS) associated with polyalanine expansions in HOXA13 that afforded rare opportunities to investigate the mechanism. The first patient with HFGS was heterozygous for a de novo nine codon polyalanine expansion. Haplotype investigation showed that the expansion arose on the maternally inherited chromosome but not through unequal crossing over between homologs, leaving unequal sister chromatid exchange during mitosis or meiosis or slipped mispairing as possible explanations. The asymptomatic father of the second patient with HFGS was mosaic for a six codon polyalanine expansion. Multiple tissue PCR and clonal analysis of paternal fibroblasts showed only expansion/WT and WT/WT clones, and haplotype data showed that two unaffected offspring inherited the same paternal allele without the expansion, supporting a postzygotic origin. Absence of the contracted allele in the mosaic father does not support sister chromatid exchange in the origin of the expansion. Mosaicism for HOXA13 polyalanine expansions may be associated with a normal phenotype, making examination of parental DNA essential in apparently de novo HFGS cases to predict accurate recurrence risks. We could not find an example in the literature where unequal sister chromatid exchange has been proven for any polyalanine expansion, suggesting that the principal mechanism for polyalanine expansions (and contractions) is slipped mispairing without repair or that the true frequency of unequal sister chromatid exchange involving these repeats is low.


Assuntos
Anormalidades Múltiplas/genética , Expansão das Repetições de DNA/genética , Deformidades Congênitas do Pé/genética , Deformidades Congênitas da Mão/genética , Proteínas de Homeodomínio/genética , Anormalidades Urogenitais/genética , Adolescente , Adulto , Feminino , Humanos , Recém-Nascido , Masculino , Mutação , Peptídeos , Fenótipo
15.
BMC Med Res Methodol ; 12: 73, 2012 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-22681630

RESUMO

BACKGROUND: Multiple Imputation as usually implemented assumes that data are Missing At Random (MAR), meaning that the underlying missing data mechanism, given the observed data, is independent of the unobserved data. To explore the sensitivity of the inferences to departures from the MAR assumption, we applied the method proposed by Carpenter et al. (2007).This approach aims to approximate inferences under a Missing Not At random (MNAR) mechanism by reweighting estimates obtained after multiple imputation where the weights depend on the assumed degree of departure from the MAR assumption. METHODS: The method is illustrated with epidemiological data from a surveillance system of hepatitis C virus (HCV) infection in France during the 2001-2007 period. The subpopulation studied included 4343 HCV infected patients who reported drug use. Risk factors for severe liver disease were assessed. After performing complete-case and multiple imputation analyses, we applied the sensitivity analysis to 3 risk factors of severe liver disease: past excessive alcohol consumption, HIV co-infection and infection with HCV genotype 3. RESULTS: In these data, the association between severe liver disease and HIV was underestimated, if given the observed data the chance of observing HIV status is high when this is positive. Inference for two other risk factors were robust to plausible local departures from the MAR assumption. CONCLUSIONS: We have demonstrated the practical utility of, and advocate, a pragmatic widely applicable approach to exploring plausible departures from the MAR assumption post multiple imputation. We have developed guidelines for applying this approach to epidemiological studies.


Assuntos
Estudos Epidemiológicos , Infecções por HIV/complicações , Hepatite C/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/virologia , Consumo de Bebidas Alcoólicas , Interpretação Estatística de Dados , Usuários de Drogas , Feminino , França/epidemiologia , Hepacivirus , Hepatite C/complicações , Humanos , Masculino , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/complicações
16.
Gut ; 61(2): 290-6, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21930731

RESUMO

OBJECTIVE: The combination of pegylated interferon (PEG-IFN), ribavirin (RBV) and a protease inhibitor (PI) has been approved in summer 2011 for the treatment of genotype 1 (G1) hepatitis C virus (HCV)-infected patients, with a substantially improved efficacy. The aim of this study was to estimate the number of G1 patients to be treated in France in 2012 and associated costs. METHODS: A published model of HCV and data on PEG-IFN sales were used to estimate patients needing treatment using three scenarios. (1) HCV screening rate unchanged versus 2010; proportion of treated F0-F1 patients unchanged, proportion of treated F2-F4 patients increased to the current proportion of treated F2-F4 G2/3 patients. (2) Scenario 1 but the proportion of treated F0-F1 patients increased to the current proportion of treated F0-F1 G2/3 patients. (3) Scenario 2 but a 5% increase in the HCV screening rate. To estimate cost, treatment duration was multiplied by drug unit cost. Probabilities corresponding to treatment duration were estimated based on liver fibrosis stage, treatment-naive or experienced status of the patient and virological response kinetics on treatment. RESULTS: Compared with the 5100 G1 patients treated in 2010, the number of G1 patients receiving treatment in 2012 would be 15,000 in scenario 1, 18,300 in scenario 2 and 19,400 in scenario 3, among whom 2.5-3.7% may receive PEG-IFN/RBV and 96.3-97.5% PEG-IFN/RBV+PI. Costs associated with this regimen use ranged from 497 to 638 million Euros. CONCLUSION: These model-based estimates indicate that new anti-HCV treatments may result in a three- to fourfold increase in the number of G1 patients to be treated in France in 2012.


Assuntos
Antivirais/uso terapêutico , Custos de Medicamentos , Uso de Medicamentos/estatística & dados numéricos , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Inibidores de Proteases/uso terapêutico , Ribavirina/uso terapêutico , Adolescente , Adulto , Idoso , Antivirais/economia , Simulação por Computador , Progressão da Doença , Quimioterapia Combinada , Uso de Medicamentos/economia , França , Hepacivirus/genética , Hepatite C Crônica/economia , Humanos , Interferon alfa-2 , Interferon-alfa/economia , Cadeias de Markov , Pessoa de Meia-Idade , Modelos Econômicos , Polietilenoglicóis/economia , Inibidores de Proteases/economia , Proteínas Recombinantes/economia , Proteínas Recombinantes/uso terapêutico , Ribavirina/economia , Adulto Jovem
17.
PLoS One ; 6(8): e23069, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21829694

RESUMO

The homeobox gene (HOXA13) codes for a transcription factor protein that binds to AT-rich DNA sequences and controls expression of genes during embryonic morphogenesis. Here we present the NMR structure of HOXA13 homeodomain (A13DBD) bound to an 11-mer DNA duplex. A13DBD forms a dimer that binds to DNA with a dissociation constant of 7.5 nM. The A13DBD/DNA complex has a molar mass of 35 kDa consistent with two molecules of DNA bound at both ends of the A13DBD dimer. A13DBD contains an N-terminal arm (residues 324 - 329) that binds in the DNA minor groove, and a C-terminal helix (residues 362 - 382) that contacts the ATAA nucleotide sequence in the major groove. The N370 side-chain forms hydrogen bonds with the purine base of A5* (base paired with T5). Side-chain methyl groups of V373 form hydrophobic contacts with the pyrimidine methyl groups of T5, T6* and T7*, responsible for recognition of TAA in the DNA core. I366 makes similar methyl contacts with T3* and T4*. Mutants (I366A, N370A and V373G) all have decreased DNA binding and transcriptional activity. Exposed protein residues (R337, K343, and F344) make intermolecular contacts at the protein dimer interface. The mutation F344A weakens protein dimerization and lowers transcriptional activity by 76%. We conclude that the non-conserved residue, V373 is critical for structurally recognizing TAA in the major groove, and that HOXA13 dimerization is required to activate transcription of target genes.


Assuntos
DNA/metabolismo , Proteínas de Homeodomínio/metabolismo , Sequência de Aminoácidos , DNA/química , DNA/genética , Dimerização , Proteínas de Homeodomínio/química , Proteínas de Homeodomínio/genética , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Dados de Sequência Molecular , Peso Molecular , Mutagênese , Homologia de Sequência de Aminoácidos
18.
Rev Prat ; 61(1): 25-7, 30-2, 2011 Jan.
Artigo em Francês | MEDLINE | ID: mdl-21452538

RESUMO

Viral hepatitis A is a vaccine preventable disease. It frequently occurs in France at the end of the summer among individuals back from high endemic countries. It is a notificable disease with an incidence threefold higher among children below fifteen years of age. Prevention is based on personal and collective hygiene and contacts' vaccination around a case. In France viral hepatitis E cases are more likely autochthonous than imported. In most of autochthonous cases, the source of infection and the transmission route remain unexplained. Following the implementation of mandatory notification in 2003, over 750 cases of acute symptomatic hepatitis B have been notified between 2005 and 2009. Half of them could have been avoided, if current immunisation recommendations would have been applied adequately. In France, more than 500,000 individuals are living with chronic hepatitis B or C, with 4000 deaths attributable to these hepatitis. Improved and reinforced HBV and HCV screening for individuals at risks are priority issues to better access to care and application of prevention measures around a case.


Assuntos
Hepatite Viral Humana/epidemiologia , França/epidemiologia , Humanos , Fatores de Risco
19.
PLoS One ; 6(12): e29322, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22216248

RESUMO

OBJECTIVES: The HEPAIG study was conducted to better understand Hepatitis C virus (HCV) transmission among human immuno-deficiency (HIV)-infected men who have sex with men (MSM) and assess incidence of HCV infection among this population in France. METHODS AND RESULTS: Acute HCV infection defined by anti-HCV or HCV ribonucleic acid (RNA) positivity within one year of documented anti-HCV negativity was notified among HIV-infected MSM followed up in HIV/AIDS clinics from a nationwide sampling frame. HIV and HCV infection characteristics, HCV potential exposures and sexual behaviour were collected by the physicians and via self-administered questionnaires. Phylogenetic analysis of the HCV-NS5B region was conducted. HCV incidence was 48/10 000 [95% Confidence Interval (CI):43-54] and 36/10 000 [95% CI: 30-42] in 2006 and 2007, respectively. Among the 80 men enrolled (median age: 40 years), 55% were HIV-diagnosed before 2000, 56% had at least one sexually transmitted infection in the year before HCV diagnosis; 55% were HCV-infected with genotype 4 (15 men in one 4d-cluster), 32.5% with genotype 1 (three 1a-clusters); five men were HCV re-infected; in the six-month preceding HCV diagnosis, 92% reported having casual sexual partners sought online (75.5%) and at sex venues (79%), unprotected anal sex (90%) and fisting (65%); using recreational drugs (62%) and bleeding during sex (55%). CONCLUSIONS: This study emphasizes the role of multiple unprotected sexual practices and recreational drugs use during sex in the HCV emergence in HIV-infected MSM. It becomes essential to adapt prevention strategies and inform HIV-infected MSM with recent acute HCV infection on risk of re-infection and on risk-reduction strategies.


Assuntos
Infecções por HIV/complicações , Hepatite C/complicações , Homossexualidade Masculina , Adulto , Sequência de Bases , Primers do DNA , Hepacivirus/classificação , Hepacivirus/genética , Hepatite C/virologia , Humanos , Masculino , Filogenia
20.
Hepatology ; 52(6): 1915-21, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21064156

RESUMO

UNLABELLED: Acute hepatitis C continues to be a concern in men who have sex with men (MSM), and its optimal management has yet to be established. In this study, the clinical, biological, and therapeutic data of 53 human immunodeficiency virus (HIV)-infected MSM included in a multicenter prospective study on acute hepatitis C in 2006-2007 were retrospectively collected and analyzed. The mean hepatitis C virus (HCV) viral load at diagnosis was 5.8 ± 1.1 log(10) IU/mL (genotype 4, n = 28; genotype 1, n = 14, genotype 3, n = 7). The cumulative rates of spontaneous HCV clearance were 11.0% and 16.5% 3 and 6 months after diagnosis, respectively. Forty patients were treated, 38 of whom received pegylated interferon and ribavirin. The mean duration of HCV therapy was 39 ± 17 weeks (24 ± 4 weeks in 14 cases). On treatment, 18/36 (50.0%; 95% confidence interval 34.3-65.7) patients had undetectable HCV RNA at week 4 (RVR), and 32/39 (82.1%; 95 confidence interval 70.0-94.1) achieved sustained virological response (SVR). SVR did not correlate with pretreatment parameters, including HCV genotype, but correlated with RVR (predictive positive value of 94.4%) and with effective duration of HCV therapy (64.3% for 24 ± 4 weeks versus 92.0% for longer treatment; P = 0.03). CONCLUSION: The low rate of spontaneous clearance and the high SVR rates argue for early HCV therapy following diagnosis of acute hepatitis C in HIV-infected MSM. Pegylated interferon and ribavirin seem to be the best option. The duration of treatment should be modulated according to RVR, with a 24-week course for patients presenting RVR and a 48-week course for those who do not, irrespectively of HCV genotype.


Assuntos
Antivirais/uso terapêutico , Infecções por HIV/complicações , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Doença Aguda , Adulto , Infecções por HIV/tratamento farmacológico , Hepatite C/complicações , Anticorpos Anti-Hepatite C/análise , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Estudos Retrospectivos , Carga Viral/efeitos dos fármacos
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