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OBJECTIVES: HIV infection has been associated with lower rates of sustained viral response (SVR) with direct-acting antivirals (DAAs). There are few data on glecaprevir/pibrentasvir (G/P) in HIV/HCV coinfection outside clinical trials. METHODS: The HEPAVIR-DAA cohort, which recruits HIV/HCV-coinfected patients (NCT02057003) and the GEHEP-MONO cohort (NCT02333292), including HCV-monoinfected individuals, are two concurrent ongoing multicentre cohorts of patients receiving anti-HCV treatment. Patients starting G/P included in those cohorts were analysed. Overall SVR (ITT), discontinuations due to adverse effects, and dropouts were evaluated and compared between both cohorts. RESULTS: Of the 644 patients who started G/P with evaluable SVR, 132 were HIV/HCV coinfected. Overall SVR rates were 487/512 (95.1%) in HCV-monoinfected patients versus 126/132 (95.5%) in HIV/HCV-coinfected patients (Pâ=â1.000). One patient (0.8%) relapsed, and another (0.8%) discontinued treatment due to side effects. SVR to 8 or 12 weeks of treatment with G/P was similar in HIV/HCV-coinfected versus HCV-monoinfected patients. The main reason for not reaching SVR among HIV/HCV-coinfected patients was premature dropout linked to active drug use. CONCLUSIONS: G/P in HIV/HCV coinfection was highly effective and tolerable in clinical practice. SVR to 8 or 12 weeks of treatment with G/P was similar in HIV/HCV-coinfected compared with HCV-monoinfected patients but active drug use is still a barrier to reach HCV microelimination.
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Coinfecção , Infecções por HIV , Hepatite C Crônica , Humanos , Antivirais/farmacologia , Coinfecção/tratamento farmacológico , Coinfecção/complicações , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Ensaios Clínicos como Assunto , Estudos Multicêntricos como AssuntoRESUMO
INTRODUCTION: patients with advanced chronic liver disease (CLD) may be at an increased risk of a severe course due to cirrhosis-associated immune dysfunction. The aim of this study was to determine the prevalence of CLD in COVID-19 patients and to analyze the course of the infection, compared with patients with non-liver disease. MATERIALS AND METHODS: this was a retrospective single center study of all patients with a positive SARS-CoV-2 polymerase chain reaction (PCR) test from March 23rd to April 30th, 2020. Clinical and biochemical data of patients with and without CLD and COVID-19 were collected from the medical records. RESULT: four hundred and forty-seven patients with a SARS-CoV-2 positive PCR were included, 6.3 % had CLD; 69.7 % of patients with CLD were male, with a median age of 65.5 years and active alcohol consumption and smoking; 75 % had non-advanced liver fibrosis and most had non-alcoholic fatty liver disease (NAFLD). The hospital admission rate (92.9 % vs 47.7 %, p < 0.001), concomitant comorbidities (diabetes 38.5 vs 16.5 %, p = 0.011; obesity 30.8 vs 8.5 %, p = 0.033; cancer 23.1 vs 5 %, p = 0.027; and chronic obstructive pulmonary disease (COPD) 19.2 vs 9 %, p = 0.009) and concomitant antibiotics treatment (19.3 vs 5 %, p = 0.018) were higher in patients with CLD than in those without CLD. In-patient hospital mortality rates were similar in both groups (30.8 vs 19.6 %, p = 0.289). The presence of CLD was not associated with mortality (OR = 1.06; 95 % CI = 0.35-3.18; p = 0.924). However, patients with CLD and COVID-19 who were male, obese or under concomitant antibiotic treatment had the highest risk of mortality according to the univariate analysis. CONCLUSION: patients with CLD had a higher risk of hospital admission, with worse outcomes during the COVID-19 infection associated to other concomitant comorbidities and a suspicion of bacterial co-infection.
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COVID-19/complicações , Hepatopatias/complicações , Hepatopatias/epidemiologia , Idoso , Doença Crônica , Feminino , Humanos , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos RetrospectivosRESUMO
BACKGROUND: People living with human immunodeficiency virus (PLWH) are at increased risk of cirrhosis and esophageal varices. Baveno VI criteria, based on liver stiffness measurement (LSM) and platelet count, have been proposed to avoid unnecessary esophagogastroduodenoscopy (EGD) screening for esophageal varices needing treatment (EVNT). This approach has not been validated in PLWH. METHODS: PLWH from 8 prospective cohorts were included if they fulfilled the following criteria: (1) compensated advanced chronic liver disease (LSM >10 kPa); (2) availability of EGD within 6 months of reliable LSM. Baveno VI (LSM <20 kPa and platelets >150 000/µL), expanded Baveno VI (LSM <25 kPa and platelets >110 000/µL), and Estudio de las Hepatitis Víricas (HEPAVIR) criteria (LSM <21 kPa) were applied to identify patients not requiring EGD screening. Criteria optimization was based on the percentage of EGDs spared, while keeping the risk of missing EVNT <5%. RESULTS: Five hundred seven PLWH were divided into a training (n = 318) and a validation set (n = 189). EVNT were found in 7.5%. In the training set, Baveno VI, expanded Baveno VI, and HEPAVIR criteria spared 10.1%, 25.5%, and 28% of EGDs, while missing 0%, 1.2%, and 2.2% of EVNT, respectively. The best thresholds to rule out EVNT were platelets >110 000/µL and LSM <30 kPa (HIV cirrhosis criteria), with 34.6% of EGDs spared and 0% EVNT missed. In the validation set, HEPAVIR and HIV cirrhosis criteria spared 54% and 48.7% of EGDs, while missing 4.9% and 2.2% EVNT, respectively. CONCLUSIONS: Baveno VI criteria can be extended to HEPAVIR and HIV cirrhosis criteria while sparing a significant number of EGDs, thus improving resource utilization for PLWH with compensated advanced chronic liver disease.
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Técnicas de Imagem por Elasticidade , Varizes Esofágicas e Gástricas , Infecções por HIV , Hepatopatias , Plaquetas , Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/etiologia , Infecções por HIV/complicações , Humanos , Cirrose Hepática/complicações , Estudos ProspectivosRESUMO
INTRODUCTION: Orbital myositis (OM) is a serious inflammation of extraocular muscles with unknown etiology. Pe diatric presentation is rare and often affects more than one individual in a family, suggesting a genetic predisposition. OBJECTIVE: To describe a pediatric case of orbital myositis, its clinical characteristics, and the usefulness of MRI for confirming the diagnosis. CLINICAL CASE: A 13-year-old female patient presenting with acute headache, right periorbital pain, exacerbated by eye movements, and blurred vision. We ruled out thyrotoxic myopathy, infectious diseases, autoimmunity, and malignancy. An MRI showed right medial rectus muscle myositis and no evidence of optic neuritis. She was treated with intravenous systemic glucocorticoids followed by oral steroids with complete clinical resolution. CONCLUSIONS: OM has unknown etiology and can present a malignant course. Due to its unspecific clinical presentation, a comprehensive differential diagnosis should be made and it should consider performing MRI. Early treatment avoids permanent damage of extraocular muscles.
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Glucocorticoides/administração & dosagem , Músculos Oculomotores/diagnóstico por imagem , Miosite Orbital/diagnóstico por imagem , Síndrome de Tolosa-Hunt/etiologia , Adolescente , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Músculos Oculomotores/patologia , Miosite Orbital/tratamento farmacológico , Síndrome de Tolosa-Hunt/tratamento farmacológicoRESUMO
BACKGROUND: Our objective was to assess the predictive value of the changes of liver stiffness (LS) for clinical outcome in HIV/HCV-coinfected patients with compensated liver cirrhosis and a LS value < 40 kPa. METHODS: Prospective cohort of 275 HIV/HCV-coinfected patients with cirrhosis, no previous liver decompensation (LD) and LS < 40 kPa. The time from diagnosis to LD and/or hepatocellular carcinoma (HCC) and the predictors of this outcome were evaluated. Significant progression of LS was defined as an increase ≥ 30 % over the baseline value at any time during the follow-up. RESULTS: After a median (Q1-Q3) follow-up of 32 (20-48) months, 19 (6.9 %, 95 % CI: 3.8 %-9.9 %) patients developed a first LD and/or HCC. At the end of the follow-up, 247 (90 %) patients had undergone a further LS examination. Of them, 77 (31 %) patients had a significant progression of LS. The mean (SD) survival time free of LD and/or HCC was 67 (3) and 77 (1) months in patients with or without significant progression of LS (p = 0.01). Significant progression of LS was an independent predictor of LD and/or HCC (Adjusted Hazard Ratio 4.63; 95 % confidence interval: 1.34-16.02; p = 0.015). CONCLUSIONS: Significant progression of LS is associated with a higher risk of clinical events in HIV/HCV-coinfected patients with compensated cirrhosis and LS < 40 kPa.
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Infecções por HIV/complicações , Hepatite C/complicações , Cirrose Hepática/etiologia , Fígado/patologia , Adulto , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/virologia , Coinfecção/complicações , Feminino , Seguimentos , Infecções por HIV/patologia , Hepatite C/patologia , Humanos , Fígado/virologia , Cirrose Hepática/mortalidade , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Análise de SobrevidaRESUMO
BACKGROUND: To report the clinical and epidemiological characteristics of hepatocellular carcinoma (HCC) diagnosed in a cohort of human immunodeficiency virus (HIV)-infected patients in Spain. METHODS: All HIV-infected patients diagnosed of HCC in 18 hospitals in Spain before 31 December 2010 were included. The main characteristics of HCC cases are described and comparisons between cases according to the year of diagnosis are presented. RESULTS: Eighty-two cases of HCC in HIV-infected patients were included, all of them related to viral hepatitis coinfection: hepatitis C virus (HCV) in 66 (81%), hepatitis B virus (HBV) in 6 (7%), and HBV/HCV in 10 (12%). From 1999, when the first case of HCC was diagnosed, a progressive increment in the incidence of HCC in the cohort has occurred. In patients coinfected with HIV/HCV-coinfected patients, the incidence HCC increased from 0.2 to 2.8 cases per 1000 person-years between 2000 and 2009. Death occurred in 65 patients (79%), with a median survival of 91 days (interquartile range, 31-227 days). Three of 11 patients (28%) who received potentially curative therapy died, compared with 62 of 71 patients (87%) who did not receive curative therapy (P = .0001). Compared with cases of HCC diagnosed before 2005, cases diagnosed later did not show a higher survival rate. CONCLUSIONS: HCC is an emerging complication of cirrhosis in HIV-infected patients. A sharp increase in its incidence has occurred in those also infected by HCV in the recent years. Unfortunately, HCC is frequently diagnosed at an advanced stage, and mortality continues to be very high, with no significant changes in recent years. Earlier diagnosis, which may allow potentially curative therapy, is necessary.
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Carcinoma Hepatocelular/epidemiologia , Infecções por HIV/epidemiologia , Neoplasias Hepáticas/epidemiologia , Carcinoma Hepatocelular/virologia , Estudos de Coortes , Feminino , Infecções por HIV/complicações , Hepatite B/epidemiologia , Hepatite B/virologia , Hepatite C/epidemiologia , Hepatite C/virologia , Humanos , Incidência , Cirrose Hepática/epidemiologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Espanha/epidemiologia , Análise de SobrevidaAssuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Infecções por HIV/complicações , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Falência Hepática Aguda/etiologia , Sofosbuvir/uso terapêutico , Ativação Viral , Fármacos Anti-HIV/uso terapêutico , Coinfecção , Substituição de Medicamentos , Evolução Fatal , Infecções por HIV/tratamento farmacológico , Hepacivirus/isolamento & purificação , Vírus da Hepatite B/isolamento & purificação , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferon alfa-2/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/uso terapêutico , Ribavirina/uso terapêuticoRESUMO
BACKGROUND: The FilmArray Meningitis/Encephalitis(FA/ME) panel brings benefits in clinical practice, but its diagnostic test accuracy (DTA) remains unclear. We aimed to determine the DTA of FA/ME for the aetiological diagnostic in patients with suspected central nervous system(CNS) infection. METHODS: We performed a systematic review with DTA meta-analysis (PROSPERO: CRD42020139285). We searched Embase, Medline (Ovid), and Web of Science from inception until September 1st, 2021. We assessed the study-level risk of bias with the QUADAS-2 tool and applied the GRADE approach to assess the certainty of the synthesised evidence. We included studies that simultaneously measured the reference test (CSF/blood culture for bacteria, and specific polymerase chain reaction for viruses) and the FA/ME in patients with suspected CNS infection. We performed random-effects bivariate meta-analysis models of combined sensitivity and specificity using CSF/blood cultures(reference test 1) and a final diagnosis adjudication based on clinical/laboratory criteria (reference test 2). FINDINGS: We included 19 studies (11,351 participants). For all bacteria with reference test 1 (16 studies/6183 patients) sensitivity was estimated at 89·5% (95%CI 81·1-94·4), and specificity at 97·4% (95%CI 94-98·9). With reference test 2 (15 studies/5,524 patients), sensitivity was estimated at 92·1%(95%CI 86·8-95·3) and specificity at 99.2(95%CI 98·3-99·6) For herpes simplex virus-2(HSV-2), enteroviruses, and Varicella-Zoster virus (VZV), we obtained sensitivities between 75·5 and 93·8%, and specificities above 99% (reference test 1). Certainty of the evidence was low. INTERPRETATION: FA/ME may have acceptable-to-high sensitivities and high specificities for identifying bacteria, especially for S.pneumoniae, and viruses, especially for HSV-2, and enteroviruses. Sensitivities for L.monocytogenes, H.influenzae, E.coli, and HSV-1 were suboptimal. FUNDING: None.
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OBJECTIVES: To evaluate if the detection of N antigen of SARS-CoV-2 in plasma by a rapid lateral flow test predicts 90-day mortality in COVID-19 patients hospitalized at the wards. METHODS: The presence of N-antigenemia was evaluated in the first 36 hours after hospitalization in 600 unvaccinated COVID-19 patients, by using the Panbio COVID-19 Ag Rapid Test Device from Abbott (Abbott Laboratories Inc., Chicago, IL, USA). The impact of N-antigenemia on 90-day mortality was assessed by multivariable Cox regression analysis. RESULTS: Prevalence of N-antigenemia at hospitalization was higher in nonsurvivors (69% (82/118) vs. 52% (250/482); p < 0.001). The patients with N-antigenemia showed more frequently RNAemia (45.7% (148/324) vs. 19.8% (51/257); p < 0.001), absence of anti-SARS-CoV-2 N antibodies (80.7% (264/327) vs. 26.6% (69/259); p < 0.001) and absence of S1 antibodies (73.4% (240/327) vs. 23.6% (61/259); p < 0.001). The patients with antigenemia showed more frequently acute respiratory distress syndrome (30.1% (100/332) vs. 18.7% (50/268); p = 0.001) and nosocomial infections (13.6% (45/331) vs. 7.9% (21/267); p = 0.026). N-antigenemia was a risk factor for increased 90-day mortality in the multivariable analysis (HR, 1.99 (95% CI,1.09-3.61), whereas the presence of anti-SARS-CoV-2 N-antibodies represented a protective factor (HR, 0.47 (95% CI, 0.26-0.85). DISCUSSION: The presence of N-antigenemia or the absence of anti-SARS-CoV-2 N-antibodies after hospitalization is associated to increased 90-day mortality in unvaccinated COVID-19 patients. Detection of N-antigenemia by using lateral flow tests is a quick, widely available tool that could contribute to early identify those COVID-19 patients at risk of deterioration.
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COVID-19 , Anticorpos Antivirais , COVID-19/diagnóstico , Teste para COVID-19 , Humanos , Estudos Prospectivos , SARS-CoV-2RESUMO
In this work the level and structure of consanguinity is analysed in two Spanish rural regions of similar geographic and orographic characteristics for the period between 1880 and 1979, employing two different methodologies. The estimates according dispensations shows that the total levels (alpha4 = 0.00552 in La Cabrera and 0.00405 in Fuentes Carrionas) and the structures of consanguinity (C22/C33 = 0.43 and 0.34) are similar in both regions, but have evolved differently. Whereas in La Cabrera both parameters have remained stable, in Fuentes Carrionas they fluctuated through the period analysed. On studying the structure of consanguinity more closely using the isonymic method, it can be seen that in La Cabrera total consanguinity (Ft = 0.0206) should be attributed mainly to environmental factors (Fr = 0.0193) and to a lesser extent to socio-cultural factors (Fn = 0.0013), whereas in Fuentes Carrionas it derives, almost exclusively, from the former (Ft = 0.01270; Fr = 0.01589; Fn = -0.00325).
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Consanguinidade , Nomes , Evolução Biológica , Humanos , EspanhaRESUMO
OBJECTIVE: First seizures are always challenging for physicians. Determining etiology, risk of recurrence, need for diagnostic electroencephalogram (EEG) or neuroimaging, balancing starting anti-seizure medication (ASM) versus its potential adverse effects, and addressing patient and family concerns about social or emotional impact in lifestyle issues is always demanding. METHOD: a narrative review providing information from a database search between January 1970 to November 2020 was conducted, with the following search terms: first seizure, epidemiology, treatment, neuroimaging, electroencephalogram, impact, lifestyle. RESULTS: Incidence rates of single unprovoked seizures range from 23 to 64.1 /100000/person-years. The risk of recurrence depends on several clinical, etiological, EEG, and neuroimaging findings that should be approached on an individual basis. Initiating ASM is not generally advised, but shall be considered in individual situations. The emotional and social impact of single seizures must not be underestimated. Some interesting clues are pointing out at risks to present or prevent a first seizure. CONCLUSION: Presentation of first seizure, diagnostic workup, treatment, and impact should be considered individually based on continuously updated knowledge of treating physicians.
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Epilepsias Parciais , Epilepsia Generalizada , Adulto , Anticonvulsivantes/uso terapêutico , Carbamazepina/uso terapêutico , Criança , Eletroencefalografia , Epilepsias Parciais/tratamento farmacológico , Epilepsia Generalizada/tratamento farmacológico , Humanos , Recidiva , Convulsões/diagnóstico , Convulsões/epidemiologia , Convulsões/terapiaRESUMO
The biodemography of isolated populations with a subsistence economy is of special interest because the conditions to which the populations have been subjected are similar to those present over a large part of the history of our species, and hence the conclusions drawn can be extrapolated to other similar populations. In the present work, we used two recently employed techniques (self-organizing maps and Monmonier's algorithm) to study the genetic structure of a small rural region: Fuentes Carrionas (province of Palencia, Spain). The study was based on information contained in marriage registers and family reconstructions for the period 1880-1979. We calculated the coefficients of relationships (Hedrick) among the parishes (by isonymy and parent-offspring matrix) and studied their relationship with geographic distances (Mantel). Then, using Monmonier's algorithm, we examined the genetic barriers. Finally, by applying self-organizing maps, we studied the distribution of surnames. The correlation between genetic distance matrices estimated through surnames and gene flow was high (p < 0.01), and geographic distance was found to be significantly related to both surnames and gene flow (p < 0.01); geographic distance therefore seems to be the main factor of isolation. However, the genetic barriers revealed a region divided in two, and the surname distribution displayed an identical division: 29.56% of the surnames appeared almost exclusively in the northeastern half and 21.91% appeared only in the southwest. Both techniques afforded coherent and complementary results. Their combined use allows a detailed study to be made. Although geographic distance was the strongest determining factor, we detected others factors (orographic and socioeconomic) that seem to have left their mark on the genetic structure of Fuentes Carrionas.
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Fluxo Gênico , Genética Populacional/estatística & dados numéricos , Nomes , População Rural/estatística & dados numéricos , Algoritmos , Geografia , Humanos , Espanha , Estatística como AssuntoRESUMO
BACKGROUND: Whereas HIV-1 has spread globally, HIV-2 is mainly found in West Africa where dual HIV-1/HIV-2 coinfection is nowadays uncommon. Herein, we report the rate, main characteristics, and treatment outcomes of all dually infected patients living in Spain. METHODS: We identified retrospectively all persons coinfected with HIV-1 recorded at the Spanish HIV-2 registry. Dual infection had been confirmed using PCR in plasma and/or cells, and/or using discriminatory serological tests. RESULTS: From a total of 373 individuals with HIV-2 recorded at the Spanish registry, 34 (9.1%) were coinfected with HIV-1. Compared with HIV-2 monoinfected persons, dually infected patients were more often male (67.6%), presented with lower median CD4 cell counts (204âcells/µl), and had developed more frequently AIDS events (26.5%). Although 61.7% came from West Africa, 6 (17.6%) were native Spaniards. HIV-1 non-B subtypes were recognized in 75% of coinfected patients, being the most prevalent CRF02_AG. At baseline, 45% of dually infected patients had undetectable plasma HIV-2 RNA. After a median follow-up of 32 (13-48) months on antiretroviral therapy, dually infected patients achieved undetectable viremia in 85% for HIV-1, in 80% for HIV-2; and in 70% for both viruses. Median CD4 cell counts reached up to 418âcells/µl. CONCLUSION: Roughly 9% of individuals with HIV-2 infection living in Spain are coinfected with HIV-1. Overall, 70% of dually infected patients achieved viral suppression for both viruses under antiretroviral therapy. Given the relatively large population of West Africans living in Spain and the continuous migration flow from HIV-2 endemic areas, HIV-1/HIV-2 coinfection should always be excluded at first diagnosis in all HIV-seroreactive persons.
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Fármacos Anti-HIV/uso terapêutico , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , HIV-2/isolamento & purificação , Adulto , Contagem de Linfócito CD4 , Coinfecção/virologia , Feminino , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha , Resultado do Tratamento , Carga Viral , Viremia/tratamento farmacológicoRESUMO
OBJECTIVE: To assess the impact of HIV coinfection on the risk of developing liver-related complications in HCV-infected patients with advanced fibrosis treated with direct-acting antivirals (DAA) after sustained virological response (SVR). DESIGN: Prospective cohort study. SETTING: Multicenter. SUBJECTS: Patients from the GEHEP and HEPAVIR cohorts were selected if they fulfilled the following criteria: treatment against HCV with all oral DAA combination; SVR achievement, defined as undetectable plasma HCV RNA 12 weeks after the end of therapy; pretreatment liver stiffness equal to or higher than 9.5âkPa; liver stiffness measurement at the time of SVR. MAIN OUTCOME MEASURE(S): The primary variable was the time until the development of a liver complication or requiring liver transplant. RESULTS: Seven hundred and seventeen patients were included and 507 (71%) were coinfected with HIV. After a median follow-up time of 21 (14-25) months, 15 (2.1%) patients developed a liver complication and/or underwent a liver transplant and 15 (2.0%) died. The probability of remaining free of hepatic complications or transplant at 1 and 2 was, respectively, 99 and 96% in HCV-monoinfected patients and 99 and 98% in coinfected patients (Pâ=â0.648). In a multivariate analysis, in which nonliver-related death was considered as a competing event, HIV coinfection was not associated with the appearance of hepatic complications or requiring liver transplant [hazard ratioâ=â0.24; 95% CI (0.03-1.93), Pâ=â0.181]. Having presented hepatic decompensation prior to SVR [hazard ratioâ=â29.06; 95% CI (3.91-216.16), Pâ<â0.001] and the value of liver stiffness at the SVR time-point (hazard ratioâ=â1.12; 95% CI (1.07-1.18), Pâ<â0.001] were associated with a higher probability of development of liver events. CONCLUSION: HIV coinfection is not associated with a higher probability of developing liver complications in HCV-infected patients with advanced fibrosis, who achieved SVR with interferon-free regimens.
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Antivirais/uso terapêutico , Coinfecção/virologia , Infecções por HIV/tratamento farmacológico , Hepatite C/tratamento farmacológico , Quimioterapia Combinada , Feminino , HIV/efeitos dos fármacos , Infecções por HIV/virologia , Hepacivirus/efeitos dos fármacos , Hepatite C/complicações , Hepatite C/virologia , Humanos , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Resposta Viral Sustentada , Transplantados , Carga ViralRESUMO
Since domestication, a large number of livestock breeds adapted to local conditions have been created by natural and artificial selection, representing one of the most powerful ways in which human groups have constructed niches to meet their need. Although many authors have described local breeds as the result of culturally and environmentally mediated processes, this study, located in mainland Spain, is the first aimed at identifying and quantifying the environmental and human contributions to the spatial structure of local breed diversity, which we refer to as livestock niche. We found that the more similar two provinces were in terms of human population, ecological characteristics, historical ties, and geographic distance, the more similar the composition of local breeds in their territories. Isolation by human population distance showed the strongest effect, followed by isolation by the environment, thus supporting the view of livestock niche as a socio-cultural product adapted to the local environment, in whose construction humans make good use of their ecological and cultural inheritances. These findings provide a useful framework to understand and to envisage the effects of climate change and globalization on local breeds and their livestock niches.
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Criação de Animais Domésticos/métodos , Criação de Animais Domésticos/tendências , Seleção Artificial , Animais , Cruzamento , Mudança Climática , Conservação dos Recursos Naturais , Ecologia , Variação Genética , Humanos , Gado , EspanhaRESUMO
TRIAL DESIGN: The QoLKAMON study evaluated quality of life, efficacy and treatment safety in HIV patients receiving lopinavir/ritonavir in monotherapy (MT) versus continuing combined antiretroviral triple treatment with a boosted protease inhibitor (TT). METHODS: This was a 24-week, open-label, multicentre study in virologically-suppressed HIV-infected participants (N = 225) with a 2:1 randomization: 146 patients who switched to MT were compared with 79 patients who remained on a TT regimen. The primary endpoint was change in patient-reported outcomes in quality of life as measured by the MOS-HIV and EQ-5D questionnaires. Secondary endpoints included treatment adherence, patient satisfaction, incidence of adverse events and differences in plasma HIV-1 RNA viral load (VL) and CD4 cell counts. RESULTS: Baseline quality of life, measured with the MOS-HIV score, was very good (overall score of 83 ± 10.5 in the MT arm and 82.3 ± 11.3 in the TT arm) and suffered no change during the study in any of the arms (at week 24, 83.5 ± 12.2 in MT arm and 81.9 ± 12.7 in TT arm), without statistically significant differences when compared. In regards to adherence to therapy and patient satisfaction, some aspects (number of doses forgotten in the last week and satisfaction of treatment measured with the CESTA score, dimension 1) improved significantly with MT. There were also no differences in the incidence and severity of adverse events, even though 22.8% of those in the MT arm switched their treatment when they were included in the study. Moreover, there was also no significant difference between the immunological and virological evolution of MT and TT. In the MT arm, the VL was always undetectable in 83% of patients (vs 90.7% in the TT arm) and there were only 6.7% of virological failures with VL > 50 copies/mL (vs 2.3% in the TT arm), without resistance mutations and with resuppression of VL after switching back to TT. CONCLUSIONS: In a new clinical trial, monotherapy as a treatment simplification strategy in HIV-1 infected patients with sustained viral suppression has demonstrated quality of life, safety and efficacy profiles comparable to those of conventional triple therapy regimens.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Lopinavir/administração & dosagem , Qualidade de Vida , Ritonavir/administração & dosagem , Adulto , Contagem de Linfócito CD4 , Feminino , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/uso terapêutico , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Espanha , Inquéritos e Questionários , Resultado do Tratamento , Carga Viral/efeitos dos fármacosRESUMO
In a previous study concerning 33,753 single Spanish surnames (considered as tokens) occurring 51,419,788 times we have shown that the present-day geography of contemporary surname variability in Spain still corresponds to the political geography of the country at the end of the Middle Ages. Here we reprocess the same database, by clustering surnames with Self-Organizing Maps (SOMs) according to their geographic distribution, to identify the monophyletic surnames showing a geo-historical origin in one of the 47 provinces of continental Spain. They are 25,714, and they occur 12,348,109 times, meaning that about 75% of the Spanish population bears a surname that had a polyphyletic origin. From monophyletic surnames we compute migration matrices accounting for the internal migrations that took place since five centuries ago, when Spanish surnames started to be patrilineally inherited. The mono/ polyphyletic classification we obtain fits ancient census data and is compatible with published molecular diversity of the Y-chromosomes associated to selected Spanish surnames. Monophyletic surnames indicate that i) the provinces exhibiting a higher percentage of autochthonous surnames are also ii) those from which emigration corresponds to a local isolation-by-distance model of diffusion and iii) those that attracted a lower number of immigrants. These are also the provinces where languages other than Castilian are spoken. We suggest that demographic stability explains linguistic resilience, as people prefer to move to areas in which the linguistic variety is more similar to their own. So far the reciprocal influence of migration and language has been investigated at local scales, here we outline how to investigate it at national scales and for time-depths of centuries.
Assuntos
Variação Genética , Migração Humana , Idioma , Nomes , Antropologia , Emigrantes e Imigrantes , Humanos , EspanhaRESUMO
BACKGROUND: A liver stiffness below 21âkPa has a high negative predictive value to exclude the presence of esophageal varices at risk of bleeding in HIV/hepatitis C virus (HCV)-coinfected patients. Consequently, upper gastrointestinal endoscopy (UGE) for the screening of esophageal varices could be avoided in these patients. However, this strategy has not been widely accepted due to concerns about its safety. OBJECTIVE: To assess the ability of liver stiffness to predict the risk of portal hypertensive gastrointestinal bleeding (PHGB) in HIV/HCV-coinfected patients with compensated cirrhosis. METHODS: Prospective study of 446 HIV/HCV-coinfected patients with a new diagnosis of cirrhosis and no previous decompensation. All patients underwent a UGE for the screening of esophageal varices at entry in the cohort before November 2009. From this date, UGE was not recommended in patients with liver stiffness below 21âkPa. The time from diagnosis of cirrhosis to the emergence of PHGB was evaluated. RESULTS: After a median (quartile1-quartile3) follow-up of 49 (25-68) months, 15 (3.4%, 95% confidence interval 1.7-5%) patients developed a first PHGB episode. In all cases, baseline liver stiffness was at least 21âkPa. Thus, the negative predictive value of a liver stiffness below 21âkPa to predict PHGB during follow-up was 100%. At the time of the bleeding episode, liver stiffness was above this threshold in all patients. CONCLUSIONS: Liver stiffness identifies HIV/HCV-coinfected patients with compensated cirrhosis with a very low risk of PHGB. In fact, no individual with liver stiffness below 21âkPa developed this outcome. Our results confirm that UGE can be safely spared in patients with liver stiffness below 21âkPa.
Assuntos
Coinfecção/complicações , Varizes Esofágicas e Gástricas/complicações , Hemorragia Gastrointestinal/epidemiologia , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Cirrose Hepática/complicações , Fígado/patologia , Adulto , Técnicas de Apoio para a Decisão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
To assess whether the present-day geographical variability of Spanish surnames mirrors historical phenomena occurred at the times of their introduction (13th-16th century), and to infer the possible effect of foreign immigration (about 11% of present-day) on the observed patterns of diversity, we have analyzed the frequency distribution of 33,753 unique surnames (tokens) occurring 51,419,788 times, according to the list of Spanish residents of the year 2008. Isonymy measures and surname distances have been computed for, and between, the 47 mainland Spanish provinces and compared to a numerical classification of corresponding language varieties spoken in Spain. The comparison of the two bootstrap consensus trees, representing surname and linguistic variability, suggests a similar picture; major clusters are located in the east (Aragón, Cataluña, Valencia), and in the north of the country (Asturias, Galicia, León). Remaining regions appear to be considerably homogeneous. We interpret this pattern as the long-lasting effect of the surname and linguistic normalization actively led by the Christian kingdoms of the north (Reigns of Castilla y León and Aragón) during and after the southwards reconquest (Reconquista) of the territories ruled by the Arabs from the 8th century to the late 15th century, that is when surnames became transmitted in a fixed way and when Castilian linguistic varieties became increasingly prestigious and spread out. The geography of contemporary surname and linguistic variability in Spain corresponds to the political geography at the end of the Middle-Ages. The synchronicity between surname adoption and the political and cultural effects of the Reconquista have permanently forged a Spanish identity that subsequent migrations, internal or external, did not deface.