AIM:To determine the rates and impact of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections on response to long-term highly active antiretroviral therapy(HAART) in a large human immunodeficiency virus(HIV) p...AIM:To determine the rates and impact of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections on response to long-term highly active antiretroviral therapy(HAART) in a large human immunodeficiency virus(HIV) population in Nigeria.METHODS:HBV and HCV as well as HIV infections are endemic in sub Saharan Africa.This was a retrospective cohort study of 19 408 adults who were recruited between June 2004 and December 2010 in the AIDS Prevention Initiative in Nigeria in Nigeria programme at Jos University Teaching Hospital.Serological assays,including HBV surface antigen(HBsAg) and hepatitis C antibody were used to categorise hepatitis status of the patients.HBsAg was determined using enzyme immunoassay(EIA)(Monolisa HBsAg Ultra3;Bio-Rad).HCV antibody was tested using third generation EIA(DIA.PRO Diagnostic,Bioprobes srl,Milan,Italy).HIV RNA levels were measured using Roche COBAS Amplicor HIV-1 monitor test version 1.5(Roche Diagnostics,GmbH,Mannheim,Germany) with a detection limit of 400 copies/mL.Flow cytometry was used to determine CD4+ cell count(Partec,GmbH Munster,Germany).Comparison of categorical and continuous variables were achieved using Pearson's χ 2 and Kruskal Wallis tests respectively,on MedCalc for Windows,version 9.5.0.0(MedCalc Software,Mariakerke,Belgium).RESULTS:With an overall hepatitis screening rate of over 90% for each virus;HBV,HCV and HBV/HCV were detected in 3162(17.8%),1983(11.3%) and 453(2.5%) HIV infected adults respectively.The rate of liver disease was low,but highest among HIV monoinfected patients(29,0.11%),followed by HBV coinfected patients(15,0.08%).Patients with HBV coinfection and triple infection had higher log 10 HIV RNA loads(HBV:4.6 copies/mL vs HIV only:4.5 copies/mL,P<0.0001) and more severe immune suppression(HBV:645,55.4%;HBV/HCV:97,56.7%) prior to initiation of HAART compared to HIV mono-infected patients(1852,48.6%)(P<0.0001).Of 3025 patients who were 4.4 years on HAART and whose CD4 cell counts results at baseline and end of follow up were available for analyses,CD4 increase was significantly lower in those with HBV co-infection(HBV:144 cells/mm3 ;HBV/HCV:105 cells/mm3) than in those with HCV co-infection(165 cells/mm3) and HIV mono-infection(150 cells/mm3)(P=0.0008).CONCLUSION:High rates of HBV and HCV infections were found in this HIV cohort.CD4 recovery was significantly diminished in patients with HBV co-infection.展开更多
A standard approach for analyses of survival data is the Cox proportional hazards model. It assumes that covariate effects are constant over time, i.e. that the hazards are proportional. With longer follow-up times, t...A standard approach for analyses of survival data is the Cox proportional hazards model. It assumes that covariate effects are constant over time, i.e. that the hazards are proportional. With longer follow-up times, though, the effect of a variable often gets weaker and the proportional hazards (PH) assumption is violated. In the last years, several approaches have been proposed to detect and model such time-varying effects. However, comparison and evaluation of the various approaches is difficult. A suitable measure is needed that quantifies the difference between time-varying effects and enables judgement about which method is best, i.e. which estimate is closest to the true effect. In this paper we adapt a measure proposed for the area between smoothed curves of exposure to time-varying effects. This measure is based on the weighted area between curves of time-varying effects relative to the area under a reference function that represents the true effect. We introduce several weighting schemes and demonstrate the application and performance of this new measure in a real-life data set and a simulation study.展开更多
Background: Total lymphocyte count has been proposed as an alternative to the percentage of CD4+ T-cells to indicate when antiretroviral therapy should be started in children with HIV in resource-poor settings. We aim...Background: Total lymphocyte count has been proposed as an alternative to the percentage of CD4+ T-cells to indicate when antiretroviral therapy should be started in children with HIV in resource-poor settings. We aimed to assess thresholds of total lymphocyte count at which antiretroviral therapy should be considered, and compared monitoring of total lymphocyte count with monitoring of CD4- cell percentage. Methods: Longitudinal data on 3917 children with HIV infection were pooled from observational and randomised studies in Europe and the USA. The 12- month risks of death and AIDS by most recent total lymphocyte count and age were estimated by parametric survival models, based on measurements before antiretroviral therapy or during zidovudine monotherapy. Risks were derived and compared at thresholds of total lymphocyte count and CD4- cell percentage for starting antiretroviral therapy recommended in WHO 2003 guidelines. Findings: Total lymphocyte count was a powerful predictor of the risk of disease progression despite a weak correlation with CD4- cell percentage (r=0.08- 0.19 dependent on age). For children older than 2 years, the 12- month risk of death and AIDS increased sharply at values less than 1500- 2000 cells per μ L, with little trend at higher values. Younger children had higher risks and total lymphocyte count was less prognostic. Mortality risk was substantially higher at thresholds of total lymphocyte count recommended by WHO than at corresponding thresholds of CD4- cell percentage. When the markers were compared at the threshold values at which mortality risks were about equal, total lymphocyte count was as effective as CD4- cell percentage for identifying children before death, but resulted in an earlier start of antiretroviral therapy. Interpretation: In this population, total lymphocyte count was a strong predictor of short-term disease progression, being only marginally less predictive than CD4- cell percentage. Confirmatory studies in resource-poor settings are needed to identify the most cost-effective markers to guide initiation of antiretroviral therapy.展开更多
Approximately 25%of individuals with colorectal cancer(CRC)present with metastatic disease,and it is estimated that throughout the course of the disease,up to 50%of individuals may develop liver metastases,the majorit...Approximately 25%of individuals with colorectal cancer(CRC)present with metastatic disease,and it is estimated that throughout the course of the disease,up to 50%of individuals may develop liver metastases,the majority of which are unresectable(1).However,thermal ablation is a treatment modality increasingly used to manage individuals with liver metastases.Recently Takahashi et al.published a comprehensive review of the various approaches to thermal ablation and summarised the recent evidence demonstrating an associated survival benefit supporting its use in the management of metastatic CRC(mCRC)(2).It is however critical to analyse the studies evaluated to ensure the strength of the evidence presented.展开更多
基金Supported by The United States Health Resources and Services Administration (U51HA02522-01-01)the Prevention of Liver Fibrosis and Carcinoma in Africa (PROLIFICA) project(EU-Framework 7)+1 种基金the United Kingdom National Institute for Healthcare Research (NIHR)the London Clinic Research Fellowship Scheme
文摘AIM:To determine the rates and impact of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections on response to long-term highly active antiretroviral therapy(HAART) in a large human immunodeficiency virus(HIV) population in Nigeria.METHODS:HBV and HCV as well as HIV infections are endemic in sub Saharan Africa.This was a retrospective cohort study of 19 408 adults who were recruited between June 2004 and December 2010 in the AIDS Prevention Initiative in Nigeria in Nigeria programme at Jos University Teaching Hospital.Serological assays,including HBV surface antigen(HBsAg) and hepatitis C antibody were used to categorise hepatitis status of the patients.HBsAg was determined using enzyme immunoassay(EIA)(Monolisa HBsAg Ultra3;Bio-Rad).HCV antibody was tested using third generation EIA(DIA.PRO Diagnostic,Bioprobes srl,Milan,Italy).HIV RNA levels were measured using Roche COBAS Amplicor HIV-1 monitor test version 1.5(Roche Diagnostics,GmbH,Mannheim,Germany) with a detection limit of 400 copies/mL.Flow cytometry was used to determine CD4+ cell count(Partec,GmbH Munster,Germany).Comparison of categorical and continuous variables were achieved using Pearson's χ 2 and Kruskal Wallis tests respectively,on MedCalc for Windows,version 9.5.0.0(MedCalc Software,Mariakerke,Belgium).RESULTS:With an overall hepatitis screening rate of over 90% for each virus;HBV,HCV and HBV/HCV were detected in 3162(17.8%),1983(11.3%) and 453(2.5%) HIV infected adults respectively.The rate of liver disease was low,but highest among HIV monoinfected patients(29,0.11%),followed by HBV coinfected patients(15,0.08%).Patients with HBV coinfection and triple infection had higher log 10 HIV RNA loads(HBV:4.6 copies/mL vs HIV only:4.5 copies/mL,P<0.0001) and more severe immune suppression(HBV:645,55.4%;HBV/HCV:97,56.7%) prior to initiation of HAART compared to HIV mono-infected patients(1852,48.6%)(P<0.0001).Of 3025 patients who were 4.4 years on HAART and whose CD4 cell counts results at baseline and end of follow up were available for analyses,CD4 increase was significantly lower in those with HBV co-infection(HBV:144 cells/mm3 ;HBV/HCV:105 cells/mm3) than in those with HCV co-infection(165 cells/mm3) and HIV mono-infection(150 cells/mm3)(P=0.0008).CONCLUSION:High rates of HBV and HCV infections were found in this HIV cohort.CD4 recovery was significantly diminished in patients with HBV co-infection.
文摘A standard approach for analyses of survival data is the Cox proportional hazards model. It assumes that covariate effects are constant over time, i.e. that the hazards are proportional. With longer follow-up times, though, the effect of a variable often gets weaker and the proportional hazards (PH) assumption is violated. In the last years, several approaches have been proposed to detect and model such time-varying effects. However, comparison and evaluation of the various approaches is difficult. A suitable measure is needed that quantifies the difference between time-varying effects and enables judgement about which method is best, i.e. which estimate is closest to the true effect. In this paper we adapt a measure proposed for the area between smoothed curves of exposure to time-varying effects. This measure is based on the weighted area between curves of time-varying effects relative to the area under a reference function that represents the true effect. We introduce several weighting schemes and demonstrate the application and performance of this new measure in a real-life data set and a simulation study.
文摘Background: Total lymphocyte count has been proposed as an alternative to the percentage of CD4+ T-cells to indicate when antiretroviral therapy should be started in children with HIV in resource-poor settings. We aimed to assess thresholds of total lymphocyte count at which antiretroviral therapy should be considered, and compared monitoring of total lymphocyte count with monitoring of CD4- cell percentage. Methods: Longitudinal data on 3917 children with HIV infection were pooled from observational and randomised studies in Europe and the USA. The 12- month risks of death and AIDS by most recent total lymphocyte count and age were estimated by parametric survival models, based on measurements before antiretroviral therapy or during zidovudine monotherapy. Risks were derived and compared at thresholds of total lymphocyte count and CD4- cell percentage for starting antiretroviral therapy recommended in WHO 2003 guidelines. Findings: Total lymphocyte count was a powerful predictor of the risk of disease progression despite a weak correlation with CD4- cell percentage (r=0.08- 0.19 dependent on age). For children older than 2 years, the 12- month risk of death and AIDS increased sharply at values less than 1500- 2000 cells per μ L, with little trend at higher values. Younger children had higher risks and total lymphocyte count was less prognostic. Mortality risk was substantially higher at thresholds of total lymphocyte count recommended by WHO than at corresponding thresholds of CD4- cell percentage. When the markers were compared at the threshold values at which mortality risks were about equal, total lymphocyte count was as effective as CD4- cell percentage for identifying children before death, but resulted in an earlier start of antiretroviral therapy. Interpretation: In this population, total lymphocyte count was a strong predictor of short-term disease progression, being only marginally less predictive than CD4- cell percentage. Confirmatory studies in resource-poor settings are needed to identify the most cost-effective markers to guide initiation of antiretroviral therapy.
基金资助 （Funding）： KGMM, YV, and DEG are supported by the Netherlands Organisation for Scientific Research （ZON-MW 917. 46. 360）. PR is supported by the UK Medical Research Council （U. 1228. 06. 001. 00002.01 ）. DGA is supported by Cancer Research UK.
文摘Approximately 25%of individuals with colorectal cancer(CRC)present with metastatic disease,and it is estimated that throughout the course of the disease,up to 50%of individuals may develop liver metastases,the majority of which are unresectable(1).However,thermal ablation is a treatment modality increasingly used to manage individuals with liver metastases.Recently Takahashi et al.published a comprehensive review of the various approaches to thermal ablation and summarised the recent evidence demonstrating an associated survival benefit supporting its use in the management of metastatic CRC(mCRC)(2).It is however critical to analyse the studies evaluated to ensure the strength of the evidence presented.
