The possibility of safe discontinuation of therapy with nucleos(t)ide analogues (NAs) remains one of the most controversial topics in the management of chronic hepatitis B. Therefore, we systematically reviewed the existing data on NA... more
The possibility of safe discontinuation of therapy with nucleos(t)ide analogues (NAs) remains one of the most controversial topics in the management of chronic hepatitis B. Therefore, we systematically reviewed the existing data on NA discontinuation in this setting and tried to identify factors affecting the probability of posttherapy remission. A literature search was performed in order to identify all published studies including patients who discontinued NAs in virological remission (VR) and were followed for ≥12 months thereafter. Twenty-five studies with 1716 patients were included. The pooled rates of durable VR remission were 51.4%, 39.3%, and 38.2% at 12, 24, and 36 months, respectively, after NA discontinuation, being relatively higher in initially hepatitis B e antigen (HBeAg)-positive patients (62.5%, 53.4%, 51.5%) than HBeAg-negative patients (43.7%, 31.3%, 30.1%) (P = 0.064). The weighted probability of durable biochemical remission was 65.4%, being numerically higher in HBeAg-positive than HBeAg-negative patients (76.2% versus 56.7%, P = 0.130). The weighted probability of hepatitis B surface antigen loss was 2.0%. The rates of durable VR did not significantly differ according to the VR definition (hepatitis B virus DNA <200, < 2000, < 20,000 IU/mL) or duration of on-therapy VR in HBeAg-positive patients, but they were significantly higher in studies with HBeAg-negative patients and on-therapy VR > 24 than ≤ 24 months (VR at 12 months off-NAs: 75.0% versus 35.6%, P = 0.005). The weighted probability of durable HBeAg seroconversion was 91.9% and 88.0% at 12 and 24 months, respectively, after NA discontinuation without being affected by the duration of on-therapy VR or consolidation therapy (>6 months in all studies). Durable VR seems to be feasible in a substantial proportion of patients who discontinue long-term NA therapy; on-therapy VR > 24 months offers higher chances of off-NA VR in patients with HBeAg-negative chronic hepatitis B.
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UNAIDS has set a 90-90-90 target to curb the HIV epidemic by 2020, but methods used to assess whether countries have reached this target are not standardised, hindering comparisons. Through a collaboration formed by the European Centre... more
UNAIDS has set a 90-90-90 target to curb the HIV epidemic by 2020, but methods used to assess whether countries have reached this target are not standardised, hindering comparisons. Through a collaboration formed by the European Centre for Disease Prevention and Control (ECDC) with European HIV cohorts and surveillance agencies, we constructed a standardised, four-stage continuum of HIV care for 11 European Union (EU) countries for 2013. Stages were defined as: 1) number of people living with HIV (PLHIV) in the country by end of 2013; 2) proportion of stage 1 ever diagnosed; 3) proportion of stage 2 ever initiated ART; and 4) proportion of stage 3 who became virally-suppressed (≤200 copies/mL). Case surveillance data were used primarily to derive stages 1 (using back-calculation models) and 2, and cohort data for stages 3 and 4. In 2013, 674,500 people in the 11 countries were estimated to be living with HIV, ranging from 5,500 to 153,400 in each country. Overall HIV prevalence was ...
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Clinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals.... more
Clinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals. In this observational study, we used data from prospective studies of HIV-positive individuals in Europe (France, Greece, the Netherlands, Spain, Switzerland, and the UK) and North and South America (Brazil, Canada, and the USA) in The HIV-CAUSAL Collaboration and The Centers for AIDS Research Network of Integrated Clinical Systems. We compared three monitoring strategies that differ in the threshold used to measure CD4 cell count and HIV RNA viral load every 3-6 months (when below the threshold) or every 9-12 months (when above the threshold). The strategies were defined by the threshold CD4 counts of 200 cells per μL, 350 cells per μL, and 500 cells per μL. Using inverse probability weighting to adjust for baseline and time-varying confounders, we ...
Two models are mostly used to predict survival in cirrhosis: the Child-Pugh score (CP score) and the model for end-stage liver disease score (MELD score). The aim of this study is to evaluate the CP score and the MELD score for short- and... more
Two models are mostly used to predict survival in cirrhosis: the Child-Pugh score (CP score) and the model for end-stage liver disease score (MELD score). The aim of this study is to evaluate the CP score and the MELD score for short- and long-term prognosis in cirrhosis, as well as CP-creatinine score, MELD-Na score, and UKELD score. One thousand and forty-seven patients from five referral centers were included: men/women: 620/427, median age: 58 years (IQR 48-66), median follow-up: 33 months (IQR 12-74), CP (A/B/C): 493/357/147, CP score: 7 (IQR 5-9), MELD score: 12 (IQR 9-16). The performance of each score was evaluated by the Cox hazard model in terms of their: discrimination ability (C-index and Somer's D) and calibration (3, 12 months). Internal validation was done with bootstrapping (100 samples). Three hundred and fifty-two patients (33.6%) died. All scores were significantly associated with overall mortality, when assessed by univariate Cox analysis. CP-creatinine score performed significantly better than all other scores [bootstrap C-index 0.672, 95% CI 0.642-0.703, bootstrap Somer's D 0.344 (0.285-0.401)], apart from CP score, which showed similar performance. Inclusion in the multivariable Cox model of age together with CP-creatinine score improved the discriminative ability of the model [bootstrap C-index (95% CI) 0.700 (0.661-0.740)]. In terms of calibration, CP-creatinine score was the best for both 3- and 12-month survival in the total population. CP score and CP-creatinine score have better prognostic value compared to MELD score, MELD-Na score, and UKELD score for predicting short- and long-term mortality in patients with stable cirrhosis.
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To compare regimens consisting of either ritonavir-boosted atazanavir or efavirenz and a nucleoside reverse transcriptase inhibitor (NRTI) backbone with respect to clinical, immunologic, and virologic outcomes. Prospective studies of... more
To compare regimens consisting of either ritonavir-boosted atazanavir or efavirenz and a nucleoside reverse transcriptase inhibitor (NRTI) backbone with respect to clinical, immunologic, and virologic outcomes. Prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States included in the HIV-CAUSAL Collaboration. HIV-positive, antiretroviral therapy-naive, and acquired immune deficiency syndrome (AIDS)-free individuals were followed from the time they started an atazanavir or efavirenz regimen. We estimated an analog of the "intention-to-treat" effect for efavirenz versus atazanavir regimens on clinical, immunologic, and virologic outcomes with adjustment via inverse probability weighting for time-varying covariates. A total of 4301 individuals started an atazanavir regimen (83 deaths, 157 AIDS-defining illnesses or deaths) and 18,786 individuals started an efavirenz regimen (389 deaths, 825 AIDS-defining illnesses or deaths...
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Athens has a serious air pollution problem which became evident in the early 1970s. Studies for the years 1975-1982 have indicated a positive association of sulphur dioxide (SO2) with total daily mortality. Since 1983 the pollution... more
Athens has a serious air pollution problem which became evident in the early 1970s. Studies for the years 1975-1982 have indicated a positive association of sulphur dioxide (SO2) with total daily mortality. Since 1983 the pollution profile in Athens has gradually changed but the levels of smoke, SO2 and carbon monoxide (CO) remain relatively high. The association of air pollution with daily all-cause mortality in Athens for the years 1984-1988 was investigated using daily values of SO2, smoke and CO. Autoregressive models with log-transformed daily mortality as the dependent variable, were used to adjust for temperature and relative humidity (both lagged by 1 day), year, season and day of week, as well as for serial correlations in mortality. Graphic analysis revealed non-linear monotonically increasing relationships between total mortality and SO2, smoke and CO, with steeper exposure-response slopes at lower air pollution levels. Air pollution data lagged by 1 day had the strongest association with daily mortality. In three separate autoregression models for log(SO2), log(smoke) and log(CO) the regression coefficients for each were highly statistically significant (P < 0.001). Further multiple regression modelling showed that SO2 and smoke are both independent predictors of daily mortality, though to a lesser extent than temperature and relative humidity. The inclusion of CO in the model did not further improve the prediction of daily mortality. The magnitude of association is small, for instance, a 10% reduction in smoke is estimated to decrease daily mortality by 0.75% (95% confidence interval [CI]: 0.51-0.99). However, it cannot be accounted for by climatic and seasonal effects, so that a causal influence of air pollution on daily mortality seems plausible. These findings suggest that current air pollution levels in Athens (and many other industrialized cities) may be responsible for substantial numbers of premature deaths, and hence remain an important public health issue.
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Research Interests: Environmental Health, Air pollution, Risk assessment, Adolescent, Mortality, and 18 moreEnvironmental Sciences, Humans, Europe, Female, Male, Lung Diseases, Heart Disease, Aged, Middle Aged, Theoretical Models, Adult, Time Factors, Age Factors, Urban Population, Risk Assessment, Epidemiologic Studies, Air Pollutants, and Heart Diseases
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Although the association between particulate matter and mortality or morbidity is generally accepted, controversy remains about the importance of the association. If it is due solely to the deaths of frail individuals, which are brought... more
Although the association between particulate matter and mortality or morbidity is generally accepted, controversy remains about the importance of the association. If it is due solely to the deaths of frail individuals, which are brought forward by only a brief period of time, the public health implications of the association are fewer than if there is an increase in the number of deaths. Recently, other research has addressed the mortality displacement issue in single-city analysis. We analyzed this issue with a distributed lag model in a multicity hierarchic modeling approach, within the Air Pollution and Health: A European Approach (APHEA-2) study. We fit a Poisson regression model and a polynomial distributed lag model with up to 40 days of delay in each city. In the second stage we combined the city-specific results. We found that the overall effect of particulate matter less than 10 microM in aerodynamic diameter (PM10) per 10 microg/m3 for the fourth-degree distributed lag model is a 1.61% increase in daily deaths (95% CI = 1.02-2.20), whereas the mean of PM10 on the same day and the previous day is associated with only a 0.70% increase in deaths (95% CI = 0.43-0.97). This result is unchanged using an unconstrained distributed lag model. Our study confirms that the effects observed in daily time-series studies are not due primarily to short-term mortality displacement. The effect size estimate for airborne particles more than doubles when we consider longer-term effects, which has important implications for risk assessment.
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AIM: Model of End-stage Liver Disease (MELD) score has recently gained wide acceptance over the old Child-Pugh score in predicting survival in patients with decompensated cirrhosis, although it is more sophisticated. We compared the... more
AIM: Model of End-stage Liver Disease (MELD) score has recently gained wide acceptance over the old Child-Pugh score in predicting survival in patients with decompensated cirrhosis, although it is more sophisticated. We compared the predictive values of MELD, Child-Pugh and creatinine-modified Child-Pugh scores in decompensated cirrhosis.METHODS: A cohort of 102 patients with decompensated cirrhosis followed-up for a median of 6 mo was studied. Two types of modified Child-Pugh scores estimated by adding 0-4 points to the original score using creatinine levels as a sixth categorical variable were evaluated.RESULTS: The areas under the receiver operating characteristic curves did not differ significantly among the four scores, but none had excellent diagnostic accuracy (areas: 0.71-0.79). Child-Pugh score appeared to be the worst, while the accuracy of MELD was almost identical with that of modified Child-Pugh in predicting short-term and slightly better in predicting medium-term survival. In Cox regression analysis, all four scores were significantly associated with survival, while MELD and creatinine-modified Child-Pugh scores had better predictive values (c-statistics: 0.73 and 0.69-0.70) than Child-Pugh score (c-statistics: 0.65). Adjustment for gamma-glutamate transpeptidase levels increased the predictive values of all systems (c-statistics: 0.77-0.81). Analysis of the expected and observed survival curves in patients subgroups according to their prognosis showed that all models fit the data reasonably well with MELD probably discriminating better the subgroups with worse prognosis.CONCLUSION: MELD compared to the old Child-Pugh and particularly to creatinine-modified Child-Pugh scores does not appear to offer a clear advantage in predicting survival in patients with decompensated cirrhosis in daily clinical practice.
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To characterize the magnitude and the predictors of highly active antiretroviral therapy (HAART) interruption (TI) and to investigate its immunologic and virological consequences. Using Concerted Action on Seroconversion to AIDS and Death... more
To characterize the magnitude and the predictors of highly active antiretroviral therapy (HAART) interruption (TI) and to investigate its immunologic and virological consequences. Using Concerted Action on Seroconversion to AIDS and Death in Europe data from 8,300 persons with well-documented seroconversion dates, we identified subjects with stable first HAART (for at least 90 days) not initiated during primary infection. A TI was defined as an interruption of all antiretroviral therapy drugs for at least 14 days. Of 1,551 subjects starting HAART, 299 (19.3%) interrupted treatment. Median (interquartile range) duration of the TI was 189 (101-382) days. The cumulative probability (95% confidence interval) of TI at 2 years was 15.9% (14.0%-18.1%). Women were more likely to have a TI than men in the same exposure group (35.8% vs 24.2% among drug users, 22.1% vs 13.3% among heterosexuals; P < 0.05). Higher baseline viremia and poor immunologic response to HAART were associated with higher probabilities of TI. Median (interquartile range) individual CD4 cell loss during TI was 94 (1-220) cells/microL. Older age at HAART (>40 yr), lower pre-HAART nadir (<200 cells/microL), and lower CD4 at start of TI (<350 cells/microL) were significantly associated with greater relative CD4 loss during TI. We estimate that almost 1 in 6 subjects on HAART interrupts treatment by 2 years. Further research is needed to investigate the reasons why TI is higher in women. We have identified characteristics of subjects with the greatest risk for CD4 loss in whom TI may have greater risks.
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To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL... more
To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. Antiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 ± 1 months, (2) 6 ± 1 months, and (3) 9-12 ± 1 months. We used inverse-probability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes. In 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9-12 month ...
Research Interests:
Research Interests:
When a clinical treatment fails or shows suboptimal results, the question of when to switch to another treatment arises. Treatment switching strategies are often dynamic because the time of switching depends on the evolution of an... more
When a clinical treatment fails or shows suboptimal results, the question of when to switch to another treatment arises. Treatment switching strategies are often dynamic because the time of switching depends on the evolution of an individual's time-varying covariates. Dynamic strategies can be directly compared in randomized trials. For example, HIV-infected individuals receiving antiretroviral therapy could be randomized to switching therapy within 90 days of HIV-1 RNA crossing above a threshold of either 400 copies/ml (tight-control strategy) or 1000 copies/ml (loose-control strategy). We review an approach to emulate a randomized trial of dynamic switching strategies using observational data from the Antiretroviral Therapy Cohort Collaboration, the Centers for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration. We estimated the comparative effect of tight-control vs. loose-control strategies on death and AIDS or death via inverse-probability...
Research Interests:
Research Interests:
To characterize the magnitude and the predictors of highly active antiretroviral therapy (HAART) interruption (TI) and to investigate its immunologic and virological consequences. Using Concerted Action on Seroconversion to AIDS and Death... more
To characterize the magnitude and the predictors of highly active antiretroviral therapy (HAART) interruption (TI) and to investigate its immunologic and virological consequences. Using Concerted Action on Seroconversion to AIDS and Death in Europe data from 8,300 persons with well-documented seroconversion dates, we identified subjects with stable first HAART (for at least 90 days) not initiated during primary infection. A TI was defined as an interruption of all antiretroviral therapy drugs for at least 14 days. Of 1,551 subjects starting HAART, 299 (19.3%) interrupted treatment. Median (interquartile range) duration of the TI was 189 (101-382) days. The cumulative probability (95% confidence interval) of TI at 2 years was 15.9% (14.0%-18.1%). Women were more likely to have a TI than men in the same exposure group (35.8% vs 24.2% among drug users, 22.1% vs 13.3% among heterosexuals; P < 0.05). Higher baseline viremia and poor immunologic response to HAART were associated with higher probabilities of TI. Median (interquartile range) individual CD4 cell loss during TI was 94 (1-220) cells/microL. Older age at HAART (>40 yr), lower pre-HAART nadir (<200 cells/microL), and lower CD4 at start of TI (<350 cells/microL) were significantly associated with greater relative CD4 loss during TI. We estimate that almost 1 in 6 subjects on HAART interrupts treatment by 2 years. Further research is needed to investigate the reasons why TI is higher in women. We have identified characteristics of subjects with the greatest risk for CD4 loss in whom TI may have greater risks.
Research Interests:
Eleven years after a diabetes detection drive--conducted in a sample of 21,410 individuals--a follow-up study showed that 207 persons had died from a total of 489 previously known diabetics. Ten year survival rates were lower in male and... more
Eleven years after a diabetes detection drive--conducted in a sample of 21,410 individuals--a follow-up study showed that 207 persons had died from a total of 489 previously known diabetics. Ten year survival rates were lower in male and female diabetics as compared to those observed in the general population. In addition it was shown that diabetic patients died more often from cardiovascular causes compared to sex and age matched samples of the general population (males 63.3% vs 44.3%; females 76.0% vs 51.7%). No mortality differences by the type of hypoglycaemic treatment were noted.
Research Interests: Mortality, Greece, Humans, Diabetes mellitus, Female, and 5 moreMale, Sex Factors, Age Factors, Cohort Studies, and Diabetic Diet
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The polymerase chain reaction was used to measure the DNA copy number of human immunodeficiency virus (HIV). Differences in polymerase chain reaction amplification efficiency were controlled by amplifying known amounts of HIV DNA in... more
The polymerase chain reaction was used to measure the DNA copy number of human immunodeficiency virus (HIV). Differences in polymerase chain reaction amplification efficiency were controlled by amplifying known amounts of HIV DNA in parallel with samples. This technique is a sensitive, accurate, and reproducible method for the quantitation of HIV DNA.
Research Interests: Risk assessment, Probability, HIV, Clinical Microbiology, Biological Sciences, and 14 moreProspective studies, Pregnancy, Humans, Female, Polymerase Chain Reaction, Newborn Infant, Vagina, Adult, Reproducibility of Results, Risk Assessment, Sensitivity and Specificity, Acquired immunodeficiency syndrome, Viral Load, and Reference standards
Nicolas P Jewell. Chapman and Hall/CRC, 2004, $69.95, pp xiv+333. ISBN 1-58488-433-9. A range of books, some excellent, have been published on the analysis of epidemiological data. While some focus mainly on the underlying epidemiological... more
Nicolas P Jewell. Chapman and Hall/CRC, 2004, $69.95, pp xiv+333. ISBN 1-58488-433-9. A range of books, some excellent, have been published on the analysis of epidemiological data. While some focus mainly on the underlying epidemiological concepts glossing out ...
The Stata Journal (2010) 10, Number 2, pp. 226251 Analyzing longitudinal data in the presence of informative drop-out: The jmre1 command Nikos Pantazis Department of Hygiene, Epidemiology, and Medical Statistics University of Athens... more
The Stata Journal (2010) 10, Number 2, pp. 226251 Analyzing longitudinal data in the presence of informative drop-out: The jmre1 command Nikos Pantazis Department of Hygiene, Epidemiology, and Medical Statistics University of Athens Medical School Athens, Greece ...
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To carry out a prospective combined quantitative analysis of the associations between all cause mortality and ambient particulate matter and sulphur dioxide. Analysis of time series data on daily number of deaths from all causes and... more
To carry out a prospective combined quantitative analysis of the associations between all cause mortality and ambient particulate matter and sulphur dioxide. Analysis of time series data on daily number of deaths from all causes and concentrations of sulphur dioxide and particulate matter (measured as black smoke or particles smaller than 10 microns in diameter (PM10)) and potential confounders. 12 European cities in the APHEA project (Air Pollution and Health: a European Approach). Relative risk of death. In western European cities it was found that an increase of 50 micrograms/m3 in sulphur dioxide or black smoke was associated with a 3% (95% confidence interval 2% to 4%) increase in daily mortality and the corresponding figure for PM10 was 2% (1% to 3%). In central eastern European cities the increase in mortality associated with a 50 micrograms/m3 change in sulphur dioxide was 0.8% (-0.1% to 2.4%) and in black smoke 0.6% (0.1% to 1.1%). Cumulative effects of prolonged (two to fo...
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Recommendations have differed nationally and internationally with respect to the best time to start antiretroviral therapy (ART). We compared effectiveness of three strategies for initiation of ART in high-income countries for... more
Recommendations have differed nationally and internationally with respect to the best time to start antiretroviral therapy (ART). We compared effectiveness of three strategies for initiation of ART in high-income countries for HIV-positive individuals who do not have AIDS: immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL. We used data from the HIV-CAUSAL Collaboration of cohort studies in Europe and the USA. We included 55 826 individuals aged 18 years or older who were diagnosed with HIV-1 infection between January, 2000, and September, 2013, had not started ART, did not have AIDS, and had CD4 count and HIV-RNA viral load measurements within 6 months of HIV diagnosis. We estimated relative risks of death and of death or AIDS-defining illness, mean survival time, the proportion of individuals in need of ART, and the proportion of individuals with HIV-RNA viral load less than 50 copies per mL, as would have been recorded under each ART initiation strategy after 7 years of HIV diagnosis. We used the parametric g-formula to adjust for baseline and time-varying confounders. Median CD4 count at diagnosis of HIV infection was 376 cells per μL (IQR 222-551). Compared with immediate initiation, the estimated relative risk of death was 1·02 (95% CI 1·01-1·02) when ART was started at a CD4 count less than 500 cells per μL, and 1·06 (1·04-1·08) with initiation at a CD4 count less than 350 cells per μL. Corresponding estimates for death or AIDS-defining illness were 1·06 (1·06-1·07) and 1·20 (1·17-1·23), respectively. Compared with immediate initiation, the mean survival time at 7 years with a strategy of initiation at a CD4 count less than 500 cells per μL was 2 days shorter (95% CI 1-2) and at a CD4 count less than 350 cells per μL was 5 days shorter (4-6). 7 years after diagnosis of HIV, 100%, 98·7% (95% CI 98·6-98·7), and 92·6% (92·2-92·9) of individuals would have been in need of ART with immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL, respectively. Corresponding proportions of individuals with HIV-RNA viral load less than 50 copies per mL at 7 years were 87·3% (87·3-88·6), 87·4% (87·4-88·6), and 83·8% (83·6-84·9). The benefits of immediate initiation of ART, such as prolonged survival and AIDS-free survival and increased virological suppression, were small in this high-income setting with relatively low CD4 count at HIV diagnosis. The estimated beneficial effect on AIDS is less than in recently reported randomised trials. Increasing rates of HIV testing might be as important as a policy of early initiation of ART. National Institutes of Health.
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Hepatitis C virus (HCV) infection is an important health problem worldwide. The aim of the study is to describe the baseline characteristics and possible epidemiological changes of the patients with chronic HCV infection included in a... more
Hepatitis C virus (HCV) infection is an important health problem worldwide. The aim of the study is to describe the baseline characteristics and possible epidemiological changes of the patients with chronic HCV infection included in a nationwide Greek study. two thousand eight hundred seventeen (2817) patients, followed-up at 20 hepatology centres throughout Greece between the years 1997 and 2006 were enrolled in the study. Intravenous drug use (IDU) and history of blood transfusion prior to 1992 was reported in 30.7% and 22.6% of our patients, respectively. In 1865 (66.2%) patients with known genotypes, the distribution for genotype 1, 2, 3 and 4 was 45.1%, 7%, 34% and 13.9% respectively. Genotype 1 was more common in older people, in women (55.9% p<0.001) and patients with transfusion-related hepatitis (61.6% p<0.001). Genotype 3 was more common in younger patients, in men (43% p<0.001) and in IDUs (63.3% p<0.001). A significant reduction of transfusion-related hepatit...
Model of End-stage Liver Disease (MELD) score has recently gained wide acceptance over the old Child-Pugh score in predicting survival in patients with decompensated cirrhosis, although it is more sophisticated. We compared the predictive... more
Model of End-stage Liver Disease (MELD) score has recently gained wide acceptance over the old Child-Pugh score in predicting survival in patients with decompensated cirrhosis, although it is more sophisticated. We compared the predictive values of MELD, Child-Pugh and creatinine-modified Child-Pugh scores in decompensated cirrhosis. A cohort of 102 patients with decompensated cirrhosis followed-up for a median of 6 mo was studied. Two types of modified Child-Pugh scores estimated by adding 0-4 points to the original score using creatinine levels as a sixth categorical variable were evaluated. The areas under the receiver operating characteristic curves did not differ significantly among the four scores, but none had excellent diagnostic accuracy (areas: 0.71-0.79). Child-Pugh score appeared to be the worst, while the accuracy of MELD was almost identical with that of modified Child-Pugh in predicting short-term and slightly better in predicting medium-term survival. In Cox regressi...
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Chronic hepatitis C appears to have a highly variable natural course with 20% of patients developing cirrhosis within 20 years, while the majority of them run a relatively mild course. We studied the relationships of epidemiological,... more
Chronic hepatitis C appears to have a highly variable natural course with 20% of patients developing cirrhosis within 20 years, while the majority of them run a relatively mild course. We studied the relationships of epidemiological, biochemical and virological features with histological severity (grade) and liver disease progression (stage). Liver histology, serum HCV RNA level and HCV genotype were determined in a well-defined cohort of 152 consecutive (100 males, 52 females) patients with chronic hepatitis C. Patients with minimal or mild chronic hepatitis were significantly younger than those with moderate or severe chronic hepatitis (mean age: 41.1 vs 49.5 years respectively, p=0.003). On the other hand, patients with no or mild fibrosis compared to those with moderate or severe fibrosis and to those with cirrhosis were significantly more frequently males (73%, 64% and 43%, p=0.01), parenteral drug users (36%, 11% and 11%, p=0.01) and infected with other than 1b genotype (86%, ...
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To evaluate the biochemical and virological response in chronic hepatitis C patients treated with interferon-alpha at the usual dosage of 3 MU thrice weekly for 6 or 12 months, and to analyse the significance of clearance of serum HCV RNA... more
To evaluate the biochemical and virological response in chronic hepatitis C patients treated with interferon-alpha at the usual dosage of 3 MU thrice weekly for 6 or 12 months, and to analyse the significance of clearance of serum HCV RNA and of HCV genotype in the prediction of sustained biochemical remission. Liver Unit, Western Attica General Hospital, Athens, Greece. Sixty consecutive patients with histologically confirmed chronic hepatitis C. All patients received interferon-alpha-2b in a dose of 3 MU thrice weekly for 6 (n = 26) or 12 (n = 34) months. Serial serum samples were retrospectively tested for the presence of HCV RNA by a polymerase chain reaction assay and pretreatment serum samples for the determination of HCV genotype. Sustained biochemical response rate was significantly higher in the 12-month group (62% vs. 35%, P = 0.037). Clearance of serum HCV RNA at the end of treatment was achieved in 33 (58.9%) of the 56 patients with detectable pretreatment HCV RNA. HCV R...
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Our objective was to determine the relative efficacy of 6 months of treatment with 10 MU versus 3 MU of interferon-alpha 2b (IFN-alpha), three times weekly, in chronic hepatitis C (HCV) in a randomized trial. Ten megaunits of IFN-alpha... more
Our objective was to determine the relative efficacy of 6 months of treatment with 10 MU versus 3 MU of interferon-alpha 2b (IFN-alpha), three times weekly, in chronic hepatitis C (HCV) in a randomized trial. Ten megaunits of IFN-alpha were given to 28 patients (group A), and 3 MU were given to 30 patients (group B). After treatment ended, follow-up was continued for 26 wk. Overall, the sustained response rate was higher in group A than in group B (16/26 or 61.5% vs. 12/28 or 42.9%, p = 0.17), but the difference did not reach statistical significance. However, it was higher in group A than in group B among patients with minimal or mild chronic hepatitis (15/20 or 75% vs. 9/24 or 37.5%, p = 0.013) and among those with mild or moderate fibrosis (15/17 or 88.2% vs. 11/19 or 57.9%, p = 0.042). IFN-alpha treatment significantly reduced histological activity index (HAI) scoring and all its parameters, except fibrosis, but the decrease was similar in the two groups. Sex, age, stage, and HC...
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The seasonal variation of neonatal and infant deaths in Greece was analyzed for nine consecutive years (1979-1987) by cause of death, age of death and urbanization of permanent residence. Data were supplied by the National Statistical... more
The seasonal variation of neonatal and infant deaths in Greece was analyzed for nine consecutive years (1979-1987) by cause of death, age of death and urbanization of permanent residence. Data were supplied by the National Statistical Service of Greece. Statistical analysis was done using the Edward's method. The seasonal patterns of the number of deaths and death rates were similar. Neonatal deaths in total did not show significant seasonality but postneonatal deaths showed seasonal variation with a peak in the winter, more evident in rural areas. Neonatal deaths from prematurity showed statistically significant seasonal variation with a peak in May. Postneonatal deaths from infections and mainly those from pneumonia showed very significant seasonal variation with a peak in February that was more prominent in rural areas. Seasonal pattern with peak in late winter was also found for postneonatal deaths from injuries. The seasonal patterns for neonatal and postneonatal deaths fro...
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There are several forms of human immunodeficiency virus type 1 (HIV-1) DNA in peripheral blood T cells and lymph nodes in untreated HIV-1-infected individuals and in patients whose plasma HIV-1 RNA levels are suppressed by long-term... more
There are several forms of human immunodeficiency virus type 1 (HIV-1) DNA in peripheral blood T cells and lymph nodes in untreated HIV-1-infected individuals and in patients whose plasma HIV-1 RNA levels are suppressed by long-term combination antiretroviral therapy. However, it remains to be established whether the concentration of HIV-1 DNA in cells predicts the clinical outcome of HIV-1 infection. In this report, we measured the concentration of HIV-1 DNA forms which has undergone the second template switch (STS DNA) and 2-long-terminal-repeat DNA circles in peripheral blood mononuclear cell (PBMC) samples. To do this, we used molecular-beacon-based real-time PCR assays and studied 130 patients with hemophilia in the Multicenter Hemophilia Cohort Study. We assessed the influence of baseline HIV-1 STS DNA levels on the progression of HIV-1 disease in the absence of combination antiretroviral therapy by Kaplan-Meier and Cox regression analysis. Among the patients who progressed to...
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Our objectives are to describe the progression of HIV disease and to assess the influence of hemophilia-related variables, age at infection, and antibodies to cytomegalovirus infection (anti-CMV) in a Greek cohort of 158 HIV-1-positive... more
Our objectives are to describe the progression of HIV disease and to assess the influence of hemophilia-related variables, age at infection, and antibodies to cytomegalovirus infection (anti-CMV) in a Greek cohort of 158 HIV-1-positive hemophilic men, who received prospective follow-up for up to 16 years after infection. A total of 79 patients had died, representing a cumulative progression rate of 72.4% (95% confidence interval [CI], 56.6-83.3). A significant proportion of the mortality (30%) resulted from conditions not formally related to AIDS, with liver failure and cerebral hemorrhage predominant. At 16 years after seroconversion, 66 patients had developed clinical AIDS, a cumulative progression rate of 58.2% (95% CI, 47.1%-86.3%) whereas 15 years after infection 81.5% (95% CI, 74.2%-87.9%) of the patients had AIDS or a CD4 cell count &lt;200 cells/mm3. Hemophilia-related variables or presence of anti-CMV were not significantly associated with disease progression. Age at infection was a strong prognostic factor for all three endpoints. Appropriate modeling showed a nonlinear age effect, with a steeper increase of relative hazard for patients &gt;40 years of age at seroconversion. The age effect remained significant even after controlling for current CD4 cell count. Further investigation is required to elucidate the mechanisms of the age effect and the contribution of HCV coinfection on the disease progression.
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Marginal structural models (MSMs) have been proposed for estimating a treatment&amp;amp;amp;amp;amp;amp;#39;s effect, in the presence of time-dependent confounding. We aimed to evaluate the performance of the Cox MSM in the presence... more
Marginal structural models (MSMs) have been proposed for estimating a treatment&amp;amp;amp;amp;amp;amp;#39;s effect, in the presence of time-dependent confounding. We aimed to evaluate the performance of the Cox MSM in the presence of missing data and to explore methods to adjust for missingness. We simulated data with a continuous time-dependent confounder and a binary treatment. We explored two classes of missing data: (i) missed visits, which resemble clinical cohort studies; (ii) missing confounder&amp;amp;amp;amp;amp;amp;#39;s values, which correspond to interval cohort studies. Missing data were generated under various mechanisms. In the first class, the source of the bias was the extreme treatment weights. Truncation or normalization improved estimation. Therefore, particular attention must be paid to the distribution of weights, and truncation or normalization should be applied if extreme weights are noticed. In the second case, bias was due to the misspecification of the treatment model. Last observation carried forward (LOCF), multiple imputation (MI), and inverse probability of missingness weighting (IPMW) were used to correct for the missingness. We found that alternatives, especially the IPMW method, perform better than the classic LOCF method. Nevertheless, in situations with high marker&amp;amp;amp;amp;amp;amp;#39;s variance and rarely recorded measurements none of the examined method adequately corrected the bias.
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Measures of CD4 T-cell count and HIV-1 plasma viral load before antiretroviral therapy are proxies for virulence. Whether these proxies are changing over time has implications for prevention and treatment. The aim of this study was to... more
Measures of CD4 T-cell count and HIV-1 plasma viral load before antiretroviral therapy are proxies for virulence. Whether these proxies are changing over time has implications for prevention and treatment. The aim of this study was to investigate those trends. Data were derived from the Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) collaboration of mainly European seroconverter cohorts. Longitudinal CD4 cell counts and plasma viral load measurements before the initiation of antiretroviral therapy or AIDS onset were analysed by use of linear or fractional polynomials mixed models adjusting for all available potential confounders. Calendar time effects were modelled through natural cubic splines. 15 875 individuals seroconverting from 1979 to 2008 fulfilled the inclusion criteria; 3215 (20·3%) were women; median follow-up was 31 months (IQR 14-62); dropout before starting antiretroviral therapy or AIDS onset was 8·1%. Estimated CD4 counts at seroconversion for a typical individual declined from about 770 cells per μL (95% CI 750-800) in the early 1980s to a plateau of about 570 cells per μL (555-585) after 2002. CD4 cell rate of loss increased up to 2002. Estimated set-point plasma viral loads increased from 4·05 log10 copies per mL (95% CI 3·98-4·12) in 1980 to 4·50 log10 copies per mL (4·45-4·54) in 2002 with a tendency of returning to lower loads thereafter. Results were similar when we restricted analyses to various subsets, including adjusting for plasma viral load assay, censored follow-up at 3 years, or used variations of the main statistical approach. Our results provide strong indications of increased HIV-1 virulence and transmissibility during the course of the epidemic and a potential plateau effect after about 2002. European Union Seventh Framework Programme.
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Research Interests: Time Series, Asthma, Air pollution, Adolescent, Urban Health, and 23 moreSeasonality, Humans, Child, Europe, Emergency Room, Thorax, Regression Analysis, Risk factors, Patient Admission, Meta Analysis, Clinical Sciences, Middle Aged, Ozone, Adult, Urban Air Pollution, Regression Model, Emergencies, Risk Factors, Nitrogen Dioxide, Sulfur Dioxide, Air Pollutants, Relative Risk, and Sulphur dioxide
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Research Interests: Statistics, Survival Analysis, Biometry, Multivariate Analysis, Stochastic processes, and 16 moreHumans, Computer Simulation, Missing Data, Sample Size, Robustness, Longitudinal Studies, Public health systems and services research, Longitudinal data, Simulation Study, Reproducibility of Results, Biological markers, Disease Progression, Sensitivity and Specificity, Bias (Epidemiology), Statistical Distributions, and Parametric Model
Several methods for the estimation and comparison of rates of change in longitudinal studies with staggered entry and informative drop-outs have been recently proposed. For multivariate normal linear models, REML estimation is used. There... more
Several methods for the estimation and comparison of rates of change in longitudinal studies with staggered entry and informative drop-outs have been recently proposed. For multivariate normal linear models, REML estimation is used. There are various approaches to maximizing the corresponding log-likelihood; in this paper we use a restricted iterative generalized least squares method (RIGLS) combined with a nested EM algorithm. An important statistical problem in such approaches is the estimation of the standard errors adjusted for the missing data (observed data information matrix). Louis has provided a general technique for computing the observed data information in terms of completed data quantities within the EM framework. The multiple imputation (MI) method for obtaining variances can be regarded as an alternative to this. The aim of this paper is to develop, apply and compare the Louis and a modified MI method in the setting of longitudinal studies where the source of missing data is either death or disease progression (informative) or end of the study (assumed non-informative). Longitudinal data are simultaneously modelled with the missingness process. The methods are illustrated by modelling CD4 count data from an HIV-1 clinical trial and evaluated through simulation studies. Both methods, Louis and MI, are used with Monte Carlo simulations of the missing data using the appropriate conditional distributions, the former with 100 simulations, the latter with 5 and 10. It is seen that naive SEs based on the completed data likelihood can be seriously biased. This bias was largely corrected by Louis and modified MI methods, which gave broadly similar estimates. Given the relative simplicity of the modified MI method, it may be preferable.
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A major statistical challenge in air pollution and health time-series studies is to adequately control for confounding effects of time-varying covariates. Daily health outcome counts are most commonly analysed by Poisson regression... more
A major statistical challenge in air pollution and health time-series studies is to adequately control for confounding effects of time-varying covariates. Daily health outcome counts are most commonly analysed by Poisson regression models, adjusted for overdispersion, with air pollution levels included as a linear predictor and smooth functions for calendar time and weather variables to adjust for time-varying confounders. Various smoothers have been used so far, but the optimal strategy for choosing smoothers and their degree of smoothing remains controversial. In this work, we evaluate the performance of various smoothers with different criteria for choosing the degree of smoothing in terms of bias and efficiency of the air pollution effect estimate in a simulation study. The evaluated approaches were also applied to real mortality data from 22 European cities. The simulation study imitated a multi-city study. Data were generated from a fully parametric model. Model selection methods which optimize prediction may lead to increased biases in the air pollution effect estimate. Minimization of the absolute value of the sum of the partial autocorrelation function of the model&#39;s residuals (PACF), as a criterion to choose the degree of smoothness, gave the smallest biases. The penalized splines (PS) method with a large number of effective dfs (e.g. 8-12 per year) could be used as the basic, relatively conservative, analysis whereas the PS and natural splines in combination with PACF could be applied to provide a reasonable range of the effect estimate.