Search

We aimed to assess the self-perceived health status and the presence of chronic diseases of adult Roma living in settlements in Greece, and to explore associated social determinants of health. Data were derived from the Hprolipsis Health Survey. Multivariable regression models were applied. In total, 534 adults, 287 women, and 247 men were recruited from twelve Roma settlements in four prefectures. Although 62% of the participants perceived their health status as good/very good, about half of them had been diagnosed with at least one chronic disease. Several structural and intermediary social determinants of health were found to be significantly associated with the health outcomes, prefecture, settlement type, sex, age group, living with a partner, presence of depression symptoms, food insecurity, and alcohol consumption were associated with self-perceived health status, settlement type, sex, age group, presence of anxiety symptoms, food insecurity and number of persons living in the house with the presence of a chronic disease. This is one of the few studies assessing the self-perceived health status and presence of chronic diseases in Roma settlements in Greece and investigating the associated social determinants of health in the world. Community-based participatory action research and health literacy programs are needed to mitigate health inequalities in Roma settlements.

Background Nationwide data on thyroid disease prevalence in Greece is lacking. Using the national health examination survey EMENO data resources, we aimed to estimate the prevalence of hypothyroidism and hyperthyroidism and associated risk factors in adults living in Greece. Methods A random sample of the adults (≥18 years) living in Greece was drawn by multi-stage stratified random sampling based on the 2011 census. During home visits, trained interviewers administered a standardized questionnaire to study participants. All participants answered questions concerning demographic parameters (e.g., age, sex, degree of urbanization, income) and questions concerning smoking habits, alcohol, dietary habits and psychological parameters such as anxiety and thyroid disease. Weighted logistic regression models were fitted to assess factors associated with thyroid disease. Results In total, 6006 individuals were recruited in the Greek Health Examination Survey EMENO (response rate 72%) of whom 5981 were eligible for this study. The prevalence of thyroid disease was 9%, where 0.4% was related to hyperthyroidism and 8.6% to hypothyroidism. The prevalence of thyroid disease was higher in women (14.9%) than men (2.7%) (p Conclusion The prevalence of thyroid disease in Greece is higher in women. Age, habits, and characteristics of geographic areas determine the distribution of thyroidopathies in Greece.

BackgroundAlthough combined antiretroviral therapy has substantially improved the prognosis of people living with HIV (PLHIV), mortality remains higher compared to the general population, mainly due to higher prevalence of non-HIV-related comorbidities, including cardiovascular diseases (CVD). We assessed the prevalence of CVD risk and its contributing factors in adult PLHIV versus general population controls in Greece.SettingsCross-sectional comparison of PLHIV (Athens-Multicenter-AIDS-Cohort-Study; AMACS) versus general population controls (National health examination survey; EMENO).MethodsAll HIV-infected adults with ≥1 measurement of interest (blood pressure, lipids, glucose, weight, height) between 2012-2014 and all EMENO participants (2014-2016) were included. Ten-year total CVD risk was estimated using the Framingham (FRS) or the Systematic Coronary Risk Evaluation (SCORE) equations.Results5839 PLHIV (median age:41.6 years, 85.4% males) and 4820 controls (median age:48 years, 48.4% males) were included. Adjusting for age, sex and origin, PLHIV were more likely to be current smokers (adjusted OR:1.53 [95% CI:1.35-1.74]) and dyslipidemic (aOR:1.18; [1.04-1.34]), less likely to be obese (aOR:0.44 [0.38-0.52], with no differences in hypertension, diabetes or high (≥20%) FRS but with greater odds of high (≥5%) SCORE (aOR:1.55 [1.05-2.30]). Further adjustment for educational level, anti-HCV positivity and BMI showed higher prevalence of hypertension in PLHIV.ConclusionsDespite the relative absence of obesity, PLHIV have higher prevalence of traditional CVD risk factors and higher risk of fatal CVD compared to general population. Regular screening and early management of CVD risk factors in PLHIV should be of high priority for CVD prevention.

BackgroundAlthough infectious diseases are globally on the decline, they remain a major global public health problem. Among them, the hepatitis B virus (HBV) or hepatitis C virus (HCV) and HIV infection are of primary interest. Valid prevalence data on these infections are sparse in Greece, especially for vulnerable populations.ObjectiveThis study aimed to present the design and methods of Hprolipsis, an integrated viral hepatitis and HIV screening program administered to adults (≥18 years) from the general, Greek Roma, and migrant populations. Its aims were to estimate the prevalence of HBV, HCV, and HIV; assess infectious disease knowledge level; design, implement, and assess population-specific awareness actions; and offer individual counseling and referral when indicated and HBV vaccination to susceptible Roma and migrants.MethodsMultistage, stratified, random sampling based on the 2011 Census was applied to select the general population sample, and nonprobability multistage quota sampling was used for Roma and migrant sample selection. Trained personnel made home (general population) or community (Roma and migrants) visits. Collected blood samples were tested for Hepatitis B surface Antigen, Hepatitis B core Antibody, Hepatitis B surface Antibody, Hepatitis C Antibody, and HIV 1,2 Antibody. The surveys were conducted during May 2013 and June 2016. To estimate an HCV prevalence of 1.5% with 0.3 precision, the required general population sample size was estimated to be 6000. As migrants constitute 10% of the whole Greek population, the migrant sample size was set to 600. A feasible sample size of 500 Greek Roma was set.ResultsIn total, 6006 individuals from the general population (response rate 72%), 534 Greek Roma, and 612 migrants were recruited. Blood test results are available for 4245 individuals from the general population, 523 Roma, and 537 migrants.ConclusionsHprolipsis is the first nationwide survey on HBV, HCV, and HIV. Its results will enhance our understanding of the health needs and disease burden of these diseases in the 3 studied populations. Its implementation provided useful recommendations for future studies, particularly in vulnerable populations.International Registered Report Identifier (IRRID)DERR1-10.2196/13578

The aim of the present study was to assess, for the first time to our knowledge

Background: Bullying is one widespread violence type that threatens adolescent’s well-being in family, school, and neighborhood. This study aimed to estimate the percentages of the last 12 months bullying behaviors- types among Greek adolescents, and to identify the associations between these behaviors and adolescents’ aggression and mental health- behavioral problems. Study design: A cross-sectional study. Methods: The sample consisted of 1934 adolescents, attending the second grade of 45 randomly selected public and private high schools and senior high schools, of the Greater Athens Metropolitan Area. Bullying involvement was examined by four questions, evaluating the occurrence and type of bullying. The Buss and Perry Questionnaire and Strength and Difficulties Questionnaire were administrated in order to estimate adolescents’ aggression and mental health-behavioral problems, respectively. Information about adolescents’ individual and family characteristics was also collected. Results: Overall, 18.4% of participants reported bullying involvement at school, as a victim (11.0%), a bully (5.0%), or both (2.4%), while verbal bullying was the most common type. Compared to uninvolved participants, victims were significantly more likely to report emotional symptoms and peer problems, bullies were more likely to report physical aggression, and bully-victims physical aggression, hostility, and lower prosocial behavior. Conclusions: Approximately one out of five adolescents were involved in bullying in the past year at school, reporting aggressive behaviors, emotional problems, and/or social difficulties. Further longitudinal research would increase understanding of the mechanisms of bullying involvement and may lead to preventative interventions promoting positive peer interactions in schools.

In most HIV-positive individuals, infection time is only known to lie between the time an individual started being at risk for HIV and diagnosis time. However, a more accurate estimate of infection time is very important in certain cases. For example, one of the objectives of the Advancing Migrant Access to Health Services in Europe (aMASE) study was to determine if HIV-positive migrants, diagnosed in Europe, were infected pre- or post-migration. We propose a method to derive subject-specific estimates of unknown infection times using information from HIV biomarkers’ measurements, demographic, clinical, and behavioral data. We assume that CD4 cell count (CD4) and HIV-RNA viral load trends after HIV infection follow a bivariate linear mixed model. Using post-diagnosis CD4 and viral load measurements and applying the Bayes’ rule, we derived the posterior distribution of the HIV infection time, whereas the prior distribution was informed by AIDS status at diagnosis and behavioral data. Parameters of the CD4–viral load and time-to-AIDS models were estimated using data from a large study of individuals with known HIV infection times (CASCADE). Simulations showed substantial predictive ability (e.g. 84% of the infections were correctly classified as pre- or post-migration). Application to the aMASE study ( n = 2009) showed that 47% of African migrants and 67% to 72% of migrants from other regions were most likely infected post-migration. Applying a Bayesian method based on bivariate modeling of CD4 and viral load, and subject-specific information, we found that the majority of HIV-positive migrants in aMASE were most likely infected after their migration to Europe.

Objective It still remains unclear whether psychotic features increase the risk of suicidal attempts in major depressive disorder. Thus, we attempted, through a systematic review coupled with a meta-analysis, to elucidate further whether unipolar psychotic depression (PMD) compared to non-PMD presents higher levels of suicidal attempts. Method A systematic search was conducted in PubMed, EMBASE, PsycINFO as well as in various databases of the so-called gray literature for all studies providing data on suicidal attempts in PMD compared to non-PMD, and the results were then subjected to meta-analysis. Results Twenty studies met our inclusion criteria, including in total 1,275 PMD patients and 5,761 non-PMD patients. An elevated risk for suicide attempt for PMD compared to non-PMD patients was found: The total (lifetime) fixed-effects pooled OR was 2.11 (95% CI: 1.81-2.47), and the fixed-effects pooled OR of the five studies of the acute phase of the disorder was 1.93 (95% CI: 1.33-2.80). This elevated risk of suicidal attempt for PMD patients remained stable across all age groups of adult patients. Conclusion Despite data inconsistency and clinical heterogeneity, this systematic review and meta-analysis showed that patients with PMD are at a two-fold higher risk, both during lifetime and in acute phase, of committing a suicidal attempt than patients with non-PMD.

The continuum of HIV care is a simple conceptual framework for monitoring HIV programmes, comprising a series of stages that people living with HIV (PLHIV) pass through to access antiretroviral treatment (ART) and achieve viral suppression [1,2]. Individual benefits of suppression include reduced risk of morbidity and mortality. At the population level, viral suppression reduces the risk of onward transmission and enables epidemic containment [3]. Transmission risk may be further reduced by lowering the number of undiagnosed PLHIV [4,5]. Complete continua are, therefore, constructed beginning with the total number of PLHIV in a given population and ending with the number virally suppressed. Intervening stages have included the numbers diagnosed, linked to HIV care, retained in care, eligible for ART, on ART and adhering to ART. Although people can move between stages, the continuum is typically conceptualized as a ‘snapshot’ at one time-point. As the Joint United Nations Programme on HIV and AIDS (UNAIDS) announced the target of reaching ‘90-90-90’ by 2020, which envisions 90% of PLHIV diagnosed, 90% of those diagnosed on ART and 90% of those on ART virally suppressed [6], interest in constructing HIV care continua to inform national programmes and policies has grown [7–11]. However, there has been limited consistency in the methods used to construct these measures and the stages presented in publications. Key stages are often missing or continua entirely absent for many countries, including in Europe, particularly the Eastern region [7,8,11–15]. Drawing from a review of recent literature and expert opinion, we highlight the methodological inconsistencies, the challenges associated with constructing each stage and recommend a standardized way forward for monitoring the continuum of HIV care in Europe.

Summary Background 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. Methods 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 estimated hazard ratios (HRs) of death and of AIDS-defining illness or death, risk ratios of virological failure, and mean differences in CD4 cell count. Findings 47 635 individuals initiated an antiretroviral therapy regimen between Jan 1, 2000, and Jan 9, 2015, and met the eligibility criteria for inclusion in our study. During follow-up, CD4 cell count was measured on average every 4·0 months and viral load every 3·8 months. 464 individuals died (107 in threshold 200 strategy, 157 in threshold 350, and 200 in threshold 500) and 1091 had AIDS-defining illnesses or died (267 in threshold 200 strategy, 365 in threshold 350, and 459 in threshold 500). Compared with threshold 500, the mortality HR was 1·05 (95% CI 0·86–1·29) for threshold 200 and 1·02 (0·91·1·14) for threshold 350. Corresponding estimates for death or AIDS-defining illness were 1·08 (0·95–1·22) for threshold 200 and 1·03 (0·96–1·12) for threshold 350. Compared with threshold 500, the 24 month risk ratios of virological failure (viral load more than 200 copies per mL) were 2·01 (1·17–3·43) for threshold 200 and 1·24 (0·89–1·73) for threshold 350, and 24 month mean CD4 cell count differences were 0·4 (−25·5 to 26·3) cells per μL for threshold 200 and −3·5 (−16·0 to 8·9) cells per μL for threshold 350. Interpretation Decreasing monitoring to annually when CD4 count is higher than 200 cells per μL compared with higher than 500 cells per μL does not worsen the short-term clinical and immunological outcomes of virally suppressed HIV-positive individuals. However, more frequent virological monitoring might be necessary to reduce the risk of virological failure. Further follow-up studies are needed to establish the long-term safety of these strategies. Funding National Institutes of Health.

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.

Objective: We aimed to estimate the proportion of postmigration HIV acquisition among HIV-positive migrants in Europe. Design: To reach HIV-positive migrants, we designed a cross-sectional study performed in HIV clinics. Methods: The study was conducted from July 2013 to July 2015 in 57 clinics (nine European countries), targeting individuals over 18 years diagnosed in the preceding 5 years and born abroad. Electronic questionnaires supplemented with clinical data were completed in any of 15 languages. Postmigration HIV acquisition was estimated through Bayesian approaches combining extensive information on migration and patients' characteristics. CD4+ cell counts and HIV-RNA trajectories from seroconversion were estimated by bivariate linear mixed models fitted to natural history data. Postmigration acquisition risk factors were investigated with weighted logistic regression. Results: Of 2009 participants, 46% were MSM and a third originated from sub-Saharan Africa and Latin America & Caribbean, respectively. Median time in host countries was 8 years. Postmigration HIV acquisition was 63% (95% confidence interval: 57-67%); 72% among MSM, 58 and 51% in heterosexual men and women, respectively. Postmigration HIV acquisition was 71% for Latin America and Caribbean migrants and 45% for people from sub-Saharan Africa. Factors associated with postmigration HIV acquisition among heterosexual women and MSM were age at migration, length of stay in host country and HIV diagnosis year and among heterosexual men, length of stay in host country and HIV diagnosis year. Conclusion: A substantial proportion of HIV-positive migrants living in Europe acquired HIV postmigration. This has important implications for European public health policies. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved

Objective Combined antiretroviral treatment (cART) results in profound immunologic improvement, but it is unclear whether CD4 cell counts return to levels similar to those of HIV-negative individuals. We explore long-term CD4 cell count evolution post-cART and its association with baseline levels, virologic suppression, pre-cART cumulative viremia and other factors. Design Data were derived from the AMACS. Included individuals were adults who started cART, at least 2003, while previously ART-naive. Methods Changes in CD4 cell counts were modeled through piecewise linear mixed models. Results A total of 3405 individuals were included. The majority was male (86.0%), homosexual (58.8%) with median (IQR) age at cART initiation 36 (31-44) years and a median (IQR) follow-up of 3.9 (2.0-6.9) years. Most persons (57%) starting cART with less than 200 cells/μl did not reach 600 cells/μl after 7 years of treatment. Those starting cART with 200-349 CD4 cells/μl could reach 600 cells/μl within less than 2 years of fully suppressive treatment. Probability of CD4 normalization (i.e. >800 cells/μl) after 7 years of suppressive treatment was 24 and 46% for those starting treatment with less than 200 or 200-349 CD4 cells/μl, respectively. Lower pre-cART cumulative viremia was associated with faster CD4 recovery. CD4 cell count increases after 4 years were either insignificant or very slow, irrespectively of baseline levels. Conclusion cART initiation before CD4 cell count drops below 350 cells/μl is crucial for achieving normal CD4 levels. These findings underline the importance of timely diagnosis and cART initiation as the risk of both AIDS and non-AIDS-related morbidity/mortality remains increased in patients with incomplete CD4 recovery.

Summary Background Since the 1918 influenza pandemic, non-randomised studies and small clinical trials have suggested that convalescent plasma or anti-influenza hyperimmune intravenous immunoglobulin (hIVIG) might have clinical benefit for patients with influenza infection, but definitive data do not exist. We aimed to evaluate the safety and efficacy of hIVIG in a randomised controlled trial. Methods This randomised, double-blind, placebo-controlled trial was planned for 45 hospitals in Argentina, Australia, Denmark, Greece, Mexico, Spain, Thailand, UK, and the USA over five influenza seasons from 2013–14 to 2017–18. Adults (≥18 years of age) were admitted for hospital treatment with laboratory-confirmed influenza A or B infection and were randomly assigned (1:1) to receive standard care plus either a single 500-mL infusion of high-titre hIVIG (0·25 g/kg bodyweight, 24·75 g maximum; hIVIG group) or saline placebo (placebo group). Eligible patients had a National Early Warning score of 2 points or greater at the time of screening and their symptoms began no more than 7 days before randomisation. Pregnant and breastfeeding women were excluded, as well as any patients for whom the treatment would present a health risk. Separate randomisation schedules were generated for each participating clinical site using permuted block randomisation. Treatment assignments were obtained using a web-based application by the site pharmacist who then masked the solution for infusion. Patients and investigators were masked to study treatment. The primary endpoint was a six-category ordinal outcome of clinical status at day 7, ranging in severity from death to resumption of normal activities after discharge. The choice of day 7 was based on haemagglutination inhibition titres from a pilot study. It was analysed with a proportional odds model, using all six categories to estimate a common odds ratio (OR). An OR greater than 1 indicated that, for a given category, patients in the hIVIG group were more likely to be in a better category than those in the placebo group. Prespecified primary analyses for safety and efficacy were based on patients who received an infusion and for whom eligibility could be confirmed. This trial is registered with ClinicalTrials.gov , NCT02287467 . Findings 313 patients were enrolled in 34 sites between Dec 11, 2014, and May 28, 2018. We also used data from 16 patients enrolled at seven of the 34 sites during the pilot study between Jan 15, 2014, and April 10, 2014. 168 patients were randomly assigned to the hIVIG group and 161 to the placebo group. 21 patients were excluded (12 from the hIVIG group and 9 from the placebo group) because they did not receive an infusion or their eligibility could not be confirmed. Thus, 308 were included in the primary analysis. hIVIG treatment produced a robust rise in haemagglutination inhibition titres against influenza A and smaller rises in influenza B titres. Based on the proportional odds model, the OR on day 7 was 1·25 (95% CI 0·79–1·97; p=0·33). In subgroup analyses for the primary outcome, the OR in patients with influenza A was 0·94 (0·55–1·59) and was 3·19 (1·21–8·42) for those with influenza B (interaction p=0·023). Through 28 days of follow-up, 47 (30%) of 156 patients in the hIVIG group and in 45 (30%) of 152 patients in the placebo group had the composite safety outcome of death, a serious adverse event, or a grade 3 or 4 adverse event (hazard ratio [HR] 1·06, 95% CI 0·70–1·60; p=0·79). Six (4%) patients in the hIVIG group and five (3%) in the placebo group died, but these deaths were not necessarily related to treatment. Interpretation When administered alongside standard care (most commonly oseltamivir), hIVIG was not superior to placebo for adults hospitalised with influenza infection. By contrast with our prespecified subgroup hypothesis that hIVIG would result in more favourable responses in patients with influenza A than B, we found the opposite effect. The clinical benefit of hIVIG for patients with influenza B is supported by antibody affinity analyses, but confirmation is warranted. Funding NIAID and NIH. Partial support was provided by the Medical Research Council (MRC_UU_12023/23) and the Danish National Research Foundation.

Background Main causes of death in Greece are cardiovascular diseases (CVDs), malignant neoplasms, respiratory diseases, and road traffic crashes. To assess the population health status, monitor health systems, and adjust policies, national population-based health surveys are recommended. The previous health surveys that were conducted in Greece were restricted to specific regions or high-risk groups. Objective This paper presents the design and methods of the Greek Health Examination Survey EMENO (National Survey of Morbidity and Risk Factors). The primary objectives are to describe morbidity (focusing on CVD, respiratory diseases, and diabetes), related risk factors, as well as health care and preventive measures utility patterns in a random sample of adults living in Greece. Methods The sample was selected by applying multistage stratified random sampling on 2011 Census. Trained interviewers and physicians made home visits. Standardized questionnaires were administered; physical examination, anthropometric and blood pressure measurements, and spirometry were performed. Blood samples were collected for lipid profile, glucose, glycated hemoglobin, and transaminases measurements. The survey was conducted from May 2013 until June 2016. Results In total, 6006 individuals were recruited (response rate 72%). Of these, 4827 participated in at least one physical examination, 4446 had blood tests, and 3622 spirometry, whereas 3580 provided consent for using stored samples for future research (3528 including DNA studies). Statistical analysis has started, and first results are expected to be submitted for publication by the end of 2018. Conclusions EMENO comprises a unique health data resource and a bio-resource in a Mediterranean population. Its results will provide valid estimates of morbidity and risk factors’ prevalence (overall and in specific subdomains) and health care and preventive measures usage in Greece, necessary for an evidence-based strategy planning of health policies and preventive activities. International Registered Report Identifier (IRRID) DERR1-10.2196/10997

The HIV‐CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems; International audience; Decisions about when to start or switch a therapy often depend on the frequency with which individuals are monitored or tested. For example, the optimal time to switch antiretroviral therapy depends on the frequency with which HIV-positive individuals have HIV RNA measured. This paper describes an approach to use observational data for the comparison of joint monitoring and treatment strategies and applies the method to a clinically relevant question in HIV research: when can monitoring frequency be decreased and when should individuals switch from a first-line treatment regimen to a new regimen? We outline the target trial that would compare the dynamic strategies of interest and then describe how to emulate it using data from HIV-positive individuals included in the HIV-CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems. When, as in our example, few individuals follow the dynamic strategies of interest over long periods of follow-up, we describe how to leverage an additional assumption: no direct effect of monitoring on the outcome of interest. We compare our results with and without the "no direct effect" assumption. We found little differences on survival and AIDS-free survival between strategies where monitoring frequency was decreased at a CD4 threshold of 350 cells/μl compared with 500 cells/μl and where treatment was switched at an HIV-RNA threshold of 1000 copies/ml compared with 200 copies/ml. The "no direct effect" assumption resulted in efficiency improvements for the risk difference estimates ranging from an 7- to 53-fold increase in the effective sample size.

Aims To report the results of the first national Health Examination Survey (HES) on the prevalence of diabetes, its pharmacologic treatment and level of control, as well as pre-diabetes in Greece. Methods Data were derived from the National Survey of Morbidity and Risk Factors (EMENO), in a randomly selected, representative sample of the adult Greek population. Sampling weights were applied to adjust for study design and post-stratification weights to match sample age/sex distribution to the population. Non-response was adjusted by inverse probability weighting. Weighted prevalence estimates are provided. Results A total of 4393 persons with HbA1c and/or fasting plasma glucose measurements were included. Total diabetes prevalence was 11.9% (95% CI: 10.9–12.9), known diabetes 10.4% (9.5–11.4), and unknown 1.5% (1.1–1.9), with considerable increase in older age groups and no difference between genders. Pre-diabetes prevalence was 12.4% (11.4–13.6). The majority of persons with known diabetes were receiving metformin. Of those with known diabetes (and measured HbA1c), 70.9% were well controlled (HbA1c Conclusions This first representative national HES showed high prevalence of diabetes in Greece, with low prevalence of unknown diabetes. Pre-diabetes prevalence is also substantial. These results will hopefully enable national authorities develop tailored and efficient strategies for disease prevention and management.

Background People who inject drugs (PWID) are at risk for human immunodeficiency virus (HIV) and hepatitis C virus (HCV). In 2009 and 2011, Athens, Greece experienced an HCV and an HIV outbreak among PWID, respectively. Of these, only the 2011 HIV outbreak was detected. However, the public health interventions implemented in response to the HIV outbreak tackled also indirectly the undetected HCV outbreak. The aim of this study is to highlight the potential benefits of an efficient notification system using as a case study the undetected 2009 HCV outbreak among PWID of Athens. More specifically, the study assesses whether an earlier implementation of the same public responses could diminish the scale of the HCV outbreak and estimates the potential cost-savings. Methods A previous dynamic, stochastic, individual‐based model was used to simulate HCV transmission among PWID of Athens, Greece. We calibrated the model to reproduce the observed HCV prevalence. We examined the effect of the non-detection scenario, the 1- or 2-years earlier detection scenarios and compared them to the status quo scenario. Results Under the non-detection scenario, 2800 additional PWID would have been infected with HCV compared to the status quo by 2019. On the contrary, if the outbreak was detected 1- or 2- years earlier with immediate interventions, 440 and 970 HCV cases could be averted by 2019, respectively. Non-detection of the outbreak would cost an additional 43.2 (95% Credible interval: 2.7, 59.4) million euros to the healthcare system, compared to the status quo. On the other hand, if there was an efficient notification system to detect the HCV outbreak 1 or 2 years earlier, 6.8–15.6 million euros could have been saved by 2019. Conclusions An efficient notification system among PWID is a cost-saving investment that could detect on time and contain future outbreaks, and save valuable resources of the healthcare system.

International audience; BACKGROUND: Achieving the UNAIDS 90-90-90 target by 2020 is expected to end the HIV epidemic by 2030. We report on progress in the WHO European Region in meeting this target.METHODS: The European Centre for Disease Prevention and Control (ECDC) sent questionnaires to 55 countries in 2016. We report estimates for 4 stages of the continuum of HIV care (living with HIV, diagnosed, treated, and virally suppressed), corresponding to the Joint United Nations Programme on HIV and AIDS (UNAIDS) target and explore differences by subregion and challenges with reporting data.FINDINGS: Forty-four countries provided data for ≥1 stage, and 29 for all 4 stages. Estimated HIV prevalence was 0.19% (range 0.02%-0.84%, n = 37 countries providing stage 1 data). The proportion diagnosed of people living with HIV ranged from 38% to 98% (n = 37 reporting number of people living with HIV and diagnosed). The proportion on ART of those diagnosed ranged from 27% to 96% (n = 40 reporting numbers diagnosed and treated), and viral suppression rates ranged from 32% to 97% (n = 31 providing numbers treated and virally suppressed). The overall continuum of care estimate for 29 countries with complete data was 81-84-88, which differed by subregion: 84-88-90, 84-69-62, and 57-45-57 for the western, central, and eastern subregions, respectively. Challenges in reporting data included absence of a single data source for all stages, shortage of expertise, and lack of financial and human resources.CONCLUSIONS: There is an urgent need to strengthen HIV testing programs throughout Europe, particularly in the eastern subregion, and to remove constraints hampering access to testing and care. Recent changes to treatment guidelines should help reduce the numbers diagnosed not treated.

Effect estimates from randomized trials and observational studies might not be directly comparable because of differences in study design, other than randomization, and in data analysis. We propose a 3-step procedure to facilitate meaningful comparisons of effect estimates from randomized trials and observational studies: 1) harmonization of the study protocols (eligibility criteria, treatment strategies, outcome, start and end of follow-up, causal contrast) so that the studies target the same causal effect, 2) harmonization of the data analysis to estimate the causal effect, and 3) sensitivity analyses to investigate the impact of discrepancies that could not be accounted for in the harmonization process. To illustrate our approach, we compared estimates of the effect of immediate with deferred initiation of antiretroviral therapy in individuals positive for the human immunodeficiency virus from the Strategic Timing of Antiretroviral Therapy (START) randomized trial and the observational HIV-CAUSAL Collaboration.

In this study, we investigated the robustness of the methods that account for independent left truncation when applied to competing risks settings with dependent left truncation. We specifically focused on the methods for the proportional cause-specific hazards model and the Fine–Gray model. Simulation experiments showed that these methods are not in general robust against dependent left truncation. The magnitude of the bias was analogous to the strength of the association between left truncation and failure times, the effect of the covariate on the competing cause of failure, and the baseline hazard of left truncation time.

Objectives Efforts are needed to improve informed consent of participants in research. The Strategic Timing of AntiRetroviral Therapy (START) study provides a unique opportunity to study the effect of length and complexity of informed consent documents on understanding and satisfaction among geographically diverse participants. Methods Interested START sites were randomized to use either the standard consent form or the concise consent form for all of the site's participants. Results A total of 4473 HIV-positive participants at 154 sites world-wide took part in the Informed Consent Substudy, with consent given in 11 primary languages. Most sites sent written information to potential participants in advance of clinic visits, usually including the consent form. At about half the sites, staff reported spending less than an hour per participant in the consent process. The vast majority of sites assessed participant understanding using informal nonspecific questions or clinical judgment. Conclusions These data reflect the interest of START research staff in evaluating the consent process and improving informed consent. The START Informed Consent Substudy is by far the largest study of informed consent intervention ever conducted. Its results have the potential to impact how consent forms are written around the world.

Summary Background 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. Methods 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. Findings 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 log 10 copies per mL (95% CI 3·98–4·12) in 1980 to 4·50 log 10 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. Interpretation 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. Funding European Union Seventh Framework Programme.

Missing data are common in longitudinal studies. Likelihood-based methods ignoring the missingness mechanism are unbiased provided missingness is at random (MAR); under not-at-random missingness (MNAR), joint modeling is commonly used, often as part of sensitivity analyses. In our motivating example of modeling CD4 count trajectories during untreated HIV infection, CD4 counts are mainly censored due to treatment initiation, with the nature of this mechanism remaining debatable. Here, we evaluate the bias in the disease progression marker's change over time (slope) of a specific class of joint models, termed shared-random-effects-models (SREMs), under MAR drop-out and propose an alternative SREM model. Our proposed model relates drop-out to both the observed marker's data and the corresponding random effects, in contrast to most SREMs, which assume that the marker and the drop-out processes are independent given the random effects. We analytically calculate the asymptotic bias in two SREMs under specific MAR drop-out mechanisms, showing that the bias in marker's slope increases as the drop-out probability increases. The performance of the proposed model, and other commonly used SREMs, is evaluated under specific MAR and MNAR scenarios through simulation studies. Under MAR, the proposed model yields nearly unbiased slope estimates, whereas the other SREMs yield seriously biased estimates. Under MNAR, the proposed model estimates are approximately unbiased, whereas those from the other SREMs are moderately to heavily biased, depending on the parameterization used. The examined models are also fitted to real data and results are compared/discussed in the light of our analytical and simulation-based findings.

BACKGROUND: There is a heavy and disproportionate burden of human immunodeficiency virus (HIV) infection among migrant communities living in Europe. Despite this, the published evidence related to HIV testing, prevention, and treatment needs for migrants is sparse. OBJECTIVE: The aim of this study was to identify the factors associated with access to primary care and HIV testing among migrant groups living in Europe. METHODS: A Web-based survey (available in 14 languages) was open to all people aged 18 years and older, living outside their country of birth in the World Health Organization (WHO) European area. Community organizations in 9 countries promoted the survey to migrant groups, focusing on those at a higher risk of HIV (sub-Saharan Africans, Latin Americans, gay or bisexual men, and people who inject drugs). Multivariable analysis examined factors associated with access to primary care and previous history of an HIV test. RESULTS: In total, 559 women, 395 heterosexual men, and 674 gay or bisexual men were included in the analysis, and 68.1% (359/527) of women, 59.5% (220/371) of heterosexual men, and 89.6% (596/664) of gay or bisexual men had tested for HIV. Low perceived risk was the reason given for not testing by 62.3% (43/69) of gay or bisexual men and 83.3% (140/168) of women and heterosexual men who reported never having tested for HIV. Access to primary care was >60% in all groups. Access to primary care was strongly positively associated with living in Northern Europe compared with Southern Europe (women: adjusted odds ratio, aOR 34.56 [95% CI 11.58-101]; heterosexual men: aOR 6.93 [95% CI 2.49-19.35], and gay or bisexual men: aOR 2.53 [95% CI 1.23-5.19]), whereas those with temporary residency permits were less likely to have access to primary care (women: aOR 0.41 [95% CI 0.21-0.80] and heterosexual men: aOR 0.24 [95% CI 0.10-0.54] only). Women who had experience of forced sex (aOR 3.53 [95% CI 1.39-9.00]) or postmigration antenatal care (aOR 3.07 [95% CI 1.55-6.07]) were more likely to have tested for HIV as were heterosexual men who had access to primary care (aOR 3.13 [95% CI 1.58-6.13]) or reported "Good" health status (aOR 2.94 [95% CI 1.41-5.88]). CONCLUSIONS: Access to primary care is limited by structural determinants such as immigration and health care policy, which varies across Europe. For those migrants who can access primary care and other health services, missed opportunities for HIV testing remain a barrier to earlier testing and diagnosis for migrants in Europe. Clinicians should be aware of these potential structural barriers to HIV testing as well as low perception of HIV risk in migrant groups. This project received funding from the European Union’s Seventh Framework Programme for research, technological development, and demonstration under EuroCoord grant agreement number 260694. IF was funded by a Doctoral Research Fellowship from the National Institute for Health Research (NIHR). The views expressed in this paper are those of the authors and not necessarily those of the National Health Service (NHS), the National Institute for Health Research (NIHR), or the Department of Health. Additional funding was received from Gilead Sciences Europe Ltd; NIHR Clinical Research Network, the United Kingdom; Foundation for AIDS Research and Prevention in Spain (FISPSE) Project 361036/10; Consortium of Biomedical Research in Epidemiology and Public Health, Spain; Spanish HIV Research Network for Excellence (RD06/006 and RD12/0017/0018); Research and Development Fund, Public Health Service of Amsterdam; and the Swiss HIV Cohort Study (project #727), supported by the Swiss National Science Foundation (grant #148522) and by the Swiss HIV Cohort Study research foundation. No funder had any role in the study, writing of the manuscript, or decision to submit for publication. Sí

Background: We evaluate differences in timing of cART (combined antiretroviral treatment) initiation by geographical origin in male and female HIV-positive patients in the Collaboration of Observational HIV Epidemiological Research Europe, a large European Collaboration of HIV Cohorts. Methods: We included individuals recruited in Western Europe between January 1997 and March 2013, with known geographical origin and at least 1 CD4(+) cell countmeasurement while cART-naive. Timing of cART was assessed through modified time-to-eventmethods, in which a scale of CD4(+) cell counts was used instead of time, with cART being the outcome. We estimated the median CD4(+) cell count at cART initiation (estimated CD4(+) levels at which the probability of having started cART is 50%) using Kaplan-Meier and adjusted hazard ratios of cART initiation using Cox regression. Results: Of 151 674 individuals, 110 592 (72.9%) were men. Median (95% confidence interval) CD4(+) cell count falls far below 250 cells/ml in all groups and was lowest in sub-Saharan African [SSA: 161 (158-167)], Caribbean men [161 (150-174)] and in Asian women [Asian Continent and Oceania: 185 (165-197)]. Among men, the adjusted probability of cART initiation was lower in migrants compared with natives, but differences depended on initial CD4(+) cell count. For example, in the group with more than 500 CD4(+) at recruitment, they were 45% (36-53%), 30% (17-40%) and 25% (19-30%) lower for Caribbean, Eastern European and SSA men, respectively. In women, no meaningful differences were observed between natives and most migrant groups. However, SSA women had a 31% (24-38%) higher probability of cART initiation when recruited at a CD4(+) more than 500 cells/ml and 9% (4-14%) lower when recruited at CD4(+) less than 100 cells/ml. Conclusion: Most migrant men initiate cART at lower CD4(+) cell count than natives, whereas this does not hold for migrant women.

Marginal structural models (MSMs) have been proposed for estimating a treatment'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'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's variance and rarely recorded measurements none of the examined method adequately corrected the bias.

Most patients on suppressive antiretroviral therapy (ART) experience improvements in CD4 T cell count. However, some patients with undetectable viral load continue to lose CD4 T cells for unknown reasons. Casp8p41 is a host-derived protein fragment that is present only in productively infected cells and that causes the death of HIV-infected cells. We questioned whether ongoing CD4(+) T cell losses while on suppressive ART were associated with subclinical HIV replication causing production of Casp8p41. We analyzed the association of Casp8p41 content with subsequent CD4 losses in patients on continuous suppressive ART and in patients who discontinued ART after Casp8p41 content was determined, adjusting for age, baseline CD4(+) T cell count, and baseline HIV RNA level. Casp8p41 expression in memory CD4(+) T cells was measured by intracellular flow cytometry and was correlated with viral load and CD4(+) T cell change over time. In patients who stopped therapy after Casp8p41 content was determined, baseline Casp8p41 content did not predict CD4(+) T cell change. However, in patients on continuous ART, higher baseline Casp8p41 content was associated with a greater odds of a CD4(+) T cell decline at 6 months (p=0.01). Therefore, patients on suppressive ART, who have ongoing production of Casp8p41, have an increased risk of CD4 T cell losses, suggesting that subclinical HIV replication is driving both Casp8p41, which in turn causes a CD4(+) T cell decline.

Time-series studies reporting associations between daily air pollution and health use pollution data from monitoring stations that vary in the frequency of recording. Within the Air Pollution and Health: A European and North American Approach (APHENA) project, we evaluated the impact of systematically missing daily measurements on the estimated effects of PM10 and ozone on daily mortality. For four cities with complete time-series data, we created patterns of systematically missing exposure measurements by deleting observations. Poisson regression-derived city-specific estimates were combined to produce overall effect estimates. Analyses based on incomplete time series gave considerably lower pooled PM10 and ozone health effects compared to those from complete data. City-specific estimates were generally lower although more variable. Systematically missing exposure data for air pollutants appears to lead to underestimation of associated health effects. Our findings indicate that the use of evidence from studies with incomplete exposure data may underestimate the impact of air pollution and highlight the advantage of having complete daily data in time-series studies.

Background: 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). Methods: 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 weighting. Results: Of 43 803 individuals who initiated an eligible antiretroviral therapy regimen in 2002 or later, 2001 met the baseline inclusion criteria for the mortality analysis and 1641 for the AIDS or death analysis. There were 21 deaths and 33 AIDS or death events in the tight-control group, and 28 deaths and 41 AIDS or death events in the loose-control group. Compared with tight control, the adjusted hazard ratios (95% confidence interval) for loose control were 1.10 (0.73, 1.66) for death, and 1.04 (0.86, 1.27) for AIDS or death. Conclusions: Although our effective sample sizes were small and our estimates imprecise, the described methodological approach can serve as an example for future analyses.

Hepatitis D virus (HDV) has decreased in Europe, but recent reports indicate a rising trend. We report the epidemiological changes, clinical progress, and effect of treatment on the natural course of HDV infection in Greece during the last 13 years.Prospective data were extracted from the HepNet.Greece Cohort-Study.Since 1997, 4673 chronic HBV (CHB) cases (4527 adults, 146 children) have been followed prospectively. Two thousand one hundred thirty-seven patients were tested for anti-HDV [101 (4.7%) positive]. Anti-HDV testing in Greece decreased significantly (57.0% before 2003, 35.3% thereafter; p0.001). Anti-HDV prevalence among HBsAg-positives was 4.2%; lower in native Greeks (2.8%) than in immigrants (7.5%) or in children (15.3%; p0.001). Within 2.3 years of follow-up, HDV occurred in 11/2047 HBsAg-positive patients (2.2 new delta-infected adults and 8.7 children per 1000 HBsAg-positive annually). HDV-positive compared to CHB adults were younger (p=0.035) and had more active and advanced disease at baseline, as indicated by laboratory indices and the higher prevalence of cirrhosis at younger age. During a 4.2-year median observation, significantly more anti-HDV-positive than CHB adults developed a liver-related first event (20.0% vs. 8.5%, p Log-rank=0.014).Treatment was received by 46/90 (51.1%) patients, 40 of them interferon-based. In multivariable analysis, interferon significantly decreased disease progression in HDV-positive patients [HR=0.14 (95% CI: 0.02-0.86; p=0.033)].In Greece, HDV serology is currently tested in only one-third of HBsAg-positive patients. HDV prevalence is lower in native Greeks compared to immigrants, who may contribute50% of the HDV infection burden in Greece. Data show that HDV infection is a rapidly progressive disease, but interferon-based treatment may alter its course.

In many medical studies, individuals are seen periodically, at a set of pre-scheduled clinical visits. In such cases, when the outcome of interest is the occurrence of an event, the corresponding times are only known to fall within an interval, formed by the times of two consecutive visits. Such data are called interval censored. Most methods for the analysis of interval-censored event times are based on a simplified likelihood function which relies on the assumption that the only information provided by the censoring intervals is that they contain the actual event time (i.e. non-informative censoring). In this simulation study, the performance of parametric models for interval-censored data when individuals miss some of the pre-scheduled visits completely at random (MCAR), at random (MAR) or not at random (MNAR) was assessed comparing also with a simpler approach that is often used in practice. A sample of HIV-RNA measurements and baseline covariates of HIV-1 infected individuals from the CASCADE study is used for illustration in an analysis of the time between the initiation of antiretroviral treatment and viral load suppression to undetectable levels. Results suggest that parametric models based on flexible distributions (e.g. generalised Gamma) can fit such data reasonably well and are robust to irregular visit times caused by an MCAR or MAR mechanism. Violating the non-informative censoring assumption though, leads to biased estimators with the direction and the magnitude of the bias depending on the direction and the strength of the association between the probability of missing visits and the actual time-to-event. Finally, simplifying the data in order to use standard survival analysis techniques, can yield misleading results even when the censoring intervals depend only on a baseline covariate.

Whether response to combination antiretroviral therapy (cART) differs between those infected with HIV-1 subtype A or B remains unclear. We compared virological and immunological response to cART in individuals infected with subtype A or B in an ethnically homogeneous population. Data derived from the Athens Multicenter AIDS Cohort Study (AMACS) and analysis were restricted to those of Greek origin. Time to virological response (confirmed HIV-RNA500 copies/ml) and time to failure (500 copies/ml at any time or no response by month 6) were analyzed using survival models and CD4 changes after cART initiation using piecewise linear mixed effects models. Of the 571 subjects included in the analysis, 412 (72.2%) were infected with subtype B and 159 (27.8%) with subtype A. After adjusting for various prognostic factors, the rate of virological response was higher for those infected with subtype A versus B (adjusted HR: 1.35; 95% CI: 1.08-1.68; p=0.009). Subtype A was also marginally associated with a lower hazard of virological failure compared to subtype B (HR=0.73; 95% CI: 0.53-1.02; p=0.062). Further adjustment for treatment adherence did not substantially changed the main results. No significant differences were observed in the rates of CD4 increases by subtype. The overall median (95% CI) CD4 increase at 2 years of cART was 193 (175, 212) cells/μl. Our study, based on one of the largest homogeneous groups of subtype A and B infections in Europe, showed that individuals infected with subtype A had an improved virological but similar immunological response to cART compared to those infected with subtype B.

BACKGROUND The burden of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected children and adolescents on combination antiretroviral therapy (cART) has not been compared globally. METHODS We analyzed cohort data from the International Epidemiologic Databases to Evaluate AIDS and the Collaboration of Observational HIV Epidemiological Research in Europe. We included HIV-infected children aged

To date no nationwide epidemiological study of asthma in the general population has been performed in Greece. The present study evaluated the prevalence of asthma and asthma related symptoms (ARS) in a randomly selected sample representative of the adult general population in Greece. The EΜEΝΟ survey (National Morbidity and Risk Factors Survey) supported by the European Social Fund and national funds, is currently performed in Greece, aiming to include 6,000 adults using a multi-stage stratified random sampling method, involving localities throughout the country. Information on asthma and ARS during the last 12 months was collected through questionnaires administered by trained interviewers. An interim analysis of participants recruited from 03/2014 to 12/2015 was performed. Prevalence of asthma and ARS was determined taking into account the design of the study and additional adjustments for age and sex. A total of 5,137 participants were included. The prevalence of asthma was 6.3% (CI 95%: 5,6%-7,0%) and it was higher in women (7.2% vs 5.3% in men, p=0.011). We also observed higher prevalences of ARS in women except wheezing. Prevalences of ARS (overall) are presented below Asthma and asthma related symptoms prevalence in the general adult population in Greece are higher than the global ones estimated by the World Health Survey (To et al, BMC Public Health 2012; 12: 204).

To date no nationwide epidemiological study of asthma in the general population has been performed in Greece. The present study examines the association of asthma and asthma-related symptoms (ARS) with obstructive pattern (OP) in the adult general population in Greece. The EΜEΝΟ survey (National Morbidity and Risk Factors Survey) supported by the European Social Fund and national funds is currently performed in Greece, aiming to include 6,000 adults using a multi-stage stratified random sampling method throughout the country. Information on asthma and ARS was collected through questionnaires administered by interviewers. Participants were also submitted to spirometry. An interim analysis of participants recruited from 03/2014 to 12/2015 was performed. A total of 1980 participants who had technically acceptable spirometry were included in the study. Individuals reporting asthma or ARS had significantly higher prevalence of OP in spirometry than those who did not report. High percentages of OP were also observed among individuals with known asthma and ARS. Our results indicate a high proportion of obstructive pattern among individuals with known asthma and ARS in the population of Greece. Partially controlled asthma may be an explanation. Further studies are needed to elucidate potential factors such as socioeconomic, under treatment, smoking, persistent environmental exposures that may be implicated.

OBJECTIVE: To describe CD4 and HIV RNA changes during treatment resumption (TR) after treatment interruption (TI) compared with response to first highly active antiretroviral therapy (HAART) and to investigate predictors. METHODS: Using Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) data, we identified subjects who interrupted first HAART, not initiated during primary infection. We estimated rate of CD4 change during TR and time from TR to HIV RNA

OBJECTIVE: To characterize the magnitude and the predictors of highly active antiretroviral therapy (HAART) interruption (TI) and to investigate its immunologic and virological consequences. METHODS: 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. RESULTS: 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 (

BackgroundImproving the effectiveness and efficiency of research informed consent is a high priority. Some express concern about longer, more complex, written consent forms creating barriers to participant understanding. A recent meta-analysis concluded that randomized comparisons were needed.MethodsWe conducted a cluster-randomized non-inferiority comparison of a standard versus concise consent form within a multinational trial studying the timing of starting antiretroviral therapy in HIV+ adults (START). Interested sites were randomized to standard or concise consent forms for all individuals signing START consent. Participants completed a survey measuring comprehension of study information and satisfaction with the consent process. Site personnel reported usual site consent practices. The primary outcome was comprehension of the purpose of randomization (pre-specified 7.5% non-inferiority margin).Results77 sites (2429 participants) were randomly allocated to use standard consent and 77 sites (2000 participants) concise consent, for an evaluable cohort of 4229. Site and participant characteristics were similar for the two groups. The concise consent was non-inferior to the standard consent on comprehension of randomization (80.2% versus 82%, site adjusted difference: 0.75% (95% CI -3.8%, +5.2%)); and the two groups did not differ significantly on total comprehension score, satisfaction, or voluntariness (p>0.1). Certain independent factors, such as education, influenced comprehension and satisfaction but not differences between consent groups.ConclusionsAn easier to read, more concise consent form neither hindered nor improved comprehension of study information nor satisfaction with the consent process among a large number of participants. This supports continued efforts to make consent forms more efficient.Trial registrationInformed consent substudy was registered as part of START study in clinicaltrials.gov #NCT00867048, and EudraCT # 2008-006439-12.

Background: Migrants form a substantial proportion of the population affected by the human immunodeficiency virus (HIV) epidemic in Europe, yet HIV prevention for this population is hindered by poor understanding of access to care and of postmigration transmission dynamics. Objective: We present the design and methods of the advancing Migrant Access to health Services in Europe (aMASE) study, the first European cross-cultural study focused on multiple migrant populations. It aims to identify the structural, cultural, and financial barriers to HIV prevention, diagnosis, and treatment and to determine the likely country of HIV acquisition in HIV-positive migrant populations. Methods: We delivered 2 cross-sectional electronic surveys across 10 countries (Belgium, France, Germany, Greece, Italy, the Netherlands, Portugal, Spain, Switzerland, and United Kingdom). A clinic survey aimed to recruit up to 2000 HIV-positive patients from 57 HIV clinics in 9 countries. A unique study number linked anonymized questionnaire data to clinical records data (viral loads, CD4 cell counts, viral clades, etc). This questionnaire was developed by expert panel consensus and cognitively tested, and a pilot study was carried out in 2 countries. A Web-based community survey (n=1000) reached those living with HIV but not currently accessing HIV clinics, as well as HIV-negative migrants. It was developed in close collaboration with a community advisory group (CAG) made up of representatives from community organizations in 9 of the participating countries. The CAG played a key role in data collection by promoting the survey to higher-risk migrant groups (sub-Saharan Africans, Latin Americans, men who have sex with men, and people who inject drugs). The questionnaires have considerable content overlap, allowing for comparison. Questions cover ethnicity, migration, immigration status, HIV testing and treatment, health-seeking behavior, sexual risk, and drug use. The electronic questionnaires, which were available in 15 languages, allowed for complex routing, preventing respondents from answering irrelevant questions. Results: In total, we recruited 2249 participants from 57 HIV clinics as part of the clinic survey and retrieved 1637 complete responses as part of the community survey. Conclusions: The findings will provide much-needed information for improving HIV prevention interventions and access to services for migrant communities. [JMIR Res Protoc 2016;5(2):e74]

Supplemental Digital Content is available in the text., It is important not only to collect epidemiologic data on HIV but to also fully utilize such information to understand the epidemic over time and to help inform and monitor the impact of policies and interventions. We describe and apply a novel method to estimate the size and characteristics of HIV-positive populations. The method was applied to data on men who have sex with men living in the UK and to a pseudo dataset to assess performance for different data availability. The individual-based simulation model was calibrated using an approximate Bayesian computation-based approach. In 2013, 48,310 (90% plausibility range: 39,900–45,560) men who have sex with men were estimated to be living with HIV in the UK, of whom 10,400 (6,160–17,350) were undiagnosed. There were an estimated 3,210 (1,730–5,350) infections per year on average between 2010 and 2013. Sixty-two percent of the total HIV-positive population are thought to have viral load

Supplemental Digital Content is Available in the Text., Objective: To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). Design: 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. Methods: 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. Results: 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 strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were −5.3 (−18.6 to 7.9) and −31.7 (−52.0 to −11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies. Conclusions: Our findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question.

The “Air Pollution and Health: A Combined European and North American Approach” (APHENA) project is a collaborative analysis of multi-city time-series data on the association between air pollution and adverse health outcomes. The main objective of APHENA was to examine the coherence of findings of time-series studies relating short-term fluctuations in air pollution levels to mortality and morbidity in 125 cities in Europe, the US, and Canada. Multi-city time-series analysis was conducted using a two-stage approach. We used Poisson regression models controlling for overdispersion with either penalized or natural splines to adjust for seasonality. Hierarchical models were used to obtain an overall estimate of excess mortality associated with ozone and to assess potential effect modification. Potential effect modifiers were city-level characteristics related to exposure to other ambient air pollutants, weather, socioeconomic status, and the vulnerability of the population. Regionally pooled risk estimates from Europe and the US were similar; those from Canada were substantially higher. The pooled estimated excess relative risk associated with a 10 µg/m3 increase in 1 h daily maximum O3 was 0.26 % (95 % CI, 0.15 %, 0.37 %). Across regions, there was little consistent indication of effect modification by age or other effect modifiers considered in the analysis. The findings from APHENA on the effects of O3 on mortality in the general population were comparable with previously reported results and relatively robust to the method of data analysis. Overall, there was no indication of strong effect modification by age or ecologic variables considered in the analysis.

BACKGROUND We examined differences by geographical origin (GO) in time from HIV seroconversion (SC) to AIDS, death, and initiation of antiretroviral therapy (cART). METHODS Data from HIV seroconverter cohorts in Europe, Australia and Canada (CASCADE) was used; GO was classified as: western countries (WE), North Africa and Middle East (NAME), sub-Saharan Africa (SSA), Latin America (LA), and Asia (ASIA). Differences by GO were assessed using Cox models. Administrative censoring date was 30 June 2008. RESULTS Of 16 941 seroconverters, 15 548 were from WE, 158 NAME, 762 SSA, 349 LA, and 124 ASIA. We found no differences by GO in risks of AIDS (P = .99) and death (P = .12), although seroconverters from NAME (adjusted hazard ratio [aHR]: 0.57; 95% CI: 0.33-.94) and SSA (aHR: 0.74; 95% CI: 0.50-1.10) appeared to have lower mortality than WE. Chances of initiating cART differed by GO (P

Objective: Effects of transient combination antiretroviral treatment (cART) initiated during early HIV infection (EHI) remain unclear. We investigate whether this intervention affects viral suppression and CD4+ cell count increase following its reinitiation in chronic infection (CHI). Design: Longitudinal observational study. Methods: We identified adult patients from Concerted Action of Seroconversion to AIDS and Death in Europe who seroconverted after 1/1/2000, had a 12 months or less HIV test interval and initiated cART from naive. We classified individuals as ‘pretreated in EHI’ if treated within 6 months of seroconversion, interrupted for at least 12 weeks, and reinitiated during CHI. Statistical analysis was performed using survival analysis methods and mixed models. Results: Pretreated and initiated in CHI groups comprised 202 and 4263 individuals, with median follow-up after CHI treatment 4.5 and 3 years, respectively. Both groups had similar virologic response and relapse rates (P = 0.585 and P = 0.206) but pretreated individuals restarted treatment with higher baseline CD4+ cell count (∼80 cells/μl; P