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BackgroundUlcerative colitis (UC) is an inflammatory disease of the colon and rectum. Treatment options include biologics and tofacitinib.ObjectivesWe aim to summarize the evidence on efficacy and safety of biologics and tofacitinib in moderate-to-severe UC.MethodsPubMed, Embase, Scopus, and the Cochrane Library were systematically searched to identify meta-analyses of randomized controlled trials assessing adalimumab, golimumab, infliximab, vedolizumab, and tofacitinib in UC. Efficacy outcomes included induction and maintenance of clinical response, clinical remission and mucosal healing. Safety outcomes included adverse events and serious adverse events.ResultsThe overview involved 31 meta-analyses. All four biologics and tofacitinib were superior to placebo regarding efficacy. Indirect comparisons suggested that infliximab may be better than adalimumab and golimumab to induce clinical response and mucosal healing. Safety analyses indicated no increased rates of adverse events, except for infliximab.ConclusionsBiologics and tofacitinib are efficacious and safe for treating UC. These findings can support clinical decision-making. 7 10 1285 1303

Identifying and linking people to care soon after HIV infection could limit viral transmission and protect their health. This work aims at describing the continuum of care among recently HIV-infected people who inject drugs (PWID) and participated in an intervention in the context of an HIV outbreak in Athens, Greece. The Transmission Reduction Intervention Project (TRIP) conducted risk network-based contact tracing and screened people for recent HIV infection. A comprehensive approach with a case management component that aimed to remove barriers to accessing care was adopted. Follow-up data on antiretroviral treatment (ART) and HIV-RNA levels were obtained from HIV clinics. TRIP enrolled 45 recently HIV-infected PWID (80% male) with a median viral load at recruitment of 5.43 log10 copies/mL. Of the recently infected persons in TRIP, 87% were linked to care of these, 77% started ART and of those on ART, 89% achieved viral load

Introduction: Viral load is one of the most important determinants for HIV transmission. Identification of people with high viral load (PHVL) can be effective in limiting onward HIV transmission. In order to improve the identification of these individuals within risk networks, we determined a) the number of PHVL recruited through risk networks b) their socio-demographic, behavioural and clinical characteristics and c) the characteristics of individuals who referred these PHVL to the study. Methodology: From November 2013 to March 2016, in Odessa, Ukraine, Transmission Reduction Intervention Project (TRIP) was implemented to identify people recently infected with HIV within the risk networks of “seeds” and “venues” where they engaged in risk behaviour. Results: TRIP identified 53 PHVL, of whom 32 (60%) injected drugs; 42 (79%) were unaware of their HIV status; 25 (47%) had more than one sex partner, and only 14 (26%) were using condoms. There were 164 people who referred individuals into the study; 33 of them (20%) referred PHVL. In terms of referrers, those with lower than secondary level of education, not living with a sex partner, and reporting regular condom use were significantly more likely (p < 0.05) to refer PHVL. Most PHVL (38, 72%) and their referrers (27, 82%) were found through venues. Conclusions: In Odessa city, PHVL are at high risk of transmitting HIV as the majority inject drugs, do not know their HIV status, and have unprotected sex and/or multiple partners. Targeting these individuals for HIV prevention, harm reduction and initiation of antiretroviral treatment (ART) is urgent.

This article presents analyzed data on new diagnoses and mortality of breast cancer, between 2005 and 2013, in the Republic of Cyprus. New diagnoses are presented by demographic and clinical/histological variables that include cancer grade, behaviour, stage, and histological type at diagnosis (always as a primary site). Breast cancer-related deaths are presented by gender. Net survival rates based on cohort and period methods are presented by age group, cancer grade, behaviour, and stage at diagnosis, for all cases and for cases of Greek-Cypriot ethnicity. The unprocessed data of the Cyprus Cancer Registry were provided by the Health Monitoring Unit of the Ministry of Health of the Republic of Cyprus. 19 353 369

Background Biological therapies have improved the care of patients with ulcerative colitis (UC). Tofacitinib, an oral small-molecule Janus kinase inhibitor, is potentially a new treatment option. Aim To comparatively assess efficacy and harm of tofacitinib and biologics (infliximab, adalimumab, golimumab and vedolizumab) in adult patients not previously exposed to TNF antagonists. Methods We performed a comprehensive search of PubMed, Embase, Scopus, clinical trial registries, regulatory authorities' websites and major conference proceedings, through August 2017, to identify randomised, placebo-controlled or head-to-head trials assessing tofacitinib or biologics as induction and/or maintenance therapy in moderate-to-severe UC. Two reviewers independently extracted study data and outcomes, and investigated each trial's risk-of-bias. We used conventional meta-analysis to synthesise direct evidence, and network meta-analysis for adjusted indirect treatment comparisons. Results Fifteen randomised, double-blind, placebo-controlled trials (n = 3130) contributed data for induction: All treatments are superior to placebo. Indirect treatment comparisons showed that infliximab is better than adalimumab (OR: 2.01, 95% CI: 1.36-2.98) and golimumab (1.67, 1.08-2.59) in clinical response, better than adalimumab (2.10, 1.21-3.64) in clinical remission, and better than adalimumab (1.87, 1.26-2.79) and golimumab (1.75, 1.13-2.73) in mucosal healing. No indirect comparisons between tofacitinib and biologics reached statistical significance. Nine studies (n = 1776) contributed maintenance data showing that all treatments have higher clinical efficacy than placebo. Safety analyses indicated no increased rates of adverse events for the treatments under evaluation (except for infliximab), while vedolizumab may have an advantage regarding the occurrence of serious adverse events. Conclusions Tofacitinib and biologics are efficacious and safe for UC. Further high-quality research is warranted to establish the best therapeutic option. 47 4 454 465

Background: The relationship of 5-aminosalicylates’ use with the risk of colorectal neoplasia in patients with inflammatory bowel disease (IBD) has been the focus of a growing body of research. Aim: To investigate this association through an updated meta-analysis of observational studies. Methods: PubMed, Scopus and major conference proceedings were searched up to December 2016. The identified studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates were calculated using random-effect models. Detailed subgroup analyses were performed. The GRADE approach was used to assess the quality of evidence. Results: Thirty-one independent observational studies including 2137 cases of colorectal neoplasia (of which 76% were cancers) were incorporated. Between-study heterogeneity was moderate, while strong suspicion of small-study effects was raised. The overall analysis revealed a protective association between 5-aminosalicylates’ use and colorectal neoplasia (RR = 0.57, 95% CI: 0.45–0.71). When the analysis was stratified according to study design and setting, the association was significant in cohort (RR = 0.65, 95% CI: 0.43–0.99; n = 10) and case–control studies (RR = 0.53, 95% CI: 0.40–0.70; n = 21), population-based (RR = 0.70, 95% CI: 0.52–0.94; n = 12) and hospital-based studies (RR = 0.46, 95% CI: 0.34–0.61; n = 19). Exposure to 5-aminosalicylates was protective against cancer (RR = 0.58, 95% CI: 0.45–0.74) and dysplasia (RR = 0.54, 95% CI: 0.35–0.84). The reduction in colorectal neoplasia risk was strong in ulcerative colitis (RR = 0.50, 95% CI: 0.38–0.64), but nonsignificant in Crohn's disease (RR = 0.76, 95% CI: 0.43–1.33). Mesalazine (mesalamine) use was protective (RR = 0.70, 95% CI: 0.51–0.94) with evidence of a dose-effect. The effect of sulfasalazine was marginally nonsignificant (RR = 0.72, 95% CI: 0.51–1.01). Conclusions: Our findings support a potential chemopreventive role of 5-aminosalicylates in IBD. Further, high-quality prospective research is warranted. © 2017 John Wiley & Sons Ltd 45 9 1179 1192

eurosurveillance.org is the online home of Eurosurveillance, Europe's journal on infectious disease surveillance, epidemiology, prevention and control. 24 46

Introduction This paper examines the extent to which an intervention succeeded in locating people who had recently become infected with HIV in the context of the large‐scale Ukrainian epidemic. Locating and intervening with people who recently became infected with HIV (people with recent infection, or PwRI) can reduce forward HIV transmission and help PwRI remain healthy. Methods The Transmission Reduction Intervention Project (TRIP) recruited recently‐infected and longer‐term infected seeds in Odessa, Ukraine, in 2013 to 2016, and asked them to help recruit their extended risk network members. The proportions of network members who were PwRI were compared between TRIP arms (i.e. networks of recently‐infected seeds vs. networks of longer‐term infected seeds) and to the proportion of participants who were PwRI in an RDS‐based Integrated Biobehavioral Surveillance of people who inject drugs in 2013. Results The networks of PwRI seeds and those of longer‐term infected seeds had similar (2%) proportions who were themselves PwRI. This was higher than the 0.25% proportion in IBBS (OR = 7.80; p = 0.016). The odds ratio among the subset of participants who injected drugs was 11.17 (p = 0.003). Cost comparison analyses using simplified ingredients‐based methods found that TRIP spent no more than US $4513 per PwRI located whereas IBBS spent $11,924. Conclusions Further research is needed to confirm these results and improve TRIP further, but our findings suggest that interventions that trace the networks of people who test HIV‐positive are a cost‐effective way to locate PwRI and reduce HIV transmission and should therefore be implemented.

BACKGROUND & AIMS: Multiple environmental factors have been associated with the development of inflammatory bowel diseases (IBDs). We performed an umbrella review of meta-analyses to summarize available epidemiologic evidence and assess its credibility. METHODS: We systematically identified and appraised meta-analyses of observational studies examining environmental factors and risk of IBD (Crohn's disease [CD] or ulcerative colitis [UC]). For each meta-analysis, we considered the random effects estimate, its 95% confidence interval, the estimates of heterogeneity, and small-study effects, and we graded the evidence according to prespecified criteria. Methodologic quality was assessed with AMSTAR (ie, A Measurement Tool to Assess Systematic Reviews) 2. RESULTS: We examined 183 estimates in 53 meta-analyses of 71 environmental factors related to lifestyles and hygiene, surgeries, drug exposures, diet, microorganisms, and vaccinations. We identified 9 factors that increase risk of IBD: smoking (CD), urban living (CD and IBD), appendectomy (CD), tonsillectomy (CD), antibiotic exposure (IBD), oral contraceptive use (IBD), consumption of soft drinks (UC), vitamin D deficiency (IBD), and non-Helicobacter pylori-like enterohepatic Helicobacter species (IBD). We identified 7 factors that reduce risk of IBD: physical activity (CD), breastfeeding (IBD), bed sharing (CD), tea consumption (UC), high levels of folate (IBD), high levels of vitamin D (CD), and H pylori infection (CD, UC, and IBD). Epidemiologic evidence for all of these associations was of high to moderate strength we identified another 11 factors associated with increased risk and 16 factors associated with reduced risk with weak credibility. Methodologic quality varied considerably among meta-analyses. Several associations were based on findings from retrospective studies, so it is not possible to determine if these are effects of IBD or the results of recall bias. CONCLUSIONS: In an umbrella review of meta-analyses, we found varying levels of evidence for associations of different environmental factors with risk of IBD. High-quality prospective studies with analyses of samples from patients with recent diagnoses of IBD are needed to determine whether these factors cause or are results of IBD and their pathogenic mechanisms. 157 3 647 659.e4

Aims The comparative efficacy, safety and tolerability of budesonide-MMX and oral mesalamine in active, mild-to-moderate ulcerative colitis (UC) are unclear. We conducted a network meta-analysis to fill this evidence gap. Methods We searched PubMed, Scopus, Embase, the Cochrane Library, clinical trial registries, regulatory agencies' websites and international conference proceedings, up to July 2018, to identify randomized controlled trials of adult patients with active, mild-to-moderate UC, comparing budesonide-MMX or mesalamine against placebo, or against each other, or different dosing strategies, for induction of remission. Two reviewers independently abstracted study data and outcomes, and assessed each trial's risk-of-bias. Results We identified and synthesized evidence from 15 eligible trials including 4083 participants. Budesonide-MMX 9 mg/day and mesalamine >2.4 g/day had similar efficacy for induction of clinical and endoscopic remission (OR = 0.97 0.59–1.60), both showing superiority over placebo (OR = 2.68 1.75–4.10, and OR = 2.75 1.94–3.90, respectively). Furthermore, mesalamine >2.4 g/day was more efficacious than mesalamine 1.6–2.4 g/day (odds ratio = 1.27 1.03–1.56). Secondary analyses showed that mesalamine >2.4 g/day ranks at the top among comparator treatments regarding safety (serious adverse events surface under the cumulative ranking area [SUCRA] 79.2%) and tolerability (treatment discontinuations or withdrawals from the study due to adverse events SUCRA 96.7%). There was no evidence of inconsistency, while heterogeneity between studies and risk of publication bias were low. Conclusion Budesonide-MMX and mesalamine >2.4 g/day had similar efficacy for induction of clinical and endoscopic remission in active, mild-to-moderate UC however, mesalamine >2.4 g/day showed better tolerability. Further high-quality research is warranted. 85 10 2244 2254

Objective There is currently uncertainty regarding the ideal treatment to salvage thrombosed or failing synthetic arteriovenous grafts (AVGs) in patients with end stage renal disease. Therefore, a systematic review up to December 2018 and network meta-analysis of randomised control trials (RCTs) that compared three month failure risk of available treatments was carried out. Methods Medline, Scopus, Embase, and the Cochrane Library were the data sources. Pairwise meta-analyses were based on random effects models. Network meta-analysis was conducted within a frequentist framework with a multivariable random effects approach to model treatment effects across studies. The metric of choice was the odds ratio (OR) along with the associated 95% confidence interval (CI). Results Sixteen two arm RCTs were included involving 2011 patients who were randomised to six different treatments (plain balloon angioplasty, open surgical repair, stents, stent grafts, drug eluting balloons (DEBs), and cutting balloons). The network of RCTs had a star like geometry with plain balloon angioplasty being the common comparator. There were no significant differences between treatments with regards to risk of failure at three months with the exception of stent graft use that significantly reduced the risk of failure compared with plain balloon angioplasty (OR 0.53, 95% CI 0.34–0.84). Based on surface under the cumulative ranking curve (SUCRA) values, the best interventions to salvage thrombosed or failing AVGs were DEB and stent grafts. Conclusions Stent graft seems to perform better than plain balloon angioplasty in terms of saving thrombosed or failing AVGs. However, this network meta-analysis was limited by the lack of closed loops and thus unable to assess consistency between direct and indirect evidence. The efficacy of DEBs as a promising treatment deserves further investigation and new RCTs are required.

Individuals with recent/acute HIV-infection have an increased likelihood of disease transmission. To evaluate effectiveness of identifying recent infections, we compared networks of recently and long-term HIV-infected individuals. The Transmission Reduction Intervention Project included two separate arms of recruitment, networks of recently HIV-infected individuals and networks of long-term HIV-infected individuals. Networks of each were recruited and tested for HIV and syphilis infection. The per-seed yield ratios of recruitment were compared between arms. Overall, 84 (41.6%) of 202 participants were identified as HIV-positive. HIV prevalence was higher (p

Our aim is to determine the most appropriate laboratory tests, besides anti-factor Xa (anti-FXa) chromogenic assays, to estimate the degree of anticoagulation with apixaban and compare it with that of rivaroxaban in real-world patients. Twenty patients with nonvalvular atrial fibrillation treated with apixaban 5 mg twice daily and 20 patients on rivaroxaban 20 mg once daily were studied. Conventional coagulation tests, thrombin generation assay (TGA), and thromboelastometry (nonactivated TEM [NATEM] assay) were performed in the 40 patients and 20 controls. The anti-FXa chromogenic assays were used to measure apixaban and rivaroxaban plasma levels. The NATEM measurements showed no significant difference between the 2 groups of patients. Concerning TGA, endogenous thrombin potential (ETP) was significantly decreased in patients on rivaroxaban as compared to those treated with apixaban ( P < .003). A statistically significant, strong inverse correlation between apixaban plasma concentrations and ETP ( P < .001) was observed. Apixaban significantly reduces ETP compared to controls, but to a lesser extent than rivaroxaban. Thrombin generation assay might provide additional information on apixaban exposure, which is required in order to individualize treatment especially for patients with a high bleeding risk. Our findings have to be further investigated in studies with larger sample sizes, in the entire range of apixaban exposure, with other direct oral anticoagulants, and in relation to clinical outcomes.

Biological agents have proven clinical efficacy in the treatment of ulcerative colitis (UC). Their adverse effects have also been studied in a substantial number of primary studies and meta-analyses. Given the large volume of information that has been published, the aim of this umbrella review was to effectively summarize the accumulated evidence from randomized controlled trials (RCTs) on the safety of biological therapies for UC into one accessible and usable document. Pubmed and Scopus databases were systematically searched through November 2017 to identify meta-analyses of RCTs that have investigated potential harms of biological agents (adalimumab, golimumab, infliximab, and vedolizumab) in patients with UC. Ten eligible meta-analyses were included. The body of available evidence supports the safety of biologic therapies in UC. Further research is needed to clarify the risk of any infection with biologics, for elderly and high-risk groups, for longer-term effects, and for head-to-head comparisons between the different biologics.

Background The Transmission Reduction Intervention Project (TRIP) is a network-based intervention that aims at decreasing human immunodeficiency virus type 1 (HIV-1) spread. We herein explore associations between transmission links as estimated by phylogenetic analyses, and social network-based ties among persons who inject drugs (PWID) recruited in TRIP. Methods Phylogenetic trees were inferred from HIV-1 sequences of TRIP participants. Highly supported phylogenetic clusters (transmission clusters) were those fulfilling 3 different phylogenetic confidence criteria. Social network-based ties (injecting or sexual partners, same venue engagement) were determined based on personal interviews, recruitment links, and field observation. Results TRIP recruited 356 individuals (90.2% PWID) including HIV-negative controls; recently HIV-infected seeds; long-term HIV-infected seeds; and their social network members. Of the 150 HIV-infected participants, 118 (78.7%) were phylogenetically analyzed. Phylogenetic analyses suggested the existence of 13 transmission clusters with 32 sequences. Seven of these clusters included 14 individuals (14/32 [43.8%]) who also had social ties with at least 1 member of their cluster. This proportion was significantly higher than what was expected by chance. Conclusions Molecular methods can identify HIV-infected people socially linked with another person in about half of the phylogenetic clusters. This could help public health efforts to locate individuals in networks with high transmission rates.

Background: Greece experienced an unprecedented increase in HIV cases among drug injectors in 2011 after economic crisis. Network-level factors are increasingly understood to drive HIV transmission in emerging epidemics. Methods: We examined the relationship between networks, risk behaviors, and HIV serostatus among 1404 people who inject drugs in Athens, Greece. We generated networks using the chain-referral structure within a large HIV screening program. Network proportions, the proportion of a respondent's network with a given characteristic, were calculated. Multiple logistic regression models were used to assess the relationship between network proportions and individual HIV seroprevalence, injection frequency and unprotected sex. Results: Of note, 1030 networks were generated. Respondent HIV seroprevalence was associated with greater proportions of network members who were HIV infected (ie, those with ≤50% of network members HIV positive vs. those with no network members HIV positive) (AOR: 3.11; 95% CI: 2.10 to 4.62), divided drugs (AOR: 1.60; 95% CI: 1.10 to 2.35), or injected frequently (AOR: 1.50; 95% CI: 1.02 to 2.21). Homelessness was the only sociodemographic characteristic associated with a risk outcome measure\-highfrequency injecting (AOR: 1.41; 95% CI: 1.03 to 1.93). These associations were weaker for more distal second- and third-degree networks and not present when examined within random networks. Conclusions: Networks are an independently important contributor to the HIV outbreak in Athens, Greece. Network associations were strongest for the immediate network, with residual associations for distal networks. Homelessness was associated with high-frequency injecting. Prevention programs should consider including network-level interventions to prevent future emerging epidemics. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. 69 4 499 508

Attacks on peoples’ dignity help to produce and maintain stigmatization and interpersonal hostility. As part of an effort to develop innovative measures of possible pathways between structural interventions or socially-disruptive Big Events and HIV outbreaks, we developed items to measure dignity denial. These measures were administered to 300 people who inject drugs (PWID), 260 high-risk heterosexuals who do not inject drugs, and 191 men who have sex with men who do not inject drugs (MSM). All of the PWID and many of the high risk heterosexuals and MSM were referred to our study in 2012–2015 by a large New York city study that used respondent-driven sampling; the others were recruited by chain-referral. Members of all three key populations experienced attacks on their dignity fairly often and also reported frequently seeing others’ dignity being attacked. Relatives are major sources of dignity attacks. MSM were significantly more likely to report having their dignity attacked by police officers than were the other groups. 40 % or more of each key population reported that dignity attacks are followed “sometimes” or more often both by using more drugs and also by using more alcohol. Dignity attacks and their health effects require more research and creative interventions, some of which might take untraditional forms like social movements. © 2016, Springer Science+Business Media New York. 21 9 2561 2578

HIV remains an important public health issue worldwide. However, new prevention approaches have recently been developed and are very promising. Antiretroviral treatment as prevention, or as a prophylaxis after exposure to HIV, has been shown to reduce the likelihood of HIV acquisition. Over the last years, animal studies and randomized clinical trials in humans showed that antiretrovirals can also be efficacious and safe if used once daily, or intermittently, as prophylaxis before an individual is exposed to HIV (Pre-exposure Prophylaxis-PrEP). Fears about development of resistant strains have not been justified insofar given the accumulated evidence from research studies. Demonstration projects are ongoing and first results indicate that interests in the uptake of PrEP are high and adherence is satisfactory. Models suggest that PrEP could be a cost-effective or cost-saving approach under certain provisions including delivery to people at high risk of HIV infection, using less expensive medications, delivery in high HIV prevalence settings, short-term use for periods of higher risk, and evaluation in a longer-term period. The current review summarizes evidence on efficacy, safety and effectiveness of PrEP, and discusses future challenges and perspectives. © 2017 Bentham Science Publishers. 23 18 2579 2591

Summary Definitions for a 4-stage continuum of HIV care were standardized and applied to HIV surveillance and national cohort data in 11 European Union countries. These countries are nearing the UNAIDS 90-90-90 target, although reducing the proportion undiagnosed remains challenging., Background. The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set a “90-90-90” target to curb the human immunodeficiency virus (HIV) epidemic by 2020, but methods used to assess whether countries have reached this target are not standardized, hindering comparisons. Methods. Through a collaboration formed by the European Centre for Disease Prevention and Control (ECDC) with European HIV cohorts and surveillance agencies, we constructed a standardized, 4-stage continuum of HIV care for 11 European Union countries for 2013. Stages were defined as (1) number of people living with HIV in the country by end of 2013; (2) proportion of stage 1 ever diagnosed; (3) proportion of stage 2 that 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. Results. In 2013, 674500 people in the 11 countries were estimated to be living with HIV, ranging from 5500 to 153400 in each country. Overall HIV prevalence was 0.22% (range, 0.09%–0.36%). Overall proportions of each previous stage were 84% diagnosed, 84% on ART, and 85% virally suppressed (60% of people living with HIV). Two countries achieved ≥90% for all stages, and more than half had reached ≥90% for at least 1 stage. Conclusions. European Union countries are nearing the 90-90-90 target. Reducing the proportion undiagnosed remains the greatest barrier to achieving this target, suggesting that further efforts are needed to improve HIV testing rates. Standardizing methods to derive comparable continuums of care remains a challenge.

Early treatment, soon after infection, reduces HIV transmissions and benefits patients. The Transmission Reduction Intervention Project (TRIP) evaluated a network intervention to detect individuals recently infected (in the past 6 months). TRIP was conducted in Greece (2013–2015) and focused on drug injector networks. Based on HIV status, testing history, and the results of an assay to detect recent infections, TRIP classified drug injector “Seeds” into groups: Recent Seeds (RS), and Control Seeds with Long-term HIV infection (LCS). The network members of RS and LCS were traced for two steps. The analysis included 23 RS, 171 network members of the RS, 19 LCS, and 65 network members of the LCS. The per-seed number of recents detected in the network of RS was 5 times the number in the network of LCS (Ratio RS vs. LCS: 5.23; 95% Confidence Interval (CI): 1.54–27.61). The proportion of recents among HIV positives in the network of RS (27%) was approximately 3 times (Ratio RS vs. LCS: 3.30; 95% CI: 1.04–10.43) that in the network of LCS (8%). Strategic network tracing that starts with recently infected persons could support public health efforts to find and treat people early in their HIV infection.

HIV remains one of the most important public health concerns in the European Union and European Economic Area (EU/EEA). Accurate data are therefore crucial to appropriately direct and evaluate public health response. The European Centre for Disease Prevention and Control (ECDC) and the World Health Organization Regional Office for Europe (WHO/Europe) have jointly coordinated enhanced HIV/AIDS surveillance in the European Region since 2008. The general objectives of the surveillance system in EU/EEA countries include monitoring of trends over time and across countries. Specific HIV-related objectives include the monitoring of testing patterns, late HIV diagnoses, defined by low CD4+ counts (

SUMMARYThis analysis assessed the utility of the limiting antigen avidity assay (LAg). Samples of people who inject drugs (PWID) in Greece with documented duration of HIV-1 infection were tested by LAg. A LAg-normalized optical density (ODn) ⩽1·5 corresponds to a recency window period of 130 days. The proportion true recent (PTR) and proportion false recent (PFR) were estimated in 28 seroconverters and in 366 samples collected >6 months after HIV diagnosis, respectively. The association between LAg ODn and HIV RNA level was evaluated in 232 persons. The PTR was 85·7%. The PFR was 20·8% but fell to 5·9% in samples from treatment-naive individuals with long-standing infection (>1 year), and to 0 in samples with the circulating recombinant form CRF35 AD. A LAg-based algorithm with a PFR of 3·3% estimated a similar incidence trend to that calculated by analyses based on HIV-1 seroconversions. In recently infected persons indicated by LAg, the median log10HIV RNA level was high (5·30, interquartile range 4·56–5·90). LAg can help identify highly infectious HIV(+) individuals as it accurately identifies recent infections and is correlated with the HIV RNA level. It can also produce reliable estimates of HIV-1 incidence.

Background:Rotational thromboelastometry (ROTEM) is an attractive method for rapid evaluation of hemostasis in neonates. Currently, no reference values exist for ROTEM assays in full-term and pre-term neonates. Our aim was to establish reference ranges for standard extrinsically activated ROTEM assay (EXTEM) in arterial blood samples of healthy full-term and pre-term neonates.Methods:In the present study, EXTEM assay was performed in 198 full-term (≥37 weeks’ gestation) and 84 pre-term infants (Results:Median values and reference ranges (2.5th and 97.5th percentiles) for the following main parameters of EXTEM assay were determined in full-term infants: clotting time (seconds), 41 (range, 25.9–78); clot formation time (seconds), 70 (range, 40–165.2); maximum clot firmness (mm), 66 (range, 41–84.1); lysis index at 60 min (LI60, %), 97 (range, 85–100). The only parameter with a statistically significant difference between full-term and pre-term neonates was LI60 (p=0.006). Furthermore, it was inversely correlated with gestational age (p=0.002) and birth weight (p=0.016) in pre-term neonates.Conclusions:In conclusion, an enhanced fibrinolytic activity in pre-term neonates was noted. For most EXTEM assay parameters, reference ranges obtained from arterial newborn blood samples were comparable with the respective values from studies using cord blood. Modified reagents, small size samples, timing of sampling, and different kind of samples might account for any discrepancies among similar studies. Reference values hereby provided can be used in future studies.

OBJECTIVE: Men who have sex with men (MSM) are disproportionately affected by HIV in Greece. However, research on HIV incidence in this group is lacking. This study aimed at estimating HIV incidence among MSM in Athens, Greece. METHODS: The analysis included routinely collected data between January 2013-June 2015 from adult MSM who visited a community-based facility (Ath Checkpoint) at least twice and were non-reactive to the rapid INSTITM HIV-1/HIV-2 assay at baseline. HIV conversion rates were calculated by dividing the number of clients who became reactive by the person-years of observation. All statistical analyses including Poisson regression models were conducted in STATA 14. RESULTS: A total of 1,243 MSM contributed 1,102.50 person-years (py). The overall (per 100 py) conversion rate was 3.99 (95% CI: 2.97-5.36). In multivariable analyses, age less than 30 years was associated with an increased risk of HIV conversion (rate ratio: 2.01 95% CI: 1.08-3.76). CONCLUSIONS: This analysis shows high rates of HIV conversion among MSM who repeatedly visit a community-based testing site. Ath Checkpoint could contribute to HIV surveillance and identify a high-risk group that could benefit from essential health interventions. 27 1 54 57

Background & Aims Safety issues are a major concern for patients considering treatments for inflammatory bowel disease (IBD). We performed a systematic review and meta-analysis to determine whether biologic agents affect the risk of infection or malignancy in adults with IBD. Methods We searched PubMed, Embase, Scopus, Cochrane IBD Group Specialized Trials Register, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov through March 2016 for randomized placebo-controlled or head-to-head trials of biologic agents approved for treatment of adults with IBD (ie, adalimumab, certolizumab, golimumab, infliximab, natalizumab, or vedolizumab). Two reviewers independently extracted study data and outcomes (serious infections, opportunistic infections, tuberculosis, any infection, and malignancies) and rated each trial's risk of bias. We used conventional meta-analysis to synthesize direct evidence and a network meta-analysis for adjusted indirect treatment comparisons. Results We identified 49 randomized placebo-controlled studies comprising 14,590 participants. Synthesis of the evidence indicated that patients treated with biologics had a moderate increase in risk of any infection (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.10–1.29) and a significant increase in risk of opportunistic infections (OR, 1.90; 95% CI, 1.21–3.01). Risk of serious infections was not increased in patients treated with biologics (OR, 0.89; 95% CI, 0.71–1.12). On the contrary, biologics appeared to significantly reduce risk of serious infections in studies with low risk of bias (OR, 0.56; 95% CI, 0.35–0.90). We did not find an increased risk of malignancy with use of biologic agents (OR, 0.90; 95% CI, 0.54–1.50), but data were insufficient in terms of exposure and follow-up times. None of the indirect comparisons, either among the individual agents or between the anti–tumor necrosis factor and anti-integrin classes, reached significance for any of the outcomes analyzed. Conclusions On the basis of a systematic review and meta-analysis, biologic agents increase the risk of opportunistic infections in patients with IBD, but not the risk of serious infections. It is necessary to continue to monitor the comparative and long-term safety profiles of these drugs. © 2016 AGA Institute 14 10 1385 1397.e10

Mild heat-related health effects and their potential association with meteorological and personal parameters in relation to subjective and objective thermal sensation were investigated. Micrometeorological measurements and questionnaire surveys were conducted in an urban Mediterranean environment during a warm, cool, and a transitional season. The participants were asked to indicate their thermal sensation based on a seven-point scale and report whether they were experiencing any of the following symptoms: headache, dizziness, breathing difficulties, and exhaustion. Two thermal indices, Actual Sensation Vote (ASV) and Universal Thermal Climate Index (UTCI), were estimated in order to obtain an objective measure of individuals’ thermal sensation. Binary logistic regression was applied to identify risk parameters while cluster analysis was used to determine thresholds of air temperature, ASV and UTCI related to health effects. Exhaustion was the most frequent symptom reported by the interviewees. Females and smokers were more likely to report heat-related symptoms than males and nonsmokers. Based on cluster analysis, 35 °C could be a cutoff point for the manifestation of heat-related symptoms during summer. The threshold for ASV was 0.85 corresponding to “warm” thermal sensation and for UTCI was about 30.85 °C corresponding to “moderate heat stress” according to the Mediterranean assessment scale. © 2015, ISB. 60 6 917 929

OBJECTIVES The aim of our study was to validate the Genscreen HIV ½ version 2 (BIO-RAD) for detecting HIV antibodies in oral fluid specimens (OF). BACKGROUND The advantage of assays to detect HIV infection in OF lies in the on-site easy access and noninvasive sample collection. METHODS Paired serum and OF were collected from 496 subjects (263 HIV-positive and 233 HIV-negative) using the Oracol test kit (Oracle Diagnostics, Inc). The quality of OF was verified by measuring total IgGs using the Human IgG ELISA Quantitation Kit (Bethyl Lab.inc). All reactive OF samples were retested by Western blot HIV1/2 BLOT 2.2 (MP Biomedical, Singapore, China). RESULTS Of 263 OF samples from participants with blood-based HIV-positive results, 259 were positive by Genscreen HIV ½ version 2 (98.48% sensitivity, 95% CI; 96.2-99.6). The 233 individuals who had a non-reactive HIV blood test were found negative on testing their OF by Genscreen HIV ½ version 2 (100% specificity, 95% CI; 98.4-100). NPV and PPV of the assay were 98.31% (95% CI; 95.74-99.34) and 100%, (95% CI; 98.53-100.00), respectively. CONCLUSION Genscreen HIV ½ version 2 (Bio-Rad) is a prospective method for HIV surveillance studies in hard-to-reach populations with high risk behavior using non-invasive OF collection (Tab. 1, Fig. 1, Ref. 16).

Infection with Human Immunodeficiency Virus (HIV) remains a global public health problem. Although the epidemic has not been completely controlled, there was considerable progress in HIV prevention and treatment during the last 30 years. The modern prevention approaches are multi-component including also the administration of combinations of potent antiretroviral agents as a prophylaxis after occupational or non-occupational exposures to HIV. The aim of the current review is to present the chemical and pharmacological characteristics of antiretroviral drugs used in HIV prophylaxis and to describe briefly the medical management of exposures to potentially infectious body fluids. 19 35 5924 5939

Current data about the role of adamantanes and neuraminidase inhibitors (NIs) in the chemoprophylaxis against influenza viruses were reviewed. We found significant evidence favouring the role of NIs in the chemoprophylaxis of influenza. Awareness and prudent use are necessary, due to recent evidence of gradually increasing resistance of several influenza strains to these agents. On the other hand, the role of adamantanes appears to have decreased over the last decade. Both pre-pandemic and the novel pandemic A/H1N1 2009 strains exhibited either increasing rates of resistance or no susceptibility to adamantanes. Adamantanes currently only have a theoretical role in influenza chemoprophylaxis given the likelihood of the occurrence of an epidemic due to a susceptible strain. In conclusion, changes in antiviral susceptibility will affect future guidance in prophylaxis against influenza. Further investigation of novel medications with new mechanisms of action is important in this regard. Meanwhile, implementing strategies to conserve our current antivirals is necessary. © 2012 Bentham Science Publishers. 19 35 5947 5956

Concurrent infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) in patients positive for human immunodeficiency virus (HIV) is relatively common. The treatment of co-infected individuals is rather complex because the anti-viral therapy may be associated with drug-resistance, hepatotoxicity and lack of response. Herein, we present a summary of the available compounds and the recent recommendations concerning the therapeutic management of HIV/HBV and HIV/HCV co-infections. © 2012 Bentham Science Publishers. 12 9 890 904

Several studies have reported the prognostic strength of HIV-1 DNA with variable results however. The aims of the current study were to estimate more accurately the ability of HIV-1 DNA to predict progression of HIV-1 disease toward acquired immunodeficiency syndrome (AIDS) or death, and to compare the prognostic information obtained by HIV-1 DNA with that derived from plasma HIV-1 RNA. Eligible articles were identified through a comprehensive search of Medline, ISI Web of Science, Scopus, and Google Scholar. The analysis included univariate and bivariate random-effects models. The univariate meta-analysis of six studies involving 1074 participants showed that HIV-1 DNA was a strong predictive marker of AIDS [relative risk (RR): 3.01, 95% confidence interval (CI): 1.88-4.82] and of all-cause mortality (RR: 3.49, 95% CI: 2.06-5.89). The bivariate model using the crude estimates of primary studies indicated that HIV-1 DNA was a significantly better predictor than HIV-1 RNA of either AIDS alone (ratio of RRs=1.47, 95% CI: 1.05-2.07) or of combined (AIDS or death) progression outcomes (ratio of RRs=1.51, 95% CI: 1.11-2.05). HIV-1 DNA is a strong predictor of HIV-1 disease progression. Moreover, there is some evidence that HIV-1 DNA might have better predictive value than plasma HIV-1 RNA. © 2012, Mary Ann Liebert, Inc. 28 4 366 373

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Background: Platelet-rich plasma (PRP) alone or combined with other regenerative materials was previously studied in human periodontal endosseous defects. There are no sufficient data evaluating to what extent the addition of demineralized freeze-dried bone allograft (DFDBA) to PRP may enhance the effectiveness of PRP. The aim of this randomized, double-masked, controlled clinical trial was to compare the effectiveness of autologous PRP alone or a PRP + combination in periodontal endosseous defects. Methods: Twenty-four proximal endosseous defects in 24 patients with severe chronic periodontitis were randomly treated with PRP alone or in combination with DFDBA. The final evaluation at 6 months was based on clinical and radiographic parameters. Subtraction radiography was used. The primary outcome variable was clinical attachment level (CAL). Results: The two treatment groups were initially comparable (mean CAL: 8.67 ± 2.19 mm for PRP + DFDBA and 8.25 ± 1.96 mm for PRP). Both treatments achieved statistically significant and similar CAL gain (3.08 ± 1.17 mm for PRP + DFDBA and 3.08 ± 0.95mmfor PRP), probing depth, defect depth, and area surface reduction. The percentage of defect fill did not significantly differ between the two treatments. There was a non-significant trend to greater defect fill (45.42% versus 41.29%), defect depth (54.05% versus 49.52%), and area surface (58.43% versus 52.16%) reduction with the graft. In both groups, 66.66% of the defects gained ≥3 mm of CAL. Conclusion: Within its limits, this study demonstrated that both PRP and PRP combined with DFDBA resulted in significant clinical and radiographic improvement inhuman periodontal endosseous defects at 6 months, and the addition of DFDBA to PRP did not significantly enhance the treatment outcome. J Periodontol 2009;80:1911-1919. 80 12 1911 1919

Background Several reports have shown that homocysteine promotes thrombosis by disturbing the procoagulant-anticoagulant balance, whereas alterations in coagulation and fibrinolysis have been suggested as important pathogenetic and prognostic determinants of mortality in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The objective of the study was to evaluate the effect of plasma homocysteine levels on the outcomes of patients with ALI/ARDS. Methods Sixty-nine consecutive ventilated patients with ALI/ARDS were studied. Blood samples were drawn within 3 days of clinical recognition of ARDS. Measurement of plasma homocysteine, vitamin B12, folate, creatinine, protein C and plasminogen-activator inhibitor-1 antigen levels, and genotyping of the methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms were carried out. The primary outcomes were 28- and 90-day mortality, whereas secondary outcomes included nonpulmonary organ failure-free days, liberation from mechanical ventilation up to day 28, and ventilator-free days during the 28 days after enrollment. Results In the multivariable analysis, plasma homocysteine concentration adjusted for age, Acute Physiology and Chronic Health Evaluation II score, methylenetetrahydrofolate reductase C677T and A1298C polymorphisms, and levels of plasminogen-activator inhibitor-1 antigen, protein C, creatinine, vitamin B12, and folate was not found to affect significantly mortality at 28 and 90 days ( P = 0.39 and P = 0.83, respectively), days without organ failure besides lungs ( P = 0.38), the probability of being free from mechanical ventilation at day 28 ( P = 0.63), and days without ventilation assistance ( P = 0.73). Conclusion Our data suggest that increased plasma homocysteine levels, either alone or in synergy with other thrombophilic risk factors, do not seem to adversely affect the prognosis in patients with ALI/ARDS.

Background: The platelet-collagen receptor, glycoprotein (GP) la/lla plays a crucial role in the adhesion of platelets to fibrillar collagen, an event contributing to the pathogenesis of thrombosis. The C807T polymorphism of the GPla gene is considered a genetic marker of the platelet GPla/lla density. The importance of the GPla gene C807T polymorphism as a genetic risk factor for coronary artery disease (CAD) remains controversial. To assess this association, we performed a meta-analysis of published data. Methods: A comprehensive meta-analysis of 19 studies, with a total sample of 13 835 subjects using random effects models. Results: The C versus T allele contrast gave an OR of 0.998 with 95% Cl 0.937-1.064. Similarly, comparing the C homozygotes with the T homozygotes, the CC genotype versus the others and the TT genotype versus the rest, no evidence of any gene-disease association was obtained. Furthermore, the meta-regression analysis did not disclose any variable that could modify the role of this polymorphism in the development of CAD. Conclusion: Our findings support the view that C807T polymorphism of the GPla gene is not a significant risk factor for CAD, either alone or in combination with other major cardiovascular risk factors. © 2006 Elsevier Ireland Ltd. All rights reserved. 118 2 189 196

We conducted a meta-analysis concerning the association of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene polymorphisms with the risk of developing multiple sclerosis (MS). We identified 18 eligible studies summarizing information about 3375 MS cases and 2930 healthy controls. Two polymorphisms were of interest: the exon 1+49 A/G polymorphism (in 18 studies) and the promoter —318 C/T polymorphism (in 10 studies). Using random-effects methods we found no evidence for association of the various contrasts of genotypes (or allele frequencies) with the disease. There was significant between-studies heterogeneity that could not be explained by the ethnicity of the populations studied or by other summary measures (gender, disease course, latitude). The major finding of the meta-analysis, apart from the lack of an overall association, consists of detecting a significant time trend of the OR for the contrast of GA versus GG + AA genotypes of the exon 1 +49 A/G polymorphism. In particular, using cumulative meta-analysis we found that the large number of conflicting results on the subject was triggered by the early appearance of a highly significant published result (a study that indicated a significant association of the genotype with the disease). Multiple Sclerosis 2007; 13: 156–168. http://msj.sagepub.com

Objective: This systematic review and meta-analysis aimed to reassess the effectiveness of condoms in reducing heterosexual transmission of HIV. Methods: Medline, Scopus, and the ISI Web of Science databases were searched up to June 2014. Eligible studies were synthesized using random-effects models. Results: Twenty-five studies with 10,676 HIV serodiscordant heterosexual couples were analyzed. The risk of HIV transmission was considerably lower among couples that were always using condoms compared to never-users (RR: 0.29, 95% CI: 0.20–0.43) or inconsistent users (RR: 0.23, 0.13–0.40). The protective effect was slightly higher when the male rather than the female partner was infected (RR: 0.31, 0.20–0.48; vs. RR: 0.44, 0.24–0.80), and very high in Asian settings (RR: 0.06, 0.01–0.46). Conclusions: Though imperfect, condoms reduce HIV transmission by more than 70% when used consistently by HIV serodiscordant heterosexual couples. Social, cultural and biological differences need to be studied further to inform projection modelers and policy makers. © 2015 Informa UK Limited, trading as Taylor & Francis Group. 16 4 489 499

Big Events are processes like macroeconomic transitions that have lowered social well-being in various settings in the past. Greece has been hit by the global crisis and experienced an HIV outbreak among people who inject drugs. Since the crisis began (2008), Greece has seen population displacement, inter-communal violence, cuts in governmental expenditures, and social movements. These may have affected normative regulation, networks, and behaviors. However, most pathways to risk remain unknown or unmeasured. We use what is known and unknown about the Greek HIV outbreak to suggest modifications in Big Events models and the need for additional research. © 2015 Informa Healthcare USA, Inc. 50 7 828 838

Background There is sparse evidence that demonstrates the association between macro-environmental processes and drug-related HIV epidemics. The present study explores the relationship between economic, socio-economic, policy and structural indicators, and increases in reported HIV infections among people who inject drugs (PWID) in the European Economic Area (EEA). Methods We used panel data (2003–2012) for 30 EEA countries. Statistical analyses included logistic regression models. The dependent variable was taking value 1 if there was an outbreak (significant increase in the national rate of HIV diagnoses in PWID) and 0 otherwise. Explanatory variables included the growth rate of Gross Domestic Product (GDP), the share of the population that is at risk for poverty, the unemployment rate, the Eurostat S80/S20 ratio, the Gini coefficient, the per capita government expenditure on health and social protection, and variables on drug control policy and drug-using population sizes. Lags of one to three years were investigated. Findings In multivariable analyses, using two-year lagged values, we found that a 1% increase of GDP was associated with approximately 30% reduction in the odds of an HIV outbreak. In GDP-adjusted analyses with three-year lagged values, the effect of the national income inequality on the likelihood of an HIV outbreak was significant [S80/S20 Odds Ratio (OR) = 3.89; 95% Confidence Interval (CI): 1.15 to 13.13]. Generally, the multivariable analyses produced similar results across three time lags tested. Interpretation Given the limitations of ecological research, we found that declining economic growth and increasing national income inequality were associated with an elevated probability of a large increase in the number of HIV diagnoses among PWID in EEA countries during the last decade. HIV prevention may be more effective if developed within national and European-level policy contexts that promote income equality, especially among vulnerable groups.

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Human immunodeficiency virus (HIV) transmission remains significant in Europe. Rates of acquired immunodeficiency syndrome (AIDS) have declined, but not in all countries. New HIV diagnoses have increased among native and foreign-born men who have sex with men. Median CD4 + T-cell count at diagnosis has increased, but not in all groups, and late diagnosis remains common. HIV infection and AIDS can be eliminated in Europe with resolute prevention measures, early diagnosis and access to effective treatment. © 2015, European Centre for Disease Prevention and Control (ECDC). All rights reserved. 20 47

Systematic reviews and meta-analyses are a valuable tool to answer research questions, generate recommendations and influence health policy in an evidence-based manner [1]. However, flaws in the design, conduct, analysis, and reporting of the studies that are included in a systematic review may distort estimates of the true intervention effect in terms of magnitude and/or direction (i.e. introduce bias), mislead the analysis and conclusions of the systematic review, and adversely influence clinical practice and health policy decisions [2]. Based on a combination of empirical and theoretical considerations, the Cochrane Statistical Methods Group and the Cochrane Bias Methods Group proposed a set of criteria for assessing the risk of bias in RCTs, which address the following key domains: (1) sequence generation, (2) allocation concealment, (3) blinding of participants, personnel, and outcome assessors, (4) incomplete outcome data, (5) selective outcome reporting, and (6) other sources of bias (e.g., extreme baseline imbalance in prognostic factors, inappropriate influence of the funding source, etc) [3]. The Cochrane Collaboration’s domain-based approach has proven to be very useful; it has been widely adopted, and used in hundreds of systematic reviews and metaanalyses. However, the Cochrane Adverse Effects Methods Group proposed few additional criteria for assessing the risk of bias in RCTs selected for inclusion in systematic reviews addressing adverse effects (AEs) [4] including methods for monitoring and detecting adverse effects [4] (p. 8). The particular item for judging risk of bias was: Were the methods used for monitoring adverse effects reported? Use of prospective or routine monitoring; spontaneous reporting; patient checklist, questionnaire or diary; systematic survey of patients? [4] (p. 9). As a result, this criterion is increasingly used in the literature, with researchers considering studies providing spontaneous reporting of AEs (passive surveillance) as of higher risk of bias than studies actively monitoring for drug AEs [5–8]. We argue that this proposed risk-of-bias criterion (based on the approach used for monitoring AEs) is methodologically incorrect, and could lead reviewers to assess potentially fair (unbiased) clinical trials as having a high risk of bias. It is true that the methods used for monitoring AEs have a major influence on the detected event rates in a trial, with passive surveillance of harms leading to fewer recorded AEs than active surveillance [9, 10]. However, the relative effect measure in a trial (e.g. the ratio of the observed event rates in the comparison groups) will not change if these event rates are underestimated, to the same degree, in each comparison group. Therefore less intensive monitoring methods, although they may lead to lower observed rates of AEs, do not constitute a source of bias, but rather a cause of imprecision. A potential source of bias must be able to produce results that depart systematically & Stefanos Bonovas sbonovas@gmail.com

Background: Our aim was to identify laboratory assays in order to assess the anticoagulant effects of dabigatran etexilate (DE). Methods: Twenty patients with nonvalvular atrial fibrillation treated on DE (110 mg per os twice daily) and 20 on acenocoumarol were studied. Conventional coagulation tests, endogenous thrombin potential (ETP), thromboelastometry (ROTEM), epinephrine-induced light transmission aggregometry (LTA), and Hemoclot Thrombin Inhibitors (HTI) were performed in all patients. Results: In ROTEM analysis, the lysis index at 60 minutes was significantly lower in patients receiving DE ( P = .011). In LTA, patients on DE showed decreased aggregation compared to those on acenocoumarol, marginally insignificant ( P = .068). Regarding ETP, acenocoumarol affected thrombin generation more than dabigatran (area under the curve [AUC], P < .001), while statistically significant associations were detected between dabigatran levels, as determined by the HTI assay, and almost all parameters of ETP assay (AUC, P < .001). Conclusion: The role of ETP in estimating anticoagulant activity of dabigatran possibly requires further research.

Over the eight months following Hurricane Sandy, of October 2012, we interviewed 300 people who inject drugs in New York City. During the week after the storm, 28% rescued others or volunteered with aid groups; 60% experienced withdrawal; 27% shared drug injection or preparation equipment, or injected with people they normally would not inject with; 70% of those on opioid maintenance therapy could not obtain sufficient doses; and 43% of HIV-positive participants missed HIV medication doses. Although relatively brief, a hurricane can be viewed as a Big Event that can alter drug environments and behaviors, and may have lasting impact. The study's limitations are noted and future needed research is suggested. © 2015 Informa Healthcare USA, Inc. 50 7 878 884

We conducted a meta-analysis of studies comparing the presence of Chlamydia pneumoniae (Cpn) between multiple sclerosis (MS) patients and other neurological diseases patients or healthy controls. We identified 26 studies with 1332 MS patients and 1464 controls. Using random-effects methods, MS patients were found more likely to have detectable levels of Cpn DNA (OR = 3.216; 95% Cl: 1.204, 8.585) in their cerebrospinal fluid, and intrathecally synthesized immunoglobulins (OR = 3.842; 95% Cl: 1.317, 11.212), compared to other patients with neurological diseases. There is no evidence for increased levels of serum immunoglobulins (OR = 1.068; 95% Cl: 0.745, 1.530), even though this result is confounded by the presence of studies using normal subjects as controls. Similarly, there is no evidence for association of immunoglobulins against Cpn in the cerebrospinal fluid (OR = 3.815; 95% Cl: 0.715, 20.369). Up to 59.7% of the between-studies variability could be explained by the inappropriate matching of cases and controls for gender. In random-effects meta-regressions, adjusting for the confounding effect of gender differences results in stronger and statistically significant associations of MS with detectable levels of Cpn DNA, intrathecally synthesized immunoglobulins and immunoglobulins in the cerebrospinal fluid. Even though the presence of Cpn is clearly more likely in MS patients, these findings are insufficient to establish an etiologic relation. © 2006 Edward Arnold (Publishers) Ltd. 12 4 397 411

Background: Over the last decade, Greece has experienced a massive influx of migrants from countries in South Eastern/Central Europe, the Middle East, Asia and Africa. This study aimed to estimate the percentage and the specific characteristics of HIV-positive migrants reported in Greece, and to describe the secular trend of migrants' proportion among HIV-infected individuals. Methods: Secondary analysis of data reported to the Hellenic Centre for Infectious Diseases Control (HCIDC) during the years 1989-2003. Results: From 1989 to 2003, 6292 HIV-positive cases were reported to HCIDC. Data show that 749 people (439 males, 303 females) originated from countries other than Greece. Most HIV-positive migrants come from Sub-Saharan Africa (32.44%) and nearly 20% from Central and Eastern Europe. In the Greek population, men who have sex with men (MSM) constitute 50.47% of cases, while 16.15% are heterosexuals. The epidemic profile follows a different pattern among migrants (P < 0.05). Heterosexual transmission accounts for 41.52% of HIV-positive reported migrants, while 19.09% are MSM. An 11% increase for each subsequent year in the rate of HIV-positive migrants reported in Greece has been estimated using a Poisson regression model fitted to the data (IR 1.11; 95% confidence interval 1.08-1.13). Conclusions: The results suggest an increasing trend of HIV-seropositive migrants in Greece during recent years. Group-based interventions, better access to health care and a comprehensive public approach should be applied to migrants. © The Author 2005. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved. 15 3 296 299

Current ideas about HIV prevention include a mixture of primarily biomedical interventions, socio-mechanical interventions such as sterile syringe and condom distribution, and behavioral interventions. This article presents a framework for socially-integrated transdisciplinary HIV prevention that may improve current prevention efforts. It first describes one socially-integrated transdisciplinary intervention project, the Transmission Reduction Intervention Project. We focus on how social aspects of the intervention integrate its component parts across disciplines and processes at different levels of analysis. We then present socially-integrated perspectives about how to improve combination antiretroviral treatment (cART) processes at the population level in order to solve the problems of the treatment cascade and make “treatment as prevention” more effective. Finally, we discuss some remaining problems and issues in such a social transdisciplinary intervention in the hope that other researchers and public health agents will develop additional socially-integrated interventions for HIV and other diseases. © 2013, Springer Science+Business Media New York. 18 10 1821 1834

Background: The circulating levels of plasminogen activator inhibitor type 1 (PAI-1) are increased in individuals carrying the 4G allele at position -675 of the PAI-1 gene. In turn, overexpression of PAI-1 has been found to affect both atheroma and thrombosis. However, the association between PAI-1 levels and the incidence of myocardial infarction (MI) is complicated by the potentially confounding effects of well-known cardiovascular risk factors. The current study tried to investigate in parallel the association of PAI-1 activity with the PAI-1 4G/5G polymorphism, with MI, and some components of metabolic syndrome (MetS). Methods: Using meta-analytical Mendelian randomization approaches, genotype-disease and genotype-phenotype associations were modeled simultaneously. Results: According to an additive model of inheritance and the Mendelian randomization approach, the MI-related odd ratio for individuals carrying the 4G allele was 1.088 with 95% confidence interval (CI) 1.007, 1.175. Moreover, the 4G carriers had, on average, higher PAI-1 activity than 5G carriers by 1.136 units (95% CI 0.738, 1.533). The metaregression analyses showed that the levels of triglycerides (p =0.005), cholesterol (p=0.037) and PAI-1 (p =0.021) in controls were associated with the MI risk conferred by the 4G carriers. Conclusions: The Mendelian randomization meta-analysis confirmed previous knowledge that the PAI-1 4G allele slightly increases the risk for MI. In addition, it supports the notion that PAI-1 activity and established cardiovascular determinants, such as cholesterol and triglyceride levels, could lie in the etiological pathway from PAI-1 4G allele to the occurrence of MI. Further research is warranted to elucidate these interactions. 52 7 937 950

Objective: To evaluate the current trends in HIV transmission in Greece. Methods: A retrospective study of HIV infected individuals reported to the Hellenic Center for Infectious Diseases Control (HCIDC) was conducted. Results: Since the beginning of the epidemic in Greece and until early 1990s most cases concerned men who have sex with men (MSM). After the mid-1990s the proportion of homosexual males among HIV positive individuals decreased slightly, then was stabilised but they still remain the dominant population among HIV positive people. On the other hand, heterosexual transmission increased steadily and has become a frequent route for the spread of HIV/AIDS in recent years. Individuals originating from or travelling to countries where this mode of transmission prevails were the most frequent cases in this category. A significant proportion of cases classified as "undetermined" were also recorded and were partially attributed to the increased heterosexual transmission among people (especially women) without obvious high risk behaviours. Conclusions: The HIV/AIDS surveillance system must evolve in order to find the new unreported risk information and identify the population groups at higher risk. This will help to implement preventive policies and information campaigns addressed to target populations with special attention paid to immigrants, women, and marginalised communities. 81 3 230 232

Aim: To investigate the association between statin use and colorectal cancer risk, we conducted an updated meta-analysis of published studies. Methods: We performed a comprehensive search for studies published up to July 2013. Eligible studies for this meta-analysis were either randomized controlled trials (RCTs) or observational studies (casecontrol or cohort) evaluating any exposure to statins and the risk of colorectal cancer. Two reviewers selected studies based on predefined inclusion criteria, and abstracted the data. Pooled relative risk (RR) estimates with their 95%CI were calculated using fixedand random-effects models. Then, we assessed the potential presence of publication bias and betweenstudies heterogeneity. To evaluate the results, we also performed a "leave-one-out" sensitivity analysis. Results: A total of 40 studies, involving more than eight million subjects, contributed to the analysis. They were grouped on the basis of study design and, consequently, three separate meta-analyses were conducted. A similar modest reduction in the risk of colorectal cancer with statin use was observed, which was not statistically significant among RCTs (RR = 0.89, 95%CI: 0.74-1.07; n = 8), but reached statistical significance among cohort studies (RR = 0.91, 95%CI: 0.83-1.00; n = 13) and case-control studies (RR = 0.92, 95%CI: 0.87-0.98; n = 19). While we did not find significant evidence of selective outcome reporting or publication bias, substantial heterogeneity was detected, mainly among the observational studies. The sensitivity analysis confirmed the stability of our results. Conclusion: A modest reduction in risk of colorectal cancer among statin users cannot be disproved. Further targeted research is warranted. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved. 20 7 1858 1870