Cancer-Associated Thrombosis: Pathophysiology, Laboratory Assessment, and Current Guidelines.

Dysregulated hemostasis in cancer patients is associated with various clinical conditions, from thromboembolic complications to disseminated intravascular coagulation. Despite the well-established association between cancer and thromboembolic complications, the mechanisms involved are not completely elucidated. There are several predisposing factors in cancer for increased thrombus generation, such as immobilization and chemotherapy. The term cancer-associated thrombosis (CAT) has been introduced to describe the close bidirectional relationship between cancer and thromboembolic events. Conventional coagulation tests (PT/aPTT) are more accurate in detecting a hypocoagulable rather than a hypercoagulable state; thus, their contribution to CAT management is limited. Traditionally, D-dimer levels have been the most common laboratory study for the evaluation of thrombotic risk. However, D-dimer levels only display a snapshot of the coagulation cascade, and they cannot provide a dynamic evaluation of evolving clot formation. Non-conventional assays, such as viscoelastic methods and microparticle formation are promising tools for the identification of patients at risk for developing CAT. Recent guidelines from the American Society of Clinical Oncology counsel against the estimation of thrombotic risk through a single test and recommend the use of scoring systems that take into account several risk factors. The present review outlines the current insights into the pathophysiological mechanisms of CAT and provides a comprehensive review of the latest advances in the laboratory assessment of CAT and the recent guidelines for the management of patients at risk for developing thromboembolic complications.

Factors Associated with Extended-Spectrum ß-Lactamases and Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections: A Five-Year Retrospective Study.

Klebsiella pneumoniae is one of the leading causes of nosocomial infections. It has been estimated that nosocomial infection by Klebsiella pneumoniae comprises 3-8% of all nosocomial infections. Klebsiella pneumoniae bloodstream infections (BSIs) occur worldwide with varying mortality. Resistant strains, like those producing extended-spectrum beta-lactamases (ESBL) and carbapenemases, are becoming increasingly common, especially in hospital settings, posing therapeutic challenges. In this article, we aimed to study the epidemiology and risk factors of BSIs due to resistant Klebsiella pneumoniae strains in the period 1 January 2014-31 December 2018 at the Nicosia General Hospital, the largest tertiary hospital in Cyprus. Data on demographics, co-morbidities, prior hospitalization, prior intensive care unit (ICU) admission, previous antimicrobial use, nosocomial acquisition of the infection, the presence of a prosthetic device or surgery, and the primary site of infection were retrospectively recorded. Associations between the detection of ESBL Klebsiella pneumoniae BSIs and factors/covariates were examined using logistic regression. This study involved 175 patients with BSI caused by Klebsiella pneumoniae. Of these, 61 BSIs were caused by ESBL strains, 101 by non-ESBL, and 13 by carbapenem-resistant (CR) strains. In univariable analyses, age, sex, heart disease, antimicrobial use during current admission, previous hospitalization (ward or ICU), and primary BSI were associated with the presence of an ESBL strain. Antibiotic use during current admission and heart disease remained statistically significantly associated with ESBL Klebsiella pneumoniae BSI in multivariable models. Antibiotic use during current admission, respiratory infection, and a recent history of surgery were more prevalent among CR Klebsiella pneumoniae BSI patients than among non-CR Klebsiella pneumoniae BSI patients. Our study showed that recent antimicrobial use and heart disease were associated with BSI due to ESBL-producing Klebsiella pneumoniae. This finding could inform clinical practice in hospital settings.

A Pilot Observational Study Evaluating the Diagnostic Capacity of Rotational Thromboelastometry in Periprosthetic Joint Infections.

BACKGROUND: Periprosthetic joint infections (PJIs) are associated with altered hemostatic dynamics; therefore, coagulation laboratory methods such as rotational thromboelastometry (ROTEM) may be valuable in their diagnosis. The aim of this study was to evaluate the diagnostic role of ROTEM in PJI. METHODS: A diagnostic study was conducted including 65 patients who underwent revision total hip arthroplasty or total knee arthroplasty due to PJI (30 patients) or aseptic loosening (35 patients). Preoperative laboratory evaluation included conventional coagulation studies, inflammatory markers, and ROTEM analysis. These parameters were compared between patients with PJI and patients with aseptic loosening. RESULTS: Several ROTEM parameters differed in the patients with PJI, indicating a higher coagulation potential associated with PJI. Specifically, the development of PJI was associated with higher EXTEM maximum clot firmness (MCF) (odds ratio [OR], 1.12 [95% confidence interval (CI), 1.04 to 1.20]; p = 0.001). Among the ROTEM parameters, EXTEM MCF was found to have the highest diagnostic accuracy for PJI (area under the receiver operating characteristic curve, 0.850; sensitivity, 76.6%; specificity, 91.4%), which was comparable with C-reactive protein (CRP) (p = 0.22) and erythrocyte sedimentation rate (ESR) (p = 0.65), but higher than D-dimer (p = 0.037). Moreover, the combined diagnostic accuracy of elevated EXTEM MCF and CRP was improved compared with CRP alone (p = 0.019). CONCLUSIONS: Our results indicate that ROTEM analysis might be helpful for the detection of the hemostatic derangements that are associated with the development of PJI. However, because of the small size of this pilot study, further research is needed to investigate the value of incorporating viscoelastic studies in diagnostic scores for PJI. LEVEL OF EVIDENCE: Diagnostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Fibrinolysis shutdown and elevated D-dimer levels have high prognostic capacity for postoperative thromboembolic complications in patients with bone tumors.

Surgical resection of malignant bone tumors is associated with a high risk of venous thromboembolism (VTE). The purpose of this study was to evaluate the association between rotational thromboelastometry (ROTEM) parameters and VTE following oncologic resections, and to evaluate their prognostic capacity for this complication. A prospective observational study was conducted including 113 patients who underwent surgical resection of malignant bone tumors. ROTEM analysis and conventional coagulation studies were performed preoperatively and on the 2nd postoperative day, while patients were followed for the development of VTE. Logistic regression was used to assess the association between ROTEM parameters and occurrence of VTE. The area under the receiver operating characteristic curve (AUC), sensitivity and specificity were calculated as measures of discrimination and predictive accuracy. Fourteen patients (12.4%) developed symptomatic VTE. Development of VTE was associated with shortened INTEM CFT (Odds Ratio [OR] 0.90, 95% Confidence Interval [CI] 0.84 - 0.96, p = 0.004), higher INTEM A10 (OR 1.21, 95% CI 1.07 - 1.36, p = 0.002), higher INTEM MCF (OR 1.22, 95% CI 1.08 - 1.37, p = 0.001) and higher INTEM LI60 (OR 2.10, 95% CI 1.38 - 3.21, p = 0.001). An INTEM LI60 value indicative of fibrinolysis shutdown (≥ 98%) had the best predictive accuracy for VTE (AUC = 0.887, 95% CI 0.824 - 0.951, sensitivity = 100%, specificity = 67.0%), higher than that of D-dimer levels (p = 0.028). ROTEM parameters were promising predictors of symptomatic VTE. Fibrinolysis shutdown as reflected by ROTEM LI60 and high D-dimer levels can aid the identification of high-risk patients. Future studies should evaluate whether the addition of ROTEM findings to an expanded risk-assessing model can improve the predictive capacity and provide better guidance in thromboprophylaxis.

Risk of Cancer in Inflammatory Bowel Diseases: Umbrella Review and Reanalysis of Meta-analyses.

BACKGROUND & AIMS: To summarize the epidemiologic evidence and assess the validity of claimed associations of inflammatory bowel diseases (IBDs) with overall and site-specific cancer risk. METHODS: We systematically searched PubMed, Embase, and Scopus from inception to May 10, 2021, to identify and comprehensively reanalyze the data of meta-analyses on associations between IBDs (ie, Crohn's disease [CD] and ulcerative colitis [UC]) and subsequent risk of cancer. The strength of epidemiologic evidence was graded as high, moderate, or weak, by applying prespecified criteria that included the random effects estimate, its 95% confidence interval, and P value, estimates of heterogeneity, small-study effects, and robustness to unmeasured confounding. RESULTS: This study critically appraised 277 estimates derived from 24 published meta-analyses and our own meta-analyses. The association between pediatric-onset IBDs and overall risk of cancer showed high epidemiologic evidence. Twenty associations (15 cancer types) demonstrated moderate evidence: any cancer (pediatric-onset UC), mouth to terminal ileum (CD), small bowel (CD/UC), colon (CD), rectum (CD/UC), colon-rectum (IBDs, pediatric-onset CD/UC), bile ducts and liver (CD/UC), liver (CD), intrahepatic cholangiocarcinoma (IBDs), bile ducts (CD), skin (CD), squamous cell carcinoma of the skin (CD), nonmelanoma skin cancer (UC), kidney (CD), and thyroid cancer (IBDs). Another 40 associations (23 cancer types) showed statistical significance; however, our confidence in these effect estimates was weak. No statistical significance was found regarding further 47 associations. CONCLUSIONS: Associations between IBDs and different types of malignancy showed varying levels of evidence and magnitude of risk. Further primary research investigating the impact of a consistent set of risk factors that are known to affect cancer risk is warranted. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021254996.

Outdoor air quality and human health: An overview of reviews of observational studies.

The epidemiological evidence supporting putative associations between air pollution and health-related outcomes continues to grow at an accelerated pace with a considerable heterogeneity and with varying consistency based on the outcomes assessed, the examined surveillance system, and the geographic region. We aimed to evaluate the strength of this evidence base, to identify robust associations as well as to evaluate effect variation. An overview of reviews (umbrella review) methodology was implemented. PubMed and Scopus were systematically screened (inception-3/2020) for systematic reviews and meta-analyses examining the association between air pollutants, including CO, NOX, NO2, O3, PM10, PM2.5, and SO2 and human health outcomes. The quality of systematic reviews was evaluated using AMSTAR. The strength of evidence was categorized as: strong, highly suggestive, suggestive, or weak. The criteria included statistical significance of the random-effects meta-analytical estimate and of the effect estimate of the largest study in a meta-analysis, heterogeneity between studies, 95% prediction intervals, and bias related to small study effects. Seventy-five systematic reviews of low to moderate methodological quality reported 548 meta-analyses on the associations between outdoor air quality and human health. Of these, 57% (N = 313) were not statistically significant. Strong evidence supported 13 associations (2%) between elevated PM2.5, PM10, NO2, and SO2 concentrations and increased risk of cardiorespiratory or pregnancy/birth-related outcomes. Twenty-three (4%) highly suggestive associations were identified on elevated PM2.5, PM10, O3, NO2, and SO2 concentrations and increased risk of cardiorespiratory, kidney, autoimmune, neurodegenerative, cancer or pregnancy/birth-related outcomes. Sixty-seven (12%), and 132 (24%) meta-analyses were graded as suggestive, and weak, respectively. Despite the abundance of research on the association between outdoor air quality and human health, the meta-analyses of epidemiological studies in the field provide evidence to support robust associations only for cardiorespiratory or pregnancy/birth-related outcomes.

Pitfalls and perils of survival analysis under incorrect assumptions: the case of COVID-19 data / Escollos y peligros del análisis de supervivencia: el caso de los datos de COVID-19

Abstract | Non-parametric survival analysis has become a very popular statistical method in current medical research. However, resorting to survival analysis when its fundamental assumptions are not fulfilled can severely bias the results. Currently, hundreds of clinical studies are using survival methods to investigate factors potentially associated with the prognosis of coronavirus disease 2019 (COVID-19) and test new preventive and therapeutic strategies. In the pandemic era, it is more critical than ever to base decision-making on evidence and rely on solid statistical methods, but this is not always the case. Serious methodological errors have been identified in recent seminal studies about COVID-19: One reporting outcomes of patients treated with remdesivir and another one on the epidemiology, clinical course, and outcomes of critically ill patients. High-quality evidence is essential to inform clinicians about optimal COVID-19 therapies and policymakers about the true effect of preventive measures aiming to tackle the pandemic. Though timely evidence is needed, we should encourage the appropriate application of survival analysis methods and careful peer-review to avoid publishing flawed results, which could affect decision-making. In this paper, we recapitulate the basic assumptions underlying non-parametric survival analysis and frequent errors in its application and discuss how to handle data on COVID-19.

Resumen | El análisis de supervivencia es un método estadístico muy popular en la investigación médica actual. Sin embargo, el recurrir al análisis de supervivencia cuando no se cumplen sus supuestos fundamentales puede sesgar gravemente los resultados. Actualmente, cientos de estudios clínicos están utilizando esta metodología para estudiar los factores potencialmente asociados con el pronóstico de la COVID-19 y probar nuevas estrategias preventivas y terapéuticas. En la pandemia actual es más importante que nunca que las decisiones se basen en pruebas y en métodos estadísticos sólidos. Sin embargo, este no es siempre el caso. Se han detectado errores metodológicos graves en estudios seminales recientes sobre COVID-19: uno que informa los resultados de los pacientes tratados con remdesivir y otro sobre la epidemiología, el curso clínico y los resultados de los pacientes críticamente enfermos. La evidencia de calidad es esencial para informar a los médicos sobre las terapias óptimas contra la enfermedad y, a los legisladores, sobre el verdadero efecto de las medidas preventivas destinadas a abordar la pandemia. Aunque se necesitan pruebas oportunas, debemos fomentar la aplicación adecuada de los métodos de análisis de supervivencia y una cuidadosa revisión por pares para evitar la publicación de resultados defectuosos que pueden afectar la adopción de decisiones. En este artículo, recapitulamos los supuestos básicos que subyacen al análisis de supervivencia y los errores frecuentes en su aplicación, y discutimos cómo manejar los datos sobre la COVID-19.

The Safety and Efficacy of Tranexamic Acid in Oncology Patients Undergoing Endoprosthetic Reconstruction and a ROTEM-Based Evaluation of Their Hemostatic Profile: A Pilot Study.

BACKGROUND: An endoprosthetic reconstruction in musculoskeletal oncology patients is associated with significant blood loss. The purpose of this study is to evaluate the safety and efficacy of tranexamic acid (TXA) for these patients and to assess any changes in their hemostatic profile using rotational thromboelastometry (ROTEM). METHODS: A retrospective observational study was performed including 61 patients with primary or metastatic bone tumors who underwent surgery. Group A (n = 30) received both intravenous and local TXA whereas Group B (n = 31) was the control group. The primary outcomes were perioperative blood loss and blood unit transfusions and the secondary outcomes included the incidence of thromboembolic complications and a change in blood coagulability as reflected by ROTEM parameters. RESULTS: The median difference in blood loss between the two groups was 548.5 mL, indicating a 29.2% reduction in the 72 h blood loss following TXA administration (p < 0.001). TXA also led to a reduced transfusion of 1 red blood cell (RBC) unit per patient (p < 0.001). The two groups had similar rates of thromboembolic complications (p = 0.99). The antifibrinolytic properties of TXA were confirmed by the significantly higher INTEM, FIBTEM and EXTEM LI60 (p < 0.001, p = 0.005 and p < 0.001, respectively) values in the TXA group. CONCLUSION: Tranexamic acid was associated with a significant reduction in perioperative blood loss and transfusion requirements without a complete shutdown of the fibrinolysis. Larger studies are warranted to assess the frequency of these outcomes in musculoskeletal oncology patients.

Rotational Thromboelastometry Findings Are Associated with Symptomatic Venous Thromboembolic Complications after Hip Fracture Surgery.

BACKGROUND: Venous thromboembolism is a common complication after hip fractures. However, there are no reliable laboratory assays to identify patients at risk for venous thromboembolic (VTE) events after major orthopaedic surgery. QUESTION/PURPOSES: (1) Are rotational thromboelastometry (ROTEM) findings associated with the presence or development of symptomatic VTE after hip fracture surgery? (2) Were any other patient factors associated with the presence or development of symptomatic VTE after hip fracture surgery? (3) Which ROTEM parameters were the most accurate in terms of detecting the association of hypercoagulability with symptomatic VTE? METHODS: This retrospective study was conducted over a 13-month period. In all, 354 patients with femoral neck and peritrochanteric fractures who underwent hip hemiarthoplasty or cephallomedullary nailing were assessed for eligibility. Of those, 99% (349 of 354) were considered eligible for the study, 1% (3 of 354) of patients were excluded due to coagulation disorders, and another 1% (2 of 354) were excluded because they died before the postoperative ROTEM analysis. An additional 4% (13 of 354) of patients were lost before the minimum study follow-up of 3 months, leaving 95% (336 of 354) for analysis. A ROTEM analysis was performed in all patients at the time of their hospital admission, within hours of the injury, and on the second postoperative day. The patients were monitored for the development of symptoms indicative of VTE, and the gold standard tests for diagnosing VTE, such as CT pulmonary angiography or vascular ultrasound, were selectively performed only in symptomatic patients and not routinely in all patients. Therefore, this study evaluates the association of ROTEM with only clinically evident VTE events and not with all VTE events. ROTEM results did not affect the clinical surveillance of the study group and the decision for further work up. To determine whether ROTEM findings were associated with the presence or development of symptomatic VTE, ROTEM parameters were compared between patients with and without symptomatic VTE. To establish whether any other patient factors were associated with the presence or development of symptomatic VTE after hip fracture surgery, clinical parameters and conventional laboratory values were also compared between patients with and without symptomatic VTE. Finally, to determine which ROTEM parameters were the most accurate in terms of detecting the association of hypercoagulability with symptomatic VTE, the area under the curve (AUC) for certain cut off values of ROTEM parameters was calculated. RESULTS: We found several abnormal ROTEM values to be associated with the presence or development of symptomatic VTE. The preoperative maximum clot firmness was higher in patients with clinically evident VTE than in patients without these complications (median [interquartile range] 70 mm [68 to 71] versus 65 mm [61 to 68]; p < 0.001). The preoperative clot formation time was lower in patients with clinically evident VTE than those without clinically evident VTE (median 61 seconds [58 to 65] versus 70 seconds [67 to 74]; p < 0.001), and also the postoperative clot formation time was lower in patients with clinically evident VTE than those without these complications (median 52 seconds [49 to 59] versus 62 seconds [57 to 68]; p < 0.001). Increased BMI was also associated with clinically evident VTE (odds ratio 1.26 [95% confidence interval 1.07 to 1.53]; p < 0.001). We found no differences between patients with and without clinically evident VTE in terms of age, sex, smoking status, comorbidities, and preoperative use of anticoagulants. Lastly, preoperative clot formation time demonstrated the best performance for detecting the association of hypercoagulability with symptomatic VTE (AUC 0.89 [95% CI 0.81 to 0.97]), with 81% (95% CI 48% to 97%) sensitivity and 86% (95% CI 81% to 89%) specificity for clot formation time ≤ 65 seconds. CONCLUSION: ROTEM's performance in this preliminary study was promising in terms of its association with symptomatic VTE. This study extended our earlier work by demonstrating that ROTEM has a high accuracy in detecting the level of hypercoagulability that is associated with symptomatic VTE. However, until its performance is validated in a study that applies a diagnostic gold standard (such as venography, duplex/Doppler, or chest CT) in all patients having ROTEM to confirm its performance, ROTEM should not be used as a regular part of clinical practice. LEVEL OF EVIDENCE: Level IV, diagnostic study.

Validation of molecular clock inferred HIV infection ages: Evidence for accurate estimation of infection dates.

BACKGROUND: Improving HIV diagnosis, access to care and effective antiretroviral treatment provides our global strategy to reduce HIV incidence. To reach this goal we need to increase our knowledge about local epidemics. HIV infection dates would be an important information towards this goal, but they are largely unknown. To date, methods to estimate the dates of HIV infection are based mainly on laboratory or molecular methods. Our aim was to validate molecular clock inferred infection dates that were estimated by analysing sequences from 145 people living with HIV (PLHIV) with known transmission dates (clinically estimated infection dates). METHODS: All HIV sequences were obtained by Sanger sequencing and were previously found to belong to well-established molecular transmission clusters (MTCs). RESULTS: Our analysis showed that the molecular clock inferred infection dates were correlated with the clinically estimated ones (Spearman's Correlation coefficient = 0.93, p < 0.001) and that there was an agreement between them (Lin's concordance correlation coefficient = 0.92, p < 0.001). For the 61.4% of cases the molecular clock inferred preceded the clinically estimated infection dates. The median difference between clinically and molecularly estimated dates of infection was of 0.18 (IQR: -0.21, 0.89) years. The lowest differences were identified in people who inject drugs of our study population. CONCLUSIONS: The estimated time to more recent common ancestor (tMRCA) of nodes within clusters provides a reliable approximation of HIV infections for PLHIV infected within MTCs. Next-generation sequencing data and molecular clock estimates based on heterochronous sequences provide, probably, more reliable methods for inferring infection dates. However, since these data are not available in most of the HIV clinical laboratories, our approach, under specific conditions, can provide a reliable estimation of HIV infection dates and can be used for HIV public health interventions.

Systematic review with meta-analysis: biologics and risk of infection or cancer in elderly patients with inflammatory bowel disease.

BACKGROUND: Uncertainty exists concerning the risk of infection and cancer associated with biologic therapies in elderly patients with inflammatory bowel disease (IBD). AIMS: To identify, synthesise and critically appraise the available evidence on the topic. METHODS: We systematically searched Medline/PubMed, Embase and Scopus, through October 2019, and recent conference proceedings, to identify studies investigating the risk of serious infections, opportunistic infections, any infection and cancer in elderly IBD patients (>60 years) exposed to biologics as compared to those unexposed to biologics. Two reviewers independently extracted study data and assessed each study's risk of bias. We examined heterogeneity, and calculated summary effect estimates using fixed- and random effects models. Quality of evidence was determined with GRADE. RESULTS: We included 15 studies (one post hoc analysis of a randomised trial, nine cohort and five case-control studies). Elderly IBD patients treated with biologics were at increased risk of developing serious infections (random effects summary relative risk: 2.70, 95% CI: 1.56-4.66; seven studies; I2  = 57%) and opportunistic infections (3.16, 1.09-9.20; four studies; I2  = 73%). The occurrence of any infection (1.67, 0.51-5.43; five studies; I2  = 75%) and cancer (0.90, 0.64-1.26; nine studies; I2  = 0%) was not significantly affected. Nevertheless, our confidence in the effect estimates is rather limited; the quality of evidence is low to very low. CONCLUSIONS: Biologics are likely to increase the risk of serious and opportunistic infections in old IBD patients. Large prospective studies are needed to further assess the biologic treatments' long-term safety profile in this population.

State of knowledge of human papillomavirus (HPV), HPV vaccine and testing: a cross-sectional study among female university students in Cyprus.

This study aimed to evaluate human papillomavirus (HPV)-related knowledge of women aged 18-25 years and estimate the reported uptake of HPV vaccine and testing. A cross-sectional study was conducted among female students of the University of Cyprus between March and April 2017. The participants self-completed a questionnaire, which consisted of 37 items on demographics, general HPV-related knowledge, and HPV vaccination and testing. In total, 283 young females (mean age: 19.7 ± 1.5 years) took part in the study. Of these, about half (53.7%) reported that they were aware of HPV; one-third (30.7%) reported having been vaccinated; 38.8% had been informed of the recent introduction of the HPV vaccine in the National Immunization Schedule in Cyprus, while 14.3% reported a previous Pap-test and 3.4% a previous HPV DNA test. The mean Overall Knowledge Index (max: 25 correct answers) was 6.1 (±3.8) and was positively associated with the reported uptake of the HPV vaccine (adjusted Odds ratio: 1.14, 95% Confidence Interval (CI): 1.04-1.24). Knowledge about HPV has to be improved as it is associated with increased reported rates of HPV vaccination.

Short Term Success of Treatments to Salvage Thrombosed or Failing Synthetic Arteriovenous Grafts in End Stage Renal Disease: A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials.

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.

People with high HIV viral load within risk networks: who are these people and who refers them best?

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.

Environmental Risk Factors for Inflammatory Bowel Diseases: An Umbrella Review of Meta-analyses.

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.

HIV incidence among men who have sex with men at a community-based facility in Greece.

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.

Perceived air quality and particulate matter pollution based on field survey data during a winter period.

Outdoor air pollution and especially particulate matter pollution is a major environmental health issue that raises concerns of scientists and policy makers. This study focuses on air quality perception in relation to particulate matter in order to find potential patterns. Field questionnaire-based surveys were conducted among pedestrians on two central sites in the city of Athens, Greece, during the winter period while particulate matter of 10 µm or less in diameter (PM10) were concurrently measured on-site at 1-min resolution. The participants were asked to evaluate the dust and the overall pollution-related air quality based on 5-point bipolar scales. Air quality perception patterns were explored considering PM10 concentration, meteorological and thermal conditions, and subjective variables including gender, age, smoking status, and health status. An effect of PM10 on dust perception was identified, suggesting that dusty air quality conditions are reported more frequently when particulate concentration increases. Health status, exposure time, smoking status, and gender were found to affect air quality perception. Participants experiencing health symptoms, exposed to outdoor conditions for more than 30 min, smokers, and females were more likely to report unfavorable air quality conditions. The comparison with the results of a previous study obtained using air pollution station data confirmed the dependence of air quality perception on participants' characteristics and particularly on their health status. Ordinal logistic regression models showed that for pedestrians who were neither smokers nor experiencing health symptoms and were exposed to outdoor conditions for more than 30 min, a PM10 concentration around 64 µg·m-3 could be a threshold, to perceive dusty air quality conditions.

Epidemiology of breast cancer in Cyprus: Data on newly diagnosed cases and survival rates.

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.

Data on solar sunburning ultraviolet (UVB) radiation at an urban Mediterranean climate.

This article describes data on the intensity of ultraviolet B (UVB) radiation collected during field questionnaire-based surveys in Athens, Greece. The surveys were conducted over 11 days of July and October 2010 at three different urban, outdoor sites. A total of 1104 interviews were conducted. The participants were asked to report whether they felt they got a sunburn at the moment of the interview. Questions related to personal characteristics including skin type and exposure time (visit duration at the interview site) were also included in the questionnaire.

Biologic Therapies and Risk of Infection and Malignancy in Patients With Inflammatory Bowel Disease: A Systematic Review and Network Meta-analysis.

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.