Non-genetic factors and breast cancer: an umbrella review of meta-analyses.

BACKGROUND: Previous research has found associations between various non-genetic factors and breast cancer (BrCa) risk. This study summarises and appraises the credibility of the available evidence on the association between non-genetic factors and BrCa risk. METHODS: We conducted an umbrella review of meta-analyses. Medline, Scopus, and the Cochrane databases were systematically searched for meta-analyses examining non-genetic factors and BrCa incidence or mortality. The strength of the evidence was graded in four categories (i.e., weak, suggestive, highly suggestive, convincing). RESULTS: A total of 781 meta-analyses from 280 publications were evaluated and graded. We included exposures related to anthropometric measurements, biomarkers, breast characteristics and diseases, diet and supplements, environment, exogenous hormones, lifestyle and social factors, medical history, medication, reproductive history, and pregnancy. The largest number of examined associations was found for the category of diet and supplements and for exposures such as aspirin use and active smoking. The statistically significant (P-value < 0.05) meta-analyses were 382 (49%), of which 204 (53.4%) reported factors associated with increased BrCa risk. Most of the statistically significant evidence (n = 224, 58.6%) was graded as weak. Convincing harmful associations with heightened BrCa risk were found for increased body mass index (BMI), BMI and weight gain in postmenopausal women, oral contraceptive use in premenopausal women, increased androstenedione, estradiol, estrone, and testosterone concentrations, high Breast Imaging Reporting and Data System (BIRADS) classification, and increased breast density. Convincing protective factors associated with lower BrCa risk included high fiber intake and high sex hormone binding globulin (SHBG) levels while highly suggestive protective factors included high 25 hydroxy vitamin D [25(OH)D] levels, adherence to healthy lifestyle, and moderate-vigorous physical activity. CONCLUSIONS: Our findings suggest some highly modifiable factors that protect from BrCa. Interestingly, while diet was the most studied exposure category, the related associations failed to reach higher levels of evidence, indicating the methodological limitations in the field. To improve the validity of these associations, future research should utilise more robust study designs and better exposure assessment techniques. Overall, our study provides knowledge that supports the development of evidence-based BrCa prevention recommendations and guidance, both at an individual level and for public health initiatives. TRIAL REGISTRATION: PROSPERO CRD42022370675.

Modeling the HIV epidemic in MSM in Cyprus: reaching only the 95-95-95 cascade of care targets fails to reduce HIV incidence by 90% in 2030.

National responses should be improved and accelerated to meet the target of ending the Acquired ImmunoDeficiency Syndrome (AIDS) epidemic by 2030. In the Republic of Cyprus, Men who have Sex with Men (MSM) are disproportionately affected by Human Immunodeficiency Virus (HIV), accounting approximately for half of all annual HIV diagnoses. This study assesses the evolution of HIV incidence in MSM in Cyprus until 2030 using a model calibrated to Cypriot epidemiological data. Four scenarios were examined: status quo, two scenarios focusing on introducing Pre-Exposure Prophylaxis (PrEP), and a 90% HIV incidence reduction scenario. Reaching only the 95-95-95 HIV cascade of care targets among MSM would reduce HIV incidence by 48.6% by 2030 compared to 2015. Initiating a PrEP intervention only for high risk MSM would cause a modest further reduction in HIV incidence. To meet the 90% reduction target, PrEP should be expanded to both high and medium risk MSM and, after 2025, behavioral interventions should be implemented so as high-risk MSM gradually move to the medium-risk category. Cyprus will not reach the HIV incidence reduction target by 2030 unless PrEP is gradually promoted and delivered to all high and medium risk MSM along with awareness and behavioral interventions.

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.

Finding influential subjects in a network using a causal framework.

Researchers across a wide array of disciplines are interested in finding the most influential subjects in a network. In a network setting, intervention effects and health outcomes can spill over from one node to another through network ties, and influential subjects are expected to have a greater impact than others. For this reason, network research in public health has attempted to maximize health and behavioral changes by intervening on a subset of influential subjects. Although influence is often defined only implicitly in most of the literature, the operative notion of influence is inherently causal in many cases: influential subjects are those we should intervene on to achieve the greatest overall effect across the entire network. In this work, we define a causal notion of influence using potential outcomes. We review existing influence measures, such as node centrality, that largely rely on the particular features of the network structure and/or on certain diffusion models that predict the pattern of information or diseases spreads through network ties. We provide simulation studies to demonstrate when popular centrality measures can agree with our causal measure of influence. As an illustrative example, we apply several popular centrality measures to the HIV risk network in the Transmission Reduction Intervention Project and demonstrate the assumptions under which each centrality can represent the causal influence of each participant in the study.

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.

Machine learning and features for the prediction of thermal sensation and comfort using data from field surveys in Cyprus.

Perception can influence individuals' behaviour and attitude affecting responses and compliance to precautionary measures. This study aims to investigate the performance of methods for thermal sensation and comfort prediction. Four machine learning algorithms (MLA), artificial neural networks, random forest (RF), support vector machines, and linear discriminant analysis were examined and compared to the physiologically equivalent temperature (PET). Data were collected in field surveys conducted in outdoor sites in Cyprus. The seven- and nine-point assessment scales of thermal sensation and a two-point scale of thermal comfort were considered. The models of MLA included meteorological and physiological features. The results indicate RF as the best MLA applied to the data. All MLA outperformed PET. For thermal sensation, the lowest prediction error (1.32 points) and the highest accuracy (30%) were found in the seven-point scale for the feature vector consisting of air temperature, relative humidity, wind speed, grey globe temperature, clothing insulation, activity, age, sex, and body mass index. The accuracy increased to 63.8% when considering prediction with at most one-point difference from the correct thermal sensation category. The best performed feature vector for thermal sensation also produced one of the best models for thermal comfort yielding an accuracy of 71% and an F-score of 0.81.

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.

Sociometric Risk Network Structure, HIV Prevalence, and Drug Injection-Related Norms among People Who Inject Drugs (PWID) in Athens, Greece.

Background: Structural properties of sociometric networks have been associated with behaviors related to HIV transmission. Very few studies, however, have explored the correlation between sociometric network factors and drug injection-related norms. Methods: This exploratory work: (i) describes basic structural qualities of a sociometric risk network of participants in the Transmission Reduction Intervention Project (TRIP) in Athens, Greece, in the context of a large HIV outbreak among people who inject drugs (PWID); (ii) measures HIV prevalence within specific structures within the sociometric risk network of PWID in TRIP; and (iii) explores the association of structural properties of the sociometric risk network in TRIP with drug injection-related norms. Results: The sociometric risk network in TRIP consisted of a large component (n = 241, 67.8%), a few small components (n = 36, 10.1%) with 2-10 individuals each, and some isolates (n = 79, 22.2%). HIV prevalence was significantly higher in the large component (55.6%), the 2-core (59.1%) and 3-core (66.3%) of the large component, and the 3-cliques of the cores. Drug injection-related norms were significantly associated with structural characteristics of the sociometric risk network. A safe behavioral pattern (use of unclean cooker/filter/rinse water was never encouraged) was significantly (p = 0.03) less normative among people who TRIP participants of the 2-core injected with (40.5%) than among network contacts of TRIP participants outside the 2-core (55.6%). On the contrary, at drug-using venues, 2-core members reported that safer behaviors were normative compared to what was reported by those without 2-core membership. Conclusions: Sociometric network data can give useful insights into HIV transmission dynamics and inform prevention strategies.Supplemental data for this article is available online at https://doi.org/10.1080/10826084.2021.1914103 .

Beyond the physical risk: Psychosocial impact and coping in healthcare professionals during the COVID-19 pandemic.

AIMS AND OBJECTIVES: This study aimed to examine the psychosocial impact and identify risk factors for poor psychosocial outcomes in healthcare professionals during the Coronavirus disease 2019 (COVID-19) pandemic in Cyprus. BACKGROUND: Healthcare professionals are in the forefront of the COVID-19 pandemic facing an unprecedented global health crisis, which can have consequences on their psychosocial health. There is a need to identify risk factors for poor psychosocial outcomes to inform the design of tailored psychological interventions. DESIGN: Cross-sectional online study. METHODS: A total of 1071 healthcare professionals completed self-report questionnaires. Measures included sociodemographic information, COVID-19-related characteristics, quality of life (Brief World Health Organization Quality of Life; WHOQOL-Bref), anxiety (Generalized Anxiety Disorder-7; GAD-7), depression (Patient Health Questionnaire-8; PHQ-8), occupational burnout (Copenhagen Burnout Inventory; CBI), and coping (Brief Coping Orientation to Problems Experienced; Brief COPE). This article follows the STROBE reporting guidelines. RESULTS: The prevalence of moderate to severe anxiety and clinically significant depression was 27.6% and 26.8%, respectively. Significant risk factors for poor psychological outcomes included being female, being a nurse or doctor (vs non-medical professional), working in frontline units (inpatient, intensive care), perceptions of inadequate workplace preparation to deal with the pandemic, and using avoidance coping. Depression and occupational burnout were significant risk factors for poor quality of life. CONCLUSION: The findings suggest several individual, psychosocial, and organisational risk factors for the adverse psychological outcomes observed in healthcare professionals during the COVID-19 pandemic. RELEVANCE TO CLINICAL PRACTICE: This study highlights the urgent need for screening for anxiety and depression and psychological interventions to combat an imminent mental health crisis in healthcare professionals during the COVID-19 pandemic. Pandemic response protocols and public health initiatives aiming to improve and prevent mental health problems in healthcare professionals during the current and future health crises, need to account for the various factors at play.

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.

High-risk behaviors and their association with awareness of HIV status among participants of a large-scale prevention intervention in Athens, Greece.

BACKGROUND: Aristotle was a seek-test-treat intervention during an outbreak of human immunodeficiency virus (HIV) infection among people who inject drugs (PWID) in Athens, Greece that started in 2011. The aims of this analysis were: (1) to study changes of drug injection-related and sexual behaviors over the course of Aristotle; and (2) to compare the likelihood of risky behaviors among PWID who were aware and unaware of their HIV status. METHODS: Aristotle (2012-2013) involved five successive respondent-driven sampling rounds of approximately 1400 PWID each; eligible PWID could participate in multiple rounds. Participants were interviewed using a questionnaire, were tested for HIV, and were classified as HIV-positive aware of their status (AHS), HIV-positive unaware of their status (UHS), and HIV-negative. Piecewise linear generalized estimating equation models were used to regress repeatedly measured binary outcomes (high-risk behaviors) against covariates. RESULTS: Aristotle recruited 3320 PWID (84.5% males, median age 34.2 years). Overall, 7110 interviews and blood samples were collected. The proportion of HIV-positive first-time participants who were aware of their HIV infection increased from 21.8% in round A to 36.4% in the last round. The odds of dividing drugs at least half of the time in the past 12 months with a syringe someone else had already used fell from round A to B by 90% [Odds Ratio (OR) (95% Confidence Interval-CI): 0.10 (0.04, 0.23)] among AHS and by 63% among UHS [OR (95% CI): 0.37 (0.19, 0.72)]. This drop was significantly larger (p = 0.02) among AHS. There were also decreases in frequency of injection and in receptive syringe sharing in the past 12 months but they were not significantly different between AHS (66 and 47%, respectively) and UHS (63 and 33%, respectively). Condom use increased only among male AHS from round B to the last round [OR (95% CI): 1.24 (1.01, 1.52)]. CONCLUSIONS: The prevalence of risky behaviors related to drug injection decreased in the context of Aristotle. Knowledge of HIV infection was associated with safer drug injection-related behaviors among PWID. This highlights the need for comprehensive interventions that scale-up HIV testing and help PWID become aware of their HIV status.

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.

Comparative assessment of budesonide-MMX and mesalamine in active, mild-to-moderate ulcerative colitis: A systematic review and network meta-analysis.

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.

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.

A Network Intervention to Locate Newly HIV Infected Persons Within MSM Networks in Chicago.

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 < 0.001) among networks of recent seeds (33/96, 34.4%) compared to long-term seeds (6/31, 19.4%). More individuals were identified with active syphilis infection (p = 0.007) among networks of recent seeds (15/96, 15.6%), compared to networks of long-term seeds (3/31, 9.7%). Network-based recruitment of recently HIV-infected individuals was more effective at identifying HIV and syphilis infection. Allocation of public health resources may be improved by targeting interventions toward networks of recently HIV-infected individuals.

Identifying, linking, and treating people who inject drugs and were recently infected with HIV in the context of a network-based intervention.

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 <200 copies/mL. TRIP and its public health allies managed to get most of the recently HIV-infected PWID who were identified by the program into care and many of them onto ART. This resulted in very low HIV-RNA levels. Treatment as prevention can work if individuals are aided in overcoming difficulties in entry to, or attrition from care.

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.

Molecular Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Individuals in a Network-Based Intervention (Transmission Reduction Intervention Project): Phylogenetics Identify HIV-1-Infected Individuals With Social Links.

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.

Comparative safety of systemic and low-bioavailability steroids in inflammatory bowel disease: Systematic review and network meta-analysis.

AIMS: Oral systemic corticosteroids have been used to induce remission in patients with active inflammatory bowel disease (IBD) for over 50 years; however, the wide array of adverse events (AEs) associated with these drugs prompted the development of steroid compounds with targeted delivery and low systemic bioavailability. This study assessed corticosteroids' comparative harm using network meta-analysis. METHODS: We searched PubMed, Scopus, Embase, the Cochrane Library, clinical trial registries, regulatory authorities' websites and major conference proceedings, through March 2017. Randomized controlled trials that recruited adult IBD patients and compared oral systemic corticosteroids (prednisone/prednisolone) or compounds/formulations with low systemic bioavailability (budesonide, budesonide MMX, and beclomethasone dipropionate) with placebo, or against each other, were considered eligible for inclusion. Two reviewers independently extracted study data and outcomes, and rated each trial's risk-of-bias. RESULTS: We identified and synthesized evidence from 31 trials including 5689 IBD patients. Budesonide MMX was associated with significantly fewer corticosteroid-related AEs than oral systemic corticosteroids [odds ratio (OR): 0.25, 95% confidence interval (CI): 0.13-0.49] and beclomethasone (OR: 0.35, 95% CI: 0.13-1.00), but not significantly fewer AEs than budesonide (OR: 0.64, 95% CI: 0.37-1.11); it performed equally good with placebo. By contrast, the occurrence of serious AEs, and treatment discontinuations due to AEs, did not differ between the comparator treatments. CONCLUSIONS: Budesonide MMX is associated with fewer corticosteroid-related AEs than its comparator steroid treatments for adult IBD patients. Further high-quality research is warranted to illuminate the steroid drugs' comparative safety profiles.

Comparison between Nageotte and flow cytometric counting of residual leucocytes in freshly prepared leucocyte-reduced red blood cell components.

BACKGROUND: Flow cytometry (FC) and Nageotte hemocytometry represent the most widely accepted methods for counting residual white blood cells (rWBCs) in leucocyte-reduced (LR) blood components. Our aim was to study the agreement between the two methods, under real working blood bank conditions. MATERIALS AND METHODS: 94 freshly produced LR red blood cell (RBC) units were tested for rWBC concentrations by FC and Nageotte. To assess the precision of each method, we calculated the intra-assay coefficients of variation (CV), and followed the Bland-Altman methodology to study the agreement between the two methods. RESULTS: CV was 18.5% and 26.2% for the Nageotte and the FC, respectively. However, the agreement between the duplicate observations, using the binary cut-off threshold of 1 × 106 WBCs per unit to define the results as "pass/fail", was 71.9% for the Nageotte and 93.3% for the FC. Linear regression analysis did not show any correlation (R-squared = 0.01, p = 0.35) between the two methods, while the Bland-Altman analysis for the measuring agreement showed a bias toward a higher Nageotte count of 0.77 × 106 leucocytes per unit (p < 0.001) with the 95% limits of agreement (d ± 2 sd) ranging from -0.40 × 106 to 1.94 × 106 leucocytes per unit. CONCLUSION: The absence of agreement between Nageotte and FC method, with the differences within d ± 2 sd being of high clinical importance, suggests that the two methods cannot be used for clinical purposes interchangeably. The Nageotte seems unsuitable for quality control even with a pass-fail criterion, under real working blood bank conditions.