Stefanos Bonovas

Vaccination recommendations for the adult immunosuppressed patient: A systematic review and comprehensive field synopsis

BACKGROUNDnImmunosuppressed patients are at risk of severe viral infections-related complications. National and international vaccination guidelines have been developed to decrease the mortality risk associated with these infections. However, a summary of these guidelines and the value of immunisation in this population is missing.nnnOBJECTIVESnTo summarize specific guidelines regarding vaccination in immunosuppressed patients.nnnMETHODSnWe performed a literature search based on last update vaccine guidelines in immunosuppressed adult patients published between 1/1/2005-1/31/2016 in English or French language using PubMed, Cochrane and Embase, as well as relevant medical society websites.nnnRESULTSnOf the 389 citations identified, 12 guidelines were selected Three additional guidelines were selected by searching on the websites from medical societies of each specialty. 15 guidelines were included, involving 19 medical societies issued from the US (nxa0=xa06), international collaboration (nxa0=xa03), UK (nxa0=xa02), Canada (nxa0=xa01), Australia (nxa0=xa01), France (nxa0=xa01), and Germany (nxa0=xa01). These guidelines provide recommendations on vaccination in asplenic patients (nxa0=xa05), cancer patients (nxa0=xa04), HIV patients (nxa0=xa05), hematopoietic stem cell recipients (nxa0=xa04), inflammatory bowel diseases patients (nxa0=xa05), psoriasis patients (nxa0=xa04), primary immunocompromised patients (nxa0=xa03), inflammatory rheumatic diseases patients (nxa0=xa06), and solid organ transplant recipients (nxa0=xa05). All guidelines recommended pneumococcal and injectable influenza vaccines. Other inactivated vaccines were recommended only in high risk patients. Live vaccines were usually contraindicated in patients under immunosuppressive therapy and/or in HIV patients with a CD4 count under 200/mm3.nnnCONCLUSIONnPneumococcal and injectable influenza are the two essential vaccines recommended in all immunocompromised patients. Other inactivated vaccines are only indicated in high risk patients. Live vaccines are usually contraindicated.

Systematic review with meta-analysis: use of 5-aminosalicylates and risk of colorectal neoplasia in patients with inflammatory bowel disease

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.

Systematic review with network meta-analysis: comparative assessment of tofacitinib and biological therapies for moderate-to-severe ulcerative colitis

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.

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

AIMSnOral systemic corticosteroids have been used to induce remission in patients with active inflammatory bowel disease (IBD) for over 50xa0years; 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.nnnMETHODSnWe 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 trials risk-of-bias.nnnRESULTSnWe 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.nnnCONCLUSIONSnBudesonide 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.

Loss of Response to Vedolizumab and Ability of Dose Intensification to Restore Response in Patients With Crohn’s Disease or Ulcerative Colitis: A Systematic Review and Meta-analysis

BACKGROUND & AIMS: Vedolizumab is effective and safe for the treatment of Crohns disease (CD) and ulcerative colitis (UC). Little is known about the incidence rate of loss of response to vedolizumab maintenance therapy or whether dose intensification restores response to this drug. METHODS: We searched PubMed, Scopus and conference abstracts (Digestive Disease Week, European Crohns and Colitis Organization, and United European Gastroenterology Week), through December 2017, for experimental or observational cohort studies of vedolizumab use in adult patients with CD or UC; we identified studies that provided sufficient data to determine the incidence rate of loss of response among initial responders and the ability of dose intensification to restore response. Two reviewers independently abstracted study data and outcomes and rated each studys risk of bias. The studies were evaluated for heterogeneity and publication bias. Summary estimates were calculated using random effects models. RESULTS: We analyzed data from 10 eligible cohorts; most patients had received prior treatment with a tumor necrosis factor antagonist. The pooled incidence rates of loss of response were 47.9 per 100 person‐years of follow up (95% CI, 26.3–87.0; I2 = 74%) among patients with CD and 39.8 per 100 person‐years of follow up (95% CI, 35.0–45.3; I2 = 0%) among patients with UC. Dose intensification restored response to the drug in 53.8% of secondary non‐responders (95% CI, 21.8%‐82.9%; I2 = 77%). CONCLUSIONS: In a systematic review and meta‐analysis, we found high proportions of patients with CD or UC to lose responsiveness to vedolizumab maintenance therapy. Dose intensification restores responsiveness to more than half of these patients. Additional studies are warranted to inform clinical decision making.

Detailed Molecular Surveillance of the HIV-1 Outbreak Among People who Inject Drugs (PWID) in Athens During a Period of Four Years

BACKGROUNDnNew diagnoses of HIV-1 infection among people who inject drugs (PWID) increased significantly during 2011 in Athens.nnnOBJECTIVEnOur aim was to investigate the patterns of HIV epidemic spread among PWID and to estimate the transmission dynamics for the major local transmission networks (LTNs).nnnMETHODSnWe analyzed sequences from 2,274 HIV-infected subjects sampled in Greece during 01/01/2011-31/10/2014. Of specimens in our sample, 874 sequences were isolated from HIV-infected PWID. Phylodynamic analysis was performed using birth-death serial skyline models.nnnRESULTSnPhylogenetic analysis revealed that the majority of sequences from PWID (N=746, 85.4%) fell within four LTNs: CRF14_BG (N=456, 58.3%), CRF35_AD (N=149, 19.1%), subtype B (N=118, 15.1%) and A1 (N=59, 7.5%). In addition to PWID, we also found that sequences from 36 non-PWID belonged to the LTNs corresponding to cross-group transmissions. Based on the estimated plots of the effective reproductive number (Re) over time, subtype A1 and CRF35_AD LTNs showed a sharp increase before and during 2011 (maximum value of Re=3.0 and Re=4.6, respectively). For subtype B and CRF14_BG LTNs, the Re was increasing until the end of 2012 (maximum value of Re=3.2 and Re=3.0, respectively).nnnCONCLUSIONnHIV transmissions within subtype A1 and CRF35_AD LTNs increased sharply during the early stage of the outbreak, in contrast to subtype B and CRF14_BG. A significant reduction in the number of infections was estimated on all transmission networks from the beginning of 2013 onwards. Prevention measures that took place in the Athens metropolitan area at the end of 2012 including also the ARISTOTLE program may explain this decrease.

Interleukin gene polymorphisms and susceptibility to HIV-1 infection: a meta-analysis

Some subjects are repeatedly exposed to human immunodeficiency virus (HIV), yet they remain uninfected. This suggests the existence of host-resistance mechanisms. The current study synthesizes the evidence regarding the association between interleukin (IL) gene polymorphisms and HIV susceptibility. Medline, Scopus and the Web of Science databases were systematically searched, and a meta-analysis of case–control studies was conducted. Univariate and bivariate methods were used. The literature search identified 42 eligible studies involving 15,727 subjects. Evidence was obtained on eight single-nucleotide polymorphisms (SNPs): IL1A −889 C>T (rs1800587), IL1B +3953/4 C>T (rs1143634), IL4 −589/90 C>T (rs2243250), IL6 −174 G>C (rs1800795), IL10 −592 C>A (rs1800872), IL10−1082 A>G (rs1800896), IL12B −1188 A>C (rs3212227) and IL28B C>T (rs12979860). The IL1B +3953/4 C>T variant appears to increase the risk of HIV acquisition, under the assumption of a recessive genetic model (odds ratio (OR): 4.47, 95% CI: 2.35–8.52). The AA homozygotes of the IL10 -592 C>A SNP had an increased, marginally nonsignificant, risk (OR: 1.39, 95% CI: 0.97–2.01). It reached, however, significance in subanalyses (OR: 1.49, 95% CI: 1.04–2.12). Finally, the well-studied hepatitis C virus (HCV) infection IL28B (rs12979860) CT/TT genotypes were associated with a 27% decrease in HIV infection risk, especially in populations infected with HCV (OR: 0.73, 95% CI: 0.57–0.95). Interleukin signalling is perhaps important in HIV infection and some interleukin genetic variants may affect the risk of HIV acquisition. Approaches targeting specific genes and genomewide association studies should be conducted to decipher the effect of these polymorphisms.

Editorial: tofacitinib and biologics for moderate-to-severe ulcerative colitis-what is best in class? Authors’ reply

ulcerative colitis. Inflamm Bowel Dis. 2010;16:338-346. 3. Vickers AD, Ainsworth C, Mody R, et al. Systematic review with network meta-analysis: comparative efficacy of biologics in the treatment of moderately to severely active ulcerative colitis. PLoS ONE. 2016;11:e0165435. 4. Cholapranee A, Hazlewood GS, Kaplan GG, Peyrin-Biroulet L, Ananthakrishnan AN. Systematic review with meta-analysis: comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn’s disease and ulcerative colitis controlled trials. Aliment Pharmacol Ther. 2017;45:1291-1302.

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

BACKGROUNDnFlow 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.nnnMATERIALS AND METHODSn94 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.nnnRESULTSnCV 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 1u202f×u202f106 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-squaredu202f=u202f0.01, pu202f=u202f0.35) between the two methods, while the Bland-Altman analysis for the measuring agreement showed a bias toward a higher Nageotte count of 0.77u202f×u202f106 leucocytes per unit (pu202f<u202f0.001) with the 95% limits of agreement (d ± 2u202fsd) ranging from -0.40u202f×u202f106 to 1.94u202f×u202f106 leucocytes per unit.nnnCONCLUSIONnThe absence of agreement between Nageotte and FC method, with the differences within d ± 2u202fsd 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.

FluHMM: A simple and flexible Bayesian algorithm for sentinel influenza surveillance and outbreak detection

Timely detection of the seasonal influenza epidemic is important for public health action. We introduce FluHMM, a simple but flexible Bayesian algorithm to detect and monitor the seasonal epidemic on sentinel surveillance data. No comparable historical data are required for its use. FluHMM segments a typical influenza surveillance season into five distinct phases with clear interpretation (pre-epidemic, epidemic growth, epidemic plateau, epidemic decline and post-epidemic) and provides the posterior probability of being at each phase for every week in the period under surveillance, given the available data. An alert can be raised when the probability that the epidemic has started exceeds a given threshold. An accompanying R package facilitates the application of this method in public health practice. We apply FluHMM on 12 seasons of sentinel surveillance data from Greece, and show that it achieves very good sensitivity, timeliness and perfect specificity, thereby demonstrating its usefulness. We further discuss advantages and limitations of the method, providing suggestions on how to apply it and highlighting potential future extensions such as with integrating multiple surveillance data streams.