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Epidemiology and Health 2018John Cunningham virus (JCV) is a polyoma virus that infects humans, mainly in childhood or adolescence, and presents no symptomatic manifestations. JCV can cause... (Review)
Review
OBJECTIVES
John Cunningham virus (JCV) is a polyoma virus that infects humans, mainly in childhood or adolescence, and presents no symptomatic manifestations. JCV can cause progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals, including those undergoing treatment for multiple sclerosis (MS) and neuromyelitis optica (NMO). PML is a severe and potentially fatal disease of the brain. The prevalence of JCV antibodies in human serum has been reported to be between 50.0 and 90.0%. The aim of the present study was to review worldwide data on populations of patients with MS and NMO in order to establish the rates of JCV seropositivity in these individuals.
METHODS
The present review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and used the following search terms: "JCV" OR "JC virus" AND "multiple sclerosis" OR "MS" OR "NMO" OR "neuromyelitis optica" AND "prevalence." These terms were searched for both in smaller and in larger clusters of words. The databases searched included PubMed, MEDLINE, SciELO, LILACS, Google Scholar, and Embase.
RESULTS
After the initial selection, 18 papers were included in the review. These articles reported the prevalence of JCV antibodies in the serum of patients with MS or NMO living in 26 countries. The systematic review identified data on 29,319 patients with MS/NMO and found that 57.1% of them (16,730 individuals) were seropositive for the anti-JCV antibody (range, 40.0 to 69.0%).
CONCLUSIONS
The median worldwide prevalence of JCV among adults with MS or NMO was found to be 57.1%.
Topics: Antibodies, Viral; Global Health; Humans; JC Virus; Multiple Sclerosis; Neuromyelitis Optica; Prevalence
PubMed: 29370683
DOI: 10.4178/epih.e2018001 -
Alimentary Pharmacology & Therapeutics Jul 2017Vedolizumab specifically recognises the α4β7 integrin and selectively blocks gut lymphocyte trafficking: potentially, it offers gut-specific immunosuppression. (Review)
Review
BACKGROUND
Vedolizumab specifically recognises the α4β7 integrin and selectively blocks gut lymphocyte trafficking: potentially, it offers gut-specific immunosuppression.
AIM
To review the safety of vedolizumab and summarise post-marketing data to assess if any safety concerns that differ from registration trials have emerged.
METHOD
A systematic bibliographic search identified six registration trials and nine cohort studies.
RESULTS
Integrated data from registration trials included 2830 vedolizumab-exposed patients (4811 person-years exposure [PYs]) and 513 placebo patients. This reported lower exposure-adjusted incidence rates of infection (63.5/100 PYs; 95% CI: 59.6-67.3) and serious adverse events (20.0/100 PYs; 95% CI: 18.5-21.5) compared to placebo (82.9/100 PYs; 95% CI: 68.3-97.5) and (28.3/100 PYs 95% CI: 20.6-35.9) respectively. Higher, but statistically insignificant rates of enteric infections occurred in vedolizumab-exposed patients (7.4/100 PYs; 95% CI: 6.6-8.3) compared to placebo (6.7 PYs; 95% CI: 3.2-10.1). Six post-marketing cohort studies (1049 patients, 403 PYs) demonstrated rates of infection of 8% (82/1049); enteric infection of 2% (21/1049) and adverse events of 16% (166/1049). Multivariate analysis in one cohort study suggested increased risk of surgical site infection with perioperative VDZ. Human experience in pregnancy is limited.
CONCLUSIONS
Post-marketing data confirm the excellent safety of vedolizumab observed in registration trials. The signal of post-operative complications should be interpreted with caution, but warrants further study. Although comparative studies are needed, Vedolizumab may be a safe alternative in patients who best avoid systematic immunosuppression, including those pre-disposed to infection, malignancy or the elderly.
Topics: Animals; Antibodies, Monoclonal, Humanized; Female; Gastrointestinal Agents; Humans; Infections; Inflammatory Bowel Diseases; Infusions, Intravenous; JC Virus; Lactation; Leukoencephalopathy, Progressive Multifocal; Neoplasms; Pregnancy; Vaccines
PubMed: 28449273
DOI: 10.1111/apt.14075 -
The Cochrane Database of Systematic... Sep 2015Bronchiolitis is the leading cause of hospitalisation among infants in high-income countries. Acute viral bronchiolitis is associated with airway obstruction and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bronchiolitis is the leading cause of hospitalisation among infants in high-income countries. Acute viral bronchiolitis is associated with airway obstruction and turbulent gas flow. Heliox, a mixture of oxygen and the inert gas helium, may improve gas flow through high-resistance airways and decrease the work of breathing. In this review, we selected trials that objectively assessed the effect of the addition of heliox to standard medical care for acute bronchiolitis.
OBJECTIVES
To assess heliox inhalation therapy in addition to standard medical care for acute bronchiolitis in infants with respiratory distress, as measured by clinical endpoints (in particular the rate of endotracheal intubation, the rate of emergency department discharge, the length of treatment for respiratory distress) and pulmonary function testing (mainly clinical respiratory scores).
SEARCH METHODS
We searched CENTRAL (2015, Issue 2), MEDLINE (1966 to March week 3, 2015), EMBASE (1974 to March 2015), LILACS (1982 to March 2015) and the National Institutes of Health (NIH) website (May 2009).
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs of heliox in infants with acute bronchiolitis.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed trial quality.
MAIN RESULTS
We included seven trials involving 447 infants younger than two years with respiratory distress secondary to viral bronchiolitis. All children were recruited from a paediatric intensive care unit (PICU; 378 infants), except in one trial (emergency department; 69 infants). All children were younger than two (under nine months in two trials and under three months in one trial). Positive tests for respiratory syncytial virus (RSV) were required for inclusion in five trials. The two other trials were carried out in the bronchiolitis seasons. Seven different protocols were used for inhalation therapy with heliox.When heliox was used in the PICU, we observed no significant reduction in the rate of intubation: risk ratio (RR) 2.73 (95% confidence interval (CI) 0.96 to 7.75, four trials, 408 infants, low quality evidence). When heliox inhalation was used in the emergency department, we observed no increase in the rate of discharge: RR 0.51 (95% CI 0.17 to 1.55, one trial, 69 infants, moderate quality evidence).There was no decrease in the length of treatment for respiratory distress: mean difference (MD) -0.19 days (95% CI -0.56 to 0.19, two trials, 320 infants, moderate quality evidence). However, in the subgroup of infants who were started on nasal continuous positive airway pressure (nCPAP) right from the start, because of severe respiratory distress, heliox therapy reduced the length of treatment: MD -0.76 days (95% CI -1.45 to -0.08, one trial, 21 infants, low quality evidence). No adverse events related to heliox inhalation were reported.We found that infants treated with heliox inhalation had a significantly lower mean clinical respiratory score in the first hour after starting treatment when compared to those treated with air or oxygen inhalation: MD -1.04 (95% CI -1.60 to -0.48, four trials, 138 infants, moderate quality evidence). This outcome had statistical heterogeneity, which remained even after removing the study using a standard high-concentration reservoir mask. Several factors may explain this heterogeneity, including first the limited number of patients in each trial, and the wide differences in the baseline severity of disease between studies, with the modified Wood Clinical Asthma Score (m-WCAS) in infants treated with heliox ranging from less than two to more than seven.
AUTHORS' CONCLUSIONS
Current evidence suggests that the addition of heliox therapy may significantly reduce a clinical score evaluating respiratory distress in the first hour after starting treatment in infants with acute RSV bronchiolitis. We noticed this beneficial effect regardless of which heliox inhalation protocol was used. Nevertheless, there was no reduction in the rate of intubation, in the rate of emergency department discharge, or in the length of treatment for respiratory distress. Heliox could reduce the length of treatment in infants requiring CPAP for severe respiratory distress. Further studies with homogeneous logistics in their heliox application are needed. Inclusion criteria must include a clinical severity score that reflects severe respiratory distress to avoid inclusion of children with mild bronchiolitis who may not benefit from heliox inhalation. Such studies would provide the necessary information as to the appropriate place for heliox in the therapeutic schedule for severe bronchiolitis.
Topics: Acute Disease; Administration, Inhalation; Bronchiolitis, Viral; Bronchodilator Agents; Helium; Humans; Infant; Intensive Care Units, Pediatric; Intubation, Intratracheal; Length of Stay; Oxygen; Randomized Controlled Trials as Topic; Respiratory Syncytial Virus Infections
PubMed: 26384333
DOI: 10.1002/14651858.CD006915.pub3 -
Urologic Oncology Oct 2013The potential role of genitourinary infection in the etiology of prostate cancer (CaP) has been extensively investigated for 30 years. Two basic approaches have been... (Review)
Review
BACKGROUND
The potential role of genitourinary infection in the etiology of prostate cancer (CaP) has been extensively investigated for 30 years. Two basic approaches have been used: tissue-based methods (polymerase chain reaction, immunohistochemistry, and in situ hybridization) and serologic assays (enzyme-linked immunosorbent assay, immunofluorescence, etc.). The objective of this review was to answer the question of whether infection of the male genitourinary tract may have a role in the etiology of CaP.
MATERIALS AND METHODS
We have carried out a systematic review of the evidence that was published in the MEDLINE/PubMed database until December 2011. The search terms included "prostate cancer," "infection," and the explicit names of the various infectious agents. Additional studies were identified using a reference search. A total of 74 papers were included in the review, which cover the following infectious agents: human papillomavirus, cytomegalovirus, herpes simplex virus, Epstein-Barr virus, human herpesvirus, BK virus, JC virus, chlamydia, mycoplasma, ureaplasma, trichomonas, neisseria, treponema, Propionibacterium acnes, xenotropic murine leukemia virus-related virus and Candida albicans.
RESULTS
Despite the variable study designs and methodological approaches that were used, most of the pathogens that were studied were unlikely to be directly involved in prostate carcinogenesis.
CONCLUSIONS
The role of infection in the etiology of CaP has yet to be determined despite 30 years of research efforts. A discovery of an infectious agent that is associated with CaP would be of great medical importance; however, such a link would have to be firmly established before impacting on patient care.
Topics: Bacterial Infections; Humans; Male; Mycoses; Prostatic Neoplasms; Risk Assessment; Risk Factors; Virus Diseases
PubMed: 22459691
DOI: 10.1016/j.urolonc.2012.01.013 -
The Cochrane Database of Systematic... Jan 2007The pathogenesis of Crohn's disease involves migration of leukocytes into gut tissue and subsequent inflammation. Natalizumab (Tysabri(R), Elan Pharmaceuticals and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The pathogenesis of Crohn's disease involves migration of leukocytes into gut tissue and subsequent inflammation. Natalizumab (Tysabri(R), Elan Pharmaceuticals and Biogen Idec) a recombinant humanized IgG4 monoclonal antibody that blocks adhesion and subsequent migration of leukocytes into the gut by binding the alpha4 integrin is a member of a new class of molecules known as selective adhesion molecule (SAM) inhibitors. The results of animal studies suggest that alpha4 integrin blockade could be a useful therapy for inflammatory bowel disease. The results of randomized controlled trials suggest that natalizumab may be an effective therapy for active Crohn's disease. This systematic review summarizes the current evidence on the use of natalizumab for the induction of remission in Crohn's disease.
OBJECTIVES
To determine the efficacy and safety of natalizumab for induction of remission in Crohn's disease.
SEARCH STRATEGY
A computer assisted search of the Cochrane Central Register of Controlled Trials, the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Review Group Specialized Trials Register, MEDLINE and EMBASE was performed to identify relevant publications between 1966 and September 2006. The medical subject heading (MeSH) terms "Crohn disease" or "inflammatory bowel disease", "Natalizumab" or "Antegren" or "Tysabri" and "Antibodies, Monoclonal" were used to perform key word searches of each database. Manual searches of reference lists from potentially relevant papers were performed in order to identify additional studies that may have been missed using the computer-assisted search strategy. Abstracts from major gastroenterological meetings were searched to identify research submitted in abstract form only. Personal contacts, leaders in the field, and the manufacturers were contacted to identify other studies which may not be published.
SELECTION CRITERIA
We included only randomized controlled trials comparing natalizumab to a placebo or control therapy for the induction of remission in Crohn's disease.
DATA COLLECTION AND ANALYSIS
Data were analyzed using Review Manager (RevMan 4.2.8). All data were analyzed on an intention-to-treat basis. For pooled data, summary test statistics were derived using the relative risk and 95% confidence intervals. Fixed and random effects models were used where appropriate. The definitions of treatment success, remission and clinical improvement were set by the authors of each paper, and the data were combined for analysis only if these definitions were sufficiently similar.
MAIN RESULTS
Pooled data from the four included studies suggest that natalizumab (300 mg or 3 to 4 mg/kg) is effective for induction of clinical response and remission in patients with moderately to severely active Crohn's disease. This benefit is statistically significant for one, two and three infusion treatments. There was a trend toward increased benefit with additional infusions of natalizumab. Natalizumab appears to provide greater benefit for patient subgroups characterized by objective confirmation of active inflammation or chronically active disease despite conventional therapies. These subgroup analyses demonstrated significantly greater clinical response and remission rates for natalizumab compared with placebo in patients with elevated C-reactive protein levels, active disease despite the use of immunosuppressants, or prior anti-tumor necrosis factor therapy. These benefits were apparent for both short term (one infusion) and longer term treatment (two or three infusions). Natalizumab was generally well tolerated and the safety profile observed in the four included studies was similar. Adverse events occurred infrequently and were experienced by a similar proportion of natalizumab and placebo treated patients. There were no statistically significant differences between natalizumab and placebo treated patients in the proportions of patients who withdrew due to adverse events or those who experienced serious adverse events. The included trials lacked adequate power to detect serious adverse events that occur infrequently. Recently, two patients with multiple sclerosis treated with natalizumab in combination with interferon beta-1a and one patient with Crohn's disease treated with natalizumab in combination with azathioprine developed progressive multifocal leukoencephalopathy (PML) resulting in two patient deaths. A retrospective investigation was conducted to assess the risk of PML in natalizumab treated patients and no new cases were identified.
AUTHORS' CONCLUSIONS
Pooled data suggest that natalizumab is effective for induction of clinical response and remission in some patients with moderately to severely active Crohn's disease. The clinical benefit of induction therapy with natalizumab in Crohn's disease should be weighed against the potential risk of serious adverse events. Preliminary data from the retrospective investigation of adverse events associated with natalizumab suggest that it may be possible to identify patients at risk for PML by testing for the appearance of JC virus in plasma.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Crohn Disease; Humans; Integrin alpha4; Integrins; Natalizumab; Randomized Controlled Trials as Topic; Remission Induction; Treatment Failure
PubMed: 17253580
DOI: 10.1002/14651858.CD006097.pub2 -
The Cochrane Database of Systematic... Jul 2006The pathogenesis of Crohn's disease involves migration of leukocytes into gut tissue and subsequent inflammation. Natalizumab (Tysabri, Elan Pharmaceuticals and Biogen... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The pathogenesis of Crohn's disease involves migration of leukocytes into gut tissue and subsequent inflammation. Natalizumab (Tysabri, Elan Pharmaceuticals and Biogen Idec) a recombinant humanized IgG4 monoclonal antibody that blocks adhesion and subsequent migration of leukocytes into the gut by binding the alpha4 integrin is a member of a new class of molecules known as selective adhesion molecule (SAM) inhibitors. The results of animal studies suggest that alpha4 integrin blockade could be a useful therapy for inflammatory bowel disease. The results of randomized controlled trials suggest that natalizumab may be an effective therapy for active Crohn's disease. This systematic review summarizes the current evidence on the use of natalizumab for the induction of remission in Crohn's disease.
OBJECTIVES
To determine the efficacy and safety of natalizumab for induction of remission in Crohn's disease.
SEARCH STRATEGY
A computer assisted search of the Cochrane Central Register of Controlled Trials, the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Review Group Specialized Trials Register, MEDLINE and EMBASE was performed to identify relevant publications between 1966 and June 2005. The medical subject heading (MeSH) terms "Crohn disease" or "inflammatory bowel disease", "Natalizumab" or "Antegren" or "Tysabri" and "Antibodies, Monoclonal" were used to perform key word searches of each database. Manual searches of reference lists from potentially relevant papers were performed in order to identify additional studies that may have been missed using the computer-assisted search strategy. Abstracts from major gastroenterological meetings were searched to identify research submitted in abstract form only. Personal contacts, leaders in the field, and the manufacturers were contacted to identify other studies which may not be published.
SELECTION CRITERIA
We included only randomized controlled trials comparing natalizumab to a placebo or control therapy for the induction of remission in Crohn's disease.
DATA COLLECTION AND ANALYSIS
Data were analyzed using Review Manager (RevMan 4.2.8). All data were analyzed on an intention-to-treat basis. For pooled data, summary test statistics were derived using the relative risk and 95% confidence intervals. Fixed and random effects models were used where appropriate. The definitions of treatment success, remission and clinical improvement were set by the authors of each paper, and the data were combined for analysis only if these definitions were sufficiently similar.
MAIN RESULTS
Pooled data from the three included studies suggest that natalizumab (3 to 4 mg/kg) may be effective for induction of clinical response and remission in patients with moderately to severely active Crohn's disease. This benefit is statistically significant for one, two and three infusion treatments. There was a trend toward increased benefit with additional infusions of natalizumab. Natalizumab appears to provide greater benefit for patient subgroups characterized by objective confirmation of active inflammation or chronically active disease despite conventional therapies. These subgroup analyses demonstrated significantly greater clinical response and remission rates for natalizumab compared with placebo in patients with elevated C-reactive protein levels, active disease despite the use of immunosuppressants, or prior anti-tumor necrosis factor therapy. These benefits were apparent for both short term (one infusion) and longer term treatment (two or three infusions). Natalizumab was generally well tolerated and the safety profile observed in the three included studies was similar. Adverse events occurred infrequently and were experienced by a similar proportion of natalizumab and placebo treated patients. There were no statistically significant differences between natalizumab and placebo treated patients in the proportions of patients who withdrew due to adverse events or those who experienced serious adverse events. The included trials lacked adequate power to detect serious adverse events that occur infrequently. Recently, two patients with multiple sclerosis treated with natalizumab in combination with interferon beta-1a and one patient with Crohn's disease treated with natalizumab in combination with azathioprine developed progressive multifocal leukoencephalopathy (PML) resulting in two patient deaths. As a result all dosing in clinical trials and commercial use of natalizumab has been suspended. A retrospective investigation was conducted to assess the risk of PML in natalizumab treated patients and no new cases were identified.
AUTHORS' CONCLUSIONS
Pooled data and the results of an ongoing study suggest that natalizumab may be effective for induction of clinical response and remission in patients with moderately to severely active Crohn's disease. The clinical benefit of induction therapy with natalizumab in Crohn's disease should be weighed against the potential risk of serious adverse events. Currently natalizumab is not available on the market for routine clinical use as a consequence of the unexpected association with PML. However, preliminary data from the retrospective investigation of adverse events associated with natalizumab suggest that it may be possible to identify patients at risk for PML by testing for the appearance of JC virus in plasma.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Crohn Disease; Humans; Integrin alpha4; Natalizumab; Randomized Controlled Trials as Topic; Remission Induction; Treatment Failure
PubMed: 16856112
DOI: 10.1002/14651858.CD006097