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BMJ Clinical Evidence Jun 2015Chickenpox is extremely contagious. More than 90% of unvaccinated people will become infected during their lifetime, but infection occurs at different ages in different... (Review)
Review
INTRODUCTION
Chickenpox is extremely contagious. More than 90% of unvaccinated people will become infected during their lifetime, but infection occurs at different ages in different parts of the world. In the US, the UK, and Japan, more than 80% of people have been infected by the age of 10 years, and by the age of 20 to 30 years in India, South East Asia, and the West Indies. It is usually a mild and self-limiting disease, but it can be severely complicated by pneumonitis or disseminated disease in some individuals, particularly neonates and those who are immunocompromised.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatment for chickenpox in healthy adults and children (including neonates) within 24 hours after onset of rash? What are the effects of treatment for chickenpox in healthy adults and children (including neonates) later than 24 hours after onset of rash? What are the effects of treatment for chickenpox in immunocompromised adults and children (including neonates)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review).
RESULTS
We found six studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic overview we present information relating to the effectiveness and safety of aciclovir, within 24 hours of onset of rash or later than 24 hours of onset of rash, in otherwise-healthy adults and children (including neonates); and aciclovir in immunocompromised adults and children (including neonates).
Topics: Acyclovir; Chickenpox; Humans; Immunocompromised Host; India; Treatment Outcome
PubMed: 26077272
DOI: No ID Found -
BMC Ophthalmology Apr 2015This objective of the review and analysis is to demonstrate that acyclovir (ACV) 3% ophthalmic ointment is superior to idoxuridine (IDU) in treating herpetic keratitis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This objective of the review and analysis is to demonstrate that acyclovir (ACV) 3% ophthalmic ointment is superior to idoxuridine (IDU) in treating herpetic keratitis (HK) presenting as dendritic and geographic ulcer sub-types.
DATA SOURCES
Publications in human subjects were identified by searching the Ovid MEDLINE database through April 2011, combining medical subject headings (MESH) "Keratitis, Herpetic/" AND "Acyclovir/" limiting by the key words "topical" OR "ointment" and also restricted to MESH "Administration, Topical/" OR "Ointments/". The results were cross checked with the references used in the Cochrane Database Syst Rev. 1:1-134, 2009 and GlaxoSmithKline clinical documents related to acyclovir.
STUDY SELECTION
Randomized, double-masked studies in subjects diagnosed with HK with head to head comparator arms of ACV ophthalmic ointment and topical IDU that had actual or calculable healing rates at Day seven.
DATA EXTRACTION
Data independently extracted from identified articles by two authors of this manuscript.
DATA SYNTHESIS
Data from seven randomized, controlled trials (RCT) evaluating 432 subjects that met inclusion criteria (214 were treated with ACV and 218 were treated with IDU) and had Day seven healing rates calculable. All sub-classified lesions were identified as either dendritic ulcers (n = 185) or geographic ulcers (n = 35). The Cochran-Mantel-Haenszel (CMH) method in Biometrics 10:417-51, 1954 and JNCI 22:719-48, 1959, controlling for study, was performed as the primary analysis using SAS v9. Homogeneity was assessed using Breslow-Day-Tarone (BDT) test in IARC 1:1-32, 1980 and Biometrika 72:91-5, 1985. The analysis was performed with outliers removed to assess their impact.
RESULTS
ACV showed statistically significant greater odds of healing HK at Day seven in all subjects (Odds Ratio 3.95, 95% CI2.60, 6.00, p < 0.0001), in dendritic ulcers (Odds Ratio 4.22, 95% CI: 2.14, 8.32; p < 0.0001) and geographic ulcers (Odds Ratio 5.31, 95% CI: 1.09, 25.93; p = 0.0244).
CONCLUSION
ACV 3% ophthalmic ointment is a valuable intervention for dendritic and geographic corneal ulcers. ACV and IDU were generally well tolerated in the studies reviewed.
Topics: Acyclovir; Antiviral Agents; Follow-Up Studies; Humans; Idoxuridine; Keratitis, Herpetic; Ointments; Time Factors; Treatment Outcome
PubMed: 25928630
DOI: 10.1186/s12886-015-0022-2 -
BMC Infectious Diseases Feb 2015Recurrent herpes labialis (RHL) is one of the most common viral infections worldwide. The available treatments have limited efficacy in preventing the recurrence of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recurrent herpes labialis (RHL) is one of the most common viral infections worldwide. The available treatments have limited efficacy in preventing the recurrence of ulcerative lesions and reducing the duration of illness. The objective of this review was to identify the effectiveness of topical corticosteroids in addition to antiviral therapy in the treatment of RHL infection.
METHODS
A systematic review of randomized clinical trials comparing the efficacy of combined therapy (topical corticosteroids with antiviral) with placebo or antiviral alone in the management of RHL was conducted. MEDLINE, EMBASE, CINAHL, Web of Science, the Cochrane library, and Google Scholar databases were searched. We used RevMan software to conduct the meta-analysis. A fixed-effects model was used for mild to moderate heterogeneity, whereas a random-effects model was used for significant heterogeneity. Heterogeneity among trials was established using I(2) and chi-square test for heterogeneity.
RESULTS
Four studies that fulfilled the selection criteria were included in this review. The total number of participants across included studies was 1,891 (range, 29 to 1,443). The antiviral drugs used were acyclovir, famciclovir, and valacyclovir. Corticosteroids used were 1% hydrocortisone and 0.05% fluocinonide. Pooled results showed that patients receiving combined therapy had a significantly lower recurrence rate of ulcerative lesions compared to those in both the placebo group (OR, 0.50; 95% CI, 0.39-0.66; P < .001) and the antiviral treatment alone group (OR, 0.73, 95% CI, 0.58-0.92; P = .007). The healing time was also significantly shorter in combined therapy in comparison to placebo (P < .001). However, there were no significant differences in healing time between combined therapy and antiviral alone. The adverse reactions in combined therapy were not significantly different than the placebo group (OR, 1.09; 95% C, 0.75-1.59; P = .85).
CONCLUSION
Treatment with combined therapy is safe and more effective than placebo or antiviral alone for preventing the recurrence of ulcerative lesions in RHL infection.
Topics: 2-Aminopurine; Acyclovir; Administration, Cutaneous; Administration, Oral; Adrenal Cortex Hormones; Antiviral Agents; Drug Therapy, Combination; Famciclovir; Female; Herpes Labialis; Humans; Recurrence; Treatment Outcome; Valacyclovir; Valine
PubMed: 25887308
DOI: 10.1186/s12879-015-0824-0 -
The Cochrane Database of Systematic... Jan 2015Eye disease due to herpes simplex virus (HSV) commonly presents as epithelial keratitis which, though usually self-limiting, may persist or progress without treatment. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Eye disease due to herpes simplex virus (HSV) commonly presents as epithelial keratitis which, though usually self-limiting, may persist or progress without treatment.
OBJECTIVES
To compare the relative effectiveness of antiviral agents, interferon, and corneal debridement in the treatment of HSV epithelial keratitis.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 12), PubMed (January 1946 to 31 December 2014), EMBASE (January 1980 to 31 December 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to 31 December 2014), System for Information on Grey Literature in Europe (OpenGrey) (January 1995 to 31 December 2014), BIOSIS (January 1926 to 5 May 2014), Scopus (January 1966 to 31 December 2014), Japan Science and Technology Institute (J-Global) (January 1975 to 31 December 2014), China National Knowledge Infrastructure (CNKI) (January 1979 to 31 December 2014), British Library's Electronic Table of Contents (Zetoc) (January 1993 to 7 May 2014). We looked for trials listed on the the metaRegister of Controlled Trials (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en), Chinese Clinical Trial Registry, the U.S. Food and Drug Administration (FDA) (www.fda.gov/), National Institute for Health and Clinical Excellence (NICE) (www.
EVIDENCE
nhs.uk) and the European Medicines Agency (EMA) (www.ema.europa.eu/ema/) as of 31 December 2014. There were no language or date restrictions in the search for trials. We also culled literature digests and conference proceedings as of 15 April 2014. There were no language or date restrictions in the search for trials.
SELECTION CRITERIA
Randomised and quasi-randomised trials of HSV dendritic or geographic epithelial keratitis were included that reported the proportion of eyes healed at one week, two weeks, or both after enrolment.
DATA COLLECTION AND ANALYSIS
We tabulated data on study characteristics, risk of bias, and outcomes and used direct comparisons to estimate a risk ratio (RR) and, when feasible, a hazard ratio (HR) with a 95% confidence interval (CI). Heterogeneity was assessed by an inconsistency index. A multiple treatment comparison meta-analysis consolidated direct and indirect comparisons of relative healing at 14 days.
MAIN RESULTS
One hundred thirty-seven studies involving 8333 eyes met the inclusion criteria. Placebo-controlled studies were heterogeneous in comparison with idoxuridine (RR 1.74; 95% CI 1.03 to 2.91) and few in number for vidarabine (RR 1.81; 95% CI 1.09 to 3.01), interferon (RR 1.32; 95% CI 1.06 to 1.64), and debridement. Vidarabine (RR 1.13; 95% CI 1.02 to 1.25), trifluridine (RR 1.30; 95% CI 1.18 to 1.43), acyclovir (RR 1.23; 95% CI 1.14 to 1.34), and brivudine (RR 1.34; 95% CI 1.18 to 1.51) were more effective than idoxuridine. Trifluridine (RR 1.17; 95% CI 1.03 to 1.32) and acyclovir (RR 1.11; 95% CI 1.03 to 1.19) were more effective than vidarabine. No significant differences in healing emerged among trifluridine, acyclovir, brivudine, and foscarnet although few studies compared brivudine or foscarnet with other antivirals. Any potential advantage of ganciclovir compared to acyclovir was mitigated by study heterogeneity and possible publication bias. Only one study evaluated the joint use of two topical antivirals. In a limited number of studies, oral acyclovir (RR 0.92; 95% CI 0.79 to 1.07) or the combination of oral acyclovir with a topical antiviral (RR 1.36; 95% CI 0.68 to 2.74) appeared as effective as a single topical antiviral agent. Compared to topical antiviral monotherapy, the combination of an antiviral with either interferon or debridement had inconsistent effects on expediting healing and improving outcome.
AUTHORS' CONCLUSIONS
Placebo-controlled studies of HSV epithelial keratitis are limited to superseded interventions. Trifluridine and acyclovir are more effective than idoxuridine or vidarabine and similar in therapeutic effectiveness. Brivudine and foscarnet do not substantially differ in effectiveness from trifluridine or acyclovir. Ganciclovir is at least as effective as acyclovir. The addition of interferon to a nucleoside antiviral agent and the combination of debridement with antiviral treatment need to be further assessed to substantiate any possible advantage in healing.
Topics: Administration, Oral; Administration, Topical; Antiviral Agents; Combined Modality Therapy; Debridement; Humans; Interferons; Keratitis, Herpetic; Randomized Controlled Trials as Topic
PubMed: 25879115
DOI: 10.1002/14651858.CD002898.pub5 -
BMJ Clinical Evidence Apr 2015Genital herpes is an infection with herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2), and is among the most common sexually transmitted diseases. (Review)
Review
INTRODUCTION
Genital herpes is an infection with herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2), and is among the most common sexually transmitted diseases.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of different oral antiviral treatments versus each other for a first episode of genital herpes in HIV-negative people? What are the effects of different antiviral treatments for genital herpes in HIV-positive people? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found eight studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: aciclovir, famciclovir, and valaciclovir.
Topics: Administration, Oral; Antiviral Agents; Herpes Genitalis; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Treatment Outcome
PubMed: 25853497
DOI: No ID Found -
American Journal of Transplantation :... Feb 2015We systematically reviewed and meta-analyze the efficacy of universal prophylaxis (UP) and preemptive (PE) strategies (using ganciclovir or valganciclovir) in preventing... (Comparative Study)
Comparative Study Meta-Analysis Review
We systematically reviewed and meta-analyze the efficacy of universal prophylaxis (UP) and preemptive (PE) strategies (using ganciclovir or valganciclovir) in preventing cytomegalovirus (CMV) disease (CMD) among liver transplant recipients (LTRs). We performed an electronic search of MEDLINE, EMBASE and the Cochrane Database till December 2013. Studies that assessed UP or PE for preventing CMD in LTRs were included. The risk of bias was assessed using the Newcastle-Ottawa scale. The primary outcome was CMD, secondary outcomes being acute cellular rejection (ACR), graft loss (GL) and mortality. Due to the heterogeneity of comparative studies, an indirect comparison was performed. Pooled incidence rates with 95% confidence interval (CI) are calculated for each outcome using a random-effects model. Thirty-two studies involving 2456 LTRs were included. The majority of the studies were of low risk of bias. Irrespective of donor/recipient CMV sero-status, CMD was 10% with UP (95% CI: 6-14; I(2) = 87%; 16 studies, n = 1581) and 7% with PE (95% CI: 3-10; I(2) = 84%; 16 studies, n = 875) (mean difference 2.6; 95% CI: -3.25 to 8.45, p = 0.34). Likewise, ACR and mortality were similar with the two strategies. However, GL was significantly lower in the UP group, regardless of donor/recipient sero-status. In indirect comparison, the incidence of CMD, ACR and mortality in LTRs were similar with two strategies. Trials comparing the two strategies directly are needed.
Topics: Adult; Aged; Antiviral Agents; Cytomegalovirus Infections; Female; Ganciclovir; Graft Rejection; Humans; Incidence; Liver Diseases; Liver Transplantation; Male; Middle Aged; Risk Assessment; Survival Rate; Valganciclovir
PubMed: 25522141
DOI: 10.1111/ajt.13044 -
The Cochrane Database of Systematic... Sep 2014Behçet's disease is a chronic inflammatory vasculitis that can affect multiple systems. Mucocutaneous involvement is common, as is the involvement of many other systems... (Review)
Review
BACKGROUND
Behçet's disease is a chronic inflammatory vasculitis that can affect multiple systems. Mucocutaneous involvement is common, as is the involvement of many other systems such as the central nervous system and skin. Behç̧et's disease can cause significant morbidity, such as loss of sight, and can be life threatening. The frequency of oral ulceration in Behçet's disease is thought to be 97% to 100%. The presence of mouth ulcers can cause difficulties in eating, drinking, and speaking leading to a reduction in quality of life. There is no cure for Behçet's disease and therefore treatment of the oral ulcers that are associated with Behçet's disease is palliative.
OBJECTIVES
To determine the clinical effectiveness and safety of interventions on the pain, episode duration, and episode frequency of oral ulcers and on quality of life for patients with recurrent aphthous stomatitis (RAS)-type ulceration associated with Behçet's disease.
SEARCH METHODS
We undertook electronic searches of the Cochrane Oral Health Group Trials Register (to 4 October 2013); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9); MEDLINE via Ovid (1946 to 4 October 2013); EMBASE via Ovid (1980 to 4 October 2013); CINAHL via EBSCO (1980 to 4 October 2013); and AMED via Ovid (1985 to 4 October 2013). We searched the US National Institutes of Health trials register (http://clinicaltrials.gov) and the World Health Organization (WHO) Clinical Trials Registry Platform for ongoing trials. There were no restrictions on language or date of publication in the searches of the electronic databases. We contacted authors when necessary to obtain additional information.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that looked at pre-specified oral outcome measures to assess the efficacy of interventions for mouth ulcers in Behçet's disease. The oral outcome measures included pain, episode duration, episode frequency, safety, and quality of life. Trials were not restricted by outcomes alone.
DATA COLLECTION AND ANALYSIS
All studies meeting the inclusion criteria underwent data extraction and an assessment of risk of bias, independently by two review authors and using a pre-standardised data extraction form. We used standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
A total of 15 trials (n = 888 randomised participants) were included, 13 were placebo controlled and three were head to head (two trials had more than two treatment arms). Eleven of the trials were conducted in Turkey, two in Japan, one in Iran and one in the UK. Most trials used the International Study Group criteria for Behçet's disease. Eleven different interventions were assessed. The interventions were grouped into two categories, topical and systemic. Only one study was assessed as being at low risk of bias. It was not possible to carry out a meta-analysis. The quality of the evidence ranged from moderate to very low and there was insufficient evidence to support or refute the use of any included intervention with regard to pain, episode duration, or episode frequency associated with oral ulcers, or safety of the interventions.
AUTHORS' CONCLUSIONS
Due to the heterogeneity of trials including trial design, choice of intervention, choice and timing of outcome measures, it was not possible to carry out a meta-analysis. Several interventions show promise and future trials should be planned and reported according to the CONSORT guidelines. Whilst the primary aim of many trials for Behç̧et's disease is not necessarily reduction of oral ulceration, reporting of oral ulcers in these studies should be standardised and pre-specified in the methodology. The use of a core outcome set for oral ulcer trials would be beneficial.
Topics: Acyclovir; Adrenal Cortex Hormones; Alanine; Behcet Syndrome; Colchicine; Cyclosporine; Etanercept; Humans; Immunoglobulin G; Interferon-alpha; Oral Ulcer; Quinolones; Randomized Controlled Trials as Topic; Receptors, Tumor Necrosis Factor; Stomatitis, Aphthous; Sucralfate; Thalidomide
PubMed: 25254615
DOI: 10.1002/14651858.CD011018.pub2 -
The Cochrane Database of Systematic... Aug 2014Genital herpes is caused by herpes simplex virus 1 (HSV-1) or 2 (HSV-2). Some infected people experience outbreaks of genital herpes, typically, characterized by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Genital herpes is caused by herpes simplex virus 1 (HSV-1) or 2 (HSV-2). Some infected people experience outbreaks of genital herpes, typically, characterized by vesicular and erosive localized painful genital lesions.
OBJECTIVES
To compare the effectiveness and safety of three oral antiviral drugs (acyclovir, famciclovir and valacyclovir) prescribed to suppress genital herpes outbreaks in non-pregnant patients.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the search portal of the World Health Organization International Clinical Trials Registry Platform and pharmaceutical company databases up to February 2014. We also searched US Food and Drug Administration databases and proceedings of seven congresses to a maximum of 10 years. We contacted trial authors and pharmaceutical companies.
SELECTION CRITERIA
We selected parallel-group and cross-over randomized controlled trials including patients with recurrent genital herpes caused by HSV, whatever the type (HSV-1, HSV-2, or undetermined), with at least four recurrences per year (trials concerning human immunodeficiency virus (HIV)-positive patients or pregnant women were not eligible) and comparing suppressive oral antiviral treatment with oral acyclovir, famciclovir, and valacyclovir versus placebo or another suppressive oral antiviral treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected eligible trials and extracted data. The Risk of bias tool was used to assess risk of bias. Treatment effect was measured by the risk ratio (RR) of having at least one genital herpes recurrence. Pooled RRs were derived by conventional pairwise meta-analyses. A network meta-analysis allowed for estimation of all possible two-by-two comparisons between antiviral drugs.
MAIN RESULTS
A total of 26 trials (among which six had a cross-over design) were included. Among the 6950 randomly assigned participants, 54% (range 0 to 100%) were female, mean age was 35 years (range 26 to 45.1), and the mean number of recurrences per year was 11 (range 6.3 to 17.8). Duration of treatment was two to 12 months. Risk of bias was considered high for half of the studies and unclear for the other half. A total of 14 trials compared acyclovir versus placebo, four trials compared valacyclovir versus placebo and 2 trials compared valacyclovir versus no treatment. Three trials compared famciclovir versus placebo. Two trials compared valacyclovir versus famciclovir and one trial compared acyclovir versus valacyclovir versus placebo.We analyzed data from 22 trials for the outcome: risk of having at least one clinical recurrence. We could not obtain the outcome data for four trials. In placebo-controlled trials, there was a low quality evidence that the risk of having at least one clinical recurrence was reduced with acyclovir (nine parallel-group trials, n = 2049; pooled RR 0.48, 95% confidence interval (CI) 0.39 to 0.58), valacyclovir (four trials, n = 1788; pooled RR 0.41, 95% CI 0.24 to 0.69), or famciclovir (two trials, n = 732; pooled RR 0.57, 95% CI 0.50 to 0.64). The six cross-over trials showed larger treatment effects on average than the parallel-group trials. We found evidence of a small-study effect for acyclovir placebo-controlled trials (adjusted pooled RR 0.61, 95% CI 0.49 to 0.75). In analyzing parallel-group trials by daily dose, no clear evidence was found of a dose-response relationship for any drug. In head-to-head trials, the risk of having at least one recurrence was increased with valacyclovir rather than acyclovir (one trial, n = 1345; RR 1.16, 95% CI 1.01 to 1.34) and was not significantly different from that seen with famciclovir as compared with valacyclovir (one trial, n = 320; RR 1.18, 95% CI 0.86 to 1.63).We included 16 parallel-arm trials in a network meta-analysis and we were unable to determine which of the drugs was most effective in reducing the risk of at least one clinical recurrence (after adjustment for small-study effects, pooled RR 0.83, 95% CI 0.61 to 1.11 for valacyclovir vs acyclovir; pooled RR 1.04, 95% CI, 0.71 to 1.49 for famciclovir vs acyclovir; and pooled RR 1.26, 95% CI 0.89 to 1.75 for famciclovir vs valacyclovir). Safety data were sought but were reported as total numbers of adverse events.
AUTHORS' CONCLUSIONS
Owing to risk of bias and inconsistency, there is low quality evidence that suppressive antiviral therapy with acyclovir, valacyclovir or famciclovir in pacients experiencing at least four recurrences of genital herpes per year decreases the number of pacients with at least one recurrence as compared with placebo. Network meta-analysis of the few direct comparisons and the indirect comparisons did not show superiority of one drug over another.
Topics: 2-Aminopurine; Acyclovir; Administration, Oral; Adult; Antiviral Agents; Famciclovir; Female; Herpes Genitalis; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Immunocompetence; Middle Aged; Randomized Controlled Trials as Topic; Recurrence; Valacyclovir; Valine
PubMed: 25086573
DOI: 10.1002/14651858.CD009036.pub2