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Ultrasound in Obstetrics & Gynecology :... Apr 2023Universal screening for cytomegalovirus (CMV) infection in pregnancy is not recommended in most countries. One of the major deterrents is the lack of effective prenatal... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Universal screening for cytomegalovirus (CMV) infection in pregnancy is not recommended in most countries. One of the major deterrents is the lack of effective prenatal therapy. The role of valacyclovir therapy in reducing the risk of vertical transmission, symptomatic congenital CMV infection and adverse outcome is controversial. The main aim of this systematic review and meta-analysis was to investigate the safety and effectiveness of prenatal valacyclovir therapy in pregnancies with maternal CMV infection.
METHODS
MEDLINE, EMBASE and Cochrane databases and ClinicalTrials.gov were searched. The inclusion criteria were pregnancy with confirmed maternal CMV infection, treated or untreated with valacyclovir. The primary outcome was the incidence of congenital CMV infection confirmed by a positive CMV polymerase chain reaction result of the amniotic fluid. The secondary outcomes were symptomatic and asymptomatic infection, perinatal death, termination of pregnancy, anomalies detected on follow-up ultrasound, on fetal magnetic resonance imaging or at birth, severe and mild-to-moderate symptoms due to congenital CMV infection, neurological, visual and hearing symptoms, and adverse events related to valacyclovir. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2) or Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool, as appropriate. Head-to-head meta-analyses were used to compare the risk of each of the explored outcomes according to whether pregnancies with maternal CMV infection were treated with prenatal valacyclovir therapy.
RESULTS
Eight studies (620 women) were included. Pregnancies treated with valacyclovir had a significantly lower risk of congenital CMV infection compared with those not receiving valacyclovir (three studies; 325 fetuses; pooled odds ratio (OR), 0.37 (95% CI, 0.21-0.64); I = 0%; P < 0.001). When stratifying the analysis according to gestational age at maternal infection, the risk of vertical transmission was significantly lower in pregnancies receiving valacyclovir following first-trimester maternal infection (three studies; 184 fetuses; pooled OR, 0.34 (95% CI, 0.15-0.74); I = 20.9%; P = 0.001), while there was no significant difference between the two groups in those acquiring CMV infection in the periconceptional period or in the third trimester of pregnancy. Only one study reported on the risk of vertical transmission in women infected in the second trimester, demonstrating a lower risk of congenital infection in women taking valacyclovir, although this was based on a small number of cases. Pregnancies treated with valacyclovir therapy had an increased likelihood of asymptomatic congenital CMV infection compared with those not receiving valacyclovir (two studies; 132 fetuses; pooled OR, 2.98 (95% CI, 1.18-7.55); I = 0%; P = 0.021), while there was no significant difference between the two groups in the risk of perinatal death (P = 0.923), termination of pregnancy (P = 0.089), anomalies detected at follow-up imaging assessment during pregnancy or at birth (P = 0.934) and symptoms due to CMV infection in the newborn (P = 0.092). The occurrence of all adverse events in pregnant individuals taking valacyclovir was 3.17% (95% CI, 1.24-5.93%) (six studies; 210 women), with 1.71% (95% CI, 0.41-3.39%) experiencing acute renal failure, which resolved after discontinuation of the drug. On GRADE assessment, the quality of evidence showing that valacyclovir reduced the risk of congenital CMV infection and adverse perinatal outcome was very low.
CONCLUSIONS
Prenatal valacyclovir administration in pregnancies with maternal CMV infection reduces the risk of congenital CMV infection. Further evidence is needed to elucidate whether valacyclovir can affect the course of infection in the fetus and the risk of symptomatic fetal or neonatal infection. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Amniotic Fluid; Cytomegalovirus Infections; Infectious Disease Transmission, Vertical; Perinatal Death; Pregnancy Complications, Infectious; Prenatal Care; Valacyclovir
PubMed: 36484439
DOI: 10.1002/uog.26136 -
British Journal of Clinical Pharmacology Sep 2022This systematic literature review and meta-analysis aimed to evaluate the risk factors for vancomycin-associated acute kidney injury (AKI) incidence. (Meta-Analysis)
Meta-Analysis Review
AIMS
This systematic literature review and meta-analysis aimed to evaluate the risk factors for vancomycin-associated acute kidney injury (AKI) incidence.
METHODS
This study assessed risk factors for vancomycin-associated AKI in adult patients by searching studies from PubMed, the Cochrane Library and Embase. Random effect models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS
Fifty-three studies were included in our meta-analysis. For patient factors, black race (OR 1.47, 95% CI: 1.16-1.87), Caucasian (OR 0.72, 95% CI: 0.58-0.90) and obesity (OR 1.46, 95% CI: 1.12-1.90) were associated with an increase in vancomycin-associated AKIs. In terms of vancomycin-related factors, longer treatment duration (>14 d; OR 1.73, 95% CI: 1.06-2.83), serum vancomycin trough level >15 μg/mL (OR 2.10, 95% CI: 1.43-3.07) and vancomycin trough level >20 μg/mL (OR 2.84, 95% CI: 1.48-5.44) increased the risks of vancomycin-associated AKI. For comorbidities and clinical factors, renal disease (OR 2.19, 95% CI: 1.51-3.17) showed the highest odds of vancomycin-associated AKI, followed by hepatic disease, intensive care unit admission, heart failure, sepsis, coronary heart disease and diabetes mellitus. For concomitant nephrotoxic drugs, amphotericin B (OR 5.21, 95% CI: 3.44-7.87) showed the highest odds of vancomycin-associated AKI, followed by acyclovir (OR 3.22, 95% CI: 1.39-7.46), vasopressors, loop diuretics, piperacillin-tazobactam and aminoglycoside. The use of any concomitant nephrotoxic agent (OR 1.74, 95% CI: 1.17-2.58) increased the odds of vancomycin-associated AKI.
CONCLUSION
Our results may help predict the risk of vancomycin-associated AKI in the clinical setting.
Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Retrospective Studies; Risk Factors; Vancomycin
PubMed: 35665530
DOI: 10.1111/bcp.15429 -
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 -
The Cochrane Database of Systematic... Aug 2015Herpes simplex labialis (HSL), also known as cold sores, is a common disease of the lips caused by the herpes simplex virus, which is found throughout the world. It... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Herpes simplex labialis (HSL), also known as cold sores, is a common disease of the lips caused by the herpes simplex virus, which is found throughout the world. It presents as a painful vesicular eruption, forming unsightly crusts, which cause cosmetic disfigurement and psychosocial distress. There is no cure available, and it recurs periodically.
OBJECTIVES
To assess the effects of interventions for the prevention of HSL in people of all ages.
SEARCH METHODS
We searched the following databases up to 19 May 2015: the Cochrane Skin Group Specialised Register, the Oral Health Group Specialised Register, CENTRAL in the Cochrane Library (Issue 4, 2015), MEDLINE (from 1946), EMBASE (from 1974), LILACS (from 1982), the China National Knowledge Infrastructure (CNKI) database, Airiti Library, and 5 trial registers. To identify further references to relevant randomised controlled trials, we scanned the bibliographies of included studies and published reviews, and we also contacted the original researchers of our included studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of interventions for preventing HSL in immunocompetent people.
DATA COLLECTION AND ANALYSIS
Two authors independently selected trials, extracted data, and assessed the risk of bias. A third author was available for resolving differences of opinion.
MAIN RESULTS
This review included 32 RCTs, with a total of 2640 immunocompetent participants, covering 19 treatments. The quality of the body of evidence was low to moderate for most outcomes, but was very low for a few outcomes. Our primary outcomes were 'Incidence of HSL' and 'Adverse effects during use of the preventative intervention'.The evidence for short-term (≤ 1 month) use of oral aciclovir in preventing recurrent HSL was inconsistent across the doses used in the studies: 2 RCTs showed low quality evidence for a reduced recurrence of HSL with aciclovir 400 mg twice daily (risk ratio (RR) 0.26, 95% confidence interval (CI) 0.13 to 0.51; n = 177), while 1 RCT testing aciclovir 800 mg twice daily and 2 RCTs testing 200 mg 5 times daily found no similar preventive effects (RR 1.08, 95% CI 0.62 to 1.87; n = 237; moderate quality evidence and RR 0.46, 95% CI 0.20 to 1.07; n = 66; low quality evidence, respectively). The direction of intervention effect was unrelated to the risk of bias. The evidence from 1 RCT for the effect of short-term use of valaciclovir in reducing recurrence of HSL by clinical evaluation was uncertain (RR 0.55, 95% CI 0.23 to 1.28; n = 125; moderate quality evidence), as was the evidence from 1 RCT testing short-term use of famciclovir.Long-term (> 1 month) use of oral antiviral agents reduced the recurrence of HSL. There was low quality evidence from 1 RCT that long-term use of oral aciclovir reduced clinical recurrences (1.80 versus 0.85 episodes per participant per a 4-month period, P = 0.009) and virological recurrence (1.40 versus 0.40 episodes per participant per a 4-month period, P = 0.003). One RCT found long-term use of valaciclovir effective in reducing the incidence of HSL (with a decrease of 0.09 episodes per participant per month; n = 95). One RCT found that a long-term suppressive regimen of valaciclovir had a lower incidence of HSL than an episodic regimen of valciclovir (difference in means (MD) -0.10 episodes per participant per month, 95% CI -0.16 to -0.05; n = 120).These trials found no increase in adverse events associated with the use of oral antiviral agents (moderate quality evidence).There was no evidence to show that short-term use of topical antiviral agents prevented recurrent HSL. There was moderate quality evidence from 2 RCTs that topical aciclovir 5% cream probably has little effect on preventing recurrence of HSL (pooled RR 0.91, 95% CI 0.48 to 1.72; n = 271). There was moderate quality evidence from a single RCT that topical foscarnet 3% cream has little effect in preventing HSL (RR 1.08, 95% CI 0.82 to 1.40; n = 295).The efficacy of long-term use of topical aciclovir cream was uncertain. One RCT found significantly fewer research-diagnosed recurrences of HSL when on aciclovir cream treatment than on placebo (P < 0.05), but found no significant differences in the mean number of participant-reported recurrences between the 2 groups (P ≥ 0.05). One RCT found no preventive effect of topical application of 1,5-pentanediol gel for 26 weeks (P > 0.05). Another RCT found that the group who used 2-hydroxypropyl-β-cyclo dextrin 20% gel for 6 months had significantly more recurrences than the placebo group (P = 0.003).These studies found no increase in adverse events related to the use of topical antiviral agents.Two RCTs found that the application of sunscreen significantly prevented recurrent HSL induced by experimental ultraviolet light (pooled RR 0.07, 95% CI 0.01 to 0.33; n = 111), but another RCT found that sunscreen did not prevent HSL induced by sunlight (RR 1.13, 95% CI 0.25 to 5.06; n = 51). These RCTs did not report adverse events.There were very few data suggesting that thymopentin, low-level laser therapy, and hypnotherapy are effective in preventing recurrent HSL, with one to two RCTs for each intervention. We failed to find any evidence of efficacy for lysine, LongoVital® supplementation, gamma globulin, herpes simplex virus (HSV) type I subunit vaccine, and yellow fever vaccine in preventing HSL. There were no consistent data supporting the efficacy of levamisole and interferon, which were also associated with an increased risk of adverse effects such as fever.
AUTHORS' CONCLUSIONS
The current evidence demonstrates that long-term use of oral antiviral agents can prevent HSL, but the clinical benefit is small. We did not find evidence of an increased risk of adverse events. On the other hand, the evidence on topical antiviral agents and other interventions either showed no efficacy or could not confirm their efficacy in preventing HSL.
Topics: Antiviral Agents; Herpes Labialis; Humans; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention
PubMed: 26252373
DOI: 10.1002/14651858.CD010095.pub2 -
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 -
Supportive care and antiviral treatments in primary herpetic gingivostomatitis: a systematic review.Clinical Oral Investigations Nov 2023Herpes simplex virus 1 (HSV-1) is the main pathogen responsible for herpes infections. In 13-30% of the cases, primary HSV-1 leads to the primary herpetic... (Review)
Review
OBJECTIVES
Herpes simplex virus 1 (HSV-1) is the main pathogen responsible for herpes infections. In 13-30% of the cases, primary HSV-1 leads to the primary herpetic gingivostomatitis (PHGS), often a self-limiting infection; however, it can limit the ability to drink/eat with, sometimes, the need for hospitalization. Multiple therapeutic methods have been proposed. This systematic review aims to collect and critically appraise the available evidence about the clinical management of PHGS.
MATERIALS AND METHODS
Literature search including three databases (PubMed, Scopus, Embase), study design, and data analysis were performed following PRISMA guidelines, according to the PICO tool (PROSPERO n° CRD42023391386). Risk of bias was assessed with RoB 2 and ROBINS-I.
RESULTS
Five studies on a total of 364 patients (average age: 7.6 years) were identified. The treatment regimens were summarized in acyclovir; acyclovir + honey; fluids and analgesic; maalox + diphenhydramine; lidocaine; chlorhexidine (CHX); CHX + ialuronic acid; CHX + Mucosyte®; antimicrobial photodynamic therapy (aPDT); topical antiviral; topical antiviral + aPDT; and others.
CONCLUSIONS
Although PHGS is a disease with a high worldwide prevalence, the lack of consensus about therapeutic management indicates gaps in existing evidence. Most of the proposed treatment consists in symptomatic drugs with empiric regimens which are ineffective for the viral replication. The main limit to realize randomized clinical trial is due to the rapid onset and remission of the disease. In fact, the diagnostic delay, estimated in 72 h, decreases the effectiveness of any antiviral drugs.
CLINICAL RELEVANCE
Out of the five studies included in this systematic review, only one was able to provide some weak evidence that ACV is an effective treatment, improving healing of oral lesions and reducing duration of symptoms.
Topics: Humans; Child; Stomatitis, Herpetic; Delayed Diagnosis; Antiviral Agents; Acyclovir; Lidocaine; Randomized Controlled Trials as Topic
PubMed: 37733027
DOI: 10.1007/s00784-023-05250-5 -
Anais Brasileiros de Dermatologia 2018There is a lack of evidence to support acyclovir administration in pityriasis rosea. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is a lack of evidence to support acyclovir administration in pityriasis rosea.
OBJECTIVE
To determine the efficacy of acyclovir in patients with typical pityriasis rosea.
METHODS
A systematic review and meta-analysis of experimental studies was performed in MEDLINE, SCOPUS, EMBASE and others, from January 1990 to October 2016 on acyclovir for pityriasis rosea. Random effect model was used to find the pooled Risk Ratio. Outcomes, evaluated between weeks 1 to 8, were regression of lesions, cessation of lesions, decrease of symptoms and duration of disease. Comparisons were acyclovir vs. placebo; acyclovir vs. symptomatic treatment; acyclovir vs. antibiotic; acyclovir vs. observation and combined therapy (acyclovir plus symptomatic treatment) vs. symptomatic treatment alone.
RESULTS
Seven papers were analyzed with 324 participants, of which 159 received acyclovir and 165 were controls. Acyclovir was superior to placebo for complete regression of lesions at week 1 (Risk Ratio 5.72, CI95% 2.36-13.88). However, combined therapy was not superior to symptomatic treatment at week 4 (Risk Ratio 1.46, CI95% 0.93-2.29). Individual studies showed the superiority of acyclovir for the control of symptoms and pruritus.
STUDY LIMITATIONS
We faced differences designs of trials and inconsistency between reports.
CONCLUSION
Symptomatic treatment is a reasonable option for pityriasis rosea, and the addition of acyclovir is justified for the control of symptoms and pruritus.
Topics: Acyclovir; Administration, Topical; Adult; Antiviral Agents; Child; Female; Follow-Up Studies; Humans; Male; Pityriasis Rosea; Placebos; Treatment Outcome
PubMed: 30156618
DOI: 10.1590/abd1806-4841.20187252 -
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 -
Acta Obstetricia Et Gynecologica... Sep 2021Immunosuppressant drugs are increasingly being used in the reproductive years. Theoretically, such medications could affect fetal health either through changes in the...
INTRODUCTION
Immunosuppressant drugs are increasingly being used in the reproductive years. Theoretically, such medications could affect fetal health either through changes in the sperm DNA or through fetal exposure caused by a presence in the seminal fluid. This systematic overview summarizes existing literature on the spermatotoxic and genotoxic potentials of methotrexate (MTX), a drug widely used to treat rheumatic and dermatologic diseases, and mycophenolate mofetil (MMF), which alone or supplemented with ganciclovir (GCV) may be crucial for the survival of organ transplants.
MATERIAL AND METHODS
The systematic overview was performed in accordance with the PRISMA guidelines: A systematic literature search of the MEDLINE and Embase databases was done using a combination of relevant terms to search for studies on spermatotoxic or genotoxic changes related to treatment with MTX, GCV or MMF. The search was restricted to English language literature, and to in vivo animal studies (mammalian species) and clinical human studies.
RESULTS
A total of 102 studies were identified, hereof 25 human and 77 animal studies. For MTX, human studies of immunosuppressive dosages show transient effect on sperm quality parameters, which return to reference values within 3 months. No human studies have investigated the sperm DNA damaging effect of MTX, but in other organs the genotoxic effects of immunosuppressive doses of MTX are fluctuating. In animals, immunosuppressive and cytotoxic doses of MTX adversely affect sperm quality parameters and show widespread genotoxic damages in various organs. Cytotoxic doses transiently change the DNA material in all cell stages of spermatogenesis in rodents. For GCV and MMF, data are limited and the results are indeterminate, for which reason spermatotoxic and genotoxic potentials cannot be excluded.
CONCLUSIONS
Data from human and animal studies indicate transient spermatotoxic and genotoxic potentials of immunosuppressive and cytotoxic doses of MTX. There are a limited number of studies investigating GCV and MMF.
Topics: DNA Damage; Ganciclovir; Humans; Immunosuppressive Agents; Male; Methotrexate; Mycophenolic Acid; Spermatozoa
PubMed: 33755191
DOI: 10.1111/aogs.14151 -
Pain Physician Jul 2023The most refractory symptom of herpes zoster (HZ) is pain. Approximately 90% of people who have HZ suffer from pain. Early use of antiviral medications has been found to... (Meta-Analysis)
Meta-Analysis
A Network Meta-Analysis of Randomized Clinical Trials to Assess the Efficacy and Safety of Antiviral Agents for Immunocompetent Patients with Herpes Zoster-Associated Pain.
BACKGROUND
The most refractory symptom of herpes zoster (HZ) is pain. Approximately 90% of people who have HZ suffer from pain. Early use of antiviral medications has been found to reduce pain across all stages of the disease. Although many antiviral agents via oral or intravenous administration were recommended by clinical practice, the best approach to prevent HZ-associated pain remains uncertain.
OBJECTIVES
The purpose of this study was to compare the efficacy and adverse events of various antiviral agents used for the treatment of HZ-associated pain through a network meta-analysis.
STUDY DESIGN
A systematic review and meta-analysis.
SETTING
The Cochrane Register of Controlled Trials, Embase, and PubMed were searched from inception to Feb 2020.
METHODS
Randomized clinical trials evaluating antiviral agents currently available for treating HZ-associated pain were included. We extracted data in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and conducted network meta-analyses with random-effects models. The primary outcome was the presence of acute pain at the end of anti-virus treatment, and the secondary outcomes included the presence of pain at 28-30 days after the onset of the acute herpetic rash, the presence of postherpetic neuralgia (PHN), and any other adverse events.
RESULTS
A total of 17 randomized control trials with 5,579 participants were included in this study. According to the results of the network meta-analysis, for the treatment of acute pain, there was no significant difference between oral acyclovir and intravenous acyclovir. Furthermore, oral famciclovir was the most effective treatment concerning both the odds ratio (OR) (superior to placebo OR = 0.25; 95% CI: 0.13~0.48) and the surface under the cumulative ranking curve (SUCRA) values of 0.84 for the treatment of acute pain among all the oral antiviral agents. For the presence of pain at 28-30 days, no significant difference was observed in efficacy between all antiviral treatments and placebo concerning the OR; however, oral valaciclovir ranked first (SUCRA values of 0.96). For the presence of NPH, oral famciclovir was determined to be the most effective (SUCRA values of 0.77) treatment with an efficacy of 0.42 (95% CI: 0.18~0.99) versus placebo. For adverse events, there was no significant difference between oral antivirals and placebo; however, intravenous acyclovir ranked last with a score of OR 4.31 (95% CI: 1.26~14.75) versus placebo.
LIMITATIONS
The distribution of severity of pain was different in various studies; then, the lack of availability of individual data prevented us from analyzing the effects of the risk factors.
CONCLUSIONS
For the treatment of acute pain and PHN, oral famciclovir was the most effective treatment among all the oral antiviral agents. For alleviating pain after 28-30 days, oral valaciclovir appeared to be the most effective among all antiviral agents. Additionally, all oral antiviral agents were well tolerated.
CLINICAL TRIAL REGISTRATION INFORMATION
PROSPERO under the identification CRD42020212834.
Topics: Humans; Antiviral Agents; Valacyclovir; Famciclovir; Network Meta-Analysis; Acute Pain; Randomized Controlled Trials as Topic; Acyclovir; Herpes Zoster; Neuralgia, Postherpetic
PubMed: 37535772
DOI: No ID Found