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The Cochrane Database of Systematic... May 2018Hepatitis C virus (HCV)-associated mixed cryoglobulinaemia is the manifestation of an inflammation of small and medium-sized vessels produced by a pathogenic IgM with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatitis C virus (HCV)-associated mixed cryoglobulinaemia is the manifestation of an inflammation of small and medium-sized vessels produced by a pathogenic IgM with rheumatoid factor activity generated by an expansion of B-cells. The immune complexes formed precipitate mainly in the skin, joints, kidneys or peripheral nerve fibres. Current therapeutic approaches are aimed at elimination of HCV infection, removal of cryoglobulins and also of the B-cell clonal expansions. The optimal treatment for it has not been established.
OBJECTIVES
This review aims to look at the benefits and harms of the currently available treatment options to treat the HCV-associated mixed cryoglobulinaemia with active manifestations of vasculitis (cutaneous or glomerulonephritis).
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Specialised Register to 30 November 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
All randomised controlled trials (RCTs) and quasi-RCTs looking at interventions directed at treatment of HCV-associated cryoglobulinaemic vasculitis (immunosuppressive medications and plasma exchange therapy) have been included.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the retrieved titles and abstracts. Authors of included studies were contacted to obtain missing information. Statistical analyses were performed using random effects models and results expressed as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). The planned primary outcomes were kidney disease, skin vasculitis, musculoskeletal symptoms, peripheral joint arthralgia, peripheral neuropathies, liver involvement, interstitial lung involvement, widespread vasculitis and death. Other planned outcomes were: therapy duration, laboratory findings, adverse effects, antiviral therapy failure, B-cell lymphoma, endocrine disorders and costs of treatment.
MAIN RESULTS
Ten studies were included in the review (394 participants). None of them evaluated direct-acting antivirals. Seven studies were single-centre studies and three were multicentre. The duration of the studies varied from six to 36 months. The risk of bias was generally unclear or low. Three different interventions were examined: use of rituximab (3 studies, 118 participants); interferon (IFN) (IFN compared to other strategies (5 studies, 223 participants); six IFN months versus one year (1 study, 36 participants), and immunoadsorption apheresis versus only immunosuppressive therapy (1 study, 17 participants).The use of rituximab may slightly improve skin vasculitis (2 studies, 78 participants: RR 0.57, 95% CI 0.28 to 1.16; moderate certainty evidence) and made little of no difference to kidney disease (moderate certainty evidence). In terms of laboratory data, the effect of rituximab was uncertain for cryocrit (MD -2.01%, 95% CI -10.29% to 6.27%, low certainty evidence) and HCV replication. Rituximab may slightly increase infusion reactions compared to immunosuppressive medication (3 studies, 118 participants: RR 4.33, 95%CI 0.76 to 24.75, moderate certainty evidence) however discontinuations of the treatment due to adverse reactions were similar (3 studies, 118 participants: RR 0.97, 95% CI 0.22 to 4.36, moderate certainty evidence).Effects of lFN on clinical symptoms were evaluated only in narrative results. When laboratory parameters were assessed, IFN made little or no difference in levels of alanine transaminase (ALT) at six months (2 studies, 39 participants: MD -5.89 UI/L, 95%CI -55.77 to 43.99); rheumatoid factor activity at six months (1 study, 13 participants: MD 97.00 UI/mL, 95%CI -187.37 to 381.37), or C4 levels at 18 months (2 studies, 49 participants: MD -0.04 mg/dL, 95%CI -2.74 to 2.67). On the other hand, at 18 months IFN may probably decrease ALT (2 studies, 39 participants: MD -28.28 UI/L, 95%CI -48.03 to -8.54) and Ig M (-595.75 mg/dL, 95%CI -877.2 to -314.3), but all with low certainty evidence. One study reported infusion reactions may be higher in IFN group compared to immunosuppressive therapy (RR 27.82, 95%CI 1.72 to 449.18), and IFN may lead to higher discontinuations of the treatment due to adverse reactions (4 studies, 148 participants: RR 2.32, 95%CI 0.91 to 5.90) with low certainty evidence. Interferon therapy probably improved skin vasculitis (3 studies, 95 participants: RR 0.60, 95% CI 0.36 to 1.00) and proteinuria (2 studies, 49 participants: MD -1.98 g/24 h, 95% CI -2.89 to -1.07), without changing serum creatinine at 18 months (2 studies, 49 participants: MD -30.32 μmol/L, 95%CI -80.59 to 19.95).Six months versus one year treatment with IFN resulted in differences terms of the maintenance of the response, 89% of patients in the six months group presented a relapse and only 11% maintained a long-term response at one year, while in the one year group only 78% relapsed and long-term response was observed in 22%. The one-year therapy was linked to a higher number of side-effects (severe enough to cause the discontinuation of treatment in two cases) than the six-month schedule.One study reported immunoadsorption apheresis had uncertain effects on skin vasculitis (RR 0.44, 95% CI 0.05 to 4.02), peripheral neuropathies (RR 2.70, 95%CI 0.13 to 58.24), and peripheral joint arthralgia (RR 2.70, 95%CI 0.13 to 58.24), cryocrit (MD 0.01%, 95%CI -1.86 to 1.88) at six months, and no infusion reactions were reported. However when clinical scores were evaluated, they reported changes were more favourable in immunoadsorption apheresis with higher remission of severe clinical complications (80% versus 33%, P = 0.05) compared to immunosuppressive treatment alone.In terms of death, it was not possible to present a pooled intervention effect estimate because most of the studies reported no deaths, or did not report death as an outcome.
AUTHORS' CONCLUSIONS
To treat HCV-associated mixed cryoglobulinaemia, it may be beneficial to eliminate HCV infection by using antiviral treatment and to stop the immune response by using rituximab. For skin vasculitis and for some laboratory findings, it may be appropriate to combine antiviral treatment with deletion of B-cell clonal expansions by using of rituximab. The applicability of evidence reviewed here is limited by the absence of any studies with direct-acting antivirals, which are urgently needed to guide therapy.
Topics: Antiviral Agents; Blood Component Removal; Cryoglobulinemia; Hepacivirus; Hepatitis C; Humans; Immunologic Factors; Immunosorbent Techniques; Immunosuppressive Agents; Interferons; Randomized Controlled Trials as Topic; Rituximab; Skin Diseases; Vasculitis
PubMed: 29734473
DOI: 10.1002/14651858.CD011403.pub2 -
Frontiers in Cellular and Infection... 2022Many antiviral agents have been studied in clinical trials for allograft rejection prevention following cytomegalovirus (CMV) prophylaxis in high-risk kidney transplant... (Meta-Analysis)
Meta-Analysis
Efficacy and Safety of Antiviral Agents in Preventing Allograft Rejection Following CMV Prophylaxis in High-Risk Kidney Transplantation: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.
Many antiviral agents have been studied in clinical trials for allograft rejection prevention following cytomegalovirus (CMV) prophylaxis in high-risk kidney transplant patients. However, data on the most effective and safest treatment are lacking. We conducted a systematic review and network meta-analysis to rank CMV prophylaxis agents for allograft rejection prevention following CMV prophylaxis in high-risk kidney transplant patients according to their efficacy and safety. We conducted searches on the MEDLINE, Embase, SCOPUS, and CENTRAL databases, as well as the reference lists of selected studies up to December 2021, for published and peer-reviewed randomized controlled trials assessing the efficacy of CMV prophylaxis agents in high-risk kidney transplant patients. Thirteen studies were independently selected by three reviewers and included post-kidney transplant patients indicated for CMV prophylaxis who had been randomized to receive prophylactic antiviral agents or standard of care. The reviewers independently extracted data from the included studies, and direct and network meta-analyses were applied to assess the study outcomes. The probability of efficacy and safety was evaluated, and the drugs were assigned a numerical ranking. We evaluated the risk of bias using the Cochrane Risk of Bias 2.0 tool. The primary outcome was an incidence of biopsy-proven acute rejection, whereas the secondary outcome was a composite of major adverse drug reactions. Each outcome referred to the definition provided in the original studies. Valganciclovir, valacyclovir, and ganciclovir were identified to significantly decrease the incidence of biopsy-proven acute rejection with pooled risk differences (RDs) of -20.53% (95% confidence interval [CI] = -36.09% to -4.98%), -19.3% (95% CI = -32.7% to -5.93%), and -10.4% (95% CI = -19.7% to -0.12%), respectively. The overall major adverse drug reaction was 5.7% without a significant difference when compared with placebo. Valganciclovir had the best combined efficacy and safety among the examined antiviral agents and was the most effective and safest antiviral agent overall for allograft rejection prevention following CMV prophylaxis. Valacyclovir was the optimal alternative antiviral agent for patients who were unable to tolerate intravenous ganciclovir or access oral valganciclovir as financial problem. However, compliance and dose-related toxicities should be closely monitored.
Topics: Allografts; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Kidney Transplantation; Network Meta-Analysis; Randomized Controlled Trials as Topic; Valacyclovir; Valganciclovir
PubMed: 35433502
DOI: 10.3389/fcimb.2022.865735 -
Value in Health : the Journal of the... Nov 2020To review published economic evaluations of antiviral treatment for pandemics and outbreaks of respiratory illnesses. (Review)
Review
Cost-Effectiveness of Antiviral Treatments for Pandemics and Outbreaks of Respiratory Illnesses, Including COVID-19: A Systematic Review of Published Economic Evaluations.
OBJECTIVE
To review published economic evaluations of antiviral treatment for pandemics and outbreaks of respiratory illnesses.
METHODS
We conducted a systematic review to identify economic evaluations of antiviral treatment for pandemics and outbreaks of respiratory illnesses, including coronavirus disease 2019 (COVID-19). We searched Medline (EBSCOhost), EMBASE (Ovid), EconLit (Ovid), National Health Service Economic Evaluation Database (Ovid), and Health Technology Assessment (Ovid). The search was last rerun on July 5, 2020. Citation tracking and reference checking were used. Only full economic evaluations published as peer-reviewed articles in the last 10 years were included. Studies were quality assessed using the National Institute for Health and Care Excellence economic evaluation checklist.
RESULTS
Overall, 782 records were identified, of which 14 studies met the inclusion criteria. The studies were mostly conducted in high-income countries. All were model-based. Seven (50%) were cost-utility analyses, 4 (28.6%) were cost-effectiveness analyses, 2 (14.3%) were cost-consequences analyses, and 1 (7.1%) was a cost-benefit analysis. Strategies including antiviral treatment were found to be either cost-saving or cost-effective, at the study-specific willingness-to-pay thresholds. Empirical treatment was more cost-effective than test-guided treatment for young adults but less so for older adults.
CONCLUSIONS
Antiviral treatment for managing pandemics and outbreaks of respiratory illnesses that have very high case fatality rate, similar to COVID-19 pandemic, are likely to be cost-effective either as a standalone intervention or part of a multifaceted strategy. Investing in the development of such curative treatments and promptly evaluating their cost-effectiveness, relative to other strategies in use at the time of their introduction should be the focus going forward to inform resource allocation decisions particularly in low- and middle-income countries.
Topics: Antiviral Agents; Betacoronavirus; COVID-19; Coronavirus Infections; Cost-Benefit Analysis; Disease Outbreaks; Humans; Pandemics; Pneumonia, Viral; Respiratory Insufficiency; SARS-CoV-2; Technology Assessment, Biomedical
PubMed: 33127010
DOI: 10.1016/j.jval.2020.07.002 -
Virology Journal Aug 2023Our study aimed to compare the predictive performance of different hepatocellular carcinoma (HCC) prediction models in chronic hepatitis B patients receiving entecavir... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Our study aimed to compare the predictive performance of different hepatocellular carcinoma (HCC) prediction models in chronic hepatitis B patients receiving entecavir or tenofovir, including discrimination, calibration, negative predictive value (NPV) in low-risk, and proportion of low-risk.
METHODS
We conducted a systematic literature research in PubMed, EMbase, the Cochrane Library, and Web of Science before January 13, 2022. The predictive performance was assessed by area under receiver operating characteristic curve (AUROC), calibration index, negative predictive value, and the proportion in low-risk. Subgroup and meta-regression analyses of discrimination and calibration were conducted. Sensitivity analysis was conducted to validate the stability of the results.
RESULTS
We identified ten prediction models in 23 studies. The pooled 3-, 5-, and 10-year AUROC varied from 0.72 to 0.84, 0.74 to 0.83, and 0.76 to 0.86, respectively. REAL-B, AASL-HCC, and HCC-RESCUE achieved the best discrimination. HCC-RESCUE, PAGE-B, and mPAGE-B overestimated HCC development, whereas mREACH-B, AASL-HCC, REAL-B, CAMD, CAGE-B, SAGE-B, and aMAP underestimated it. All models were able to identify people with a low risk of HCC accurately. HCC-RESCUE and aMAP recognized over half of the population as low-risk. Subgroup analysis and sensitivity analysis showed similar results.
CONCLUSION
Considering the predictive performance of all four aspects, we suggest that HCC-RESCUE was the best model to utilize in clinical practice, especially in primary care and low-income areas. To confirm our findings, further validation studies with the above four components were required.
Topics: Humans; Tenofovir; Carcinoma, Hepatocellular; Hepatitis B, Chronic; Liver Neoplasms; Antiviral Agents
PubMed: 37582759
DOI: 10.1186/s12985-023-02145-5 -
Reviews in Medical Virology Nov 2021SARS Coronavirus-2 is one of the most widespread viruses globally during the 21 century, whose severity and ability to cause severe pneumonia and death vary. We... (Meta-Analysis)
Meta-Analysis
SARS Coronavirus-2 is one of the most widespread viruses globally during the 21 century, whose severity and ability to cause severe pneumonia and death vary. We performed a comprehensive systematic review of all studies that met our standardised criteria and then extracted data on the age, symptoms, and different treatments of Covid-19 patients and the prognosis of this disease during follow-up. Cases in this study were divided according to severity and death status and meta-analysed separately using raw mean and single proportion methods. We included 171 complete studies including 62,909 confirmed cases of Covid-19, of which 148 studies were meta-analysed. Symptoms clearly emerged in an escalating manner from mild-moderate symptoms, pneumonia, severe-critical to the group of non-survivors. Hypertension (Pooled proportion (PP): 0.48 [95% Confident interval (CI): 0.35-0.61]), diabetes (PP: 0.23 [95% CI: 0.16-0.33]) and smoking (PP: 0.12 [95% CI: 0.03-0.38]) were highest regarding pre-infection comorbidities in the non-survivor group. While acute respiratory distress syndrome (PP: 0.49 [95% CI: 0.29-0.78]), (PP: 0.63 [95% CI: 0.34-0.97]) remained one of the most common complications in the severe and death group respectively. Bilateral ground-glass opacification (PP: 0.68 [95% CI: 0.59-0.75]) was the most visible radiological image. The mortality rates estimated (PP: 0.11 [95% CI: 0.06-0.19]), (PP: 0.03 [95% CI: 0.01-0.05]), and (PP: 0.01 [95% CI: 0-0.3]) in severe-critical, pneumonia and mild-moderate groups respectively. This study can serve as a high evidence guideline for different clinical presentations of Covid-19, graded from mild to severe, and for special forms like pneumonia and death groups.
Topics: Antiviral Agents; COVID-19; Comorbidity; Cough; Diabetes Mellitus; Dyspnea; Fatigue; Fever; Humans; Hypertension; Immunologic Factors; Prognosis; Respiratory Distress Syndrome; SARS-CoV-2; Severity of Illness Index; Smoking; Survival Analysis; COVID-19 Drug Treatment
PubMed: 34472152
DOI: 10.1002/rmv.2288 -
The Cochrane Database of Systematic... Oct 2019Pityriasis rosea is a scaly, itchy rash that mainly affects young adults and lasts for 2 to 12 weeks. The effects of many available treatments are uncertain. This is an... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pityriasis rosea is a scaly, itchy rash that mainly affects young adults and lasts for 2 to 12 weeks. The effects of many available treatments are uncertain. This is an update of a Cochrane Review first published in 2007.
OBJECTIVES
To assess the effects of interventions for the management of pityriasis rosea in any individual diagnosed by a medical practitioner.
SEARCH METHODS
We updated our searches of the following databases to October 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched five trials registers. We also checked the reference lists of included and excluded studies, contacted trial authors, scanned the abstracts from major dermatology conference proceedings, and searched the CAB Abstracts database. We searched PubMed for adverse effects to November 2018.
SELECTION CRITERIA
Randomised controlled trials of interventions in pityriasis rosea. Treatment could be given in a single therapy or in combination. Eligible comparators were no treatment, placebo, vehicle only, another active compound, or placebo radiation treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by the Cochrane. Our key outcomes were good or excellent rash improvement within two weeks, rated separately by the participant and medical practitioner; serious adverse events; resolution of itch within two weeks (participant-rated); reduction in itch score within two weeks (participant-rated); and minor participant-reported adverse events not requiring withdrawal of the treatment.
MAIN RESULTS
We included 14 trials (761 participants). In general, risk of selection bias was unclear or low, but risk of performance bias and reporting bias was high for 21% of the studies. Participant age ranged from 2 to 60 years, and sex ratio was similar. Disease severity was measured by various severity indices, which the included studies did not categorise. Six studies were conducted in India, three in Iran, two in the Philippines, and one each in Pakistan, the USA, and China. The included studies were conducted in dermatology departments and a paediatric clinic. Study duration ranged from 5 to 26 months. Three studies were funded by drug manufacturers; most studies did not report their funding source. The included studies assessed macrolide antibiotics, an antiviral agent, phototherapy, steroids and antihistamine, and Chinese medicine. None of the studies measured participant-rated good or excellent rash improvement. All reported outcomes were assessed within two weeks of treatment, except for adverse effects, which were measured throughout treatment. There is probably no difference between oral clarithromycin and placebo in itch resolution (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.47 to 1.52; 1 study, 28 participants) or rash improvement (medical practitioner-rated) (RR 1.13, 95% CI 0.89 to 1.44; 1 study, 60 participants). For this comparison, there were no serious adverse events (1 study, 60 participants); minor adverse events and reduction in itch score were not measured; and all evidence was of moderate quality. When compared with placebo, erythromycin may lead to increased rash improvement (medical practitioner-rated) (RR 4.02, 95% CI 0.28 to 56.61; 2 studies, 86 participants, low-quality evidence); however, the 95% CI indicates that the result may also be compatible with a benefit of placebo, and there may be little or no difference between treatments. Itch resolution was not measured, but one study measured reduction in itch score, which is probably larger with erythromycin (MD 3.95, 95% CI 3.37 to 4.53; 34 participants, moderate-quality evidence). In the same single, small trial, none of the participants had a serious adverse event, and there was no clear difference between groups in minor adverse events, which included gastrointestinal upset (RR 2.00, CI 0.20 to 20.04; moderate-quality evidence). Two trials compared oral azithromycin to placebo or vitamins. There is probably no difference between groups in itch resolution (RR 0.83, 95% CI 0.28 to 2.48) or reduction in itch score (MD 0.04, 95% CI -0.35 to 0.43) (both outcomes based on one study; 70 participants, moderate-quality evidence). Low-quality evidence from two studies indicates there may be no difference between groups in rash improvement (medical practitioner-rated) (RR 1.02, 95% CI 0.52 to 2.00; 119 participants). In these same two studies, no serious adverse events were reported, and there was no clear difference between groups in minor adverse events, specifically mild abdominal pain (RR 5.82, 95% CI 0.72 to 47.10; moderate-quality evidence). Acyclovir was compared to placebo, vitamins, or no treatment in three trials (all moderate-quality evidence). Based on one trial (21 participants), itch resolution is probably higher with placebo than with acyclovir (RR 0.34, 95% CI 0.12 to 0.94); reduction in itch score was not measured. However, there is probably a significant difference between groups in rash improvement (medical practitioner-rated) in favour of acyclovir versus all comparators (RR 2.45, 95% CI 1.33 to 4.53; 3 studies, 141 participants). Based on the same three studies, there were no serious adverse events in either group, and there was probably no difference between groups in minor adverse events (only one participant in the placebo group experienced abdominal pain and diarrhoea). One trial compared acyclovir added to standard care (calamine lotion and oral cetirizine) versus standard care alone (24 participants). The addition of acyclovir may lead to increased itch resolution (RR 4.50, 95% CI 1.22 to 16.62) and reduction in itch score (MD 1.26, 95% CI 0.74 to 1.78) compared to standard care alone. Rash improvement (medical practitioner-rated) was not measured. The trial reported no serious adverse events in either group, and there may be no difference between groups in minor adverse events, such as headache (RR 7.00, 95% CI 0.40 to 122.44) (all results based on low-quality evidence).
AUTHORS' CONCLUSIONS
When compared with placebo or no treatment, oral acyclovir probably leads to increased good or excellent, medical practitioner-rated rash improvement. However, evidence for the effect of acyclovir on itch was inconclusive. We found low- to moderate-quality evidence that erythromycin probably reduces itch more than placebo. Small study sizes, heterogeneity, and bias in blinding and selective reporting limited our conclusions. Further research is needed to investigate different dose regimens of acyclovir and the effect of antivirals on pityriasis rosea.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antiviral Agents; Child; Child, Preschool; Dermatologic Agents; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Phototherapy; Pityriasis Rosea; Pruritus; Randomized Controlled Trials as Topic; Young Adult
PubMed: 31684696
DOI: 10.1002/14651858.CD005068.pub3 -
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 -
Molecules (Basel, Switzerland) Sep 2017, as a traditional Chinese medicine, has been widely used both as a single herb and in compound prescriptions in Asia, mainly due to its heat-clearing and detoxifying... (Review)
Review
, as a traditional Chinese medicine, has been widely used both as a single herb and in compound prescriptions in Asia, mainly due to its heat-clearing and detoxifying effects. Modern pharmacology has proved possesses various therapeutic effects, both in vitro and in vivo, such as anti-inflammatory, antibacterial and antiviral activities. Up to now, three hundred and twenty-one compounds have been identified and sensitive analytical methods have been established for its quality control. Recently, the pharmacokinetics of and its bioactive compounds have been reported, providing valuable information for its clinical application. Therefore, this systematic review focused on the newest scientific reports on and extensively summarizes its phytochemistry, pharmacology, pharmacokinetics and standardization procedures, especially the difference between the two applied types-unripe and ripe -in the hope of providing a helpful reference and guide for its clinical applications and further studies.
Topics: Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Antiviral Agents; Drug Discovery; Drugs, Chinese Herbal; Forsythia; Humans; Phytochemicals
PubMed: 28869577
DOI: 10.3390/molecules22091466 -
Clinical Transplantation Jan 2024Human-cytomegalovirus (hCMV) infection involving the gastrointestinal tract represents a leading cause of morbidity and mortality among kidney transplant (KT) recipients... (Review)
Review
BACKGROUND
Human-cytomegalovirus (hCMV) infection involving the gastrointestinal tract represents a leading cause of morbidity and mortality among kidney transplant (KT) recipients (KTRs). Signs and symptoms of the disease are extremely variable. Prompt anti-viral therapy administration and immunosuppression modification are key factors for optimizing management. However, complex work-up strategies are generally required to confirm the preliminary diagnosis. Unfortunately, solid evidence and guidelines on this specific topic are not available. We consequently aimed to summarize current knowledge on post-KT hCMV-related gastrointestinal disease (hCMV-GID).
METHODS
We conducted a systematic review (PROSPERO ID: CRD42023399363) about hCMV-GID in KTRs.
RESULTS
Our systematic review includes 52 case-reports and ten case-series, published between 1985 and 2022, collectively reporting 311 cases. The most frequently reported signs and symptoms of hCMV-GID were abdominal pain, diarrhea, epigastric pain, vomiting, fever, and GI bleeding. Esophagogastroduodenoscopy and colonoscopy were the primary diagnostic techniques. In most cases, the preliminary diagnosis was confirmed by histology. Information on anti-viral prophylaxis were extremely limited as much as data on induction or maintenance immunosuppression. Treatment included ganciclovir and/or valganciclovir administration. Immunosuppression modification mainly consisted of mycophenolate mofetil or calcineurin inhibitor minimization and withdrawal. In total, 21 deaths were recorded. Renal allograft-related outcomes were described for 26 patients only. Specifically, reported events were acute kidney injury (n = 17), transplant failure (n = 5), allograft rejection (n = 4), and irreversible allograft dysfunction (n = 3).
CONCLUSIONS
The development of local and national registries is strongly recommended to improve our understanding of hCMV-GID. Future clinical guidelines should consider the implementation of dedicated diagnostic and treatment strategies.
Topics: Humans; Kidney Transplantation; Cytomegalovirus; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Gastrointestinal Diseases
PubMed: 38063324
DOI: 10.1111/ctr.15218 -
The Cochrane Database of Systematic... Aug 2021Remdesivir is an antiviral medicine with properties to inhibit viral replication of SARS-CoV-2. Positive results from early studies attracted media attention and led to...
BACKGROUND
Remdesivir is an antiviral medicine with properties to inhibit viral replication of SARS-CoV-2. Positive results from early studies attracted media attention and led to emergency use authorisation of remdesivir in COVID-19. A thorough understanding of the current evidence regarding the effects of remdesivir as a treatment for SARS-CoV-2 infection based on randomised controlled trials (RCTs) is required.
OBJECTIVES
To assess the effects of remdesivir compared to placebo or standard care alone on clinical outcomes in hospitalised patients with SARS-CoV-2 infection, and to maintain the currency of the evidence using a living systematic review approach.
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register (which comprises the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and medRxiv) as well as Web of Science (Science Citation Index Expanded and Emerging Sources Citation Index) and WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions. We conducted the searches on 16 April 2021.
SELECTION CRITERIA
We followed standard Cochrane methodology. We included RCTs evaluating remdesivir for the treatment of SARS-CoV-2 infection in hospitalised adults compared to placebo or standard care alone irrespective of disease severity, gender, ethnicity, or setting. We excluded studies that evaluated remdesivir for the treatment of other coronavirus diseases.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology. To assess risk of bias in included studies, we used the Cochrane RoB 2 tool for RCTs. We rated the certainty of evidence using the GRADE approach for outcomes that were reported according to our prioritised categories: all-cause mortality at up to day 28, duration to liberation from invasive mechanical ventilation, duration to liberation from supplemental oxygen, new need for mechanical ventilation (high-flow oxygen or non-invasive or invasive mechanical ventilation), new need for invasive mechanical ventilation, new need for non-invasive mechanical ventilation or high-flow oxygen, new need for oxygen by mask or nasal prongs, quality of life, adverse events (any grade), and serious adverse events.
MAIN RESULTS
We included five RCTs with 7452 participants diagnosed with SARS-CoV-2 infection and a mean age of 59 years, of whom 3886 participants were randomised to receive remdesivir. Most participants required low-flow oxygen (n=4409) or mechanical ventilation (n=1025) at baseline. We identified two ongoing studies, one was suspended due to a lack of COVID-19 patients to recruit. Risk of bias was considered to be of some concerns or high risk for clinical status and safety outcomes because participants who had died did not contribute information to these outcomes. Without adjustment, this leads to an uncertain amount of missing values and the potential for bias due to missing data. Effects of remdesivir in hospitalised individuals Remdesivir probably makes little or no difference to all-cause mortality at up to day 28 (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.81 to 1.06; risk difference (RD) 8 fewer per 1000, 95% CI 21 fewer to 7 more; 4 studies, 7142 participants; moderate-certainty evidence). Considering the initial severity of condition, only one study showed a beneficial effect of remdesivir in patients who received low-flow oxygen at baseline (RR 0.32, 95% CI 0.15 to 0.66, 435 participants), but conflicting results exists from another study, and we were unable to validly assess this observations due to limited availability of comparable data. Remdesivir may have little or no effect on the duration to liberation from invasive mechanical ventilation (2 studies, 1298 participants, data not pooled, low-certainty evidence). We are uncertain whether remdesivir increases or decreases the chance of clinical improvement in terms of duration to liberation from supplemental oxygen at up to day 28 (3 studies, 1691 participants, data not pooled, very low-certainty evidence). We are very uncertain whether remdesivir decreases or increases the risk of clinical worsening in terms of new need for mechanical ventilation at up to day 28 (high-flow oxygen or non-invasive ventilation or invasive mechanical ventilation) (RR 0.78, 95% CI 0.48 to 1.24; RD 29 fewer per 1000, 95% CI 68 fewer to 32 more; 3 studies, 6696 participants; very low-certainty evidence); new need for non-invasive mechanical ventilation or high-flow oxygen (RR 0.70, 95% CI 0.51 to 0.98; RD 72 fewer per 1000, 95% CI 118 fewer to 5 fewer; 1 study, 573 participants; very low-certainty evidence); and new need for oxygen by mask or nasal prongs (RR 0.81, 95% CI 0.54 to 1.22; RD 84 fewer per 1000, 95% CI 204 fewer to 98 more; 1 study, 138 participants; very low-certainty evidence). The evidence suggests that remdesivir may decrease the risk of clinical worsening in terms of new need for invasive mechanical ventilation (67 fewer participants amongst 1000 participants; RR 0.56, 95% CI 0.41 to 0.77; 2 studies, 1159 participants; low-certainty evidence). None of the included studies reported quality of life. Remdesivir probably decreases the serious adverse events rate at up to 28 days (RR 0.75, 95% CI 0.63 to 0.90; RD 63 fewer per 1000, 95% CI 94 fewer to 25 fewer; 3 studies, 1674 participants; moderate-certainty evidence). We are very uncertain whether remdesivir increases or decreases adverse events rate (any grade) (RR 1.05, 95% CI 0.86 to 1.27; RD 29 more per 1000, 95% CI 82 fewer to 158 more; 3 studies, 1674 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
Based on the currently available evidence, we are moderately certain that remdesivir probably has little or no effect on all-cause mortality at up to day 28 in hospitalised adults with SARS-CoV-2 infection. We are uncertain about the effects of remdesivir on clinical improvement and worsening. There were insufficient data available to validly examine the effect of remdesivir on mortality in subgroups depending on the extent of respiratory support at baseline. Future studies should provide additional data on efficacy and safety of remdesivir for defined core outcomes in COVID-19 research, especially for different population subgroups. This could allow us to draw more reliable conclusions on the potential benefits and harms of remdesivir in future updates of this review. Due to the living approach of this work, we will update the review periodically.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Bias; COVID-19; Cause of Death; Confidence Intervals; Disease Progression; Humans; Middle Aged; Oxygen; Randomized Controlled Trials as Topic; Respiration, Artificial; SARS-CoV-2; Ventilator Weaning; COVID-19 Drug Treatment
PubMed: 34350582
DOI: 10.1002/14651858.CD014962