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Frontiers in Pediatrics 2020This study aimed to identify alterations in pharmacokinetics in children on extracorporeal membrane oxygenation (ECMO), identify knowledge gaps, and inform future...
This study aimed to identify alterations in pharmacokinetics in children on extracorporeal membrane oxygenation (ECMO), identify knowledge gaps, and inform future pharmacology studies. We systematically searched the databases MEDLINE, CINAHL, and Embase from earliest publication until November 2018 using a controlled vocabulary and keywords related to "ECMO" and "pharmacokinetics," "pharmacology," "drug disposition," "dosing," and "pediatrics." Inclusion criteria were as follows: study population aged <18 years, supported on ECMO for any indications, received any medications while on ECMO, and reported pharmacokinetic data. Clearance and/or volume of distribution values were extracted from included studies. Forty-one studies (total patients = 574) evaluating 23 drugs met the inclusion criteria. The most common drugs studied were antimicrobials ( = 13) and anticonvulsants ( = 3). Twenty-eight studies (68%) were conducted in children <1 year of age. Thirty-three studies (80%) were conducted without intra-study comparisons to non-ECMO controls. Increase in volume of distribution attributable to ECMO was demonstrated for nine (56%) drugs: cefotaxime, gentamicin, piperacillin/tazobactam, fluconazole, micafungin, levetiracetam, clonidine, midazolam, and sildenafil (range: 23-345% increase relative to non-ECMO controls), which may suggest the need for higher initial dosing. Decreased volume of distribution was reported for two drugs: acyclovir and ribavirin (50 and 69%, respectively). Decreased clearance was reported for gentamicin, ticarcillin/clavulanate, bumetanide, and ranitidine (range: 26-95% decrease relative to non-ECMO controls). Increased clearance was reported for caspofungin, micafungin, clonidine, midazolam, morphine, and sildenafil (range: 25-455% increase relative to non-ECMO controls). There were substantial pharmacokinetic alterations in 70% of drugs studied in children on ECMO. However, studies evaluating pharmacokinetic changes of many drug classes and those that allow direct comparisons between ECMO and non-ECMO patients are still lacking. Systematic evaluations of pharmacokinetic alterations of drugs on ECMO that incorporate multidrug opportunistic trials, physiologically based pharmacokinetic modeling, and other methods are necessary for definitive dose recommendations. : CRD42019114881.
PubMed: 32670992
DOI: 10.3389/fped.2020.00260 -
Evidence-based Complementary and... 2020This study aimed to evaluate the efficacy and safety of Qidong Yixin (QY) oral liquid in the treatment of viral myocarditis (VMC). (Review)
Review
OBJECTIVE
This study aimed to evaluate the efficacy and safety of Qidong Yixin (QY) oral liquid in the treatment of viral myocarditis (VMC).
METHODS
We searched seven databases for randomized clinical trials on QY for treating VMC. The retrieval period was from database establishment to December 31, 2019. Cochrane risk of bias tool in the Cochrane Handbook was used to assess the methodological quality. Review Manager (RevMan) 5.3 was used to analyze the results.
RESULTS
We included 19 studies comprising 2,608 patients, albeit with low methodological quality. Our meta-analysis revealed that combination therapy with QY and western medicine was more effective than western medicine alone (QY vs other Chinese patent medicines: RR = 1.37, 95% Cl: 1.23∼1.52, < 0.00001; QY + coenzyme Q10 + routine treatment vs coenzyme Q10 + routine treatment: RR = 1.20, 95% Cl: 1.14∼1.27, < 0.00001; QY + trimetazidine + acyclovir vs trimetazidine + acyclovir: RR = 1.59, 95% Cl: 1.38∼1.83, < 0.00001; QY + routine treatment vs routine treatment: RR = 1.09, 95% Cl: 1.03∼1.15, < 0.003). A study on posttreatment myocardial enzyme levels revealed that QY with western medicine downregulated creatine kinase isoenzyme (CK-MB) (QY + antiviral treatment + routine treatment vs antiviral treatment + routine treatment group: MD = -11.28, 95% CI: -13.33∼-9.22, < 0.00001; QY + routine treatment vs routine treatment: MD = -4.96, 95% CI: -5.56∼-4.32, < 0.00001), creatine kinase (CK) (MD = -32.10, 95% CI: -35.63∼-28.57, < 0.00001), and lactate dehydrogenase (LDH) (QY + antiviral treatment + routine treatment vs antiviral treatment + routine treatment: MD = -48.76 95% CI: -58.18∼-39.33, < 0.00001; QY + routine treatment vs routine treatment: MD = -23.52, 95% CI: -30.10-16.94, < 0.00001) rather than western medicine alone, with no evidence of aspartate aminotransferase (AST) downregulation on treatment with QY with western medicine (MD = 2.88, 95% CI: -0.95∼6.71, < 0.00001) in patients. Two studies reported adverse events, indicating that QY is relatively safe.
CONCLUSION
Although QY may have potential advantages in treating VMC, they remain unclear owing to the poor methodological quality of most studies. Larger, multicenter, high-quality randomized controlled trials are required to verify the effectiveness of QY.
PubMed: 32565861
DOI: 10.1155/2020/4704535 -
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 -
Neuro-oncology Practice Jul 2019Herpes simplex encephalitis (HSE) occurring within 30 days after neurosurgery for solid CNS tumors is underrecognized and underreported but remains important because of...
BACKGROUND
Herpes simplex encephalitis (HSE) occurring within 30 days after neurosurgery for solid CNS tumors is underrecognized and underreported but remains important because of high morbidity and mortality. We present the case of a 41-year-old woman who had HSE after craniopharyngioma surgery, and delayed recognition and treatment led to a poor outcome. Subsequently, we review reported HSE cases after neurosurgery for solid CNS tumors and describe outcomes after treatment with and without acyclovir.
METHODS
A literature search was performed for cases meeting the above criteria. Information was gathered regarding patient demographics, tumor types, symptoms, diagnostic workup, therapy, and outcomes.
RESULTS
Eighteen cases were studied. Encephalopathy, fever, and seizures were the most common symptoms. A majority of patients (78%) received IV acyclovir, with a 79% survival rate with treatment. Mortality rate was 100% in untreated cases. The median time to starting acyclovir was 17 postoperative days (range, 8-53 days). Most patients received steroids, but its use was not associated with a specific outcome.
CONCLUSIONS
HSE may develop following neurosurgical resection, and the threshold for suspicion of this condition should be extremely low in a patient who shows compatible symptoms (encephalopathy, fever, or seizures) or does not recover as planned. Moreover, in case of suspicion of HSE, acyclovir should be promptly started until infection can be definitely ruled out. A delay in diagnosis of HSE and failure to treat may result in severe morbidity as well as mortality. This observation may warrant further study.
PubMed: 31386089
DOI: 10.1093/nop/npz007 -
Medicine Apr 2019Clinical researches indicate that acyclovir can be used to herpes simplex encephalitis (HSE). However, no systematic review has explored its efficacy for the treatment...
BACKGROUND
Clinical researches indicate that acyclovir can be used to herpes simplex encephalitis (HSE). However, no systematic review has explored its efficacy for the treatment of HSE. Therefore, this study systematically will investigate the efficacy and safety of acyclovir for patients with HSE.
METHODS
We will search the following databases from inceptions to March 1, 2019 without any language restrictions: Cochrane Library, Embase, MEDICINE, PsycINFO, Web of Science, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. This study will include randomized controlled trials that assess the efficacy and safety of acyclovir for patients with HSE. Two authors will independently carry out the study selection, data extraction, and risk of bias assessment. Cochrane risk of bias tool will be used to assess the risk of bias assessment.
RESULTS
This study will systematically assess the efficacy and safety of acyclovir for HSE. The primary outcome is mortality rate, which is measured by Glasgow coma score, or other instruments. The secondary outcomes include quality of life, as assessed by 36-Item Short Form Health Survey or relevant scales; overall survival, the number of patient who died; the number of patient who had severe sequelae, and adverse events.
CONCLUSIONS
The findings of this study may provide the existing evidence on the efficacy and safety of acyclovir for HSE.
PROSPERO REGISTRATION NUMBER
PROSPERO CRD42019125999.
Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Humans; Randomized Controlled Trials as Topic; Research Design
PubMed: 30985731
DOI: 10.1097/MD.0000000000015254 -
Antiviral Research Mar 2019Double-stranded (ds) DNA virus infections often occur concomitantly in immunocompromised patients. We performed a systematic search of published in vitro activity for... (Comparative Study)
Comparative Study
BACKGROUND
Double-stranded (ds) DNA virus infections often occur concomitantly in immunocompromised patients. We performed a systematic search of published in vitro activity for nine approved and investigational antivirals to understand the spectrum of in vitro activity against dsDNA viruses.
METHODS
A literature search was performed (PubMed and the WoS Core Collection) using keywords related to: 1) targeted approved/developmental antivirals (acyclovir, artesunate, brincidofovir, cidofovir, cyclopropavir (filociclovir), foscarnet, ganciclovir, letermovir, and maribavir); 2) pathogenic dsDNA viruses; 3) in vitro activity. We summarized data from 210 publications.
RESULTS
Activity against ≤3 viruses was documented for maribavir (cytomegalovirus, Epstein-Barr virus), and letermovir, while activity against > 3 viruses was shown for ganciclovir, cidofovir, acyclovir, foscarnet, cyclopropavir, artesunate, and brincidofovir. The EC values of brincidofovir were the lowest, ranging from 0.001 to 0.27 μM, for all viruses except papillomaviruses. The next most potent agents included cidofovir, ganciclovir, foscarnet, and acyclovir with EC values between 0.1 μM and >10 μM for cytomegalovirus, herpes simplex virus, and adenovirus.
CONCLUSION
Most of the identified antivirals had in vitro activity against more than one dsDNA virus. Brincidofovir and cidofovir have broad-spectrum activity, and brincidofovir has the lowest EC values. These findings could assist clinical practice and developmental research.
Topics: Antiviral Agents; DNA Viruses; DNA, Viral; Drug Resistance, Viral; Drugs, Investigational; Humans
PubMed: 30677427
DOI: 10.1016/j.antiviral.2019.01.008 -
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 -
Biology of Blood and Marrow... Oct 2018Over the past 25 years, several randomized controlled trials have investigated the efficacy of different antiviral agents for cytomegalovirus (CMV) prophylaxis in... (Comparative Study)
Comparative Study Meta-Analysis
Comparative Efficacy and Safety of Different Antiviral Agents for Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Cell Transplantation: A Systematic Review and Meta-Analysis.
Over the past 25 years, several randomized controlled trials have investigated the efficacy of different antiviral agents for cytomegalovirus (CMV) prophylaxis in allogeneic hematopoietic cell transplantation. We performed a systematic literature review, conventional meta-analysis, and network meta-analysis using a random-effects model and risk ratios (RRs) with corresponding 95% confidence intervals (CIs) as effect estimates. Fifteen randomized controlled trials were identified, including 7 different antiviral agents: acyclovir, ganciclovir, maribavir, brincidofovir, letermovir, valacyclovir, and vaccine. Twelve trials used placebo as comparator while 3 trials compared different antiviral agents. We found evidence for CMV disease and infection being significantly reduced by antiviral prophylaxis, with an RR of .66 (95% CI, .48 to .90) and .63 (95% CI, .50 to .79). Across the network, ganciclovir showed the best relative efficacy for CMV disease while letermovir provided first rank of being the best option for CMV infection. The risk for death was not significantly influenced by antiviral prophylaxis in the meta-analysis, with an RR of .92 (95% CI, .78 to 1.08), as well as in the network meta-analysis. In terms of safety, letermovir was at least similar in comparison with placebo and most agents while both letermovir and acyclovir showed significantly reduced risk for serious adverse events compared with ganciclovir, with RRs of .55 (95% CI, .30 to 1.00) for letermovir and .63 (95% CI, .42 to .93) for acyclovir. With a probability of 81%, letermovir appears to be the best option in terms of safety. Future randomized head-to-head comparisons are needed to evaluate the definite efficacy and safety of different prophylactic strategies.
Topics: Acetates; Acyclovir; Allografts; Antiviral Agents; Benzimidazoles; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Hematopoietic Stem Cell Transplantation; Humans; Male; Quinazolines; Ribonucleosides; Risk Factors; Valacyclovir
PubMed: 29777868
DOI: 10.1016/j.bbmt.2018.05.017 -
Folia Medica Cracoviensia 2017Herpes simplex virus (HSV) encephalitis is an acute infection of the Central Nervous System (CNS). During the last two decades its incidence has a ten-fold increase,...
Herpes simplex virus (HSV) encephalitis is an acute infection of the Central Nervous System (CNS). During the last two decades its incidence has a ten-fold increase, while mortality rate exceeds 70%, if left undiagnosed and thus untreated. Clinical manifestations, imaging studies, cerebrospinal fluid (CSF) analysis and electroencephalogram (EEG) are the basis of diagnostic approach. Even when CSF analysis seems normal, imaging studies are not specific and HSV polymerase chain reaction (PCR) test is negative, the clinician should be more aggressive, if clinical presentation is indicative for HSV encephalitis, by administrating acyclovir early after patient's admission. The aim of this short review article, after systematic research of the relevant up to date literature, is to emphasize the insight of the clinician as for the early diagnosis and the prompt therapeutic intervention, which are crucial for the outcome and vital for the affected patient.
Topics: Antiviral Agents; Cerebrospinal Fluid; DNA, Viral; Encephalitis, Herpes Simplex; Humans; Magnetic Resonance Imaging; Polymerase Chain Reaction; Simplexvirus
PubMed: 29337981
DOI: No ID Found -
Journal of Pharmacy & Pharmaceutical... 2017Valganciclovir 900 mg/day is approved for cytomegalovirus (CMV) prophylaxis, but 450 mg/day is seems also effective. We systematically reviewed the efficacy and safety... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Valganciclovir 900 mg/day is approved for cytomegalovirus (CMV) prophylaxis, but 450 mg/day is seems also effective. We systematically reviewed the efficacy and safety of low-dose versus high-dose valganciclovir prophylaxis in renal transplantation recipients.
METHODS
An electronic search was conducted up to November 29, 2016. The primary outcomes were incidences of CMV, CMV disease, mortality and opportunistic infection. The second outcomes were acute rejection, allograft loss, adverse drug reaction (ADR).
RESULTS
7 cohort studies, all with high quality involving (1431 patients) were included. There was no significant difference of the incidence of following CMV disease (1271 patients, odds ratio [OR] 0.74, 95% confidence interval [CI], 0.38-1.43, p=0.36), acute rejection (1343 patients, OR 0.77, 95%CI 0.53-1.14, p=0.19), allograft loss (1271 patients, OR 0.64, 95%CI 0.31-1.35, p=0.24), mortality (1271 patients, OR 0.55, 95%CI 0.20-1.47, p=0.23) and opportunistic infections (OI) (985 patients, OR 0.76, 95%CI 0.52-1.10, p=0.14) between the low-dose and the high-dose valganciclovir prophylaxis. And no significant difference was observed for premature valganciclovir discontinuation (1010 patients, OR 0.81, 95%CI 0.52-1.25, p=0.33) and the incidence of leukopenia (1082 patients, OR 0.65, 95%CI 0.34-1.22, p=0.18) between the two regimens.
CONCLUSION
450 mg and 900 mg doses of valganciclovir are equipotent for CMV universal prophylaxis. CMV 450 mg prophylaxis should be used for renal transplant recipients. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
Topics: Antibiotic Prophylaxis; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Ganciclovir; Humans; Kidney Transplantation; Valganciclovir
PubMed: 28719361
DOI: 10.18433/J3805B