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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