Abstract
Background
Data are limited regarding the clinical effectiveness and safety of intravenous colistin for treatment of infections due to MDR Gram-negative bacilli (GNB) in paediatric ICUs ...(PICUs).
Methods
Systematic review of intravenous colistin use in critically ill paediatric patients with MDR-GNB infection in PubMed, Scopus and EMBASE (up to 31 January 2018).
Results
Out of 1181 citations, 7 studies were included on the use of intravenous colistin for 405 patients in PICUs. The majority of patients were diagnosed with lower respiratory tract infections, Acinetobacter baumannii being the predominant pathogen. Colistin dosages ranged between 2.6 and 18 mg/kg/day, with only one case reporting a loading dose. Emergence of colistin resistance during treatment was reported in two cases. Nephrotoxicity and neurotoxicity were reported in 6.1% and 0.5%, respectively, but concomitant medications and severe underlying illness limited our ability to definitively associate use of colistin with nephrotoxicity. Crude mortality was 29.5% (95% CI = 21.7%–38.1%), whereas infection-related mortality was 16.6% (95% CI = 12.2%–21.5%).
Conclusions
While the reported incidence of adverse events related to colistin was low, reported mortality rates for infections due to MDR-GNB in PICUs were notable. In addition to severity of disease and comorbidities, inadequate daily dosage and the absence of a loading dose may have contributed to mortality. As the use of colistin for treatment of MDR-GNB infections increases, it is imperative to understand whether optimal dosing of colistin in paediatric patients differs across different age groups. Thus, future studies to establish the pharmacokinetic properties of colistin in different paediatric settings are warranted.
Background
The interplay between COVID‐19 pandemic and asthma in children is still unclear. We evaluated the impact of COVID‐19 pandemic on childhood asthma outcomes.
Methods
The PeARL multinational ...cohort included 1,054 children with asthma and 505 non‐asthmatic children aged between 4 and 18 years from 25 pediatric departments, from 15 countries globally. We compared the frequency of acute respiratory and febrile presentations during the first wave of the COVID‐19 pandemic between groups and with data available from the previous year. In children with asthma, we also compared current and historical disease control.
Results
During the pandemic, children with asthma experienced fewer upper respiratory tract infections, episodes of pyrexia, emergency visits, hospital admissions, asthma attacks, and hospitalizations due to asthma, in comparison with the preceding year. Sixty‐six percent of asthmatic children had improved asthma control while in 33% the improvement exceeded the minimal clinically important difference. Pre‐bronchodilatation FEV1 and peak expiratory flow rate were improved during the pandemic. When compared to non‐asthmatic controls, children with asthma were not at increased risk of LRTIs, episodes of pyrexia, emergency visits, or hospitalizations during the pandemic. However, an increased risk of URTIs emerged.
Conclusion
Childhood asthma outcomes, including control, were improved during the first wave of the COVID‐19 pandemic, probably because of reduced exposure to asthma triggers and increased treatment adherence. The decreased frequency of acute episodes does not support the notion that childhood asthma may be a risk factor for COVID‐19. Furthermore, the potential for improving childhood asthma outcomes through environmental control becomes apparent.
This study evaluates the frequency of acute respiratory and febrile presentations furing the first wave of COVID‐19 pandemic in childhood asthma. Data from the multinational PeARL cohort reveal improved health and asthma activity during the first wave of the COVID‐19 pandemic, probably attributed to decreased exposure to asthma triggers and increased treatment adherence. During that period, children with asthma experienced fewer URTIs, episodes of pyrexia, emergency visits, hospital admissions, asthma attacks and hospitalizations due to asthma, in comparison to the preceding year.
Abbreviations: COVID‐19, coronavirus disease 2019; LRTI, lower respiratory tract infections; FEV1, forced expiratory value in 1 second; PeARL, Pediatric Asthma in Real Life; PFR, peak respiratory flow rate; URTI, upper respiratory tract infections.
Leukotriene-receptor antagonists (LTRAs) are recommended as an alternative treatment in patients with mild asthma, but their effect compared with placebo is unclear.
To determine the benefits and ...harms of LTRAs as monotherapy or in combination with inhaled corticosteroids compared with placebo in adults and adolescents with asthma.
MEDLINE and the Cochrane Central Register of Controlled Trials from inception through June 2015.
Peer-reviewed, English-language, randomized, controlled trials in patients with asthma that reported the effect of LTRAs versus placebo on measures of asthma control.
Three researchers extracted data on study population, interventions, outcome measures, and adverse events. One researcher assessed risk of bias.
Of the 2008 abstracts that were screened, 50 trials met eligibility criteria. Random-effects meta-analyses of 6 trials of LTRA monotherapy showed that LTRAs reduced the risk for an exacerbation (summary risk ratio RR, 0.60 95% CI, 0.44 to 0.81). In 4 trials of LTRAs as add-on therapy to inhaled corticosteroids, the summary RR for exacerbation was 0.80 (CI, 0.60 to 1.07). Leukotriene-receptor antagonists either as monotherapy or as add-on therapy to inhaled corticosteroids increased FEV1, whereas FEV1 percentage of predicted values was improved only in trials of LTRA monotherapy. Adverse event rates were similar in the intervention and comparator groups.
Variation in definitions and reporting of outcomes, high risk of bias in some studies, heterogeneity of findings, possible selective outcome reporting bias, and inability to assess the effect of asthma severity on summary estimates.
Leukotriene-receptor antagonists as monotherapy improved asthma control compared with placebo, but which patients are most likely to respond to treatment with LTRAs remains unclear.
National Institutes of Health.
Purpose
We aimed to provide a meta-analysis of the factors affecting vitreomacular traction (VMT) resolution after ocriplasmin use. A comprehensive systematic review of the complications after ...ocriplasmin use for VMT and macular hole was also done.
Methods
A literature search in PubMed was performed for studies about ocriplasmin published before 30 June 2015. Then a meta-analysis of the factors affecting the VMT resolution after ocriplasmin use was done, providing the pooled odds ratios for each factor and 95 % confidence intervals (CIs). We also described the potential adverse events after ocriplasmin use in a systematic review.
Results
A total of 194 abstracts were screened and 19 eligible studies were included in the meta-analysis. Age <65 years, female gender, vitreomacular adhesion diameter <1500 μm, phakic lens status and epiretinal membrane absence were found as positive predictive factors for VMT resolution, while macular hole size <250 μm was significantly associated with macular hole closure at the meta-analytical level. Various complications after ocriplasmin use were reported by frequency, including mainly vitreous floaters, photopsias, visual acuity decrease, ellipsoid zone changes, subretinal fluid development, enlargement of macular hole, anterior segment changes and electroretinogram alterations. It has to be noted that significant methodological weaknesses were identified, such as the absence of control groups or lack of transparency in the recruitment process and the examination procedure.
Conclusions
It is important to carefully select patients for ocriplasmin injection, taking into account the various predictive factors for VMT resolution. Patients should be informed about the potential adverse events of ocriplasmin, although they mainly seemed to be transient and usually mild/moderate in severity, suggesting that ocriplasmin is a safe and effective new treatment alternative for VMT and macular hole. However, due to the limited study quality, the uncertainty concerning the efficacy of this new approach is increased.
Abstract
Background and Aims
Response to calcineurin inhibitors (CNI) is associated with a significant improvement in long-term kidney survival of children with non-genetic steroid resistant ...nephrotic syndrome (SRNS). On the contrary, these agents are considered non-efficacious in monogenic SRNS and are contraindicated according to the latest International Pediatric Nephrology Association (IPNA) Clinical Practice Recommendations for SRNS. However, there is evidence suggesting that remission with CNI therapy in this subgroup of children with SRNS is possible, but no studies to date have assessed this question in a systematic way. We aimed to study the incidence of response to CNI in children with monogenic SRNS, factors predictive of remission and the effect of treatment on kidney survival.
Method
Retrospective cohort study of children 0–18 years with genetically confirmed SRNS treated with a CNI for at least 3 months. Demographic, clinical, genetic, biochemical, histopathologic and treatment data were collected at various time points; at clinical diagnosis, 6, 12, 24 months from CNI onset, and last available follow-up. Pathogenicity of all reported variants was assessed by a dedicated geneticist according to the American College of Medical Genetics guidelines and only patients with a pathogenic genotype were included in the analysis1. Patients were classified according to their response to CNI as complete, partial or non-responders based on the IPNA Clinical Practice Recommendations for SRNS2.
Results
141 patients from 37 international paediatric nephrology centers were included in the study. At 6 months from CNI initiation and at last visit, 27.6% and 22.5%, respectively, demonstrated either complete or partial response (“at least partial response”). Median observation time between CNI initiation and last visit was 42.1 months (IQR 20.1–65.6) and was comparable between patients with no response and at least partial response (42.3 vs 41.6 months; P>0.05). No serious adverse effects mandating treatment discontinuation were reported. Children demonstrating at least partial response at 6 months had a lower risk of progression to kidney failure at last visit versus non-responders (hazard ratio 95%CI 0.25, 0.10–0.62; P = 0.003). Subgroup analysis of patients with a follow-up of at least 2 years revealed similar results with a hazard ratio of 0.35 (95%CI 0.14–0.91; P = 0.03). Of the various clinical, biochemical, genetic, histopathologic and treatment parameters tested in a multivariable logistic regression model only higher serum albumin at CNI onset was associated with higher likelihood of response at 6 months (odds ratio 95% CI 1.16, 1.08–1.24; P < 0.001).
Conclusion
Our findings suggest that CNI use could be considered in monogenic SRNS and that achievement of response in this setting can alter an otherwise dismal long-term kidney outcome.
: media-1vid110.1542/5802711151001PEDS-VA_2017-3382
OBJECTIVES: We evaluated the efficacy of adenotonsillectomy (T/A) in children with sleep-disordered breathing (SDB) in a controlled study using ...oximetry. We hypothesized that children with SDB and abnormal nocturnal oximetry in a community setting will have improved hypoxemia indices after T/A.
Children with snoring and tonsillar hypertrophy (4-10 years old) who were candidates for T/A were randomly assigned to 2 oximetry sequences (baseline and 3-month follow-up): (1) oximetry immediately before T/A and at the 3-month follow-up, which occurred postoperatively (T/A group); or (2) oximetry at the initial visit and at the end of the usual 3-month waiting period for surgery (control group). Outcomes were (1) proportion of subjects with McGill oximetry score (MOS) >1 at baseline acquiring MOS of 1 at follow-up and (2) proportion of subjects achieving oxygen desaturation (≥3%) of hemoglobin index (ODI3) <2 episodes per hour at follow-up if they had ODI3 ≥3.5 episodes per hour at baseline.
One hundred and forty children had quality oximetry tracings. Twelve of 17 (70.6%) children with MOS >1 in the T/A group and 10 of 21 (47.6%) children with MOS >1 in the control group had MOS of 1 at follow-up (
= .14). More subjects in the T/A than in the control group achieved ODI3 <2 episodes per hour at follow-up (14 of 32 43.8% vs 2 of 38 5.3%;
< .001). Three children with elevated ODI3 were treated to prevent persistently abnormal ODI3 in 1 child at follow-up.
An ODI3 ≥3.5 episodes per hour in nocturnal oximetry is related to increased resolution rate of nocturnal hypoxemia after T/A for SDB compared with no intervention.
Background
H1‐antihistamines (AHs) are widely used for the treatment of allergic diseases, being one of the most commonly prescribed classes of medications in pediatrics. Newer‐generation AHs are ...associated with fewer adverse effects compared with first‐generation AHs. However, their relative harms in the pediatric population still need scrutiny.
Methods
We performed a systematic review of randomized controlled trials (RCTs), which included comparisons of safety parameters between an orally administered newer‐generation AH and another AH (first‐ or second‐generation), montelukast, or placebo in children aged ≤12 years. We searched MEDLINE and CENTRAL, independently extracted data on study population, interventions, adverse events (AEs), and treatment discontinuations, and assessed the methodologic quality of the included RCTs using the Cochrane’s risk of bias tool.
Results
Forty‐five RCTs published between 1989 and 2017 met eligibility criteria. The majority of RCTs included school‐aged children with allergic rhinitis and had a follow‐up period of up to a month. Four RCTs reported serious AEs in patients receiving a newer‐generation AH, but only two patients experienced a possibly drug‐related serious AE. The occurrence of AEs, drug‐related AEs, and treatment discontinuations due to AEs varied between RCTs. Most AEs reported were of mild intensity. Indirect evidence indicates that cetirizine is more sedating than the other newer‐generation AHs.
Conclusion
Our findings confirm that newer‐generation AHs have a favorable safety and tolerability profile. However, we could not draw firm conclusions regarding the comparative safety profile of the newer‐generation AHs due to the paucity of head‐to‐head RCTs, variation in definitions and reporting of AEs, and short follow‐up duration.
The management of anticoagulation therapy around the time of catheter ablation (CA) procedure for adults with arrhythmia is critical and yet is variable in clinical practice. The ideal approach for ...safe and effective perioperative management should balance the risk of bleeding during uninterrupted anticoagulation while minimising the risk of thromboembolic events with interrupted therapy.
To compare the efficacy and harms of interrupted versus uninterrupted anticoagulation therapy for catheter ablation (CA) in adults with arrhythmias.
We searched CENTRAL, MEDLINE, Embase, and SCI-Expanded on the Web of Science for randomised controlled trials on 5 January 2021. We also searched three registers on 29 May 2021 to identify ongoing or unpublished trials. We performed backward and forward searches on reference lists of included trials and other systematic reviews and contacted experts in the field. We applied no restrictions on language or publication status.
We included randomised controlled trials comparing uninterrupted anticoagulation with any modality of interruption with or without heparin bridging for CA in adults aged 18 years or older with arrhythmia.
Two review authors conducted independent screening, data extraction, and assessment of risk of bias. A third review author resolved disagreements. We extracted data on study population, interruption strategy, ablation procedure, thromboembolic events (stroke or systemic embolism), major and minor bleeding, asymptomatic thromboembolic events, cardiovascular and all-cause mortality, quality of life (QoL), length of hospital stay, cost, and source of funding. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We identified 12 studies (4714 participants) that compared uninterrupted periprocedural anticoagulation with interrupted anticoagulation. Studies performed an interruption strategy by either a complete interruption (one study) or by a minimal interruption (11 studies), of which a single-dose skipped strategy was used (nine studies) or two-dose skipped strategy (two studies), with or without heparin bridging. Studies included participants with a mean age of 65 years or greater, with only two studies conducted in relatively younger individuals (mean age less than 60 years). Paroxysmal atrial fibrillation (AF) was the primary type of AF in all studies, and seven studies included other types of AF (persistent and long-standing persistent). Most participants had CHADS2 or CHADS2-VASc demonstrating a low-moderate risk of stroke, with almost all participants having normal or mildly reduced renal function. Ablation source using radiofrequency energy was the most common (seven studies). Ten studies (2835 participants) were conducted in East Asian countries (Japan, China, and South Korea), while the remaining two studies were conducted in the USA. Eight studies were conducted in a single centre. Postablation follow-up was variable among studies at less than 30 days (three studies), 30 days (six studies), and more than 30 days postablation (three studies). Overall, the meta-analysis showed high uncertainty of the effect between the interrupted strategy compared to uninterrupted strategy on the primary outcomes of thromboembolic events (risk ratio (RR) 1.76, 95% confidence interval (CI) 0.33 to 9.46; I
= 59%; 6 studies, 3468 participants; very low-certainty evidence). However, subgroup analysis showed that uninterrupted vitamin A antagonist (VKA) is associated with a lower risk of thromboembolic events without increasing the risk of bleeding. There is also uncertainty on the outcome of major bleeding events (RR 1.10, 95% CI 0.59 to 2.05; I
= 6%; 10 studies, 4584 participants; low-certainty evidence). The uncertainty was also evident for the secondary outcomes of minor bleeding (RR 1.01, 95% CI 0.46 to 2.22; I
= 87%; 9 studies, 3843 participants; very low-certainty evidence), all-cause mortality (RR 0.34, 95% CI 0.01 to 8.21; 442 participants; low-certainty evidence) and asymptomatic thromboembolic events (RR 1.45, 95% CI 0.85 to 2.47; I
= 56%; 6 studies, 1268 participants; very low-certainty evidence). There was a lower risk of the composite endpoint of thromboembolic events (stroke, systemic embolism, major bleeding, and all-cause mortality) in the interrupted compared to uninterrupted arm (RR 0.23, 95% CI 0.07 to 0.81; 1 study, 442 participants; low-certainty evidence). In general, the low event rates, different comparator anticoagulants, and use of different ablation procedures may be the cause of imprecision and heterogeneity observed.
This meta-analysis showed that the evidence is uncertain to inform the decision to either interrupt or continue anticoagulation therapy around CA procedure in adults with arrhythmia on outcomes of thromboembolic events, major and minor bleeding, all-cause mortality, asymptomatic thromboembolic events, and a composite endpoint of thromboembolic events (stroke, systemic embolism, major bleeding, and all-cause mortality). Most studies in the review adopted a minimal interruption strategy which has the advantage of reducing the risk of bleeding while maintaining a lower level of anticoagulation to prevent periprocedural thromboembolism, hence low event rates on the primary outcomes of thromboembolism and bleeding. The one study that adopted a complete interruption of VKA showed that uninterrupted VKA reduces the risk of thromboembolism without increasing the risk of bleeding. Hence, future trials with larger samples, tailored to a more generalisable population and using homogeneous periprocedural anticoagulant therapy and ablation source are required to address the safety and efficacy of the optimal management of anticoagulant therapy prior to ablation.
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