Management of asthma in childhood: study protocol of a systematic evidence update by the Paediatric Asthma in Real Life (PeARL) Think Tank

IntroductionClinical recommendations for childhood asthma are often based on data extrapolated from studies conducted in adults, despite significant differences in mechanisms and response to treatments. The Paediatric Asthma in Real Life (PeARL) Think Tank aspires to develop recommendations based on the best available evidence from studies in children. An overview of systematic reviews (SRs) on paediatric asthma maintenance management and an SR of treatments for acute asthma attacks in children, requiring an emergency presentation with/without hospital admission will be conducted.Methods and analysisStandard methodology recommended by Cochrane will be followed. Maintenance pharmacotherapy of childhood asthma will be evaluated in an overview of SRs published after 2005 and including clinical trials or real-life studies. For evaluating pharmacotherapy of acute asthma attacks leading to an emergency presentation with/without hospital admission, we opted to conduct de novo synthesis in the absence of adequate up-to-date published SRs. For the SR of acute asthma pharmacotherapy, we will consider eligible SRs, clinical trials or real-life studies without time restrictions. Our evidence updates will be based on broad searches of Pubmed/Medline and the Cochrane Library. We will use A MeaSurement Tool to Assess systematic Reviews, V.2, Cochrane risk of bias 2 and REal Life EVidence AssessmeNt Tool to evaluate the methodological quality of SRs, controlled clinical trials and real-life studies, respectively. Next, we will further assess interventions for acute severe asthma attacks with positive clinical results in meta-analyses. We will include both controlled clinical trials and observational studies and will assess their quality using the previously mentioned tools. We will employ random effect models for conducting meta-analyses, and Grading of Recommendations Assessment, Development and Evaluation methodology to assess certainty in the body of evidence.Ethics and disseminationEthics approval is not required for SRs. Our findings will be published in peer reviewed journals and will inform clinical recommendations being developed by the PeARL Think Tank.PROSPERO registration numbers CRD42020132990, CRD42020171624.</p

Corneal Collagen Cross-Linking for Infectious Keratitis: A Systematic Review and Meta-Analysis

Purpose: To assess the efficacy of corneal collagen cross-linking (CXL) in the management of infectious keratitis. Methods: Comprehensive literature search was performed in MEDLINE/PubMed and Cochrane Central Register of Controlled Trials using combinations of the following search terms: "corneal collagen cross linking" or "photoactivated riboflavin" or "UVA light and riboflavin" and "infectious keratitis" or "corneal ulcer." Last search was on March 19, 2015. Extracted data from individual studies were summarized and summary proportions of eyes healed and complications for different subgroups were estimated. Results: Twenty-five studies were included (2 randomized controlled trials, 13 case series, and 10 case reports) with a total of 210 eyes of 209 patients, of which 175 eyes underwent CXL. Causative microorganisms were bacteria, fungi, acanthamoeba, and Herpes simplex virus in 96, 32, 11, and 2 cases, respectively. Coinfections were present in 13 and cause was inconclusive in 21 cases. Sixteen of 175 eyes received no additional antibiotics, whereas 159 underwent CXL as an adjunct to antimicrobial treatment. Proportion of eyes healed with CXL was 87.2% (95% confidence interval (CI), 81.9%, 91.8%). For bacterial keratitis, the proportion of eyes healed was 85.7% (95% CI, 78.5%, 91.7%), whereas 10/11 and 25/32 eyes with acanthamoeba and fungal keratitis, respectively, were healed (available data not sufficient to provide a valid proportion analysis). Treatment resulted in corneal melting and tectonic keratoplasty in both Herpes simplex virus cases. Conclusions: CXL seems promising in the management of infectious keratitis, excluding viral infections. However, more randomized controlled trials are required to assess its efficacy. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved

Clinical effectiveness, safety profile, and pharmacokinetics of daptomycin in pediatric patients: A systematic review

Infections by Gram-positive pathogens pose a public health risk, especially due to increasing antibiotic resistance. Daptomycin has efficacy against most clinically important Gram-positive bacteria. Although experience regarding use of daptomycin in adults is increasing, studies on pediatric populations are limited.We aimed to evaluate the efficacy, safety, and pharmacokinetics of daptomycin in pediatric settings. We searched MEDLINE and Clinicaltrials.gov (through April 2016) and included 29 original studies in the final analysis. Available evidence suggests that daptomycin in pediatric patients has a favorable safety and tolerability profile and is an efficacious alternative for treatment of Gram-positive bacteremia, endocarditis, and infections of the skin, soft tissues, joints, and bones, especially when resistant strains are involved. However, future studies need to address several issues to determine the optimal dose and various pharmacokinetic parameters in different pediatric age groups. © The Author 2016

High risk of fistula formation in vacuum-assisted closure therapy in patients with open abdomen due to secondary peritonitis—a retrospective analysis

Purpose: The aim of this study was to evaluate the efficacy of vacuum-assisted closure therapy in patients with open abdomen due to secondary peritonitis and to identify possible risk factors of fistula formation. Methods: The hospital OPS-database (time period 2005–2014) was searched to identify patients treated with an open abdomen due to secondary peritonitis, who underwent vacuum-assisted closure therapy. Medical records were retrospectively analyzed for patients’ characteristics, cause of peritonitis, duration of vacuum therapy, number of relaparotomies, fascial closure rates, and risk factors of fistula formation. Results: Forty-three patients (19 male, 24 female) with a median age of 65 years (range 24–90 years) were identified. The major cause of secondary peritonitis was anastomotic leakage after intestinal anastomosis or bowel perforation, the median APACHE II score was 11. Median duration of VAC treatment was 12 days (range 3–88 days). Twenty of 43 (47 %) patients died from septic complications. Delayed fascial closure was obtained by suturing in 20 of 43 patients (47 %). Overall 16 of 43 (37 %) patients developed enteroatmospheric fistulas. Re-explorations after starting VAC treatment and duration of VAC therapy were significantly associated with the occurrence of enteroatmospheric fistulas (p < 0.001). ROC curve analysis determined the optimal duration of VAC therapy to reduce the risk of fistula formation at 13 days. Conclusions: Long-term VAC treatment of patients with an open abdomen due to secondary peritonitis results in a relatively low fascial closure rate and a high risk of fistula formation. © 2016, Springer-Verlag Berlin Heidelberg

Clinical effectiveness, safety profile, and pharmacokinetics of daptomycin in pediatric patients: A systematic review

Infections by Gram-positive pathogens pose a public health risk, especially due to increasing antibiotic resistance. Daptomycin has efficacy against most clinically important Gram-positive bacteria. Although experience regarding use of daptomycin in adults is increasing, studies on pediatric populations are limited.We aimed to evaluate the efficacy, safety, and pharmacokinetics of daptomycin in pediatric settings. We searched MEDLINE and Clinicaltrials.gov (through April 2016) and included 29 original studies in the final analysis. Available evidence suggests that daptomycin in pediatric patients has a favorable safety and tolerability profile and is an efficacious alternative for treatment of Gram-positive bacteremia, endocarditis, and infections of the skin, soft tissues, joints, and bones, especially when resistant strains are involved. However, future studies need to address several issues to determine the optimal dose and various pharmacokinetic parameters in different pediatric age groups. © The Author 2016

A Current Perspective of Allergic Asthma: From Mechanisms to Management

Asthma is a result of heterogenous, complex gene–environment interactions with variable clinical phenotypes, inflammation, and remodeling. It affects more than 330 million of people worldwide throughout their educational and working lives, while exacerbations put a heavy cost/burden on productivity. Childhood asthma is characterized by a predominance of allergic sensitization and multimorbidity, while in adults polysensitization has been positively associated with asthma occurrence. Despite significant improvements in recent decades, asthma management remains challenging. Recently, a group of specialists suggested that the term “asthma” should be preferably used as a descriptive term for symptoms. Moreover, type 2 inflammation has emerged as a pivotal disease mechanism including overlapping endotypes of specific IgE production, while type 2-low asthma includes several disease endotypes. Optimal asthma control requires both appropriate pharmacological interventions, tailored to each patient, as well as trigger avoidance measures. Regular monitoring for maintenance of symptom control, preservation of lung function, and detection of treatment-related adverse effects are warranted. Allergen-specific immunotherapy and the advent of new targeted therapies for patients with difficult to control asthma offer diverse treatment options. The current review summarizes up-to-date knowledge on epidemiology, definitions, diagnosis, and current therapeutic strategies. © 2021, Springer Nature Switzerland AG

Intravenous colistin use for infections due to MDR Gram-negative bacilli in critically ill paediatric patients: A systematic review and meta-analysis

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. © 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved

Palliative surgical bypass is superior to palliative endoscopic stenting in patients with malignant gastric outlet obstruction: systematic review and meta-analysis

Background: Gastrojejunostomy (GJ) and self-expanding metal stents (SEMS) are the two most common palliative treatment options for patients with malignant gastric outlet obstruction (GOO). Randomised trials and retrospective studies have shown discrepant results, so that there is still a controversy regarding the optimal treatment of GOO. Methods: Medline, Web of Science and Cochrane Library were systematically searched for studies comparing GJ to SEMS in patients with malignant GOO. Primary outcomes were survival and postoperative mortality. Secondary outcomes were frequency of re-interventions, major complications, time to oral intake and length of hospital stay. Results: Twenty-seven studies, with a total of 2.354 patients, 1.306 (55.5%) patients in the SEMS and 1.048 (44.5%) patients in the GJ group, were considered suitable for inclusion. GJ was associated with significantly longer survival than SEMS (mean difference 43 days, CI 12.00, 73.70, p = 0.006). Postoperative mortality (OR 0.55, CI 0.27, 1.16, p = 0.12) and major complications (OR 0.73, CI 0.5, 1.06, p = 0.10) were similar in both groups. The frequency of re-interventions, however, was almost three times higher in the SEMS group (OR 2.95, CI: 1.70, 5.14, p < 0.001), whereas the mean time to oral intake and length of hospital stay were shorter in the SEMS group (mean differences − 5 days, CI − 6.75, − 3.05 days, p < 0.001 and − 10 days, CI − 11.6, − 7.9 days, p < 0.001, respectively). Conclusions: Patients with malignant GOO and acceptable performance status should be primarily considered for a palliative GJ rather than SEMS. © 2019, Springer Science+Business Media, LLC, part of Springer Nature

Ocriplasmin use for vitreomacular traction and macular hole: A meta-analysis and comprehensive review on predictive factors for vitreous release and potential complications

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 &lt;65 years, female gender, vitreomacular adhesion diameter &lt;1500 μm, phakic lens status and epiretinal membrane absence were found as positive predictive factors for VMT resolution, while macular hole size &lt;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. © 2016, Springer-Verlag Berlin Heidelberg

Sarcopenia and sarcopenic obesity are significantly associated with poorer overall survival in patients with pancreatic cancer: Systematic review and meta-analysis

Backround: The role of sarcopenia and sarcopenic obesity in patients with pancreatic ductal adenocarcinoma(PDAC) remains controversial. Material and Methods: Medline and Web of Science were searched for studies reporting survival in sarcopenic and/or sarcopenic obese patients with pancreatic cancer. Primary outcome was mortality in patients with sarcopenia and/or sarcopenic obesity versus non-sarcopenic and/or non-sarcopenic obese patients. Secondary outcome was the incidence of major postoperative complications. Results: Eleven studies comprising 2.297 patients were considered suitable for inclusion. Overall 959 of 2.111(45.4%) patients were defined as sarcopenic and 163 of 1.254(13%) as sarcopenic obese. Patients’ age was above 60 years(range 63-69) with a male proportion ranging from 50.8% to 68.0%. Of 2.297 patients, 958(41.7%) underwent palliative treatment, 1.339(58.3%) curative resections. Follow-up ranged from 11 to 57.7 months. Median overall survival ranged from 4.3 to 12 months in palliative patients and 17.4 to 25.8 months after curative resection. Overall proportions of sarcopenic patients varied from 21.3% to 65.3%. Sarcopenia was significantly associated with poorer overall survival(HR 1.49; 95%CI 1.27-1.74,p<0.001). Sarcopenic obesity was reported in 0.6% to 25.0% of patients, and was also significantly associated with poorer overall survival(HR 2.01; 95%CI 1.55-2.61,p<0.001). The incidence of major complications ranged from 8.6% to 33.9%. Rates of clinically relevant(grade B/C) postoperative pancreatic fistulas varied from 8.3% to 17.8%. Sarcopenic obesity was an independent predictor of major postoperative complications in one study, in another study sarcopenia was significantly associated with clinically relevant pancreatic fistulas. Conclusions: Sarcopenia and sarcopenic obesity are significantly associated with poorer overall survival in patients with PDAC. © 2018 IJS Publishing Group Lt