Conservative and Surgical Modalities in the Management of Pediatric Parapneumonic Effusion and Empyema: A Living Systematic Review and Network Meta-Analysis.

BACKGROUND: The optimal treatment for community-acquired childhood pneumonia complicated by empyema remains unclear. RESEARCH QUESTION: In children with parapneumonic effusion or empyema, do hospital length of stay and other key clinical outcomes differ according to the treatment modality used? STUDY DESIGN AND METHODS: A living systematic review of randomized controlled trials (RCTs) was conducted by searching the Cochrane Central Register of Controlled Trials, Embase, Latin American and Caribbean Health Sciences Literature, Ovid MEDLINE, and Web of Science Core Collection databases. Eligible RCTs included patients aged < 18 years and compared two of the following treatment modalities: antibiotics alone, chest tube insertion with or without fibrinolytics, video-assisted thoracoscopic surgery (VATS), and decortication via thoracotomy. A network meta-analysis was performed to evaluate treatment effects on hospital length of stay (LOS), the primary outcome. RESULTS: Eleven trials including a total of 590 patients were selected for the network meta-analysis. Compared with a chest tube alone, a chest tube with fibrinolytics, thoracotomy, and VATS were all associated with shorter LOS, with a mean difference of 5.05 days (95% CI, 2.46-7.64), 6.33 days (95% CI, 3.17-9.50), and 5.86 days (95% CI, 3.38-8.35), respectively. No substantial differences in LOS were observed between the latter three interventions. None of the 11 RCTs compared antibiotics alone vs other types of treatment. Most trials reported peri-procedural complications and the need for reintervention, but the descriptions differed significantly between trials, preventing meta-analysis. In trials reporting health care-associated costs, fibrinolytics had cost advantages compared with VATS. Short- and long-term morbidity and mortality were very low, regardless of the treatment modality. INTERPRETATION: The results of this network meta-analysis showed that a chest tube alone was associated with a longer LOS compared with other treatment modalities. The lower cost associated with a chest tube plus fibrinolytics warrants consideration when choosing between treatment options, given similar LOS and clinical outcomes compared with the other modalities.

Diagnostic tools and CFTR functional assays in cystic fibrosis: utility and availability in Switzerland.

Cystic fibrosis (CF) is a genetic disease caused by a bi-allelic mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. When the diagnosis cannot be confirmed by a positive sweat test or/and the identification of two CF-causing variants, international guidelines recommend the use of CFTR functional assays. These tests assess whether CFTR activity is normal or diminished/absent through measurement of CFTR-mediated chloride secretion/absorption. CFTR functional assays are not only useful for diagnostic purposes but can also serve as a surrogate outcome for clinical trials of CFTR modulators, which are emerging therapeutic agents designed to correct the malfunctioning protein. In the near future they could also be used as precision-medicine techniques, to help guidance and optimisation of treatment. Until now, sweat testing has been the only CFTR functional assay available in Switzerland. Since 2020, the Centre Hospitalier Universitaire Vaudois (CHUV) at Lausanne and the Lucerne Children’s Hospital perform nasal potential difference measurement. Moreover, The Ecole Polytechnique Fédérale de Lausanne (EPFL) established a reliable procedure to generate adult intestinal organoids, i.e., stem cell-derived in-vitro grown mini tissues, extracted from rectal biopsies, which can be used to assess CFTR function in vitro. This narrative review describes the most popular CFTR functional assays, as well as their indications, limitations and availability in Switzerland.