scholarly journals From Ivacaftor to Triple Combination: A Systematic Review of Efficacy and Safety of CFTR Modulators in People with Cystic Fibrosis

2020 ◽  
Vol 21 (16) ◽  
pp. 5882 ◽  
Author(s):  
Andrea Gramegna ◽  
Martina Contarini ◽  
Stefano Aliberti ◽  
Rosaria Casciaro ◽  
Francesco Blasi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cystic Fibrosis ◽  
Lung Function ◽  
Real Life ◽  
Scientific Data ◽  
Current Evidence ◽  
Symptom Improvement ◽  
Efficacy And Safety ◽  
Beneficial Effects ◽  
Cftr Modulators

Over the last years CFTR (cystic fibrosis transmembrane conductance regulator) modulators have shown the ability to improve relevant clinical outcomes in patients with cystic fibrosis (CF). This review aims at a systematic research of the current evidence on efficacy and tolerability of CFTR modulators for different genetic subsets of patients with CF. Two investigators independently performed the search on PubMed and included phase 2 and 3 clinical trials published in the study period 1 January 2005–31 January 2020. A final pool of 23 papers was included in the systematic review for a total of 4219 patients. For each paper data of interest were extracted and reported in table. In terms of lung function, patients who had the most beneficial effects from CFTR modulation were those patients with one gating mutation receiving IVA (ivacaftor) and patients with p.Phe508del mutation, both homozygous and heterozygous, receiving ELX/TEZ/IVA (elexacaftor/tezacaftor/ivacaftor) had the most relevant beneficial effects in term of lung function, pulmonary exacerbation decrease, and symptom improvement. CFTR modulators showed an overall favorable safety profile. Next steps should aim to systematize our comprehension of scientific data of efficacy and safety coming from real life observational studies.

scholarly journals Airway Inflammation and Host Responses in the Era of CFTR Modulators

2020 ◽  
Vol 21 (17) ◽  
pp. 6379
Author(s):  
Karen Keown ◽  
Ryan Brown ◽  
Declan F. Doherty ◽  
Claire Houston ◽  
Michael C. McKelvey ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Lung Disease ◽  
Airway Inflammation ◽  
Host Responses ◽  
Current Evidence ◽  
Future Research ◽  
Clinical Endpoints ◽  
New Class ◽  
Cftr Modulators

The arrival of cystic fibrosis transmembrane conductance regulator (CFTR) modulators as a new class of treatment for cystic fibrosis (CF) in 2012 represented a pivotal advance in disease management, as these small molecules directly target the upstream underlying protein defect. Further advancements in the development and scope of these genotype-specific therapies have been transformative for an increasing number of people with CF (PWCF). Despite clear improvements in CFTR function and clinical endpoints such as lung function, body mass index (BMI), and frequency of pulmonary exacerbations, current evidence suggests that CFTR modulators do not prevent continued decline in lung function, halt disease progression, or ameliorate pathogenic organisms in those with established lung disease. Furthermore, it remains unknown whether their restorative effects extend to dysfunctional CFTR expressed in phagocytes and other immune cells, which could modulate airway inflammation. In this review, we explore the effects of CFTR modulators on airway inflammation, infection, and their influence on the impaired pulmonary host defences associated with CF lung disease. We also consider the role of inflammation-directed therapies in light of the widespread clinical use of CFTR modulators and identify key areas for future research.

scholarly journals A Systematic Review of the Clinical Efficacy and Safety of CFTR Modulators in Cystic Fibrosis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Al-Rahim R. Habib ◽  
Majid Kajbafzadeh ◽  
Sameer Desai ◽  
Connie L. Yang ◽  
Kate Skolnik ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cystic Fibrosis ◽  
Clinical Efficacy ◽  
Efficacy And Safety ◽  
Cftr Modulators

scholarly journals Efficacy and safety of microbiota transfer therapy for the management of autism spectrum disorder in children: a systematic review

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 48
Author(s):  
Pablo Daniel Estrella Porter ◽  
Luis Eduardo Guzmán Freire ◽  
Joseth Paulina Adatty Molina ◽  
María Verónica Burneo Raza ◽  
Henry Alejandro Carrión Celi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Autism Spectrum Disorder ◽  
Intervention Group ◽  
Autism Spectrum ◽  
Nervous System Development ◽  
Spectrum Disorder ◽  
Current Evidence ◽  
Cochrane Library ◽  
Efficacy And Safety ◽  
Level Of Evidence

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with an unclear etiologic mechanism. Following suggestions in the literature of a close relation between the gut microbiota and the central nervous system development, neuroimmune and neuroendocrine systems, new theories and strategies of the management of ASD in children focus on the brain-gut axis via microbiota transfer therapy. Despite the regular appearance in the news, the level of evidence supporting this intervention is unclear and to this date, no systematic review on this issue has been published. Methods: We conducted a systematic literature review of the efficacy and safety of microbiota transfer therapy for the management of ASD in children. MEDLINE via PubMed, LILACS IBECS via BVS, EMBASE via Ovid, Scopus and Cochrane Library were searched on 19th April 2018. Results: One single study published in 2017 was identified. The intervention group included 18 patients and showed significant clinical improvements in the gastrointestinal and ASD-related symptoms. The clinical procedure was reported as safe and well-tolerated with some transitory adverse effects. Conclusions: The causality and correlation of the intervention and the expected outcomes cannot be assumed with current evidence. In addition, recommendations about the effectiveness or safety of microbiota transfer therapy in children with ASD cannot be currently issued. Randomized controlled trials and clinical protocols for the intervention are needed.

scholarly journals Forced Oscillation Technique for Monitoring the Respiratory Status of Children with Cystic Fibrosis: A Systematic Review

Children ◽  
2021 ◽  
Vol 8 (10) ◽  
pp. 857
Author(s):  
Ioanna Loukou ◽  
Maria Moustaki ◽  
Agni Deligianni ◽  
Olympia Sardeli ◽  
Konstantinos Douros
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Children And Adolescents ◽  
Forced Oscillation ◽  
Clinical Symptoms ◽  
Current Evidence ◽  
Forced Oscillation Technique ◽  
Gold Standard Method ◽  
Respiratory Status ◽  
Alternative Modality

Spirometry is considered the gold standard method for monitoring lung function of patients with cystic fibrosis (CF) but it requires patients’ cooperation and therefore it is not useful for the majority of preschool-aged children. Oscillometry is an alternative modality for lung function monitoring that requires minimal cooperation and can be applied in children as young as 3 years of age. Furthermore, it generates lesser aerosol compared to spirometry, an issue that is of considerable importance in the COVID-19 era. The aim of this review was to present the existing clinical data regarding the application of oscillometry in children and adolescents with CF. The method seems to have acceptable feasibility and repeatability. However, there is conflicting data regarding the correlation of oscillometry values with the clinical symptoms of CF patients either in clinically stable or in exacerbation periods. Furthermore, it is not clear to what extent oscillometry measurements correlate with the spirometry indices. Based on current evidence, spirometry cannot be substituted by oscillometry in the monitoring of the respiratory status of children and adolescents with CF.

scholarly journals Comparison of intravitreal dexamethasone implant and anti-VEGF drugs in the treatment of retinal vein occlusion-induced oedema: a meta-analysis and systematic review

BMJ Open ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. e032128
Author(s):  
Shuai Ming ◽  
Kunpeng Xie ◽  
Mingzhu Yang ◽  
Huijuan He ◽  
Ya Li ◽  
...  
Keyword(s):  
Systematic Review ◽  
Retinal Vein Occlusion ◽  
Real World ◽  
Meta Analysis ◽  
Real Life ◽  
Cochrane Library ◽  
Efficacy And Safety ◽  
Vein Occlusion ◽  
Anti Vegf ◽  
Intravitreal Dexamethasone

ObjectiveTo compare the efficacy and safety of intravitreal dexamethasone (DEX) implant and anti-vascular endothelial growth factor (anti-VEGF) agents in the treatment of macular oedema secondary to retinal vein occlusion (RVO).DesignSystematic review and meta-analysis based on Grading of Recommendations Assessment, Development and Evaluation (GRADE).Data sourcesPubMed, Cochrane Library and ClinicalTrials.gov registry were searched from inception to 10 December 2019, without language restrictions.Eligibility criteriaRandomised controlled trials (RCTs) and real-world observation studies comparing the efficacy of DEX implant and anti-VEGF agents for the treatment of patients with RVO, naïve or almost naïve to both arms, were included.Data extraction and synthesisTwo reviewers independently extracted data for mean changes in best-corrected visual acuity (BCVA), central subfield thickness (CST) and product safety. Review Manager V.5.3 and GRADE were used to synthesise the data and validate the evidence, respectively.ResultsFour RCTs and 12 real-world studies were included. An average lower letter gain in BCVA was determined for the DEX implant (mean difference (MD) = −6.59; 95% CI −8.87 to −4.22 letters) administered at a retreatment interval of 5–6 months. Results were similar (MD6 months=−12.68; 95% CI −21.98 to −3.37 letters; MD12 months=−9.69; 95% CI −12.01 to −7.37 letters) at 6 and 12 months. The DEX implant resulted in comparable or marginally less CST reduction at months 6 and 12 but introduced relatively higher risks of elevated intraocular pressure (RR=3.89; 95% CI 2.16 to 7.03) and cataract induction (RR=5.22; 95% CI 1.67 to 16.29). Most real-life studies reported an insignificant numerical gain in letters for anti-VEGF drugs relative to that for DEX implant. However, the latter achieved comparable efficacy with a 4-month dosage interval.ConclusionCompared with anti-VEGF agents, DEX implant required fewer injections but had inferior functional efficacy and safety. Real-life trials supplemented the efficacy data for DEX implant.

scholarly journals Gastric Electrical Stimulation with the Enterra System: A Systematic Review

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Nikhil Lal ◽  
Sam Livemore ◽  
Declan Dunne ◽  
Iftikhar Khan
Keyword(s):  
Systematic Review ◽  
Electrical Stimulation ◽  
Preoperative Assessment ◽  
Gastric Electrical Stimulation ◽  
Current Evidence ◽  
Cochrane Library ◽  
Symptom Improvement ◽  
System A ◽  
Gastric Emptying Time

Background. Gastric electrical stimulation (GES) is a surgically implanted treatment option for refractory gastroparesis.Aim. To systematically appraise the current evidence for the use of gastric electrical stimulation and suggest a method of standardisation of assessment and follow-up in these patients.Methods. A systematic review of PubMed, Web of Science, DISCOVER, and Cochrane Library was conducted using the keywords including gastric electrical stimulation, gastroparesis, nausea, and vomiting and neuromodulation, stomach, central nervous system, gastric pacing, electrical stimulation, and gastrointestinal.Results. 1139 potentially relevant articles were identified, of which 21 met the inclusion criteria and were included. The quality of studies was variable. There was a variation in outcome measures and follow-up methodology. Included studies suggested significant reductions in symptom severity reporting over the study period, but improvements in gastric emptying time were variable and rarely correlated with symptom improvement.Conclusion. The evidence in support of gastric electrical stimulation is limited and heterogeneous in quality. While current evidence has shown a degree of efficacy in these patients, high-quality, large clinical trials are needed to establish the efficacy of this therapy and to identify the patients for whom this therapy is inappropriate. A consensus view on essential preoperative assessment and postoperative measurement is needed.

scholarly journals Chinese Herbal Medicine for Aspirin Resistance: A Systematic Review of Randomized Controlled Trials

2014 ◽  
Vol 2014 ◽  
pp. 1-16
Author(s):  
Ai-ju Liu ◽  
Hui-qin Li ◽  
Ji-huang Li ◽  
Yuan-yuan Wang ◽  
Dong Chen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Herbal Medicine ◽  
Randomized Controlled Trials ◽  
Chinese Herbal Medicine ◽  
Aspirin Resistance ◽  
Current Evidence ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Chinese Herbal

Aspirin resistance (AR) is a prevalent phenomenon and leads to significant clinical consequences, but the current evidence for effective interventional strategy is insufficient. The objective of this systematic review is thus to assess the efficacy and safety of Chinese herbal medicine (CHM) for AR. A systematical literature search was conducted in 6 databases until December 2012 to identify randomized controlled trials (RCTs) of CHM for AR. As a result, sixteen RCTs with a total of 1011 subjects were identified, suggesting that the interests of the medical profession and the public in the use of CHM for AR have grown considerably in the recent years. Tongxinluo capsule and Danshen-based prescriptions were the most frequently used herbal prescriptions, while danshen root, milkvetch root, Leech, and Rosewood were the most frequently used single herbs. Despite the apparent reported positive findings, it is premature to determine the efficacy and safety of CHM for the treatment of AR due to poor methodological quality and insufficient safety data. However, CHMs appeared to be well tolerated in all included studies. Thus, CHM as a promising candidate is worthy of improvement and development for further clinical AR trials. Large sample-size and well-designed rigorous RCTs are needed.

scholarly journals P051 The bigger you are the harder you fall? Short term effects of LUM/IVA (Orkambi) on lung function in children with cystic fibrosis

2019 ◽  
Vol 104 (7) ◽  
pp. e2.57-e2
Author(s):  
Emma O’ Grady ◽  
Rebecca Finnegan ◽  
Anna Smyth ◽  
Stephanie Ryan ◽  
Michael Williamson
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Pulmonary Function Tests ◽  
Real Life ◽  
Young Patients ◽  
Forced Expiratory Volume ◽  
List Type ◽  
High Resolution Computed Tomography ◽  
Air Trapping ◽  
Female Ratio

AimCystic Fibrosis conductance Transmembrane Regulator (CFTR) protein modulators represent a major breakthrough in the pharmacological management of Cystic Fibrosis (CF). Previous studies report acute changes in lung function after first administration of lumacaftor/ivacaftor (LUM/IVA) without a clear underlying mechanism.1 2 Our aim was to explore links between changes in percent predicted forced expiratory volume in one second (ppFEV1) and a number of potentially influencing factors.MethodsWe conducted a retrospective review of all children with CF who were started on LUM/IVA treatment between September 2016 and August 2017 in our institution. Data was collected from patient charts, electronic laboratory and radiology records. CT Thorax images were reviewed for evidence of air trapping using the Brody score.3 Descriptive and statistical analyses were performed using SPSS. ResultsData was collected from 15 children with CF who were started on LUM/IVA treatment. The mean (±SD) age of starting treatment was 14 years (±1.7 years), with a mean weight of 47.3 kg (±8.9 kg) and male-to-female ratio of 9:6. Ninety-three percent of patients experienced an acute decline in ppFEV1 post initiation of LUM/IVA, with an absolute mean decline of -10.8% (0–20%). There is a statistically significant inverse relationship between absolute change in ppFEV1 (FEV1) and baseline ppFEV1. There is no correlation between FEV1 and weight, gender or air trapping score.ConclusionOur results suggest that a LUM/IVA related decline in lung function is more significant in CF children with higher baseline ppFEV1. This offers reassurance when initiating LUM/IVA as the patients who experience significant declines have a greater respiratory reserve with which to support this reduction. ReferencesRatjen F, Hug C, Marigowda G, et al. Efficacy and safety of lumacaftor and ivacaftor in patients aged 6–11 years with cystic fibrosis homozygous for F508del-CFTR: a randomised, placebo-controlled phase 3 trial. Lancet Respir Med 2017;5:557–567.Labaste A, Ohlmann C, Mainguy C, et al. Real-life acute lung function changes after lumacaftor/ivacaftor first administration in paediatric patients with cystic fibrosis. J Cyst Fibros 2017;16:709–712.Brody A, Klein J, Molina P, et al. High- resolution computed tomography in young patients with cystic fibrosis: distribution of abnormalities and correlation with pulmonary function tests. Journal of Pediatrics 2004;145:32–38.

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