Efficacy, safety, and tolerability of combined pirfenidone and N-acetylcysteine therapy: A systematic review and meta-analysis

2019 ◽  
Author(s):  
Hanyu Shi(Former Corresponding Author) ◽  
Dawei Yin ◽  
Francesco Bonella ◽  
Michael Kreuter ◽  
Ute Oltmanns ◽  
...  

Abstract Background: While antifibrotic drugs significantly decrease lung function decline in idiopathic pulmonary fibrosis (IPF), there is still an unmet need to halt disease progression. Antioxidative therapy with N-acetylcysteine (NAC) is considered a potential additional therapy that can be combined with antifibrotics in some patients in clinical practice. However, data on the efficacy, tolerability, and safety of this combination are scarce. We performed a systematic review and meta-analysis to appraise the safety, tolerability, and efficacy of the combination compared to treatment with pirfenidone alone. Methods: We systematically reviewed all the published studies with combined pirfenidone (PFD) and NAC (PFD+NAC) treatment in IPF patients. The primary outcomes referred to decline in pulmonary function tests (PFTs) and the rates of IPF patients with side effects. Results: In the meta-analysis, 6 studies with 319 total IPF patients were included. The PFD+NAC group was comparable to the PFD alone group in terms of the predicted forced vital capacity (FVC%) and predicted diffusion capacity for carbon monoxide (DLco%) from treatment start to week 24. Side effects and treatment discontinuation rates were also comparable in both groups. Conclusion: This systematic review and meta-analysis suggests that combination with NAC does not alter the efficacy, safety, or tolerability of PFD in comparison to PFD alone in IPF patients.

2020 ◽  
Author(s):  
Hanyu Shi ◽  
Dawei Yin ◽  
Francesco Bonella ◽  
Michael Kreuter ◽  
Ute Oltmanns ◽  
...  

Abstract Background: While antifibrotic drugs significantly decrease lung function decline in idiopathic pulmonary fibrosis (IPF), there is still an unmet need to halt disease progression. Antioxidative therapy with N-acetylcysteine (NAC) is considered a potential additional therapy that can be combined with antifibrotics in some patients in clinical practice. However, data on the efficacy, tolerability, and safety of this combination are scarce. We performed a systematic review and meta-analysis to appraise the safety, tolerability, and efficacy of the combination compared to treatment with pirfenidone alone. Methods: We systematically reviewed all the published studies with combined pirfenidone (PFD) and NAC (PFD+NAC) treatment in IPF patients. The primary outcomes referred to decline in pulmonary function tests (PFTs) and the rates of IPF patients with side effects. Results: In the meta-analysis, 6 studies with 319 total IPF patients were included. The PFD+NAC group was comparable to the PFD alone group in terms of the predicted forced vital capacity (FVC%) and predicted diffusion capacity for carbon monoxide (DLco%) from treatment start to week 24. Side effects and treatment discontinuation rates were also comparable in both groups. Conclusion: This systematic review and meta-analysis suggests that combination with NAC does not alter the efficacy, safety, or tolerability of PFD in comparison to PFD alone in IPF patients.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hyune June Lee ◽  
Sung Min Kim ◽  
Ji Yean Kwon

Abstract Background Peripartum depression is a common disorder with very high potential hazards for both the patients and their babies. The typical treatment options include antidepressants and electroconvulsive therapy. However, these treatments do not ensure the safety of the fetus. Recently, repetitive transcranial magnetic stimulation has emerged as a promising treatment for neuropathies as well as depression. Nevertheless, many studies excluded pregnant women. This systematic review was conducted to confirm whether repetitive transcranial magnetic stimulation was a suitable treatment option for peripartum depression. Methods We performed a systematic review that followed the PRISMA guidelines. We searched for studies in the MEDLINE, PsycINFO, EMBASE, and Cochrane library databases published until the end of September 2020. Eleven studies were selected for the systematic review, and five studies were selected for quantitative synthesis. Data analysis was conducted using Comprehensive Meta-Analysis 3 software. The effect size was analyzed using the standardized mean difference, and the 95% confidence interval (CI) was determined by the generic inverse variance estimation method. Results The therapeutic effect size of repetitive transcranial magnetic stimulation for peripartum depression was 1.394 (95% CI: 0.944–1.843), and the sensitivity analysis effect size was 1.074 (95% CI: 0.689–1.459), indicating a significant effect. The side effect size of repetitive transcranial magnetic stimulation for peripartum depression was 0.346 (95% CI: 0.214–0.506), a meaningful result. There were no severe side effects to the mothers or fetuses. Conclusions From various perspectives, repetitive transcranial magnetic stimulation can be considered an alternative treatment to treat peripartum depression to avoid exposure of fetuses to drugs and the severe side effects of electroconvulsive therapy. Further research is required to increase confidence in the results.


Obesity Facts ◽  
2021 ◽  
Vol 14 (2) ◽  
pp. 222-245
Author(s):  
Giovanna Muscogiuri ◽  
Marwan El Ghoch ◽  
Annamaria Colao ◽  
Maria Hassapidou ◽  
Volkan Yumuk ◽  
...  

<b><i>Background:</i></b> The very low-calorie ketogenic diet (VLCKD) has been recently proposed as an appealing nutritional strategy for obesity management. The VLCKD is characterized by a low carbohydrate content (&#x3c;50 g/day), 1–1.5 g of protein/kg of ideal body weight, 15–30 g of fat/day, and a daily intake of about 500–800 calories. <b><i>Objectives:</i></b> The aim of the current document is to suggest a common protocol for VLCKD and to summarize the existing literature on its efficacy in weight management and weight-related comorbidities, as well as the possible side effects. <b><i>Methods:</i></b> This document has been prepared in adherence with Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Literature searches, study selection, methodology development, and quality appraisal were performed independently by 2 authors and the data were collated by means of a meta-analysis and narrative synthesis. <b><i>Results:</i></b> Of the 645 articles retrieved, 15 studies met the inclusion criteria and were reviewed, revealing 4 main findings. First, the VLCKD was shown to result in a significant weight loss in the short, intermediate, and long terms and improvement in body composition parameters as well as glycemic and lipid profiles. Second, when compared with other weight loss interventions of the same duration, the VLCKD showed a major effect on reduction of body weight, fat mass, waist circumference, total cholesterol and triglyceridemia as well as improved insulin resistance. Third, although the VLCKD also resulted in a significant reduction of glycemia, HbA1c, and LDL cholesterol, these changes were similar to those obtained with other weight loss interventions. Finally, the VLCKD can be considered a safe nutritional approach under a health professional’s supervision since the most common side effects are usually clinically mild and easily to manage and recovery is often spontaneous. <b><i>Conclusions:</i></b> The VLCKD can be recommended as an effective dietary treatment for individuals with obesity after considering potential contra-indications and keeping in mind that any dietary treatment has to be personalized. <b><i>Prospero Registry:</i></b> The assessment of the efficacy of VLCKD on body weight, body composition, glycemic and lipid parameters in overweight and obese subjects: a meta-analysis (CRD42020205189).


PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255716
Author(s):  
Náthali Felícia Mineiro dos Santos Garrett ◽  
Ana Cristina Carvalho da Costa ◽  
Elaine Barros Ferreira ◽  
Giovanni Damiani ◽  
Paula Elaine Diniz dos Reis ◽  
...  

Background Checkpoint inhibitors have revolutionized advanced melanoma care; however, their cutaneous side effects have not been definitively elucidated. Objective To identify the prevalence of cutaneous toxicity in patients with melanoma treated with immune checkpoint inhibitors as monotherapy and/or in combination with chemotherapy and/or radiotherapy. Materials and methods We performed a systematic review and meta-analysis, which encompassed both clinical trials and observational studies describing the dermatological toxicities in patients treated with immune checkpoint inhibitors. The protocol was registered in the International Prospective Register of Systematic Review under the number CRD42018091915. The searches were performed using the CINAHL, Cochrane CENTRAL, LILACS, LIVIVO, PubMed, Scopus, and Web of Science databases. The methodological quality of the studies was evaluated with the JBI Critical Appraisal Checklist for Studies Reporting Prevalence Data Results A total of 9,802 articles were identified in the databases. The final sample comprised 39 studies. The evaluated drugs were ipilimumab, tremelimumab, pembrolizumab, and nivolumab. The results suggest that the most prevalent side effect was grade 1 and 2 pruritus (24%), followed by grade 1 and 2 rash (21%) and grade 1 and 2 vitiligo (10%). Conclusion The most prevalent side effects in patients treated with checkpoint inhibitors are pruritus, rash, and vitiligo, and they are rated mostly as grades 1 and 2 adverse events. Remarkably, vitiligo is most commonly found in patients treated with PD-1 inhibitors.


BMJ Open ◽  
2018 ◽  
Vol 8 (2) ◽  
pp. e018557 ◽  
Author(s):  
Jack W O’Sullivan ◽  
Ali Albasri ◽  
Brian D Nicholson ◽  
Rafael Perera ◽  
Jeffrey K Aronson ◽  
...  

BackgroundHealth systems are currently subject to unprecedented financial strains. Inappropriate test use wastes finite health resources (overuse) and delays diagnoses and treatment (underuse). As most patient care is provided in primary care, it represents an ideal setting to mitigate waste.ObjectiveTo identify overuse and underuse of diagnostic tests in primary care.DesignSystematic review and meta-analysis.Data sources and eligibility criteriaWe searched MEDLINE and Embase from January 1999 to October 2017 for studies that measured the inappropriateness of any diagnostic test (measured against a national or international guideline) ordered for adult patients in primary care.ResultsWe included 357 171 patients from 63 studies in 15 countries. We extracted 103 measures of inappropriateness (41 underuse and 62 overuse) from included studies for 47 different diagnostic tests.The overall rate of inappropriate diagnostic test ordering varied substantially (0.2%–100%)%).17 tests were underused >50% of the time. Of these, echocardiography (n=4 measures) was consistently underused (between 54% and 89%, n=4). There was large variation in the rate of inappropriate underuse of pulmonary function tests (38%–78%, n=8).Eleven tests were inappropriately overused >50% of the time. Echocardiography was consistently overused (77%–92%), whereas inappropriate overuse of urinary cultures, upper endoscopy and colonoscopy varied widely, from 36% to 77% (n=3), 10%–54% (n=10) and 8%–52% (n=2), respectively.ConclusionsThere is marked variation in the appropriate use of diagnostic tests in primary care. Specifically, the use of echocardiography (both underuse and overuse) is consistently poor. There is substantial variation in the rate of inappropriate underuse of pulmonary function tests and the overuse of upper endoscopy, urinary cultures and colonoscopy.PROSPERO registration numberCRD42016048832.


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