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Phosphodiesterase-4 Inhibitor

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1. Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease. (PubMed)

Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease. Chronic obstructive pulmonary disease (COPD) is associated with cough, sputum production or dyspnoea and a reduction in lung function, quality of life and life expectancy. Apart from smoking cessation, there are no other treatments that slow lung function decline. Roflumilast and cilomilast are oral phosphodiesterase 4 (PDE4) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD (...) . This is an update of a Cochrane review first published in 2011 and updated in 2013.To evaluate the efficacy and safety of oral PDE4 inhibitors in the management of stable COPD.We identified randomised controlled trials (RCTs) from the Cochrane Airways Trials Register (date of last search October 2016). We found other trials from web-based clinical trials registers.We included RCTs if they compared oral PDE4 inhibitors with placebo in people with COPD. We allowed co-administration of standard COPD therapy.One

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2017 Cochrane

2. Phosphodiesterase 5 inhibitors for pulmonary hypertension. (PubMed)

Phosphodiesterase 5 inhibitors for pulmonary hypertension. Pulmonary hypertension (PH) comprises a group of complex and heterogenous conditions, characterised by elevated pulmonary artery pressure, and which left untreated leads to right-heart failure and death. PH includes World Health Organisation (WHO) Group 1 pulmonary arterial hypertension (PAH); Group 2 consists of PH due to left-heart disease (PH-LHD); Group 3 comprises PH as a result of lung diseases or hypoxia, or both; Group 4 (...) includes PH due to chronic thromboembolic occlusion of pulmonary vasculature (CTEPH), and Group 5 consists of cases of PH due to unclear and/or multifactorial mechanisms including haematological, systemic, or metabolic disorders. Phosphodiesterase type 5 (PDE5) inhibitors increase vasodilation and inhibit proliferation.To determine the efficacy of PDE5 inhibitors for pulmonary hypertension in adults and children.We performed searches of CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science up to 26

2019 Cochrane

4. Phosphodiesterase inhibitors for lower urinary tract symptoms consistent with benign prostatic hyperplasia. (PubMed)

Phosphodiesterase inhibitors for lower urinary tract symptoms consistent with benign prostatic hyperplasia. Benign prostatic hyperplasia (BPH) refers to non-malignant enlargement of the prostate gland that may cause bothersome lower urinary tract symptoms (LUTS). Alpha-blockers (ABs) and 5-alpha reductase inhibitors (5-ARIs) are the mainstay of medical treatment. Recently, phosphodiesterase inhibitors (PDEIs) that so far have been used mainly to treat erectile dysfunction were introduced

2018 Cochrane

5. Application of Topical Phosphodiesterase 4 Inhibitors in Mild to Moderate Atopic Dermatitis: A Systematic Review and Meta-analysis. (PubMed)

Application of Topical Phosphodiesterase 4 Inhibitors in Mild to Moderate Atopic Dermatitis: A Systematic Review and Meta-analysis. Topical medication is the central treatment for patients with atopic dermatitis (AD), but the options are limited. Phosphodiesterase 4 (PDE4) inhibitors are a new candidate for AD therapy.To evaluate the efficacy and safety of topical PDE4 inhibitors in mild to moderate AD.Clinical trials were identified from MEDLINE, Embase, Cochrane Controlled Register of Trials (...) , Chinese medical databases (Wanfang, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, and China Science and Technology Journal Database), ClinicalTrials.gov, and other trial registries from inception to August 15, 2018. No restrictions on languages were placed.Only double-blind randomized clinical trials with topical PDE4 inhibitors vs topical vehicle treatment for patients with mild to moderate AD were included.Two reviewers independently extracted study features

2019 JAMA dermatology (Chicago, Ill.)

6. Real-world incidence of inflammatory bowel disease among patients with other chronic inflammatory diseases treated with interleukin-17a or phosphodiesterase 4 inhibitors. (PubMed)

Real-world incidence of inflammatory bowel disease among patients with other chronic inflammatory diseases treated with interleukin-17a or phosphodiesterase 4 inhibitors. Objectives: (1) To assess the real-world incidence of inflammatory bowel disease (IBD) in patients with or without other chronic inflammatory diseases (CIDs), and (2) to understand whether IBD incidence differs in CID patients receiving interleukin-17a signaling antagonists (anti-IL-17a) or phosphodiesterase 4 inhibitors (...) (PDE4i) versus patients using a biologic not indicated for IBD or biologic-naïve patients. Methods: The MarketScan Research Databases (January 2010-July 2017) were used. A CID population was created from patients with ankylosing spondylitis, psoriatic arthritis, psoriasis or rheumatoid arthritis (RA). The CID population was stratified into different cohorts based on the baseline treatments received: (1) anti-IL-17a, (2) PDE4i, (3) biologic-naïve, and (4) non-IBD-indicated biologic (i.e. biologics

2019 Current medical research and opinion

7. Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease. (PubMed)

Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease. Chronic obstructive pulmonary disease (COPD) is associated with cough, sputum production or dyspnoea and a reduction in lung function, quality of life and life expectancy. Apart from smoking cessation, there are no other treatments that slow lung function decline. Roflumilast and cilomilast are oral phosphodiesterase 4 (PDE4) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD.To (...) evaluate the efficacy and safety of oral PDE4 inhibitors in the management of stable COPD.We identified randomised controlled trials (RCTs) from the Cochrane Airways Group Specialised Register of trials (date of last search June 2013). We found other trials from web-based clinical trial registers.We included RCTs if they compared oral PDE4 inhibitors with placebo in people with COPD. We allowed co-administration of standard COPD therapy.One review author extracted data and a second review author

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2013 Cochrane

8. Phosphodiesterase Type 5 Inhibitors for Penile Rehabilitation Post Radical Prostatectomy: A Review of Clinical Effectiveness and Guidelines

Phosphodiesterase Type 5 Inhibitors for Penile Rehabilitation Post Radical Prostatectomy: A Review of Clinical Effectiveness and Guidelines Phosphodiesterase Type 5 Inhibitors for Penile Rehabilitation Post Radical Prostatectomy: A Review of Clinical Effectiveness and Guidelines | CADTH.ca Find the information you need Phosphodiesterase Type 5 Inhibitors for Penile Rehabilitation Post Radical Prostatectomy: A Review of Clinical Effectiveness and Guidelines Phosphodiesterase Type 5 Inhibitors (...) for Penile Rehabilitation Post Radical Prostatectomy: A Review of Clinical Effectiveness and Guidelines Published on: August 24, 2017 Project Number: RC0915-000 Product Line: Research Type: Drug Report Type: Summary with Critical Appraisal Result type: Report Question What is the clinical effectiveness of phosphodiesterase type 5 inhibitors (PDE-5Is) for the treatment of adults requiring penile rehabilitation post radical prostatectomy? What are the evidence-based guidelines associated with penile

2017 Canadian Agency for Drugs and Technologies in Health - Rapid Review

9. The isozyme selective phosphodiesterase-4 inhibitor, ABI-4, attenuates the effects of lipopolysaccharide in human cells and rodent models of peripheral and CNS inflammation. (PubMed)

The isozyme selective phosphodiesterase-4 inhibitor, ABI-4, attenuates the effects of lipopolysaccharide in human cells and rodent models of peripheral and CNS inflammation. Inhibitors of phosphodiesterase-4 (PDE4) have been approved for the treatment of inflammatory disorders, but are associated with dose-limiting nausea and vomiting. These side effects are hypothesized to be mediated by inhibition of the PDE4D isozyme. Here we demonstrate the anti-inflammatory effects of the novel brain (...) penetrant PDE4D-sparing PDE4 inhibitor, ABI-4. ABI-4 was a potent (EC50∼14nM) inhibitor of lipopolysaccharide (LPS) induced TNF-α release from mouse microglia and human PBMCs. ABI-4 (0.32mg/kg) blocked LPS-induced release of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in blood and brain of mice. In a rat model of endotoxin induced uveitis, ABI-4 (0.03-0.3mg/kg) demonstrated steroid-like efficacy in preventing leucocyte infiltration of the aqueous humor when administered 4h after LPS. LPS (0.32mg/kg

2017 Brain, behavior, and immunity

10. Ertugliflozin with metformin and a dipeptidyl peptidase-4 inhibitor for treating type 2 diabetes

Ertugliflozin with metformin and a dipeptidyl peptidase-4 inhibitor for treating type 2 diabetes Ertugliflozin with metformin and a Ertugliflozin with metformin and a dipeptidyl peptidase-4 inhibitor for dipeptidyl peptidase-4 inhibitor for treating type 2 diabetes treating type 2 diabetes T echnology appraisal guidance Published: 5 June 2019 www.nice.org.uk/guidance/ta583 © NICE 2019. All rights reserved. Subject to Notice of rights (https://www.nice.org.uk/terms-and-conditions#notice (...) to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Commissioners and providers have a responsibility to promote an environmentally sustainable health and care system and should assess and reduce the environmental impact of implementing NICE recommendations wherever possible. Ertugliflozin with metformin and a dipeptidyl peptidase-4 inhibitor for treating type 2 diabetes (TA583) © NICE 2019. All rights reserved. Subject to Notice of rights (https

2019 National Institute for Health and Clinical Excellence - Technology Appraisals

11. Early Relief of Pruritus in Atopic Dermatitis with Crisaborole Ointment, A Non-steroidal, Phosphodiesterase 4 Inhibitor. (PubMed)

Early Relief of Pruritus in Atopic Dermatitis with Crisaborole Ointment, A Non-steroidal, Phosphodiesterase 4 Inhibitor. Pruritus occurs in all patients with atopic dermatitis and requires quick relief to reduce disease exacerbation and improve quality of life. Crisaborole ointment is a non-steroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis. This post hoc analysis explores crisaborole ointment for early relief of pruritus in patients with mild (...) to moderate atopic dermatitis from 2 phase III studies. Patients received crisaborole or vehicle twice daily for 28 days. Pruritus was graded on a 4-point scale of none (0) to severe (3). Early improvement in pruritus required a score of none (0) or mild (1), with a ≥ 1-grade improvement from baseline on day 6. Significantly more patients experienced early improvement in pruritus with crisaborole than with vehicle (56.6% vs 39.5%; p< 0.001), including at earliest assessment (day 2, 34.3% vs 27.3%; p

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2018 Acta Dermato-Venereologica

12. Efficacy and safety of phosphodiesterase 4 inhibitors in patients with asthma: A systematic review and meta-analysis. (PubMed)

Efficacy and safety of phosphodiesterase 4 inhibitors in patients with asthma: A systematic review and meta-analysis. Phosphodiesterase 4 (PDE4) inhibitors are a novel medication approved for airway inflammatory diseases including chronic obstructive pulmonary disease. Their role and application in asthma are controversial and not defined. A comprehensive search was performed in major databases (1946-2016) using the keywords: 'phosphodiesterase 4 inhibitor' or 'roflumilast' and 'asthma (...) .Of note, PDE4 inhibitors were accompanied with significantly higher adverse events such as headache (OR: 3.99, 95% CI: 1.65-9.66, Z = 3.07, P = 0.002) and nausea (OR: 5.53, 95% CI: 1.38-22.17, Z = 2.41, P = 0.02). In patients with mild asthma, oral PDE4 inhibitors can be considered as an alternative treatment to regular bronchodilators and inhaled controllers.© 2018 Asian Pacific Society of Respirology.

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2018 Respirology

13. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3) (PubMed)

Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3) To evaluate apremilast treatment in patients with active psoriatic arthritis, including current skin involvement, despite prior therapy with conventional disease-modifying antirheumatic drugs and/or biologic agents.Patients (N=505) were randomised (1:1:1) to placebo, apremilast 20 mg twice daily, or apremilast 30 mg twice

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2016 EvidenceUpdates

14. An experimental medicine study of the phosphodiesterase-4 inhibitor, roflumilast, on working memory-related brain activity and episodic memory in schizophrenia patients. (PubMed)

An experimental medicine study of the phosphodiesterase-4 inhibitor, roflumilast, on working memory-related brain activity and episodic memory in schizophrenia patients. Schizophrenia is associated with impairments in cognitive functioning yet there are no approved drugs to treat these deficits.Based on animal models, we investigated the potential for roflumilast, a selective inhibitor of phosphodiesterase type 4 (PDE4), to improve cognition, which may act by increasing intracellular cyclic

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2018 Psychopharmacology

15. A Novel Class of Tyrosyl-DNA Phosphodiesterase 1 Inhibitors That Contains the Octahydro-2H-chromen-4-ol Scaffold (PubMed)

A Novel Class of Tyrosyl-DNA Phosphodiesterase 1 Inhibitors That Contains the Octahydro-2H-chromen-4-ol Scaffold Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that mends topoisomerase 1-mediated DNA damage. Tdp1 is a current inhibition target for the development of improved anticancer treatments, as its inhibition may enhance the therapeutic effect of topoisomerase 1 poisons. Here, we report a study on the development of a novel class of Tdp1 inhibitors that is based (...) on the octahydro-2H-chromene scaffold. Inhibition and binding assays revealed that these compounds are potent inhibitors of Tdp1, with IC50 and KD values in the low micromolar concentration range. Molecular modelling predicted plausible conformations of the active ligands, blocking access to the enzymatic machinery of Tdp1. Our results thus help establish a structural-activity relationship for octahydro-2H-chromene-based Tdp1 inhibitors, which will be useful for future Tdp1 inhibitor development work.

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2018 Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry

16. Phosphodiesterase-4 Inhibitors for the Treatment of Inflammatory Diseases (PubMed)

Phosphodiesterase-4 Inhibitors for the Treatment of Inflammatory Diseases Phosphodiesterase-4 (PDE4), mainly present in immune cells, epithelial cells, and brain cells, manifests as an intracellular non-receptor enzyme that modulates inflammation and epithelial integrity. Inhibition of PDE4 is predicted to have diverse effects via the elevation of the level of cyclic adenosine monophosphate (cAMP) and the subsequent regulation of a wide array of genes and proteins. It has been identified (...) that PDE4 is a promising therapeutic target for the treatment of diverse pulmonary, dermatological, and severe neurological diseases. Over the past decades, numerous PDE4 inhibitors have been designed and synthesized, among which roflumilast, apremilast, and crisaborole were approved for the treatment of inflammatory airway diseases, psoriatic arthritis, and atopic dermatitis, respectively. It is regrettable that the dramatic efficacies of a drug are often accompanied by adverse effects, such as nausea

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2018 Frontiers in pharmacology

17. Safety, tolerability, and pharmacokinetics of single and repeat ascending doses of CHF6001, a novel inhaled phosphodiesterase-4 inhibitor: two randomized trials in healthy volunteers (PubMed)

Safety, tolerability, and pharmacokinetics of single and repeat ascending doses of CHF6001, a novel inhaled phosphodiesterase-4 inhibitor: two randomized trials in healthy volunteers The purpose of this study was to evaluate safety, tolerability, and pharmacokinetics (PK) of CHF6001, an inhaled phosphodiesterase-4 inhibitor.Two healthy volunteer, randomized, double-blind, placebo-controlled studies were conducted. In each, Part 1 evaluated single ascending doses, with PK sampling up to 48 hours

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2018 International journal of chronic obstructive pulmonary disease

18. Phosphodiesterase 4 inhibitor activates AMPK-SIRT6 pathway to prevent aging-related adipose deposition induced by metabolic disorder (PubMed)

Phosphodiesterase 4 inhibitor activates AMPK-SIRT6 pathway to prevent aging-related adipose deposition induced by metabolic disorder Rolipram is a selective phosphodiesterase 4 (PDE4) inhibitor that exerts a variety of effects, including anti-inflammatory, immunosuppressive, and anti-tumor effects. The aim of this study was to investigate the effect of rolipram on metabolic disorder and its underlying mechanisms. Metabolic disorder was induced in 8-week-old wild type BABL/c mice (...) by administration of D-galactose for 4 weeks. Simultaneously the mice were administered vehicle or rolipram. Alternatively, beginning at 3 or 21 months, the mice were administered db-cAMP for 3 months, with or without a high-fat-diet (HFD) to induce metabolic disorder. In both models, better metabolic function was observed in rolipram-treated mice. Rolipram reduced adipose deposition and inflammation and reserved metabolic disorder. Treatment with rolipram increased the AMPK phosphorylation and SIRT6 levels

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2018 Aging (Albany NY)

19. The Phosphodiesterase 4 Inhibitor Roflumilast Protects against Cigarette Smoke Extract-Induced Mitophagy-Dependent Cell Death in Epithelial Cells (PubMed)

The Phosphodiesterase 4 Inhibitor Roflumilast Protects against Cigarette Smoke Extract-Induced Mitophagy-Dependent Cell Death in Epithelial Cells Recent studies show that mitophagy, the autophagy-dependent turnover of mitochondria, mediates pulmonary epithelial cell death in response to cigarette smoke extract (CSE) exposure and contributes to the development of emphysema in vivo during chronic cigarette smoke (CS) exposure, although the underlying mechanisms remain unclear.In this study, we (...) investigated the role of mitophagy in the regulation of CSE-exposed lung bronchial epithelial cell (Beas-2B) death. We also investigated the role of a phosphodiesterase 4 inhibitor, roflumilast, in CSE-induced mitophagy-dependent cell death.Our results demonstrated that CSE induces mitophagy in Beas-2B cells through mitochondrial dysfunction and increased the expression levels of the mitophagy regulator protein, PTEN-induced putative kinase-1 (PINK1), and the mitochondrial fission protein, dynamin-1-like

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2018 Tuberculosis and respiratory diseases

20. Pharmacokinetic disposition of topical phosphodiesterase-4 inhibitor E6005 in patients with atopic dermatitis. (PubMed)

Pharmacokinetic disposition of topical phosphodiesterase-4 inhibitor E6005 in patients with atopic dermatitis. A novel topical phosphodiesterase-4 inhibitor E6005 shows potential as effective treatment option for atopic dermatitis (AD); however, systemic exposure may cause potentially undesirable adverse reactions. In this study, we evaluated the relationship between the systemic exposure of E6005 and clinical parameters including skin condition and the incidence of AEs in patients with AD.The

2018 Journal of Dermatological Treatment

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