Expert Opinion on Orphan Drugs最新文献_第9页

Druggable targets, clinical trial design and proposed pharmacological management in fibrodysplasia ossificans progressiva 进行性骨化性纤维发育不良的药物靶点、临床试验设计和拟议的药物治疗

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-04-02 DOI: 10.1080/21678707.2020.1751122

R. Pignolo, F. Kaplan

{"title":"Druggable targets, clinical trial design and proposed pharmacological management in fibrodysplasia ossificans progressiva","authors":"R. Pignolo, F. Kaplan","doi":"10.1080/21678707.2020.1751122","DOIUrl":"https://doi.org/10.1080/21678707.2020.1751122","url":null,"abstract":"ABSTRACT Introduction: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by heterotopic ossification, congenital skeletal abnormalities especially of the great toes, and several features of accelerated aging. Missense mutations in the in the gene for ACVR1/ALK2 encoding Activin A receptor type I/Activin-like kinase 2, a bone morphogenetic protein (BMP) type I receptor are responsible for all known cases of FOP. Progression of the condition is relentless and occurs clinically via episodic inflammatory exacerbations or flare-ups and/or spontaneously (without flare-ups). Areas covered: The current pharmacological targets, potential designs for clinical trials, and possible treatment approaches using experimental and repurposed agents for FOP are reviewed [PubMed 2000–2019, using FOP as a key search term]. Expert opinion: The growing number of pharmacological interventions for FOP includes blocking the activity of the mutant FOP receptor, quenching inflammatory triggers, inhibiting connective tissue progenitor cells that give rise to ectopic endochondral ossification, and minimizing the micro-environmental factors that promote lesion progression. In light of the rarity of FOP, new approaches to clinical trial design, including delayed start and n = 1 designs, are considered. Finally, a schema for pharmacological management of FOP in anticipation of approved medications and the availability of repurposed drugs is proposed.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2020-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1751122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45325804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

Advances in therapeutic treatment options for ANCA-associated vasculitis ANCA相关血管炎的治疗选择进展

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-04-02 DOI: 10.1080/21678707.2020.1760837

S. Carpenter, J. C. Cohen Tervaert, E. Yacyshyn

引用次数: 7

Fenfluramine hydrochloride for the treatment of Dravet syndrome 盐酸芬氟拉明治疗Dravet综合征

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-04-02 DOI: 10.1080/21678707.2020.1758930

B. Dozières-Puyravel, S. Auvin

引用次数: 0

Mexiletine (NaMuscla) for the treatment of myotonia in non-dystrophic myotonic disorders 美西律（NaMuscula）治疗非营养不良性强直性肌营养障碍的肌强直

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-03-03 DOI: 10.1080/21678707.2020.1739519

K. Suetterlin, D. R. Raja Rayan, E. Matthews, M. Hanna

{"title":"Mexiletine (NaMuscla) for the treatment of myotonia in non-dystrophic myotonic disorders","authors":"K. Suetterlin, D. R. Raja Rayan, E. Matthews, M. Hanna","doi":"10.1080/21678707.2020.1739519","DOIUrl":"https://doi.org/10.1080/21678707.2020.1739519","url":null,"abstract":"ABSTRACT Introduction: NaMuscla, (mexiletine), is the first licensed treatment for the Non-Dystrophic Myotonias (NDM). NDM are categorized by genetic ion channel dysfunction and cause significant morbidity. To date, off-license mexiletine, although less costly, has sometimes been subject to breaches in supply causing significant regional and national variation in availability. Areas covered: The evidence supporting mexiletine use in NDM, its mechanism of action, chemistry, and pharmacodynamics is reviewed. The evidence for other, unlicensed medications, used to treat myotonia as well as new antimyotonic compounds in development is also reviewed. Expert opinion: Mexiletine is an effective and safe treatment for NDM. However, while mexiletine is very effective in reducing muscle stiffness, it is less effective at treating the pain associated with NDM and some SCN4A genotypes may not respond to mexiletine treatment. In addition, gastrointestinal discomfort is frequent and may prevent adequate dose titration. Since the designation of mexiletine as an orphan drug for NDM, level 1 evidence for the antimyotonic effect of lamotrigine has emerged. However, no superiority trials have been completed. A head-to-head trial to compare the efficacy of mexiletine and lamotrigine in reducing both muscle stiffness and pain and to determine variation in genotype response would facilitate greater precision medicine in NDM.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2020-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1739519","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43283429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Acquired hemophilia A: when an overlooked autoimmune disorder causes significant bleeding 获得性血友病A:被忽视的自身免疫性疾病导致大量出血

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-03-03 DOI: 10.1080/21678707.2020.1740682

L. Al Mahmasani, Antoine Finianos, R. Bou-Fakhredin, J. Elias, A. Taher

{"title":"Acquired hemophilia A: when an overlooked autoimmune disorder causes significant bleeding","authors":"L. Al Mahmasani, Antoine Finianos, R. Bou-Fakhredin, J. Elias, A. Taher","doi":"10.1080/21678707.2020.1740682","DOIUrl":"https://doi.org/10.1080/21678707.2020.1740682","url":null,"abstract":"ABSTRACT Introduction: Acquired hemophilia A (AHA) is a rare disease caused by the presence of autoantibodies directed against factor VIII (FVIII) resulting in spontaneous bleeding. AHA is associated with high risk of mortality from bleeding, treatment complications, and the presence of underlying diseases. Because of its rarity, AHA diagnosis can be challenging and sometimes missed in the emergency setting. Management consists of bleeding control and prevention, inhibitor eradication using immunosuppressive therapy, as well as treatment of the underlying disease. Areas covered: An overview of AHA including epidemiology, pathophysiology, clinical presentation, workup, and management; as well as a review of the literature in order to better understand the disease. Expert opinion: A prompt recognition of AHA is mandatory for the initiation of early and aggressive treatment. Optimal management of AHA necessitates a multidisciplinary approach in collaboration between hematologists and physicians from various specialties. Future studies are needed to identify prognostic factors for remission and survival in patients with AHA. Clinicians who treat patients with AHA are encouraged to actively contribute to the available registries. International associations and societies are also invited to assist in the establishment of hemophilia centers and networks worldwide for the standardization of clinical practice when dealing with patients with AHA.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2020-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1740682","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48580746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Treatment options from bench to bedside for adult dermatomyositis 成人皮肌炎的治疗选择

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-03-03 DOI: 10.1080/21678707.2020.1742695

S. Shinjo, F. D. de Souza

{"title":"Treatment options from bench to bedside for adult dermatomyositis","authors":"S. Shinjo, F. D. de Souza","doi":"10.1080/21678707.2020.1742695","DOIUrl":"https://doi.org/10.1080/21678707.2020.1742695","url":null,"abstract":"ABSTRACT Introduction: Current literature has minimal solid data to guide therapeutic intervention in adult dermatomyositis and studies that include systemic inflammatory mechanism suppression, musculoskeletal and extra-muscular tissue damage prevention, and comorbidities. Area covered: This systematic literature review discusses drug and non-drug treatments in patients with adult dermatomyositis. The review includes search results on the Medline (PubMed), Cochrane, and Embase databases and lonely allows available research studies published before October 2019. Expert opinion: The importance of non-drug treatments in patients with dermatomyositis has been highlighted, especially the multidisciplinary approach of minimizing damage and paying special attention to multiple possible organ and system involvement (mainly the gastrointestinal, cardiac, lung, joint, and cutaneous impairments) and comorbidities. Considering the limitations caused by muscle involvement, special attention should be given to the establishment of early exercise programs. Concerning drug treatments, glucocorticoids with intravenous human immunoglobulin could be the first-line treatment for refractory cases and/or cases where immunosuppressive/immunomodulatory drugs are contraindicated. Among immunobiological drugs, rituximab has the most evidence in the literature to support its use.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2020-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1742695","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48980862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fetal hydrops – a review and a clinical approach to identifying the cause 胎儿水肿——一项综述和确定病因的临床方法

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-02-13 DOI: 10.1080/21678707.2020.1719827

E. Dempsey, T. Homfray, J. Simpson, S. Jeffery, S. Mansour, P. Ostergaard

引用次数: 7

Overview and surgical aspects of Uhls anomaly Uhls异常的概述和外科方面

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-01-02 DOI: 10.1080/21678707.2020.1709442

K. Cherian, Lydia Jeris W, Mohamed Thayub

{"title":"Overview and surgical aspects of Uhls anomaly","authors":"K. Cherian, Lydia Jeris W, Mohamed Thayub","doi":"10.1080/21678707.2020.1709442","DOIUrl":"https://doi.org/10.1080/21678707.2020.1709442","url":null,"abstract":"ABSTRACT Introduction: Uhls anomaly is an extremely rare congenital heart defect characterized by partial or complete absence of right ventricular myocardium. Less than 100 cases have been reported in the literature. Survival depends on the severity of the right ventricular dysfunction. The age at presentation is varied but usually presents in infancy or found during autopsy. Diagnosis is made by echocardiogram (ECHO), magnetic resonance imaging (MRI), and histopathological examination. Medical management of this condition understanding the pathology is not possible. Surgical treatment includes single ventricle strategy, one and a half ventricle repair with partial right ventriculectomy, Fontan procedure, and cardiac transplantation. Early recognition of the anomaly, institution of drugs that improves cardiac function and right surgical planning may improve the quality of life. Areas covered: An extensive literature search has been done from many Pubmed and Scopus-indexed journals pertaining to various aspects of Uhls anomaly including history of the disease, etiology, clinical presentation, differential diagnosis, diagnostic aids, and medical and surgical management. Expert opinion: Depending on the hemodynamics, a bidirectional Glenn which is septectomy or a single ventricle pathway would be a better approach. Of course heart transplantation would be the last choice when other surgical options are defied.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2020-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1709442","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48775480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Congenital cytomegalovirus infection: epidemiology, prediction, diagnosis, and emerging treatment options for symptomatic infants 先天性巨细胞病毒感染：有症状婴儿的流行病学、预测、诊断和新的治疗选择

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-01-02 DOI: 10.1080/21678707.2020.1709441

N. Nagano, I. Morioka

{"title":"Congenital cytomegalovirus infection: epidemiology, prediction, diagnosis, and emerging treatment options for symptomatic infants","authors":"N. Nagano, I. Morioka","doi":"10.1080/21678707.2020.1709441","DOIUrl":"https://doi.org/10.1080/21678707.2020.1709441","url":null,"abstract":"ABSTRACT Introduction: Congenital cytomegalovirus (CMV) infection, long known as a disease of TORCH syndrome, is a CMV infection transmitted from the mother to the fetus via the placenta, and may or may not cause any symptoms. Particularly, symptomatic infants often develop neurological sequelae in their lives. The disease and economic burden associated with congenital CMV infection is substantial in children worldwide. Areas covered: This review described the epidemiology, prediction/prevention, diagnosis, and emerging treatment options of congenital CMV infection, highlighting the laboratory diagnostics using urine and saliva, and the benefits of antiviral therapy, especially based on the Japanese evidences. Authors used PubMed for the literature search. Expert opinion: The best, fastest, and most accurate diagnostic method for congenital CMV infection would be the real-time polymerase chain reaction using urine or saliva within 3 weeks of age. Antiviral therapies using intravenous ganciclovir or oral valganciclovir, which are started during the neonatal period, are effective in improving hearing outcomes in some symptomatic infants. Given that the antiviral drugs are currently off-labels worldwide due to their strict effect and safety concerns, obtaining informed consent from the parents is warranted before their use in infants with congenital CMV disease.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2020-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1709441","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47937785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Gram negative infections in cystic fibrosis: a review of preventative and treatment options 囊性纤维化中的革兰氏阴性感染:预防和治疗方案综述

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-01-02 DOI: 10.1080/21678707.2020.1713748

C. Addy, S. Caskey, D. Downey

{"title":"Gram negative infections in cystic fibrosis: a review of preventative and treatment options","authors":"C. Addy, S. Caskey, D. Downey","doi":"10.1080/21678707.2020.1713748","DOIUrl":"https://doi.org/10.1080/21678707.2020.1713748","url":null,"abstract":"ABSTRACT Introduction: The microbial landscape of CF is changing, reflecting advances in microbial detection, CF therapies and an increasingly heterogeneous and ageing population. Gram negative organisms are important to clinical trajectory, however, some have unknown implications on disease course. Areas covered: This review covers the evolving landscape of the microbial ecosystem of the CF lung and provides an update on current diagnostic and therapeutic options for management of Gram negative bacteria. Evidence for prevention of acquisition of new organisms, and eradication of Gram negative pathogens is reviewed. There is an increasing range of inhaled antibiotic therapies for chronic suppressive antimicrobial therapy, with an urgent need for research into the efficacy of specific combinations. Intra-venous therapy for pulmonary exacerbations requires optimisation, focusing on greater precision, improved clinical outcomes, whilst reducing anti-microbial resistance and long-term side effects. The future role of CFTR modulators, anti-inflammatory agents and novel anti-infectives is also outlined. Expert opinion: Antimicrobial therapy must evolve to reflect the evolving microbial landscape and the needs of current and future CF populations. With an increasing number of Gram negative organisms, detection methods and therapeutic options, it is critical therapy is targeted appropriately to the organism and the individual.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2020-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1713748","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44241743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1