Pub Date : 2020-04-02DOI: 10.1080/21678707.2020.1760837
S. Carpenter, J. C. Cohen Tervaert, E. Yacyshyn
ABSTRACT Introduction: ANCA-associated vasculitis (AAV) is a group of life-threatening autoimmune conditions that require a combination of treatments for induction and maintenance therapy. High-dose glucocorticoids and cyclophosphamide have traditionally been the mainstay of AAV treatment. During the last decade, rituximab has proven to be an effective alternative to cyclophosphamide. Currently, significant research in alternative therapeutic options for both induction and maintenance treatment is underway. Areas covered: Guideline review of remission, induction, and maintenance therapy of AAV. Examination of current research on alternative advanced therapeutics, specifically, the evidence for rituximab, C5a inhibitors, and trimethoprim-sulfamethoxazole. Expert opinion: Toxicities of existing therapies for AAV need to be limited, with alternative methods and agents for induction and maintenance. Importantly, the side-effects of high dose and long-term steroids have now been recognized. Newer induction agents and maintenance regimes will lead the future of AAV treatment.
{"title":"Advances in therapeutic treatment options for ANCA-associated vasculitis","authors":"S. Carpenter, J. C. Cohen Tervaert, E. Yacyshyn","doi":"10.1080/21678707.2020.1760837","DOIUrl":"https://doi.org/10.1080/21678707.2020.1760837","url":null,"abstract":"ABSTRACT Introduction: ANCA-associated vasculitis (AAV) is a group of life-threatening autoimmune conditions that require a combination of treatments for induction and maintenance therapy. High-dose glucocorticoids and cyclophosphamide have traditionally been the mainstay of AAV treatment. During the last decade, rituximab has proven to be an effective alternative to cyclophosphamide. Currently, significant research in alternative therapeutic options for both induction and maintenance treatment is underway. Areas covered: Guideline review of remission, induction, and maintenance therapy of AAV. Examination of current research on alternative advanced therapeutics, specifically, the evidence for rituximab, C5a inhibitors, and trimethoprim-sulfamethoxazole. Expert opinion: Toxicities of existing therapies for AAV need to be limited, with alternative methods and agents for induction and maintenance. Importantly, the side-effects of high dose and long-term steroids have now been recognized. Newer induction agents and maintenance regimes will lead the future of AAV treatment.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"8 1","pages":"127 - 136"},"PeriodicalIF":0.8,"publicationDate":"2020-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1760837","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42304386","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}
Pub Date : 2020-04-02DOI: 10.1080/21678707.2020.1758930
B. Dozières-Puyravel, S. Auvin
ABSTRACT Introduction: Fenfluramine (3‐trifluoromethyl‐N‐ethylamphetamine), a former anorectic agent, has been successfully repurposed for Dravet syndrome (DS). Area covered: A systematic review of data on fenfluramine in the treatment of patients with DS has been conducted, with 11 published papers on the use of fenfluramine for DS (six clinical trials, of which two were randomized controlled trials (RCTs), and five preclinical studies). Following clinical observations suggesting the efficacy of fenfluramine, the effect on convulsive seizures has been confirmed by two RCTs. The first RCT demonstrated the efficacy of the two tested doses of 0.2 mg/kg/day and 0.7 mg/kg/day, while the second RCT showed the efficacy of 0.4 mg/kg/day fenfluramine in patients with DS treated with stiripentol. Expert opinion: Preclinical studies provide insights into the mechanisms of action of fenfluramine. There are still no large real-life studies. Fenfluramine is under investigation for the treatment of other epilepsy syndromes.
{"title":"Fenfluramine hydrochloride for the treatment of Dravet syndrome","authors":"B. Dozières-Puyravel, S. Auvin","doi":"10.1080/21678707.2020.1758930","DOIUrl":"https://doi.org/10.1080/21678707.2020.1758930","url":null,"abstract":"ABSTRACT Introduction: Fenfluramine (3‐trifluoromethyl‐N‐ethylamphetamine), a former anorectic agent, has been successfully repurposed for Dravet syndrome (DS). Area covered: A systematic review of data on fenfluramine in the treatment of patients with DS has been conducted, with 11 published papers on the use of fenfluramine for DS (six clinical trials, of which two were randomized controlled trials (RCTs), and five preclinical studies). Following clinical observations suggesting the efficacy of fenfluramine, the effect on convulsive seizures has been confirmed by two RCTs. The first RCT demonstrated the efficacy of the two tested doses of 0.2 mg/kg/day and 0.7 mg/kg/day, while the second RCT showed the efficacy of 0.4 mg/kg/day fenfluramine in patients with DS treated with stiripentol. Expert opinion: Preclinical studies provide insights into the mechanisms of action of fenfluramine. There are still no large real-life studies. Fenfluramine is under investigation for the treatment of other epilepsy syndromes.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"8 1","pages":"121 - 126"},"PeriodicalIF":0.8,"publicationDate":"2020-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1758930","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49646903","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}
Pub Date : 2020-03-03DOI: 10.1080/21678707.2020.1739519
K. Suetterlin, D. R. Raja Rayan, E. Matthews, M. Hanna
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.
{"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":"8 1","pages":"43 - 49"},"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}
Pub Date : 2020-03-03DOI: 10.1080/21678707.2020.1740682
L. Al Mahmasani, Antoine Finianos, R. Bou-Fakhredin, J. Elias, A. Taher
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.
{"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":"8 1","pages":"79 - 89"},"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}
Pub Date : 2020-03-03DOI: 10.1080/21678707.2020.1742695
S. Shinjo, F. D. de Souza
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.
{"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":"8 1","pages":"91 - 99"},"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}
Pub Date : 2020-02-13DOI: 10.1080/21678707.2020.1719827
E. Dempsey, T. Homfray, J. Simpson, S. Jeffery, S. Mansour, P. Ostergaard
ABSTRACT Introduction: Fetal hydrops describes abnormal fluid accumulation in two or more extravascular fetal compartments. It is a poor prognostic sign in a fetus, and many will not survive to term. Fetal hydrops is a clinical sign rather than a diagnosis and has a multitude of different causes. Areas covered: This review focusses on nonimmune fetal hydrops. We discuss in detail the most common etiologies such as infection and chromosomal abnormalities and cover rarer presentations of congenital malformation and single-gene disorders. We present a decision tree for the investigation of affected pregnancies. Expert opinion: The current approach to the investigation of fetal hydrops largely revolves around identifying the abnormal pathophysiology via ultrasound imaging. We believe that as genomic testing of a pregnancy can be undertaken with increasing accuracy, speed, accessibility and at reduced cost, genetic testing will feature earlier in the future diagnostic pathway.
{"title":"Fetal hydrops – a review and a clinical approach to identifying the cause","authors":"E. Dempsey, T. Homfray, J. Simpson, S. Jeffery, S. Mansour, P. Ostergaard","doi":"10.1080/21678707.2020.1719827","DOIUrl":"https://doi.org/10.1080/21678707.2020.1719827","url":null,"abstract":"ABSTRACT Introduction: Fetal hydrops describes abnormal fluid accumulation in two or more extravascular fetal compartments. It is a poor prognostic sign in a fetus, and many will not survive to term. Fetal hydrops is a clinical sign rather than a diagnosis and has a multitude of different causes. Areas covered: This review focusses on nonimmune fetal hydrops. We discuss in detail the most common etiologies such as infection and chromosomal abnormalities and cover rarer presentations of congenital malformation and single-gene disorders. We present a decision tree for the investigation of affected pregnancies. Expert opinion: The current approach to the investigation of fetal hydrops largely revolves around identifying the abnormal pathophysiology via ultrasound imaging. We believe that as genomic testing of a pregnancy can be undertaken with increasing accuracy, speed, accessibility and at reduced cost, genetic testing will feature earlier in the future diagnostic pathway.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"8 1","pages":"51 - 66"},"PeriodicalIF":0.8,"publicationDate":"2020-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1719827","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48350537","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}
Pub Date : 2020-01-02DOI: 10.1080/21678707.2020.1709442
K. Cherian, Lydia Jeris W, Mohamed Thayub
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.
{"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":"8 1","pages":"27 - 31"},"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}
Pub Date : 2020-01-02DOI: 10.1080/21678707.2020.1709441
N. Nagano, I. Morioka
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.
{"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":"8 1","pages":"1 - 9"},"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}
Pub Date : 2020-01-02DOI: 10.1080/21678707.2020.1713748
C. Addy, S. Caskey, D. Downey
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.
{"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":"8 1","pages":"11 - 26"},"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}
Pub Date : 2020-01-02DOI: 10.1080/21678707.2020.1715208
Luisa Natalia Pimentel Vera, G. Baldo
ABSTRACT Introduction: Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by mutations in the IDUA gene, characterized by deficient IDUA enzyme production and storage of glycosaminoglycans in tissues. Currently, therapeutic strategies approved have shown an improvement in quality of life of patients, but the majority of severe symptoms including cognitive and skeletal alterations persist. Gene therapy aimed to correct the genetic defect holds promise. Indeed, preclinical results show that it may be possible to develop a gene therapy strategy that may overcome the present limitations. In this review, authors review studies involving gene therapy for MPS I in the last years and highlight the most promising approaches. Areas covered: Authors review main studies involving gene therapy and genome editing for MPS I in the last 2–3 decades, from the initial in vitro studies up to the first clinical trials, and prospect what the future may hold for this technology in this disease. Expert opinion: Among all strategies studied, viral gene therapy and genome editing are being applied in clinical trials. Some of the results are inconclusive while scaling the process from animal models to human. The key for better outcomes relies on giving patients a proper therapy.
{"title":"The potential of gene therapy for mucopolysaccharidosis type I","authors":"Luisa Natalia Pimentel Vera, G. Baldo","doi":"10.1080/21678707.2020.1715208","DOIUrl":"https://doi.org/10.1080/21678707.2020.1715208","url":null,"abstract":"ABSTRACT Introduction: Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by mutations in the IDUA gene, characterized by deficient IDUA enzyme production and storage of glycosaminoglycans in tissues. Currently, therapeutic strategies approved have shown an improvement in quality of life of patients, but the majority of severe symptoms including cognitive and skeletal alterations persist. Gene therapy aimed to correct the genetic defect holds promise. Indeed, preclinical results show that it may be possible to develop a gene therapy strategy that may overcome the present limitations. In this review, authors review studies involving gene therapy for MPS I in the last years and highlight the most promising approaches. Areas covered: Authors review main studies involving gene therapy and genome editing for MPS I in the last 2–3 decades, from the initial in vitro studies up to the first clinical trials, and prospect what the future may hold for this technology in this disease. Expert opinion: Among all strategies studied, viral gene therapy and genome editing are being applied in clinical trials. Some of the results are inconclusive while scaling the process from animal models to human. The key for better outcomes relies on giving patients a proper therapy.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"8 1","pages":"33 - 41"},"PeriodicalIF":0.8,"publicationDate":"2020-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1715208","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41928325","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：