A consensus conference for cognitive endpoints for clinical trials and natural history studies in MPS diseases

2018 ◽  
Vol 123 (2) ◽  
pp. S130
Author(s):  
Elsa G. Shapiro ◽  
Jennifer L. Greenberg ◽  
Mark Dant ◽  
Christine Lavery ◽  
Johanna van der Lee ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Natural History ◽  
Consensus Conference ◽  
Natural History Studies

scholarly journals Spontaneous improvement of carbohydrate-deficient transferrin in PMM2-CDG without mannose observed in CDG natural history study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Peter Witters ◽  
Andrew C. Edmondson ◽  
Christina Lam ◽  
Christin Johnsen ◽  
Marc C. Patterson ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Natural History ◽  
Randomized Study ◽  
Short Term ◽  
Double Blind ◽  
Natural History Study ◽  
Natural History Studies ◽  
Carbohydrate Deficient Transferrin ◽  
Spontaneous Improvement

AbstractA recent report on long-term dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG) claimed improved glycosylation and called for double-blind randomized study of the dietary supplement in PMM2-CDG patients. A lack of efficacy of short-term mannose supplementation in multiple prior reports challenge this study’s conclusions. Additionally, some CDG types have previously been reported to demonstrate spontaneous improvement in glycosylated biomarkers, including transferrin. We have likewise observed improvements in transferrin glycosylation without mannose supplementation. This observation questions the reliability of transferrin as a therapeutic outcome measure in clinical trials for PMM2-CDG. We are concerned that renewed focus on mannose therapy in PMM2-CDG will detract from clinical trials of more promising therapies. Approaches to increase efficiency of clinical trials and ultimately improve patients’ lives requires prospective natural history studies and identification of reliable biomarkers linked to clinical outcomes in CDG. Collaborations with patients and families are essential to identifying meaningful study outcomes.

An Imaging Approach to Deep Vein Thrombosis and the Lower Extremity Thrombosis Classification

2012 ◽  
Vol 27 (1_suppl) ◽  
pp. 143-148 ◽  
Author(s):  
C W K P Arnoldussen ◽  
C H A Wittens
Keyword(s):  
Clinical Trials ◽  
Deep Vein Thrombosis ◽  
Natural History ◽  
Lower Extremity ◽  
Systematic Approach ◽  
Vein Thrombosis ◽  
Natural History Studies ◽  
Imaging Approach ◽  
Deep Vein

In this article we want to discuss the potential of lower extremity deep vein thrombosis (DVT) imaging and propose a systematic approach to DVT management based on a DVT classification of the lower extremity; the LET classification. Identifying and reporting DVT more systematically allows for accurate stratification for initial patient care, future clinical trials and appropriate descriptions for natural history studies.

Does Vascular MCI Progress at a Different Rate Than Does Amnestic MCI?

2003 ◽  
Vol 15 (S1) ◽  
pp. 257-259 ◽  
Author(s):  
Serge Gauthier ◽  
Kenneth Rockwood
Keyword(s):  
Clinical Trials ◽  
Natural History ◽  
Randomized Clinical Trials ◽  
Amnestic Mci ◽  
Natural History Studies ◽  
Similarity And Difference

This article reviews the evidence available from natural history studies and randomized clinical trials (RCT) concerning what is now coined as amnestic MCI and vascular MCI and will answer the question about the similarity and difference of their progression toward dementia. The issues to be resolved prior to the use of a survival design for conversion from vascular MCI to dementia will be discussed.

scholarly journals The LORIS MyeliNeuroGene rare disease database for natural history studies and clinical trial readiness

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Aaron Spahr ◽  
Zaliqa Rosli ◽  
Mélanie Legault ◽  
Luan T. Tran ◽  
Simon Fournier ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Natural History ◽  
Rare Disease ◽  
Rare Diseases ◽  
Parental Stress ◽  
The United States ◽  
Historical Control ◽  
Surrogate Markers ◽  
Disease Research ◽  
Natural History Studies

Abstract Background Rare diseases are estimated to affect 150–350 million people worldwide. With advances in next generation sequencing, the number of known disease-causing genes has increased significantly, opening the door for therapy development. Rare disease research has therefore pivoted from gene discovery to the exploration of potential therapies. With impending clinical trials on the horizon, researchers are in urgent need of natural history studies to help them identify surrogate markers, validate outcome measures, define historical control patients, and design therapeutic trials. Results We customized a browser-accessible multi-modal (e.g. genetics, imaging, behavioral, patient-determined outcomes) database to increase cohort sizes, identify surrogate markers, and foster international collaborations. Ninety data entry forms were developed including family, perinatal, developmental history, clinical examinations, diagnostic investigations, neurological evaluations (i.e. spasticity, dystonia, ataxia, etc.), disability measures, parental stress, and quality of life. A customizable clinical letter generator was created to assist in continuity of patient care. Conclusions Small cohorts and underpowered studies are a major challenge for rare disease research. This online, rare disease database will be accessible from all over the world, making it easier to share and disseminate data. We have outlined the methodology to become Title 21 Code of Federal Regulations Part 11 Compliant, which is a requirement to use electronic records as historical controls in clinical trials in the United States. Food and Drug Administration compliant databases will be life-changing for patients and families when historical control data is used for emerging clinical trials. Future work will leverage these tools to delineate the natural history of several rare diseases and we are confident that this database will be used on a larger scale to improve care for patients affected with rare diseases.

Bridging the Knowledge Gaps in Arrhythmogenic Cardiovascular Conditions: The Critical Role of Registries

2016 ◽  
Vol 10 (2) ◽  
pp. 1 ◽  
Author(s):  
Melody Hermel ◽  
Rebecca Duffy ◽  
Alexander Orfanos ◽  
Isabelle Hack ◽  
Shayna McEnteggart ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Natural History ◽  
Risk Stratification ◽  
Critical Role ◽  
Knowledge Gaps ◽  
Level Of Evidence ◽  
The Future

Cardiac registries have filled many gaps in knowledge related to arrhythmogenic cardiovascular conditions. Despite the less robust level of evidence available in registries when compared with clinical trials, registries have contributed a range of clinically useful information. In this review, the authors discuss the role that registries have played – related to diagnosis, natural history, risk stratification, treatment, and genetics of arrhythmogenic cardiovascular conditions – in closing knowledge gaps, and their role in the future.

Natural History of Patients Taking Rifaximin-α for Recurrent Hepatic Encephalopathy and Risk of Future Overt Episodes and Mortality: A Post-hoc Analysis of Clinical Trials Data

2016 ◽  
Vol 38 (5) ◽  
pp. 1081-1089.e4 ◽  
Author(s):  
Christian A. Bannister ◽  
James G. Orr ◽  
Alan V. Reynolds ◽  
Mark Hudson ◽  
Peter Conway ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Hepatic Encephalopathy ◽  
Natural History ◽  
Post Hoc Analysis ◽  
History Of ◽  
Post Hoc

Natural history of coronary atherosclerosis using quantitative angiography in men, and implications for clinical trials of coronary regression

1993 ◽  
Vol 71 (10) ◽  
pp. 766-772 ◽  
Author(s):  
Peter H. Stone ◽  
C. Michael Gibson ◽  
Richard C. Pasternak ◽  
Kathy McManus ◽  
Lazaro Diaz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Natural History ◽  
Coronary Atherosclerosis ◽  
History Of ◽  
Quantitative Angiography

scholarly journals Sanfilippo syndrome registry project and natural history studies: an example of patients, parents and researchers collaborating for a cure

2014 ◽  
Vol 111 (2) ◽  
pp. S115
Author(s):  
JIll Wood ◽  
Stuart Siedman ◽  
Jennifer Siedman ◽  
Paul Levy ◽  
Kyle Brown ◽  
...  
Keyword(s):  
Natural History ◽  
Sanfilippo Syndrome ◽  
Natural History Studies

scholarly journals SOD1 Mutation Spectrum and Natural History of ALS Patients in a 15-Year Cohort in Southeastern China

2021 ◽  
Vol 12 ◽  
Author(s):  
Lu-Xi Chen ◽  
Hai-Feng Xu ◽  
Pei-Shan Wang ◽  
Xin-Xia Yang ◽  
Zhi-Ying Wu ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Natural History ◽  
Diagnostic Delay ◽  
Mutation Spectrum ◽  
Survival Duration ◽  
Southeastern China ◽  
History Of ◽  
Male Patients ◽  
The Mean ◽  
Als Patients

Background: Mutations in superoxide dismutase 1 gene (SOD1) are the most frequent high penetrant genetic cause for amyotrophic lateral sclerosis (ALS) in the Chinese population. A detailed natural history of SOD1-mutated ALS patients will provide key information for ongoing genetic clinical trials.Methods: We screened for SOD1 mutations using whole exome sequencing (WES) in Chinese ALS cases from 2017 to 2021. Functional studies were then performed to confirm the pathogenicity of novel variants. In addition, we enrolled previously reported SOD1 mutations in our centers from 2007 to 2017. The SOD1 mutation spectrum, age at onset (AAO), diagnostic delay, and survival duration were analyzed.Results: We found two novel SOD1 variants (p.G17H and p.E134*) that exerted both gain-of-function and loss-of-function effects in vitro. Combined with our previous SOD1-mutated patients, 32 probands with 21 SOD1 mutations were included with the four most frequently occurring mutations of p.V48A, p.H47R, p.C112Y, and p.G148D. SOD1 mutations account for 58.9% of familial ALS (FALS) cases. The mean (SD) AAO was 46 ± 11.4 years with a significant difference between patients carrying mutations in exon 1 [n = 5, 34.6 (12.4) years] and exon 2 [n = 8, 51.4 (8.2) years] (p = 0.038). The mean of the diagnostic delay of FALS patients is significantly earlier than the sporadic ALS (SALS) patients [9.5 (4.8) vs. 20.3 (9.3) years, p = 0.0026]. In addition, male patients survived longer than female patients (40 vs. 16 months, p = 0.05).Conclusion: Our results expanded the spectrum of SOD1 mutations, highlighted the mutation distribution, and summarized the natural history of SOD1-mutated patients in southeastern China. Male patients were found to have better survival, and FALS patients received an earlier diagnosis. Our findings assist in providing a detailed clinical picture, which is important for ongoing genetic clinical trials.

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