Review

Authors: Zachary D Blount

E. coli's hardiness, versatility, broad palate and ease of handling have made it the most intensively studied and best understood organism on the planet. However, research on E.coli has primarily examined it as a model organism, one that is abstracted from any natural history. But E. coli is far more than just a microbial lab rat. Rather, it is a highly diverse organism with a complex, multi-faceted niche in the wild. Recent studies of 'wild' E. coli have, for example, revealed a great deal about its presence in the environment, its diversity and genomic evolution, as well as its role in the human microbiome and disease. These findings have shed light on aspects of its biology and ecology that pose far-reaching questions and illustrate how an appreciation of E. coli's natural history can expand its value as a model organism.

Topics: Animals; Biofilms; Biological Evolution; Environmental Microbiology; Escherichia coli; Genomics; Host-Pathogen Interactions; Humans; Intestines; Microscopy, Electron, Scanning

PubMed: 25807083
DOI: 10.7554/eLife.05826

Review

Authors: Qian-Li Xue

This article reviews the current state of knowledge regarding the epidemiology of frailty by focusing on 6 specific areas: (1) clinical definitions of frailty, (2) evidence of frailty as a medical syndrome, (3) prevalence and incidence of frailty by age, gender, race, and ethnicity, (4) transitions between discrete frailty states, (5) natural history of manifestations of frailty criteria, and (6) behavior modifications as precursors to the development of clinical frailty.

Topics: Aged; Aged, 80 and over; Aging; Asthenia; Female; Frail Elderly; Geriatric Assessment; Humans; Incidence; Male; Muscle Weakness; Natural History; Phenotype; Prevalence; Syndrome; Time Factors

PubMed: 21093718
DOI: 10.1016/j.cger.2010.08.009

Review

Authors: Eric C K Lee, Brit Trogen, Kathryn Brady...

PURPOSE OF REVIEW

This narrative review explores food allergy prevalence and natural history stratified by life stages, especially in context of evolving knowledge over the last few decades.

RECENT FINDINGS

The prevalence of food allergy remains highest in early childhood with common food triggers being cow's milk, soy, hen's egg, wheat, peanut, tree nuts, sesame, fish, and shellfish. This correlates with certain risk factors especially pertinent in the postnatal period which appear to predispose an individual to developing a food allergy. Some allergies (such as milk and egg) were previously thought to be easily outgrown in early life; however, recent studies suggest increasing rates of persistence of these allergies into young adulthood; the reason behind this is unknown. Despite this, there is also evidence demonstrating that food allergies can be outgrown in adolescents and adults. An understanding of the paradigm shifts in the natural history of food allergy allows clinicians to provide updated, age-appropriate, and tailored advice for patients on the management and prognosis of food allergy.

Topics: Child; Adolescent; Adult; Cattle; Humans; Child, Preschool; Female; Animals; Young Adult; Chickens; Food Hypersensitivity; Risk Factors; Allergens; Milk

PubMed: 38416390
DOI: 10.1007/s11882-024-01131-3

Authors: Yasmina Martí, Valerie Aponte Ribero, Sarah Batson...

BACKGROUND

Respiratory and bulbar dysfunctions (including swallowing, feeding, and speech functions) are key symptoms of spinal muscular atrophy (SMA), especially in its most severe forms. Demonstrating the long-term efficacy of disease-modifying therapies (DMTs) necessitates an understanding of SMA natural history.

OBJECTIVE

This study summarizes published natural history data on respiratory, swallowing, feeding, and speech functions in patients with SMA not receiving DMTs.

METHODS

Electronic databases (Embase, MEDLINE, and Evidence-Based Medicine Reviews) were searched from database inception to June 27, 2022, for studies reporting data on respiratory and/or bulbar function outcomes in Types 1-3 SMA. Data were extracted into a predefined template and a descriptive summary of these data was provided.

RESULTS

Ninety-one publications were included: 43 reported data on respiratory, swallowing, feeding, and/or speech function outcomes. Data highlighted early loss of respiratory function for patients with Type 1 SMA, with ventilatory support typically required by 12 months of age. Patients with Type 2 or 3 SMA were at risk of losing respiratory function over time, with ventilatory support initiated between the first and fifth decades of life. Swallowing and feeding difficulties, including choking, chewing problems, and aspiration, were reported in patients across the SMA spectrum. Swallowing and feeding difficulties, and a need for non-oral nutritional support, were reported before 1 year of age in Type 1 SMA, and before 10 years of age in Type 2 SMA. Limited data relating to other bulbar functions were collated.

CONCLUSIONS

Natural history data demonstrate that untreated patients with SMA experience respiratory and bulbar function deterioration, with a more rapid decline associated with greater disease severity. This study provides a comprehensive repository of natural history data on bulbar function in SMA, and it highlights that consistent assessment of outcomes in this area is necessary to benefit understanding and approval of new treatments.

Topics: Humans; Muscular Atrophy, Spinal; Deglutition; Deglutition Disorders; Speech; Respiration; Respiration Disorders

PubMed: 38943396
DOI: 10.3233/JND-230248

Authors: Yu Shi, Yuchen Fan, Tao Chen...

PubMed: 35360750
DOI: 10.3389/fmed.2022.867436

Review

Authors: Jing Liu, Jeffrey S Barrett, Efthimia T Leonardi...

Rare diseases represent a highly heterogeneous group of disorders with high phenotypic and genotypic diversity within individual conditions. Due to the small numbers of people affected, there are unique challenges in understanding rare diseases and drug development for these conditions, including patient identification and recruitment, trial design, and costs. Natural history data and real-world data (RWD) play significant roles in defining and characterizing disease progression, final patient populations, novel biomarkers, genetic relationships, and treatment effects. This review provides an introduction to rare diseases, natural history data, RWD, and real-world evidence, the respective sources and applications of these data in several rare diseases. Considerations for data quality and limitations when using natural history and RWD are also elaborated. Opportunities are highlighted for cross-sector collaboration, standardized and high-quality data collection using new technologies, and more comprehensive evidence generation using quantitative approaches such as disease progression modeling, artificial intelligence, and machine learning. Advanced statistical approaches to integrate natural history data and RWD to further disease understanding and guide more efficient clinical study design and data analysis in drug development in rare diseases are also discussed.

Topics: Humans; Rare Diseases; Artificial Intelligence; Drug Development; Research Design; Disease Progression

PubMed: 36461748
DOI: 10.1002/jcph.2134

Authors: Shigeo Maruyama, Tomomitsu Matono, Masahiko Koda...

BACKGROUND

Knowledge of the natural history and management of hepatic hemangiomas is lacking. The aim of this study was to investigate the natural history of hemangiomas and to elucidate the factors that determine tumor growth and optimal management.

METHODS

A total of 211 adult patients were enrolled, with follow-up for more than three years. Follow-up was performed with repeated ultrasonography (US) and laboratory tests for liver function and coagulation factors (platelets, prothrombin time (PT), fibrinogen, thrombin-antithrombin III complex (TAT), D-dimer, and fibrin and fibrinogen degradation products (FDP)).

RESULTS

Tumor size decreased in 38.9% of patients, showed no change in 31.3%, and increased in 29.8%. The incidence of a size increase was very high in patients under 40 years of age and decreased gradually with age, whereas the incidence of a size decrease increased with age and increased markedly over 60 years of age. The incidence of an increase in size decreased gradually with size enlargement, whereas the incidence of a decrease in size increased markedly with tumor size and further increased rapidly when hemangiomas became larger than 60 mm. Values of TAT, D-dimer, FDP, and Mac-2 binding protein glycosylation isomer (M2BPGi) were closely related to the change in size of hemangiomas.

CONCLUSIONS

Hemangiomas in older patients (>60 years of age) and larger tumors (>60 mm in size) had a tendency to decrease in size, resulting from the reduction in coagulation disorders and the progression of liver fibrosis. Therefore, the majority of patients with hemangiomas can be safely managed by clinical observation.

PubMed: 37685768
DOI: 10.3390/jcm12175703

Meta-Analysis Review

Authors: Xuting Chang, Jie Zhang, Yuwu Jiang...

AIMS

To investigate the natural history and genotype-phenotype correlation of pantothenate kinase-associated neurodegeneration.

METHODS

We collected data of patients with PKAN by searching from available publications in English and Chinese. Patients diagnosed in our center (Peking University First Hospital) were also included. The difference in natural history and genotype between early-onset (<10 year of age at onset) and late-onset patients (≥10 year of age at onset) with PKAN was compared.

RESULTS

A total of 248 patients were included. The median age at onset was 3.0 years in the early-onset group and 18.0 years in the late-onset group. Dystonia in lower limbs was the most common initial symptom in both groups. In the early-onset group, the median interval between the disease onset and occurrence of oromandibular dystonia, generalized dystonia, loss of independent ambulance was 6.0 years, 5.0 years, and 5.0 years. The corresponding values in late-onset group were 1.0 year, 4.0 years, and 6.0 years. About 20.0% died at median age of 12.5 years and 9.5 years after the onset in early-onset group. About 2.0% of the late-onset patients died during the follow-up. A total of 176 mutations were identified. Patients carrying two null alleles in PANK2 showed significantly earlier age of disease onset and progressed more rapidly to loss of independent ambulance.

CONCLUSIONS

This study provided a comprehensive review on the natural history and genotype of 248 patients with PKAN. The results will serve as a historical control data for future clinical trial on PKAN.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Follow-Up Studies; Genetic Association Studies; Humans; Infant; Male; Middle Aged; Pantothenate Kinase-Associated Neurodegeneration; Young Adult

PubMed: 32043823
DOI: 10.1111/cns.13294

Review

Authors: Laura Ann Adang, Anjana Sevagamoorthy, Omar Sherbini...

Growing interest in therapeutic development for rare diseases necessitate a systematic approach to the collection and curation of natural history data that can be applied consistently across this group of heterogenous rare diseases. In this study, we discuss the challenges facing natural history studies for leukodystrophies and detail a novel standardized approach to creating a longitudinal natural history study using existing medical records. Prospective studies are uniquely challenging for rare diseases. Delays in diagnosis and overall rarity limit the timely collection of natural history data. When feasible, prospective studies are often cross-sectional rather than longitudinal and are unlikely to capture pre- or early- symptomatic disease trajectories, limiting their utility in characterizing the full natural history of the disease. Therapeutic development in leukodystrophies is subject to these same obstacles. The Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN) comprises of a network of research institutions across the United States, supported by a multi-center biorepository protocol, to map the longitudinal clinical course of disease across leukodystrophies. As part of GLIA-CTN, we developed Standard Operating Procedures (SOPs) that delineated all study processes related to staff training, source documentation, and data sharing. Additionally, the SOP detailed the standardized approach to data extraction including diagnosis, clinical presentation, and medical events, such as age at gastrostomy tube placement. The key variables for extraction were selected through face validity, and common electronic case report forms (eCRF) across leukodystrophies were created to collect analyzable data. To enhance the depth of the data, clinical notes are extracted into "original" and "imputed" encounters, with imputed encounter referring to a historic event (e.g., loss of ambulation 3 months prior). Retrospective Functional Assessments were assigned by child neurologists, using a blinded dual-rater approach and score discrepancies were adjudicated by a third rater. Upon completion of extraction, data source verification is performed. Data missingness was evaluated using statistics. The proposed methodology will enable us to leverage existing medical records to address the persistent gap in natural history data within this unique disease group, allow for assessment of clinical trajectory both pre- and post-formal diagnosis, and promote recruitment of larger cohorts.

Topics: Humans; Rare Diseases; Longitudinal Studies; United States; Prospective Studies

PubMed: 38522179
DOI: 10.1016/j.ymgme.2024.108453

Review

Authors: Shun-Chiao Chang, Christian Stefan Eichinger, Polly Field...

BACKGROUND

Metachromatic leukodystrophy (MLD; OMIM 250100 and 249900) is a rare lysosomal storage disease caused by deficient arylsulfatase A activity, leading to accumulation of sulfatides in the nervous system. This systematic literature review aimed to explore the effect of MLD on the lives of patients.

METHODS

The Ovid platform was used to search Embase, MEDLINE, and the Cochrane Library for articles related to the natural history, clinical outcomes, and burden of illness of MLD; congress and hand searches were performed using 'metachromatic leukodystrophy' as a keyword. Of the 531 publications identified, 120 were included for data extraction following screening. A subset of findings from studies relating to MLD natural history and burden of illness (n = 108) are presented here.

RESULTS

The mean age at symptom onset was generally 16-18 months for late-infantile MLD and 6-10 years for juvenile MLD. Age at diagnosis and time to diagnosis varied widely. Typically, patients with late-infantile MLD presented predominantly with motor symptoms and developmental delay; patients with juvenile MLD presented with motor, cognitive, and behavioral symptoms; and patients with adult MLD presented with cognitive symptoms and psychiatric and mood disorders. Patients with late-infantile MLD had more rapid decline of motor function over time and lower survival than patients with juvenile MLD. Commonly reported comorbidities/complications included ataxia, epilepsy, gallbladder abnormalities, incontinence, neuropathy, and seizures.

CONCLUSIONS

Epidemiology of MLD by geographic regions, quantitative cognitive data, data on the differences between early- and late-juvenile MLD, and humanistic or economic outcomes were limited. Further studies on clinical, humanistic (i.e., quality of life), and economic outcomes are needed to help inform healthcare decisions for patients with MLD.

Topics: Adult; Humans; Leukodystrophy, Metachromatic; Quality of Life; Cost of Illness

PubMed: 38494502
DOI: 10.1186/s40001-024-01771-1