scholarly journals Constructing disease onset signatures using multi-dimensional network-structured biomarkers

Biostatistics ◽  
2018 ◽  
Vol 21 (1) ◽  
pp. 122-138
Author(s):  
Xiang Li ◽  
Donglin Zeng ◽  
Karen Marder ◽  
Yuanjia Wang
Keyword(s):  
Clinical Trial ◽  
Kernel Smoothing ◽  
Clinical Symptoms ◽  
Age At Onset ◽  
Disease Onset ◽  
Right Censoring ◽  
Biological Information ◽  
Partial Likelihood ◽  
Disease Stage ◽  
Linear Change

Summary Potential disease-modifying therapies for neurodegenerative disorders need to be introduced prior to the symptomatic stage in order to be effective. However, current diagnosis of neurological disorders mostly rely on measurements of clinical symptoms and thus only identify symptomatic subjects in their late disease course. Thus, it is of interest to select and integrate biomarkers that may reflect early disease-related pathological changes for earlier diagnosis and recruiting pre-sypmtomatic subjects in a prevention clinical trial. Two sources of biological information are relevant to the construction of biomarker signatures for time to disease onset that is subject to right censoring. First, biomarkers’ effects on disease onset may vary with a subject’s baseline disease stage indicated by a particular marker. Second, biomarkers may be connected through networks, and their effects on disease may be informed by this network structure. To leverage these information, we propose a varying-coefficient hazards model to induce double smoothness over the dimension of the disease stage and over the space of network-structured biomarkers. The distinctive feature of the model is a non-parametric effect that captures non-linear change according to the disease stage and similarity among the effects of linked biomarkers. For estimation and feature selection, we use kernel smoothing of a regularized local partial likelihood and derive an efficient algorithm. Numeric simulations demonstrate significant improvements over existing methods in performance and computational efficiency. Finally, the methods are applied to our motivating study, a recently completed study of Huntington’s disease (HD), where structural brain imaging measures are used to inform age-at-onset of HD and assist clinical trial design. The analysis offers new insights on the structural network signatures for premanifest HD subjects.

Adult systemic lupus erythematosus in Egypt: The nation-wide spectrum of 3661 patients and world-wide standpoint

Lupus ◽  
2021 ◽  
pp. 096120332110142
Author(s):  
Tamer A Gheita ◽  
Rasha Abdel Noor ◽  
Esam Abualfadl ◽  
Osama S Abousehly ◽  
Iman I El-Gazzar ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Age Of Onset ◽  
Wide Spectrum ◽  
Age At Onset ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Population Based ◽  
Systemic Lupus ◽  
Cross Sectional

Objective The aim of this study was to present the epidemiology, clinical manifestations and treatment pattern of systemic lupus erythematosus (SLE) in Egyptian patients over the country and compare the findings to large cohorts worldwide. Objectives were extended to focus on the age at onset and gender driven influence on the disease characteristics. Patients and method This population-based, multicenter, cross-sectional study included 3661 adult SLE patients from Egyptian rheumatology departments across the nation. Demographic, clinical, and therapeutic data were assessed for all patients. Results The study included 3661 patients; 3296 females and 365 males (9.03:1) and the median age was 30 years (17–79 years), disease duration 4 years (0–75 years) while the median age at disease onset was 25 years (4–75 years). The overall estimated prevalence of adult SLE in Egypt was 6.1/100,000 population (1.2/100,000 males and 11.3/100,000 females).There were 316 (8.6%) juvenile-onset (Jo-SLE) and 3345 adult-onset (Ao-SLE). Age at onset was highest in South and lowest in Cairo (p < 0.0001). Conclusion SLE in Egypt had a wide variety of clinical and immunological manifestations, with some similarities with that in other nations and differences within the same country. The clinical characteristics, autoantibodies and comorbidities are comparable between Ao-SLE and Jo-SLE. The frequency of various clinical and immunological manifestations varied between gender. Additional studies are needed to determine the underlying factors contributing to gender and age of onset differences.

scholarly journals AB0669 PARTICULARITIES OF TUNISIAN FEMALE AXIAL SPONDYLOARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1629.2-1629
Author(s):  
K. Ben Abdelghani ◽  
Y. Gzam ◽  
A. Fazaa ◽  
S. Miladi ◽  
K. Ouenniche ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Axial Spondyloarthritis ◽  
Activity Index ◽  
Age At Onset ◽  
Disease Onset ◽  
Disease Activity Index ◽  
Reactive Protein ◽  
Significant Difference ◽  
The Mean

Background:Axial spondyloarthritis (ax-SpA) is a chronic rheumatic disease that mainly affects men. However, the female form of ax-SpA remains insufficiently studied.Objectives:The aim of this study was to determine the clinical characteristics, the disease activity and the functional impact of female ax-SpA in comparison with male ax-SpA.Methods:This is a retrospective study including patients diagnosed with ax-SpA fulfilling the criteria of the Assessment of SpondyloArthritis international Society (ASAS) 2009.Clinical parameters, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath ankylosing spondylitis disease activity index (BASDAI) and Bath ankylosing spondylitis functional index (BASFI) were compared between groups of female and male ax-SpA.Results:Two hundred ax-SpA patients were included with 31% of female (n=62) and a mean age of 43,3 ± 11,2 years.The mean age at onset of symptoms was 31,8 ± 8,9 years for women and 25,3 ± 9,1 years for men (p <0,0001). The mean age at diagnosis was 36,4 ± 9,6 years for women and 31,7 ± 10,4 years for men (p = 0,003). Ax-SpA with juvenile onset was noted in 1,7% of women and 12,1% of men (p = 0,02). Male ax-SpA were significantly more smokers (46.8% vs 5.4%; p <0.001). The mean duration of morning stiffness was 11,3 ± 9,2 minutes for women versus 21,6 ± 19,3 minutes for men (p = 0,005).The mean ESR was 42,4 ± 29,8 mm for women and 28,3 ± 23,4 mm for men (p = 0,001). Radiographic sacroiliitis was present in 69,3% of women versus 84,7% of men (p = 0,01). The use of anti-TNF alpha was less frequent in women (29% vs 48,5%; p = 0,01).Our study didn’t found a statistically significant difference in peripheral manifestations, extraarticular manifestations, CRP, BASDAI and BASFI between the two groups.Conclusion:Female ax-SpA seems to have a better prognosis than male with older age in disease onset, less inflammation, less radiographic sacroiliitis and less use of biological treatments.References:[1]Rusman T, et al. Curr Rheumatol Rep. 2018; 20(6).[2]Siar N, et al. Curr Rheumatol Rev. 2019;Disclosure of Interests:None declared

The outcome of seven patients with hereditary tyrosinemia type 1

2016 ◽  
Vol 29 (10) ◽  
Author(s):  
Songul Gokay ◽  
Pembe Soylu Ustkoyuncu ◽  
Fatih Kardas ◽  
Mustafa Kendirci
Keyword(s):  
Clinical Symptoms ◽  
Age At Onset ◽  
Nodule Formation ◽  
First Year ◽  
Tyrosine Metabolism ◽  
Tyrosinemia Type 1 ◽  
Hereditary Tyrosinemia ◽  
Biochemical Imaging

AbstractBackground:Hereditary tyrosinemia type 1 (HT1) is a rare, inborn error of tyrosine metabolism. It is a fatal disorder without treatment. Early treatment may prevent acute liver failure, renal dysfunction, liver cirrhosis, hepatocellular carcinoma (HCC) and improves survival. The aim of the present study is to describe the clinical, biochemical, imaging and follow-up of seven patients with HT1 and to define the consequences of the late and interrupted treatment.Methods:A retrospective study was carried out with seven HT1 patients.Results:The median age at onset of clinical symptoms was 11.2 months (range, 3–28 months) and the median age at diagnosis was 22 months (range, 6–58 months). Liver enzymes and coagulation parameters were back to normal in all symptomatic patients in about 2 weeks. Alfa-fetoprotein (AFP) levels were normalized within the first year of therapy. Hypoechoic nodule formation was detected in two of the seven patients despite drug treatment without an increase of AFP and any dysplastic changes in the biopsies. One patient died due to metastatic HCC because of the late diagnosis and the poor compliance of the follow-up.Conclusions:This study showed once again that adherence to the treatment and a follow-up schedule of the patients are very important. Also it should not be forgotten that nodule formation can occur despite nitisinone treatment without an increase of AFP. Despite nitisinone treatment, HT1 patients still carry the risk of HCC. HCC must be detected before metastasis to other organs otherwise, patients may lose the chance for liver transplantation.

scholarly journals Multiple Sclerosis in Malaysia: Demographics, Clinical Features, and Neuroimaging Characteristics

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
S. Viswanathan ◽  
N. Rose ◽  
A. Masita ◽  
J. S. Dhaliwal ◽  
S. D. Puvanarajah ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Demyelinating Disease ◽  
Age At Onset ◽  
Positive Family History ◽  
Disease Onset ◽  
Demyelinating Diseases ◽  
Lesion Length ◽  
Relapsing Remitting ◽  
Spectrum Disorders

Background. Multiple sclerosis (MS) is an uncommon disease in multiracial Malaysia. Diagnosing patients with idiopathic inflammatory demyelinating diseases has been greatly aided by the evolution in diagnostic criterion, the identification of new biomarkers, and improved accessibility to neuroimaging in the country.Objectives. To investigate the spectrum of multiple sclerosis in Malaysia.Methods. Retrospective analysis with longitudinal follow-up of patients referred to a single tertiary medical center with neurology services in Malaysia.Results. Out of 245 patients with idiopathic inflammatory demyelinating disease, 104 patients had multiple sclerosis. Female to male ratio was 5 : 1. Mean age at onset was 28.6 ± 9.9 years. The Malays were the predominant racial group affected followed by the Chinese, Indians, and other indigenous groups. Subgroup analysis revealed more Chinese having neuromyelitis optica and its spectrum disorders rather than multiple sclerosis. Positive family history was reported in 5%. Optic neuritis and myelitis were the commonest presentations at onset of disease, and relapsing remitting course was the commonest disease pattern observed. Oligoclonal band positivity was 57.6%. At disease onset, 61.5% and 66.4% fulfilled the 2005 and 2010 McDonald’s criteria for dissemination in space. Mean cord lesion length was 1.86 ± 1.65 vertebral segments in the relapsing remitting group as opposed to 6.25 ± 5.18 vertebral segments in patients with neuromyelitis optica and its spectrum disorders.Conclusion. The spectrum of multiple sclerosis in Malaysia has changed over the years. Further advancement in diagnostic criteria will no doubt continue to contribute to the evolution of this disease here.

Temporomandibular Joint Involvement in Children with Juvenile Idiopathic Arthritis

2010 ◽  
Vol 38 (3) ◽  
pp. 510-515 ◽  
Author(s):  
ELVIRA CANNIZZARO ◽  
SILKE SCHROEDER ◽  
LUKAS M. MÜLLER ◽  
CHRISTIAN J. KELLENBERGER ◽  
ROTRAUD K. SAURENMANN
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Temporomandibular Joint ◽  
Upper Extremity ◽  
Age At Onset ◽  
Disease Onset ◽  
Joint Involvement ◽  
Hla B27 ◽  
Radiological Findings ◽  
Rheumatology Clinic ◽  
Younger Age

Objective.To determine the rate of temporomandibular joint (TMJ) involvement and find factors associated with TMJ arthritis in a single-center cohort of patients with juvenile idiopathic arthritis (JIA).Methods.Retrospective analysis of all patients with JIA visiting the rheumatology clinic between January 1, 2005, and December 31, 2006. Followup information was included until August 2008. A diagnosis of TMJ arthritis was based on clinical rheumatological and/or radiological findings.Results.After a mean followup time for JIA of 4.6 years (range 0.08–14.17), 86/223 patients (38.6%) had developed TMJ arthritis. The rate of TMJ involvement differed significantly among JIA subtypes (p = 0.0016), with 61% in extended oligoarticular, 52% in polyarticular rheumatoid factor (RF)-negative, 50% in psoriatic, 36% in systemic, 33% in polyarticular RF-positive, 33% in persistent oligoarticular, 30% in unclassified JIA, and 11% in enthesitis-related arthritis. The rate of TMJ involvement in our cohort was statistically significantly lower for patients who were HLA-B27-positive (p = 0.0002). In a multivariate analysis, the association of the following factors was confirmed: JIA subtype (p = 0.0001), a higher erythrocyte sedimentation rate (ESR) at diagnosis (p = 0.0038), involvement of joints of the upper extremity (p = 0.011), the absence of HLA-B27 (p = 0.023), and younger age at onset of JIA (p = 0.050).Conclusion.In our cohort of children with JIA, the overall rate of TMJ involvement was 38.6%. Patients with certain JIA subtypes, a higher ESR at disease onset, involvement of upper extremity joints, and younger age at diagnosis were more likely to develop TMJ arthritis. The presence of HLA-B27 seemed to be protective.

scholarly journals Clinical Trial of Efficacy and Toxicity of Disoproxil Tenofovir Fumarate and Emtricitabine for Mild to Moderate SARS-CoV-2 Infections

2021 ◽  
Author(s):  
Aldo A M Lima ◽  
Erico A G Arruda ◽  
Roberto J Pires-Neto ◽  
Melissa S Medeiros ◽  
J Quirino-Filho ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Vitamin C ◽  
Respiratory Infection ◽  
Clinical Symptoms ◽  
Clinical Signs ◽  
Signs And Symptoms ◽  
Clinical Suspicion ◽  
Pharmacological Intervention ◽  
Controlled Clinical Trial ◽  
Double Blind

This study aimed to evaluate the efficacy and toxicity of tenofovir (TDF) and TDF combined with emtricitabine (TDF/FTC) in patients with mild to moderate COVID-19 infections. We conducted a randomized, double-blind, placebo-controlled clinical trial in patients with clinical suspicion of mild to moderate respiratory infection caused by SARS-CoV-2 who were treated at an outpatient clinic. Patients were randomly recruited to take 10 days of TDF (300 mg/day), TDF (300 mg/day) combined with FTC (200 mg/day) or placebo Vitamin C (500 mg/day). The primary parameter was the score of symptoms and predictive signs of COVID-19, assessed on the seventh day of patient follow-up. From a total of 309 patients with clinical suspicion of SARS-CoV-2, 227 met the inclusion criteria and were randomly distributed into the following groups: (a) 75 (one did not initiate treatment) in the TDF group; (b) 74 in the TDF combined with FTC group; and (c) 77 in the Vitamin C group (placebo). Of the 226 patients, 139 (62%) were positive for SARS-CoV-2. Fever (37.8oC), ageusia or dysgeusia, anosmia or dysosmia, and two or more clinical symptoms or signs were significantly associated with SARS-CoV-2 infection. There was no significant change in clinical score based on clinical symptoms and signs between treatment groups. Patients with mild to moderate infection by SARS-CoV-2 had higher concentrations of G-CSF, IL-1β, IL-6 and TNF-α compared to patients without infection. Patients with mild to moderate respiratory infection, with fever (37.8oC), loss of smell, loss of taste and two or more symptoms, have a better prediction for the diagnosis of COVID-19. Patients with SARS-CoV-2 showed higher and more persistent proinflammatory cytokines profile compared to patients not infected with SARS-CoV-2. Pharmacological intervention with TDF or TDF combined with FTC did not change the clinical signs and symptoms score in mild to moderate respiratory infection in patients with SARS-CoV-2 compared to the Vitamin C group (placebo).

scholarly journals Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview

2021 ◽  
Vol 8 ◽  
Author(s):  
Liena E. O. Elsayed ◽  
Isra Zuhair Eltazi ◽  
Ammar E. Ahmed ◽  
Giovanni Stevanin
Keyword(s):  
Clinical Symptoms ◽  
Disease Onset ◽  
Lower Limbs ◽  
Special Focus ◽  
Clinical Genetic ◽  
Comprehensive Overview ◽  
Functional Studies ◽  
Hereditary Spastic Paraplegias ◽  
Wide Range ◽  
Complex Forms

Hereditary spastic paraplegias (HSP) are a heterogeneous group of motor neurodegenerative disorders that have the core clinical presentation of pyramidal syndrome which starts typically in the lower limbs. They can present as pure or complex forms with all classical modes of monogenic inheritance reported. To date, there are more than 100 loci/88 spastic paraplegia genes (SPG) involved in the pathogenesis of HSP. New patterns of inheritance are being increasingly identified in this era of huge advances in genetic and functional studies. A wide range of clinical symptoms and signs are now reported to complicate HSP with increasing overall complexity of the clinical presentations considered as HSP. This is especially true with the emergence of multiple HSP phenotypes that are situated in the borderline zone with other neurogenetic disorders. The genetic diagnostic approaches and the utilized techniques leave a diagnostic gap of 25% in the best studies. In this review, we summarize the known types of HSP with special focus on those in which spasticity is the principal clinical phenotype (“SPGn” designation). We discuss their modes of inheritance, clinical phenotypes, underlying genetics, and molecular pathways, providing some observations about therapeutic opportunities gained from animal models and functional studies. This review may pave the way for more analytic approaches that take into consideration the overall picture of HSP. It will shed light on subtle associations that can explain the occurrence of the disease and allow a better understanding of its observed variations. This should help in the identification of future biomarkers, predictors of disease onset and progression, and treatments for both better functional outcomes and quality of life.

scholarly journals FAKTOR-FAKTOR YANG MEMPENGARUHI SUBTIPE GEJALA MOTORIK PENYAKIT PARKINSON

2020 ◽  
Vol 5 (1) ◽  
pp. 343
Author(s):  
Attiya Istarini ◽  
Yuliarni Syafrita ◽  
Restu Susanti
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Age At Onset ◽  
Motor Symptom ◽  
Disease Stage ◽  
Motor Symptoms ◽  
Research Subjects ◽  
Cross Sectional ◽  
Duration Of Disease ◽  
Cross Sectional Design

<p><strong><em>Background</em></strong><em>: Parkinson's disease (PD) is a chronic neurodegenerative disease that manifests as movement disorders. Based on motor symptoms, PD is classified into subtypes of tremor and postural instability gait disorders (PIGD). The motor symptoms subtype is a predictor of disease progression, therapeutic response, and quality of life for Parkinson's patients. The purpose of this study is to identify some  factors that influence motor symptoms in Parkinson's disease.</em><strong><em>Methods:</em></strong><em> This research use cross sectional design. Samples were selected by consecutive sampling method that met the inclusion and exclusion criteria. Research subjects were 58 people. Statistical analysis using SPSS. p values &lt;0.05 were considered statistically significant.</em><strong><em>Results:</em></strong><em> This research include 58 patients, 55.2% were men with range of age 63.5 ± 8.5 years old. The mean age at onset was 57.9 ± 9.5 years and duration of disease 6.1 ± 4.6 years. Motor symptoms 53.4% dominant tremor. There was a significant relationship between disease stage and motor symptom subtypes (p &lt;0.001). There is no relationship between the patient's age, age at onset and duration of the disease with motor symptom subtypes.</em><strong><em>Conclusions:</em></strong><em> There is a relationship between disease stage and motor symptom. The patient's age, age at onset and duration of the disease are not related to the motor symptoms of Parkinson's patients.</em></p>

scholarly journals Intra-Articular Injection of Autologous Adipose-Derived Stromal Vascular Fractions for the Cartilage Repair of Grade 2 and 3 Knee Osteoarthritis: A Confirmatory Clinical Trial

2021 ◽  
Author(s):  
Yin Zhang ◽  
Qing Bi ◽  
Taihen Yu ◽  
Zheping Hong ◽  
Yu Tong ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Knee Osteoarthritis ◽  
Cartilage Repair ◽  
Clinical Symptoms ◽  
Rapid Development ◽  
Cartilage Regeneration ◽  
Substantial Improvement ◽  
Clinical Trial Registry ◽  
Knee Oa ◽  
Grade 3

Abstract BackgroundCartilage defect remains one of the most important reasons for the rapid development of knee osteoarthritis (OA). Numerous reports have confirmed the safety and clinical efficacy of autologous adipose-derived stromal vascular fractions (SVF), which has recently been used clinically to treat patients with knee OA. However, there is still no consensus as to whether SVF can promote cartilage regeneration. Herein, we purposed to evaluate the effectiveness of SVF in cartilage regeneration by developing cartilage model based on the 3D-FS-SPGR sequence.MethodsPatients with Kellgren-Lawrence grade 2-3 knee OA were recruited in our research. Then, we monitored patients and subsequently scored symptoms using WOMAC, VAS, and range of motion (ROM) before treatment and at 1, 3, 6, and 12 months post-treatment. The WORMS and MOCART were recorded by magnetic resonance imaging. The cartilage model of the patient was established using the 3D-FS-SPGR sequence, while the relevant parameters of the model were counted at baseline, 6, and 12 months.ResultsWe enrolled 47 patients (53 knees) with knee OA in this study, of which 29 knees were classified as grade 2, while 24 were assigned grade 3. No treatment-related adverse event was observed in our study. Notably, WOMAC, VAS, and ROM showed a significant improvement at 12 months. We further found that the thickness, volume, and surface of the cartilage defect decreased, while the volume of healthy cartilage increased in all regions, particularly in the medial femoral and tibia condyle. Moreover, the scores of WORMS and MOCART revealed a substantial improvement of cartilage repair at 12 months. ConclusionsTaken together, this study shows that intra-articular injection of SVF into the knee markedly improved the clinical symptoms of patients without the occurrence of adverse events, thereby repairing the damaged articular cartilage through cartilage regeneration.Trial registrationRetrospectively registered. Chinses Clinical Trial Registry with identifier ChiCTR2100042930. Registered 28 January 2021.

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