scholarly journals Computing Individual Risks Based on Family History in Genetic Disease in the Presence of Competing Risks

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Gregory Nuel ◽  
Alexandra Lefebvre ◽  
Olivier Bouaziz
Keyword(s):  
Family History ◽  
Posterior Distribution ◽  
Genetic Disease ◽  
Hazard Rate ◽  
Age At Onset ◽  
Disease Onset ◽  
Competing Risk ◽  
Individual Risk ◽  
Risk Of Death ◽  
The Individual

When considering a genetic disease with variable age at onset (e.g., familial amyloid neuropathy, cancers), computing the individual risk of the disease based on family history (FH) is of critical interest for both clinicians and patients. Such a risk is very challenging to compute because 1 the genotype X of the individual of interest is in general unknown, 2 the posterior distribution PX∣FH,T>t changes with t (T is the age at disease onset for the targeted individual), and 3 the competing risk of death is not negligible. In this work, we present modeling of this problem using a Bayesian network mixed with (right-censored) survival outcomes where hazard rates only depend on the genotype of each individual. We explain how belief propagation can be used to obtain posterior distribution of genotypes given the FH and how to obtain a time-dependent posterior hazard rate for any individual in the pedigree. Finally, we use this posterior hazard rate to compute individual risk, with or without the competing risk of death. Our method is illustrated using the Claus-Easton model for breast cancer. The competing risk of death is derived from the national French registry.

scholarly journals Analysis of Emergency Situations in the Russian Federation

2019 ◽  
Vol 34 (s1) ◽  
pp. s101-s101
Author(s):  
Sergei Aleksanin ◽  
Vladimir Evdokimov
Keyword(s):  
Russian Federation ◽  
Natural Phenomenon ◽  
Individual Risk ◽  
List Type ◽  
Emergency Situations ◽  
Risk Of Death ◽  
The Russian Federation ◽  
The Individual ◽  
Terrorist Acts ◽  
Polynomial Trends

Introduction:Emergency situations (ES) are situations within a certain territory, which have arisen because of an accident, a dangerous natural phenomenon, natural disaster, or other that may cause or have caused human casualties, damage to human health or the environment, significant material losses, and unbalance of living conditions of people. Important characteristics of ES are suddenness and involvement of a significant number of victims who need first aid and emergency medical care. These characteristics determined the organization of the Unified State System for Emergency Prevention and Elimination of the Russian Federation.Aim:To study the structure of ES in Russia. By the scale of spread and damage caused, ES can be local, municipal, inter-municipal, regional, interregional, or federal, by the source of origin – technogenic, natural, biological, or social. The terrorist acts are usually allocated in a separate group of ES. The structure of ES, according to the EMERCOM of Russia in 2005-2017, is as follows: 1.Technogenic (59.61%)2.Natural (29.42%)3.Biological and social (9.91%)4.Major terrorist acts (1.06%)Methods:Statistical analysis was conducted. According to the EMERCOM of Russia, every year in 2005-2017 there were 422.5 ± 46.5 ES, resulting in the death of 796 ± 56 people. Polynomial trends in the number of ES and deaths, according to the EMERCOM of Russia, (with significant coefficients of determination R2 = 0.85 and R2 = 0.64, respectively) show a decrease in the number of ES and deaths.Discussion:The resulting analysis of the structure and number of ES, the number of deaths, the risk of being in an emergency, and the individual risk of death in an emergency can predict the forces and means necessary for the elimination of the consequences of ES.

scholarly journals Younger age at onset of sporadic Parkinson’s disease among subjects occupationally exposed to metals and pesticides

2014 ◽  
Vol 7 (3) ◽  
pp. 123-133 ◽  
Author(s):  
Marcia H. Ratner ◽  
David H. Farb ◽  
Josef Ozer ◽  
Robert G. Feldman ◽  
Raymon Durso
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Family History ◽  
Occupational Exposure ◽  
Age At Onset ◽  
Disease Onset ◽  
Occupational Exposures ◽  
High Exposure ◽  
Younger Age ◽  
History Of

ABSTRACT An earlier age at onset of Parkinson’s disease (PD) has been reported to be associated with occupational exposures to manganese and hydrocarbon solvents suggesting that exposure to neurotoxic chemicals may hasten the progression of idiopathic PD. In this study the role of occupational exposure to metals and pesticides in the progression of idiopathic PD was assessed by looking at age at disease onset. The effects of heritable genetic risk factors, which may also influence age at onset, was minimized by including only sporadic cases of PD with no family history of the disease (n=58). Independent samples Student t-test revealed that subjects with occupational exposure to metals and/or pesticides (n=36) were significantly (p=0.013) younger than unexposed controls (n=22). These subjects were then divided into three groups [high (n=18), low (n=18), and unexposed (n=22)] to ascertain if duration of exposure further influenced age at onset of PD. One-way ANOVA revealed that subjects in the high exposure group were significantly (p=0.0121) younger (mean age: 50.33 years) than unexposed subjects (mean age: 60.45 years). Subjects were also stratified by exposure type (metals vs. pesticides). These results suggest that chronic exposure to metals and pesticides is associated with a younger age at onset of PD among patients with no family history of the disease and that duration of exposure is a factor in the magnitude of this effect.

scholarly journals Prediction of COVID-19 Prognosis By Heterogeneity Analysis Based on Chest CT Scans

2021 ◽  
Author(s):  
Bo Yang ◽  
Bei Zhang ◽  
Lichen Gao ◽  
Jian Zhang ◽  
Huaiming Qiu ◽  
...  
Keyword(s):  
Early Stage ◽  
Ground Glass Opacity ◽  
Histogram Analysis ◽  
Individual Risk ◽  
Study Cohort ◽  
Risk Of Death ◽  
Hospital Stays ◽  
Heterogeneity Analysis ◽  
The Individual ◽  
Performance Heterogeneity

Abstract BackgroundGround-glass opacity (GGO) and consolidation opacity (CLO) are the common CT lung opacities, and their heterogeneity may have potential for prognosis in COVID-19 patients. This study aimed to estimate clinical outcome in individual COVID-19 patient by using histogram heterogeneity analysis based on CT opacities. Methods71 COVID-19 cases’ medical records were retrospectively reviewed from a designated hospital in Wuhan, China, from January 24th to February 28th at the early stage of pandemic. Two characteristic lung abnormity opacities, GGO and CLO were drawn on CT images to identify the heterogeneity by using quantitative histogram analysis. The parameters (mean, mode, kurtosis, skewness) were derived from histograms to evaluate the accuracy of clinical classification and outcome prediction. Nomograms were built to predict the risk of death and median length of hospital stays (LOS), respectively. Results A total of 57 cases were eligible for the study cohort after exclusion 14 cases. The most highly frequency of lung abnormalities was GGO mixed with CLO in both survival population (26 in 42, 61.9%) and died population (10 in 15, 66.7%). The best performance heterogeneity parameters to discriminate severe type from mild/moderate counterparts were as following: GGO_skewness: specificity=66.67%, sensitivity=78.12%, AUC=0.706; CLO_mean: specificity=70.00%, sensitivity=76.92%, AUC=0.746. Nomogram based on histogram parameters has the ability to predict the individual risk of death and the prolonged median LOS of COVID-19 patients. C-indexes were 0.763 and 0.888 for risk of death and prolonged median LOS, respectively.ConclusionsThe histogram analysis method based on GGO and CLO has the ability for individual risk prediction in COVID-19 patients.

Disease Factors in Early Rheumatoid Arthritis Are Associated with Differential Risks for Cardiovascular Events and Mortality Depending on Age at Onset: A 10-year Observational Cohort Study

2013 ◽  
Vol 40 (12) ◽  
pp. 1958-1966 ◽  
Author(s):  
Sofia Ajeganova ◽  
Maria L.E. Andersson ◽  
Johan Frostegård ◽  
Ingiäld Hafström
Keyword(s):  
Rheumatoid Arthritis ◽  
Cox Regression ◽  
Age At Onset ◽  
Disease Onset ◽  
Age Groups ◽  
Area Under The Curve ◽  
The Elderly ◽  
Cvd Risk ◽  
Risk Of Death ◽  
Early Ra

Objective.To investigate, within the first 2 years of diagnosis with rheumatoid arthritis (RA), associations between disease-related measures and cardiovascular disease (CVD) and mortality in patients with RA onset before and after 65 years of age.Methods.The study population (n = 741; 67.5% women) was derived from the Better Anti-Rheumatic Pharmaco Therapy (BARFOT) early RA cohort, recruited 1993–1999. The mean age was 55 years (SD 14.7). The outcomes were incident CVD events and all-cause mortality until 2010. Area under the curve (AUC) for disease measures at inclusion, 1 and 2 years, and decrease in measures after 1 year were calculated.Results.In all, 177 CVD events and 151 deaths occurred over 10 years of observation. In adjusted Cox regression analyses, seropositivity for rheumatoid factor (RF) or anticitrullinated protein antibodies (ACPA); white blood (cell) count at diagnosis; and AUC of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and visual analog scale (VAS)-pain were associated with higher CVD risk among patients with disease onset before 65 years of age. Among patients with disease onset after 65 years, larger decreases in CRP, ESR, health assessment questionnaire (HAQ), and use of methotrexate decreased CVD risk, whereas use of glucocorticoids heightened CVD risk. AUC of CRP, ESR, HAQ, and HAQ after 2 years was related to risk of death in both age groups. Seropositivity and AUC for VAS-pain in the younger group and use of glucocorticoids in the elderly were associated with poorer survival.Conclusion.Early treatment of RA may improve longterm outcomes. Presence of RF or ACPA associates with CVD and mortality among RA patients with disease onset before 65 years. Age stratification may improve evaluation of risk for CVD and mortality in early RA.

scholarly journals Family history identifies sporadic schizoaffective disorder as a subtype for genetic studies

2020 ◽  
Vol 26 ◽  
Author(s):  
Nicolaas J. Van der Merwe ◽  
Maria Karayiorgou ◽  
René Ehlers ◽  
Johannes L. Roos
Keyword(s):  
Family History ◽  
Schizoaffective Disorder ◽  
De Novo ◽  
Age At Onset ◽  
Disease Onset ◽  
The United States ◽  
Founder Population ◽  
Genetic Studies ◽  
History Of ◽  
Bipolar Type

Background: Schizophrenia is a heterogeneous disorder with strong genetic vulnerability. Family history of schizophrenia has been considered in genetic studies under several models. De novo genetic events seem to play a larger role in sporadic cases.Aim: This study used the familial–sporadic distinction with the aim of identifying a more homogeneous phenotype to delineate the genetic and clinical complexity of schizophrenia.Setting: The study was conducted at Weskoppies Hospital, Pretoria, South Africa.Methods: The study included 384 participants with schizophrenia or schizoaffective disorder from the Afrikaner founder population in South Africa who are considered comparable to Caucasian patients from the United States. A comprehensive data capturing sheet was completed.Results: When schizophrenia and schizoaffective disorder diagnoses were considered jointly, we found no significant differences between the sporadic and the familial groups for age at disease onset, season of birth, comorbid diagnoses, clinical symptomatology, history of suicide or marital status. When the diagnoses were examined separately, however, the sporadic schizoaffective disorder, bipolar type, was found to have a significantly lower age at onset (mean 20.6 vs. 25.3 years).Conclusion: The sporadic schizoaffective disorder, bipolar type, forms a more homogeneous subgroup for genetic studies.

scholarly journals Individual and familial characteristics of patients with podoconiosis attending a clinic in Musanze District, Rwanda: A retrospective study

2020 ◽  
Vol 114 (12) ◽  
pp. 947-953
Author(s):  
Jean Paul Bikorimana ◽  
Ursin Bayisenge ◽  
Tonya Huston ◽  
Eugene Ruberanziza ◽  
Jean Bosco Mbonigaba ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Family History ◽  
Age Of Onset ◽  
Age At Onset ◽  
Disease Onset ◽  
Patient Characteristics ◽  
Health Concern ◽  
Red Clay ◽  
Younger Age ◽  
History Of

Abstract Background Podoconiosis is a progressive swelling of the legs affecting genetically susceptible people who live in areas with irritant red clay soils and walk barefoot. The disease is a public health concern in many countries, including Rwanda. Methods This retrospective study described individual and familial characteristics of patients with podoconiosis attending the Heart and Sole Africa (HASA) clinics in Rwanda. Data on patient characteristics and family history were retrieved from electronic medical records (January 2013 – August 2019). A multiple regression analysis was used to explore factors influencing age of onset of podoconiosis. Results Among 467 patients with podoconiosis, the mean (standard deviation) age of onset was 34.4 (19.6) years, 139 (29.8%) patients developed podoconiosis at <20 years of age, 417 (89%) came from Musanze or neighboring Burera Districts, and 238 (51.0%) had a family history of podoconiosis. Increasing patient age was associated with older age at onset of disease (p<0.001), while an increased number of relatives with podoconiosis (p<0.002) was significantly associated with earlier disease onset. Conclusion Most patients with podoconiosis were women, and more than half had a family history of podoconiosis. An increased number of relatives with podoconiosis was associated with a significantly younger age at disease onset.

scholarly journals Epidemiological, clinical, and genotype characterization of spinocerebellar ataxia type in families in Buriram province, northeast Thailand

2017 ◽  
Vol 11 (6) ◽  
pp. 469-474
Author(s):  
Suppachok Wetchaphanphesat ◽  
Anek Mungaomklang ◽  
Chutima Papsing ◽  
Teeratorn Pulkes
Keyword(s):  
Family History ◽  
Spinocerebellar Ataxia ◽  
Autosomal Dominant ◽  
Smoking Status ◽  
Age At Onset ◽  
Disease Onset ◽  
Spinocerebellar Ataxia Type ◽  
Health Determinants ◽  
Northeast Thailand ◽  
Horizontal Nystagmus

AbstractBackgroundIn Thais, the most prevalent type of spinocerebellar ataxia (SCA) is type 3, most commonly known as Machado–Joseph disease (MJD), followed by SCA type 1 (SCA1), SCA2, and SCA6.ObjectivesTo describe the epidemiological, clinical, and genotypic features of SCA in northeastern Thailand and to study 2 associations: between syndromic features and the genotype of SCA, and between health determinants and scores on the scale for the assessment and rating of ataxia (SARA).MethodsWe conducted a cross-sectional study of 24 patients with autosomal dominant SCA from 13 families recruited from Buriram province in northeast Thailand between December 2009 and January 2014. Patients provided a clinical history and were examined by a neurologist. DNA was extracted from the peripheral blood of each patient. We analyzed associations between the type of SCA and sex, age, family history, clinical features, any underlying disease, age at onset, body weight, smoking status, family history, alcohol consumption, head injury history, and SARA.ResultsSeven of the families were positive for SCA1 and 6 for MJD. There were 24 index patients from these autosomal dominant SCA families, including 13 with SCA1 and 11 with MJD. Their average age was 43.7 years (range 20–72 years), whereas their average age at disease onset was 36.9 years (range 18–59 years). Pyramidal signs between MJD and SCA1 were not significantly different. Extrapyramidal features appeared uncommon. Horizontal nystagmus and upward gaze paresis were significantly associated with MJD. There were no significant differences in demographic data between the groups with SARA scores ≥15 or <15.ConclusionsMJD and SCA1 were the 2 adult-onset cerebellar degenerative diseases found in Buriram province. Clinical clues for differentiating between them were upward gaze paresis and horizontal nystagmus, which were significantly more common in MJD.

scholarly journals Modified-Chronic Disease Score (M-CDS): Predicting the individual risk of death using drug prescriptions

PLoS ONE ◽  
2020 ◽  
Vol 15 (10) ◽  
pp. e0240899
Author(s):  
Marica Iommi ◽  
Simona Rosa ◽  
Michele Fusaroli ◽  
Paola Rucci ◽  
Maria Pia Fantini ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Drug Prescriptions ◽  
Individual Risk ◽  
Disease Score ◽  
Chronic Disease Score ◽  
Risk Of Death ◽  
The Individual

Degraded core analysis for the pressurized-water reactor

1987 ◽  
Vol 409 (1837) ◽  
pp. 209-227
Keyword(s):  
Great Majority ◽  
Individual Risk ◽  
Accidental Death ◽  
Pressurized Water Reactor ◽  
Pressurized Water ◽  
Risk Of Death ◽  
A Value ◽  
Realistic Estimate ◽  
Margin Of Safety ◽  
The Individual

An analysis of the likelihood and the consequences of ‘degraded-core accidents’ has been undertaken for the proposed Sizewell B pwr. In such accidents, degradation of the core geometry occurs as a result of overheating. Radionuclides are released and may enter the environment, causing harmful effects. The analysis concludes that degraded-core accidents are highly improbable, the plant having been designed to reduce the frequency of such accidents to a value of order 10 -6 per year. The building containing the reactor would only fail in a small proportion of degraded-core accidents. In the great majority of cases the containment would remain intact and the release of radioactivity to the environment would be small. The individual risk of accidental death is about 3 x 10 -4 per year in the U. K. For an individual living very close to the reactor, degraded-core accidents would raise this risk of accidental death by only 1 part in 100000. They would lead to an even smaller increase in that individual’s risk of death due to cancer some years later. In the extremely unlikely event of the worst degraded-core accident (frequency about 3 x 10 -8 per year), the calculated expectation is that, 130 people would die soon afterwards and 3300 would die between 10 and 40 years later from cancer attributable to the accident. A more realistic estimate of the amount of radioactivity released reduces the figure to 7 accidental and 1300 cancer deaths. Based on this more realistic estimate of release there is 1 chance in 100 that, should the worst accident actually occur, about 100 early deaths could ensue giving a frequency of about 3 x 10 -10 per year for this occurrence (less than once in the lifetime of the Earth). Consequences as severe as those exemplified above are not typical of the predicted outcome of degraded-core accidents: indeed the balance of probabilities is that a degraded-core accident would lead to no immediate fatalities at all and to cancer deaths measured in single figures or tens. Although these estimates are approximate, studies to investigate the uncertainties, and sensitivities to different assumptions, show that potential errors are small compared with the very large ‘margin of safety’ between the risks estimated for Sizewell B and those that already exist in society.

Heterogeneity Analysis of Chest CT Predict Individual Prognosis of COVID-19 Patients

2021 ◽  
Vol 17 ◽  
Author(s):  
Bo Yang ◽  
Bei Zhang ◽  
Lichen Gao ◽  
Jian Zhang ◽  
Huaiming Qiu ◽  
...  
Keyword(s):  
Early Stage ◽  
Ground Glass Opacity ◽  
Histogram Analysis ◽  
Individual Risk ◽  
Study Cohort ◽  
Risk Of Death ◽  
Hospital Stays ◽  
Heterogeneity Analysis ◽  
The Individual ◽  
Performance Heterogeneity

Background: Ground-glass opacity (GGO) and consolidation opacity (CLO) are the common CT lung opacities, and their heterogeneity may have potential for prognosis ofcoronavirus disease-19 (COVID-19) patients. Objective: This study aimed to estimate clinical outcomes in individual COVID-19 patients using histogram heterogeneity analysis based on CT opacities. Methods: 71 COVID-19 cases’ medical records were retrospectively reviewed from a designated hospital in Wuhan, China, from January 24th to February 28th at the early stage of the pandemic. Two characteristic lung abnormity opacities, GGO and CLO, were drawn on CT images to identify the heterogeneity using quantitative histogram analysis. The parameters (mean, mode, kurtosis, and skewness) were derived from histograms to evaluate the accuracy of clinical classification and outcome prediction. Nomograms were built to predict the risk of death and median length of hospital stays (LOS), respectively. Results: A total of 57 COVID-19 cases were eligible for the study cohort after excluding 14 cases. The highest lung abnormalities were GGO mixed with CLO in both the survival populations (26 in 42, 61.9%) and died population (10 in 15, 66.7%). The best performance heterogeneity parameters to discriminate severe type from mild/moderate counterparts were as follows: GGO_skewness: specificity=66.67%, sensitivity=78.12%, AUC=0.706; CLO_mean: specificity=70.00%, sensitivity=76.92%, and AUC=0.746. Nomogram based on histogram parameters can predict the individual risk of death and the prolonged median LOS of COVID-19 patients. C-indexes were 0.763 and 0.888 for risk of death and prolonged median LOS, respectively. Conclusion: Histogram analysis method based on GGO and CLO has the ability for individual risk prediction in COVID-19 patients.

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