scholarly journals Factors influencing the age at onset in familial frontotemporal lobar dementia

2017 ◽  
Vol 3 (6) ◽  
pp. e203 ◽  
Author(s):  
Mathieu Barbier ◽  
Agnès Camuzat ◽  
Marion Houot ◽  
Fabienne Clot ◽  
Paola Caroppo ◽  
...  
Keyword(s):  
Genetic Factors ◽  
Age At Onset ◽  
Proportional Hazard ◽  
Genetic Modifiers ◽  
Therapeutic Trials ◽  
Hexanucleotide Repeat ◽  
Cox Proportional Hazard ◽  
Cox Proportional Hazard Models ◽  
Repeat Expansions ◽  
Frontotemporal Lobar Dementia

Objective:To quantify the effect of genetic factors and generations influencing the age at onset (AAO) in families with frontotemporal lobar dementia (FTD) due to C9ORF72 hexanucleotide repeat expansions and GRN mutations.Methods:We studied 504 affected individuals from 133 families with C9ORF72 repeat expansions and 90 FTD families with mutations in GRN, 2 major genes responsible for FTD and/or amyotrophic lateral sclerosis. Intrafamilial correlations of AAO were analyzed, and variance component methods were used for heritability estimates. Generational effects on hazard rates for AAO were assessed using mixed-effects Cox proportional hazard models.Results:A generational effect influencing AAO was detected in both C9ORF72 and GRN families. Nevertheless, the estimated proportion of AAO variance explained by genetic factors was high in FTD caused by C9ORF72 repeat expansions (44%; p = 1.10e−4), 62% when the AAO of dementia was specifically taken into account (p = 8.10e−5), and to a lesser degree in GRN families (26%; p = 0.17). Intrafamilial correlation analyses revealed a significant level of correlations in C9ORF72 families according to the degree of kinship. A pattern of intrafamilial correlations also suggested potential X-linked modifiers acting on AAO. Nonsignificant correlation values were observed in GRN families.Conclusions:Our results provide original evidence that genetic modifiers strongly influence the AAO in C9ORF72 carriers, while their effects seem to be weaker in GRN families. This constitutes a rational to search for genetic biomarkers, which could help to improve genetic counseling, patient care, and monitoring of therapeutic trials.

Age at Onset in Schizophrenia and Risk of Illness in Relatives

1996 ◽  
Vol 169 (2) ◽  
pp. 213-218 ◽  
Author(s):  
Kenneth S. Kendler ◽  
Laura Karkowski-Shuman ◽  
Dermot Walsh
Keyword(s):  
Family Study ◽  
Age Of Onset ◽  
Age At Onset ◽  
Proportional Hazard ◽  
Common Sense Model ◽  
Cox Proportional Hazard ◽  
Developmental Effects ◽  
Cox Proportional Hazard Models ◽  
Definition Of ◽  
The Individual

BackgroundFor many common medical and neuropsychiatric disorders, early age at onset reflects high familial liability to illness. However, for schizophrenia, most studies do not find such a relationship.MethodUsing Cox proportional hazard models, we investigate this question in the epidemiologically-based Roscommon family study.ResultsNo relationship was found between age at onset in schizophrenic probands and the hazard rate for schizophrenia in their relatives. Similar results were obtained when the definition of illness was expanded to include schizoaffective disorder and other non-affective psychoses.ConclusionsFor schizophrenia, a ‘common-sense’ model for age of onset (i.e. those with highest familial liability to illness succumb first while those with lower liability survive longer before falling ill) does not seem to apply. Our results are more consistent with a model in which variation in age at onset of schizophrenia is due to random developmental effects or to environmental experiences unique to the individual.

scholarly journals LAMB1 Is Related to the T Stage and Indicates Poor Prognosis in Gastric Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382110049
Author(s):  
Tao Ran ◽  
ZhiJi Chen ◽  
LiWen Zhao ◽  
Wei Ran ◽  
JinYu Fan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Poor Prognosis ◽  
Hazard Models ◽  
Proportional Hazard ◽  
Kegg Analysis ◽  
Proportional Hazard Models ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Cox Proportional Hazard Models ◽  
Gastric Cancer Patients

Background and Objective: Gastric cancer (GC) is a common tumor malignancy with high incidence and poor prognosis. Laminin is an indispensable component of basement membrane and extracellular matrix, which is responsible for bridging the internal and external environment of cells and transmitting signals. This study mainly explored the association of the LAMB1 expression with clinicopathological characteristics and prognosis in gastric cancer. Methods: The expression data and clinical information of gastric cancer patients were downloaded from The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG). And we analyzed the relationship between LAMB1 expression and clinical characteristics through R. CIBERSORTx was used to calculate the absolute score of immune cells in gastric tumor tissues. Then COX proportional hazard models and Kaplan-Meier curves were performed to evaluate the role of LAMB1 and its influence on prognosis in gastric cancer patients. Finally, GO and KEGG analysis were applied for LAMB1-related genes in gastric cancer, and PPI network was constructed in Cytoscape software. Results: In the TCGA cohort, patients with gastric cancer frequently generated LAMB1 gene copy number variation, but had little effect on mRNA expression. Both in the TCGA and ACRG cohorts, the mRNA expression of LAMB1 in gastric cancer tissues was higher than it in normal tissues. All patients were divided into high expression group and low expression group according to the median expression level of LAMB1. The elevated expression group obviously had more advanced cases and higher infiltration levels of M2 macrophages. COX proportional hazard models and Kaplan-Meier curves revealed that patients with enhanced expression of LAMB1 have a worse prognosis. GO/KEGG analysis showed that LAMB1-related genes were enriched in PI3K-Akt signaling pathway, focal adhesion, ECM-receptor interaction, etc. Conclusions: The high expression of LAMB1 in gastric cancer is related to the poor prognosis of patients, and it may be related to microenvironmental changes in tumors.

scholarly journals Inflammatory and Hypercoagulable Biomarkers and Clinical Outcomes in COVID-19 Patients

2021 ◽  
Vol 10 (14) ◽  
pp. 3086
Author(s):  
Hiroki Kitakata ◽  
Shun Kohsaka ◽  
Shunsuke Kuroda ◽  
Akihiro Nomura ◽  
Takeshi Kitai ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
Risk Estimation ◽  
Interquartile Range ◽  
Proportional Hazard ◽  
Multicenter Observational Study ◽  
Cox Proportional Hazard ◽  
Cox Proportional Hazard Models ◽  
Time Of Admission ◽  
Mortality Hazard Ratio ◽  
D Dimer

Systemic inflammation and hypercoagulopathy are known pathophysiological processes of coronavirus disease 2019 (COVID-19), particularly in patients with known cardiovascular disease or its risk factors (CVD). However, whether a cumulative assessment of these biomarkers at admission could contribute to the prediction of in-hospital outcomes remains unknown. The CLAVIS-COVID registry was a Japanese nationwide retrospective multicenter observational study, supported by the Japanese Circulation Society. Consecutive hospitalized patients with pre-existing CVD and COVID-19 were enrolled. Patients were stratified by the tertiles of CRP and D-dimer values at the time of admission. Multivariable Cox proportional hazard models were constructed. In 461 patients (65.5% male; median age, 70.0), the median baseline CRP and D-dimer was 58.3 (interquartile range, 18.2–116.0) mg/L and 1.5 (interquartile range, 0.8–3.0) mg/L, respectively. Overall, the in-hospital mortality rate was 16.5%, and the rates steadily increased in concordance with both CRP (5.0%, 15.0%, and 28.2%, respectively p < 0.001) and D-dimer values (6.8%, 19.6%, and 22.5%, respectively p = 0.001). Patients with the lowest tertiles of both biomarkers (CRP, 29.0 mg/L; D-dimer, 1.00 mg/L) were at extremely low risk of in-hospital mortality (0% until day 50, and 1.4% overall). Conversely, the elevation of both CRP and D-dimer levels was a significant predictor of in-hospital mortality (Hazard ratio, 2.97; 95% confidence interval, 1.57–5.60). A similar trend was observed when the biomarker threshold was set at a clinically relevant threshold. In conclusion, the combination of these abnormalities may provide a framework for rapid risk estimation for in-hospital COVID-19 patients with CVD.

scholarly journals Prognostic implications of depression and inflammation in patients with metastatic lung cancer

2020 ◽  
Author(s):  
Daniel C McFarland ◽  
Rebecca M. Saracino ◽  
Andrew H. Miller ◽  
William Breitbart ◽  
Barry Rosenfeld ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Hazard Ratio ◽  
Proportional Hazard ◽  
Metastatic Lung Cancer ◽  
Proportional Hazard Models ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Metastatic Lung ◽  
Cox Proportional Hazard Models ◽  
Prognostic Implications

Background: Lung cancer-related inflammation is associated with depression. Both elevated inflammation and depression are associated with worse survival. However, outcomes of patients with concomitant depression and elevated inflammation are not known. Materials & methods: Patients with metastatic lung cancer (n = 123) were evaluated for depression and inflammation. Kaplan–Meier plots and Cox proportional hazard models provided survival estimations. Results: Estimated survival was 515 days for the cohort and 323 days for patients with depression (hazard ratio: 1.12; 95% CI: 1.05–1.179), 356 days for patients with elevated inflammation (hazard ratio: 2.85, 95% CI: 1.856–4.388), and 307 days with both (χ2 = 12.546; p < 0.001]). Conclusion: Depression and inflammation are independently associated with inferior survival. Survival worsened by inflammation is mediated by depression-a treatable risk factor.

scholarly journals Potato consumption and risk of pancreatic cancer in the HELGA cohort

2018 ◽  
Vol 119 (12) ◽  
pp. 1408-1415
Author(s):  
Lene A. Åsli ◽  
Tonje Braaten ◽  
Anja Olsen ◽  
Anne Tjønneland ◽  
Kim Overvad ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Registries ◽  
Glycaemic Index ◽  
Proportional Hazard ◽  
Cox Proportional Hazard ◽  
Cox Proportional Hazard Models ◽  
The Mean ◽  
Potato Consumption ◽  
Adjusted Model

AbstractPotatoes have been a staple food in many countries throughout the years. Potatoes have a high glycaemic index (GI) score, and high GI has been associated with several chronic diseases and cancers. Still, the research on potatoes and health is scarce and contradictive, and we identified no prospective studies that had investigated the association between potatoes as a single food and the risk of pancreatic cancer. The aim of this study was to prospectively investigate the association between potato consumption and pancreatic cancer among 114 240 men and women in the prospective HELGA cohort, using Cox proportional hazard models. Information on diet (validated FFQ’s), lifestyle and health was collected by means of a questionnaire, and 221 pancreatic cancer cases were identified through cancer registries. The mean follow-up time was 11·4 (95 % CI 0·3, 16·9) years. High consumption of potatoes showed a non-significantly higher risk of pancreatic cancer in the adjusted model (hazard ratio (HR) 1·44; 95 % CI 0·93, 2·22,Pfor trend0·030) when comparing the highestv.the lowest quartile of potato consumption. In the sex-specific analyses, significant associations were found for females (HR 2·00; 95 % CI 1·07, 3·72,Pfor trend0·020), but not for males (HR 1·01; 95 % CI 0·56, 1·84,Pfor trend0·34). In addition, we explored the associations by spline regression, and the absence of dose–response effects was confirmed. In this study, high potato consumption was not consistently associated with a higher risk of pancreatic cancer. Further studies with larger populations are needed to explore the possible sex difference.

Abstract P153: Racial Disparities in Diabetic Complications in a Middle and Low Income Population of Louisiana

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Yujie Wang ◽  
Wei Li ◽  
Liwei Chen ◽  
Ronald Horswell ◽  
Wenting Xie ◽  
...  
Keyword(s):  
African American ◽  
Low Income ◽  
Diabetic Complications ◽  
Diabetic Patients ◽  
Proportional Hazard ◽  
Cox Proportional Hazard ◽  
Cox Proportional Hazard Models ◽  
Stage Renal Disease ◽  
End Stage ◽  
Incident Rates

Background: Although coronary heart disease (CHD), heart failure (HF), stroke, and end-stage renal disease (ESRD) are major microvascular and macrovascular complications of diabetes, they are less clear for diabetic subgroups especially on those with middle and low income. Aim: To investigate racial disparities in the incidence of diabetic complications in middle and low income adults. Methods: We performed a prospective cohort study (1985-2010) on diabetic patients enrolled in the LSU Hospital-Based Longitudinal Study. Study cohorts included 89,353 diabetic patients (16,326 White men, 21,496 White women, 19,422 African American men and 32,109 African American women) who were 30 to 96 years of age. We calculated the gender specific age-standardized incident rates using the direct method to the year 2010 Census population. Cox proportional hazard models were used to compare racial or gender specific hazard ratios for CHD, HF, stroke and ESRD after adjustment for age, race, type of health insurance, family income, body mass index, smoking, systolic blood pressure, LDL cholesterol, HDL cholesterol, HbA 1c , estimated GFR, albuminuria, and drug treatments for diabetes, hypertension and hyperlipidemia. Results: During an average 4.0 years of follow-up, 16,935 CHD, 13,421 HF, 6,804 stroke, and 13,281 ESRD incident cases were ascertained. The age-standardized incident rates of the four diabetic complications are presented in table 1 . Compared with White diabetic patients, African Americans experienced higher rates of ESRD and lower rates of CHD, HF, and stroke. Female diabetic patients had lower rates of the four complications than males. Results of the Cox proportional hazard models confirmed the racial disparity and gender difference we found in the age-standardized incident rates. Conclusions: The results support the existence of racial differences in the incidence of diabetic complications in this population. Table 1 Age-adjusted incident rates of type 2 diabetes complications in the LSUHLS study Age-standardized incident rates White African American Male Female Male Female Coronary Heart Disease 101.6 (98.8-104.5) 62.0 (60.4-63.7) 50.7 (49.2-52.2) 44.4 (43.4-45.5) Heart Failure 54.9 (52.9-56.8) 41.9 (40.6-43.1) 43.4 (42.0-44.8) 38.4 (37.4-39.3) Stroke 22.1 (20.9-23.3) 20.7 (19.8-21.6) 19.9 (19.0-20.8) 18.5 (17.8-19.1) End-stage Renal Disease 43.3 (41.6-45.0) 33.4 (32.2-34.5) 51.4 (50.0-52.9) 35.2 (34.3-36.1)

Abstract 16571: The Potential Impact of Expanding Cardiac Rehabilitation Coverage in Heart Failure: Insights From Get With the Guidelines Heart Failure

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Jacob P Kelly ◽  
Brad G Hammill ◽  
Jacob A Doll ◽  
G. Michael Felker ◽  
Paul A Heidenreich ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Rehabilitation ◽  
Adverse Outcomes ◽  
P Value ◽  
Proportional Hazard ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Cox Proportional Hazard Models ◽  
Expanded Criteria ◽  
Get With The Guidelines

Background: In February 2014, coverage for cardiac rehabilitation (CR) was expanded by Centers for Medicare & Medicaid to include patients with chronic symptomatic heart failure (HF) on optimal medical therapy with ejection fraction <35%. Thus, we sought to characterize the patient population newly eligible for CR based on the expanded criteria and their associated outcomes. Methods: We analyzed the Get With The Guidelines-HF registry linked to Medicare claims data from 2008-2012 to assess three groups of patients age 65 or older: previously eligible (due to prior MI, CABG, stable angina, heart valve surgery, or PCI in the previous 12 months), newly eligible, and ineligible for CR. Ineligible patients met neither criteria. Incidence rate was calculated with Kaplan-Meier estimates and Cox proportional hazard models were used to determine the association of events. Results: Among 51,665 HF patients discharged alive, 27.2% (n=14,053) were newly eligible and 14.5% were previously eligible for CR (n=7477). Newly eligible patients were more likely to be black, have atrial fibrillation and EF < 35%, while having fewer previous hospitalizations than patients previously eligible for CR. Newly eligible and ineligible patients had similar risk for 1-year mortality compared with those previously eligible (adjusted Hazard Ratio [HR] 0.95, 95% Confidence Interval [CI] 0.88-1.02, p-value=0.13 and [HR] 1.05, 95% [CI] 0.98-1.13, p-value=0.17, respectively). However, newly eligible and ineligible patients had lower risk for 1-year readmission compared with those previously eligible (adjusted [HR] 0.89, 95% [CI] 0.85-0.93, p-value<0.001 and [HR] 0.94, 95% [CI] 0.90- 0.98, p-value<0.001). Conclusions: The extension of coverage for cardiac rehabilitation has tripled the potentially eligible HF population. As these newly eligible patients are at high risk for adverse outcomes, cardiac rehabilitation should be considered.

scholarly journals Revolutions and the Military: Endgame Coups, Instability, and Prospects for Democracy

2019 ◽  
Vol 47 (1) ◽  
pp. 148-176 ◽  
Author(s):  
Kevin Koehler ◽  
Holger Albrecht
Keyword(s):  
Distinct Type ◽  
Proportional Hazard ◽  
Data Set ◽  
Systematic Analysis ◽  
Proportional Hazard Models ◽  
Cox Proportional Hazard ◽  
Original Medium ◽  
Cox Proportional Hazard Models ◽  
The Military ◽  
Nondemocratic Regimes

This article presents a systematic analysis of military coups following popular mass uprisings in nondemocratic regimes, conceptualized as endgame coups. Drawing on our original, medium- n data set of revolutionary situations, we find that such endgame coups form a distinct type of military intervention in politics. Compared to regular coups, episodes of popular mass contestation prompt conservative interventions in politics of the military’s leadership aimed at preserving the regime’s authoritarian infrastructure. A systematic test of factors characterizing postcoup political trajectories is based on Cox proportional hazard models and provides empirical evidence in contrast to the widely held notion of “democratic coups.” Our findings reveal that endgame coups are conservative rollback coups, executed by military leaderships, that result in continued political instability and illiberal politics.

scholarly journals Low rather than high mean corpuscular volume is associated with mortality in Japanese patients under hemodialysis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hirokazu Honda ◽  
Miho Kimachi ◽  
Noriaki Kurita ◽  
Nobuhiko Joki ◽  
Masaomi Nangaku
Keyword(s):  
Mean Corpuscular Volume ◽  
Japanese Patients ◽  
Cubic Spline ◽  
Hazard Models ◽  
Proportional Hazard ◽  
Corpuscular Volume ◽  
Proportional Hazard Models ◽  
Cox Proportional Hazard ◽  
All Cause Mortality ◽  
Cox Proportional Hazard Models

Abstract Recent studies have reported that high mean corpuscular volume (MCV) might be associated with mortality in patients with advanced chronic kidney disease (CKD). However, the question of whether a high MCV confers a risk for mortality in Japanese patients remains unclear. We conducted a longitudinal analysis of a cohort of 8571 patients using data derived from the Japan Dialysis Outcomes and Practice Patterns Study (J-DOPPS) phases 1 to 5. Associations of all-cause mortality, vascular events, and hospitalization due to infection with baseline MCV were examined via Cox proportional hazard models. Non-linear relationships between MCV and these outcomes were examined using restricted cubic spline analyses. Associations between time-varying MCV and these outcomes were also examined as sensitivity analyses. Cox proportional hazard models showed a significant association of low MCV (< 90 fL), but not for high MCV (102 < fL), with a higher incidence of all-cause mortality and hospitalization due to infection compared with 94 ≤ MCV < 98 fL (reference). Cubic spline analysis indicated a graphically U-shaped association between baseline MCV and all-cause mortality (p for non-linearity p < 0.001). In conclusion, a low rather than high MCV might be associated with increased risk for all-cause mortality and hospitalization due to infection among Japanese patients on hemodialysis.

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