Development and validation of a Bayesian survival model for inclusion body myositis

Abstract Background Associations between disease characteristics and payer-relevant outcomes can be difficult to establish for rare and progressive chronic diseases with sparse available data. We developed an exploratory bridging model to predict premature mortality from disease characteristics, and using inclusion body myositis (IBM) as a representative case study. Methods Candidate variables that may be potentially associated with premature mortality were identified by disease experts and from the IBM literature. Interdependency between candidate variables in IBM patients were assessed using existing patient-level data. A Bayesian survival model for the IBM population was developed with identified variables as predictors for premature mortality in the model. For model selection and external validation, model predictions were compared to published mortality data in IBM patient cohorts. After validation, the final model was used to simulate the increased risk of premature death in IBM patients. Baseline survival was based on age- and gender-specific survival curves for the general population in Western countries as reported by the World Health Organisation. Results Presence of dysphagia, aspiration pneumonia, falls, being wheelchair-bound and 6-min walking distance (6MWD in meters) were identified as candidate variables to be used as predictors for premature mortality based on inputs received from disease experts and literature. There was limited correlation between these functional performance measures, which were therefore treated as independent variables in the model. Based on the Bayesian survival model, among all candidate variables, presence of dysphagia and decrease in 6MWD [m] were associated with poorer survival with contributing hazard ratios (HR) 1.61 (95% credible interval [CrI]: 0.84–3.50) and 2.48 (95% CrI: 1.27–5.00) respectively. Excess mortality simulated in an IBM cohort vs. an age- and gender matched general-population cohort was 4.03 (95% prediction interval 1.37–10.61). Conclusions For IBM patients, results suggest an increased risk of premature death compared with the general population of the same age and gender. In the absence of hard data, bridging modelling generated survival predictions by combining relevant information. The methodological principle would be applicable to the analysis of associations between disease characteristics and payer-relevant outcomes in progressive chronic and rare diseases. Studies with lifetime follow-up would be needed to confirm the modelling results.

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Epidemiology, morbidity and mortality in Behçet’s disease: a cohort study using The Health Improvement Network (THIN)

Rheumatology ◽

10.1093/rheumatology/keaa010 ◽

2020 ◽

Vol 59 (10) ◽

pp. 2785-2795 ◽

Cited By ~ 1

Author(s):

Tom Thomas ◽

Joht Singh Chandan ◽

Anuradhaa Subramanian ◽

Krishna Gokhale ◽

George Gkoutos ◽

...

Keyword(s):

Pulmonary Embolism ◽

Cohort Study ◽

Heart Disease ◽

General Population ◽

Venous Thrombosis ◽

Ischaemic Heart Disease ◽

Thromboembolic Disease ◽

Age And Gender ◽

Increased Risk ◽

And Gender

Abstract Objectives The epidemiology of Behçet’s disease (BD) has not been well characterized in the UK. Evidence on the risk of cardiovascular disease, thromboembolic disease and mortality in patients with BD compared with the general population is scarce. Methods We used a large UK primary care database to investigate the epidemiology of BD. A retrospective matched cohort study was used to assess the following outcomes: risk of cardiovascular, thromboembolic disease and mortality. Controls were selected at a 1:4 ratio (age and gender matched). Cox proportional hazard models were used to derive adjusted hazard ratios (aHR). Results The prevalence of BD was 14.61 (95% CI 13.35–15.88) per 100 000 population in 2017. A total of 1281 patients with BD were compared with 5124 age- and gender-matched controls. There was significantly increased risk of ischaemic heart disease [aHR 3.09 (1.28–7.44)], venous thrombosis [aHR 4.80 (2.42–9.54)] and mortality [aHR 1.40 (1.07–1.84)] in patients with BD compared with corresponding controls. Patients with BD were at higher risk of pulmonary embolism compared with corresponding controls at baseline [adjusted odds ratio 4.64 (2.66–8.09), P < 0.0001]. The majority of patients with pulmonary embolism and a diagnosis of BD had pulmonary embolism preceding the diagnosis of BD, not after (87.5%; n = 28/32). Conclusion BD has a higher prevalence than previously thought. Physicians should be aware of the increased risk of developing ischaemic heart disease, stroke/transient ischaemic attack and deep venous thrombosis in patients with BD at an earlier age compared with the general population. Risk of embolism in patients with BD might vary across the disease course.

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Incidence of Major Hemorrhage Among CLL and MCL Patients Compared to the General Elderly Population: An Analysis of the US SEER-Medicare Linked Database

Blood ◽

10.1182/blood.v126.23.3268.3268 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3268-3268 ◽

Cited By ~ 8

Author(s):

Dina M Gifkins ◽

Amy Matcho ◽

Huiying Yang ◽

Yimei Xu ◽

Mary Ann Gooden ◽

...

Keyword(s):

General Population ◽

Proportional Hazards ◽

Population Based ◽

Incidence Rates ◽

Cox Proportional Hazards ◽

Administrative Claims ◽

Age And Gender ◽

Major Hemorrhage ◽

Increased Risk ◽

And Gender

Abstract Introduction: Patients with B cell malignancies have an inherent increased risk of bleeding. However, the incidence of major hemorrhage among patients with MCL and CLL has not been described. The objective of this study is to evaluate the risk of major hemorrhage in a real world setting by using a population-based data source. Methods: The SEER-Medicare linked database, a database of SEER cancer registry data linked to individual Medicare administrative claims, was utilized to follow a cohort of persons newly treated for CLL or MCL to estimate the incidence of major hemorrhage (CNS and non-CNS). Major hemorrhage was defined as having at least one code for hemorrhage in a critical area or organ or having another bleeding code with a transfusion within 14 days of the event. Patients with a cancer diagnosis on or after 1/1/2000 were followed through disenrollment from the database, death, the occurrence of major hemorrhage, or the end of the study period (12/31/2011), whichever came first. Incidence rates (IR) of major hemorrhage were characterized in terms of incidence per person-years (pys) of follow-up with 95% confidence intervals calculated according to a Poisson distribution. Rates in the CLL and MCL populations were compared to those in the age and gender-matched general population of a sample of non-cancer Medicare patients using Cox proportional hazards models. Results: A total of 1,587 treated MCL patients, 6,717 treated CLL/SLL patients, and 14,816 age and gender-matched non-cancer patients were identified in the database. Median age among all three cohorts was approximately 75 years. Among patients treated for MCL, 287 (18%) had at least one major hemorrhage, corresponding to an incidence of 5.8 per 100 pys. Among 6,717 CLL patients, 1,211 (18%) had at least one major hemorrhage (IR: 6.0 per 100 pys). In the age and gender-matched non-cancer population, incidence of major hemorrhage was 1.6 per 100 pys. The hazard ratio for development of any major hemorrhage among CLL patients compared to the non-cancer cohort was 8.3 (95% CI: 7.5-9.2), and for MCL compared to the non-cancer cohort was 8.8 (95% CI: 7.6-10.2). IR of CNS hemorrhage was also higher among MCL and CLL patients (0.9 and 1.2 per 100 pys, respectively) compared to the non-cancer cohort (0.04 per 100 pys). Gastrointestinal hemorrhage was the most frequent site of occurrence. Conclusions: Among persons newly initiating treatment for CLL and MCL, incidence of major hemorrhage was found to be over 8 times higher than that of the age- and gender-matched general population. Additional analyses to establish whether this increased risk is attributable to the disease itself, comorbid conditions, choice of cancer therapy, or concomitant medications in the patient population and/or other risk factors are planned. Baseline risks among CLL and MCL patients should be considered when establishing risk/benefit profiles of a particular treatment. Disclosures Gifkins: Johnson and Johnson: Employment. Matcho:Johnson and Johnson: Employment. Yang:Pharmacyclics, Inc: Employment. Xu:Johnson and Johnson: Employment. Gooden:Pharmacyclics, Inc.: Employment. Wildgust:Janssen Pharmaceuticals, Inc.: Employment.

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Associations between mental illnesses and acute cardiovascular events and cancers in France in 2016

European Journal of Public Health ◽

10.1093/eurpub/ckz187.194 ◽

2019 ◽

Vol 29 (Supplement_4) ◽

Author(s):

T Lesuffleur ◽

M Coldefy ◽

A Rachas ◽

C Gastaldi-Ménager ◽

P Tuppin

Keyword(s):

Heart Failure ◽

Mental Illness ◽

Pulmonary Embolism ◽

General Population ◽

Cardiovascular Events ◽

Healthcare Professionals ◽

Mental Illnesses ◽

Age And Gender ◽

Addictive Disorder ◽

And Gender

Abstract Background People with a mental illness have higher risks of somatic diseases and higher mortality, but this has been poorly documented in France. We studied the associations between mental illnesses and acute cardiovascular events (ACEs) and cancers in the French national health data system (SNDS). Methods We included all health insurance general scheme beneficiaries ≥18 years-of-age in 2016. Mental illnesses (psychotic disorder, neurotic or mood disorder, mental retardation and addictive disorder), ACEs (acute coronary syndrome (ACS), stroke, acute heart failure and pulmonary embolism) and cancers (breast, colorectal, lung and prostate) were identified using algorithms based on long-term disease registry, hospitalization diagnoses and specific drug deliveries. The associations were measured using morbidity ratios standardized by age and gender when appropriate (SMRs). Results ACEs were more frequent in the subjects with a mental illness than in the general population: ACS (SMR: 1.6), stroke (2.3), acute heart failure (1.9), pulmonary embolism (2.4). Similar results were found for each mental illness, except for ACS, which were less frequent in those with a mental retardation (SMR: 0.5) and were not associated with psychotic disorder (SMR: 1.0). Mental illness was also associated with more frequent breast (SMR: 1.3), colorectal (1.3), lung (2.0) and prostate (1.2) cancers, in particular for those with a neurotic or mood disorder (SMRs: 1.3, 1.5, 2.3, 1.2, respectively) and, for lung cancer, those with an addictive disorder (SMR: 2.6). Conclusions Globally, ACEs and cancers were more frequent in patients with a mental illness relative to the general population after standardization by age and gender, which could be related to adverse effects of certain psychotropic drugs or behaviours or risk factors related to the mental illness. Healthcare professionals should be aware of this to more adequately account for the specificities of the patients with a mental illness. Key messages ACEs and cancers were more frequent in patients with a mental illness relative to the general population after standardization by age and gender. Healthcare professionals should be aware of this to more adequately account for the specificities of the patients with a mental illness.

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Blood Pressure and Immunoglobulins

Clinical Science ◽

10.1042/cs0650665 ◽

1983 ◽

Vol 65 (6) ◽

pp. 665-667 ◽

Cited By ~ 2

Author(s):

A. M. De Bruijn ◽

F. C. A. Geers ◽

R. S. A. J. Hylkema ◽

R. Vermeeren ◽

A. Hofman

Keyword(s):

Blood Pressure ◽

General Population ◽

Serum Concentrations ◽

Age And Gender ◽

Normotensive Subjects ◽

And Gender

1. Serum concentrations of IgG and IgM were measured in 87 hypertensive and 87 normotensive subjects, matched for age and gender, and selected from the same general population. 2. No significant differences between these two groups were found, in contrast to some previous reports. 3. The reasons for this discrepancy are discussed.

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F96. AGE AND GENDER DETERMINED DIFFERENCES IN THE ONSET OF CHRONIC PHYSICAL MULTIMORBIDITIES AMONG PATIENTS WITH SCHIZOPHRENIA OR DEPRESSION AND THE GENERAL POPULATION

Schizophrenia Bulletin ◽

10.1093/schbul/sby017.627 ◽

2018 ◽

Vol 44 (suppl_1) ◽

pp. S257-S257

Author(s):

Ivona Šimunović Filipčić ◽

Ena Ivezić ◽

Željko Milovac ◽

Ines Kašpar ◽

Sandra Kocijan Lovko ◽

...

Keyword(s):

General Population ◽

Age And Gender ◽

And Gender

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Use of driving-impairing medicines by a Spanish population: a population-based registry study

BMJ Open ◽

10.1136/bmjopen-2017-017618 ◽

2017 ◽

Vol 7 (11) ◽

pp. e017618 ◽

Cited By ~ 10

Author(s):

Eduardo Gutierrez-Abejón ◽

Francisco Herrera-Gómez ◽

Paloma Criado-Espegel ◽

F Javier Alvarez

Keyword(s):

General Population ◽

Census Data ◽

Population Based ◽

Spanish Population ◽

Registry Study ◽

Age And Gender ◽

Patterns Of Use ◽

And Gender ◽

Population Based Registry ◽

Chronic Use

ObjectiveTo assess the use of driving-impairing medicines (DIM) in the general population with special reference to length of use and concomitant use.DesignPopulation-based registry study.SettingThe year 2015 granted medicines consumption data recorded in the Castile and León (Spain) medicine dispensation registry was consulted.ParticipantsMedicines and DIM consumers from a Spanish population (Castile and León: 2.4 million inhabitants).ExposureMedicines and DIM consumption. Patterns of use by age and gender based on the length of use (acute: 1–7 days, subacute: 8–29 days and chronic use: ≥30 days) were of interest. Estimations regarding the distribution of licensed drivers by age and gender were employed to determine the patterns of use of DIM.ResultsDIM were consumed by 34.4% (95% CI 34.3% to 34.5%) of the general population in 2015, more commonly with regularity (chronic use: 22.5% vs acute use: 5.3%) and more frequently by the elderly. On average, 2.3 DIM per person were dispensed, particularly to chronic users (2.8 DIM per person). Age and gender distribution differences were observed between the Castile and León medicine dispensation registry data and the drivers’ license census data. Of all DIM dispensed, 83.8% were in the Anatomical Therapeutic Chemical code group nervous system medicines (N), which were prescribed to 29.2% of the population.ConclusionsThe use of DIM was frequent in the general population. Chronic use was common, but acute and subacute use should also be considered. This finding highlights the need to make patients, health professionals, health providers, medicine regulatory agencies and policy-makers at large aware of the role DIM play in traffic safety.

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Age and gender differences in the influences of eNOS T-786C polymorphism on arteriosclerotic parameters in general population in Japan

Environmental Health and Preventive Medicine ◽

10.1007/s12199-016-0527-1 ◽

2016 ◽

Vol 21 (4) ◽

pp. 274-282 ◽

Cited By ~ 2

Author(s):

Marowa Hashimoto ◽

Nobuyuki Miyai ◽

Sonomi Hattori ◽

Akihiko Iwahara ◽

Miyoko Utsumi ◽

...

Keyword(s):

Gender Differences ◽

General Population ◽

Age And Gender ◽

Age And Gender Differences ◽

And Gender

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Epilepsy and Mortality

Journal of the Korean Neurological Association ◽

10.17340/jkna.2020.1.1 ◽

2020 ◽

Vol 38 (1) ◽

pp. 1-8

Author(s):

Hye-Jin Moon ◽

Keun Tae Kim ◽

Kyung Wook Kang ◽

Soo Yeon Kim ◽

Yong Seo Koo ◽

...

Keyword(s):

Public Health ◽

Epilepsy Surgery ◽

Associated Factors ◽

Causes Of Death ◽

Premature Mortality ◽

Premature Death ◽

Increased Risk ◽

Significant Burden

Epilepsy is associated with an increased risk of premature death. Epilepsy-related premature mortality imposes a significant burden on public health. This review aims to update the previous assessments of mortality among people with epilepsy and to identify associated factors, causes of death, and preventable causes of death in epilepsy patients. We also reviewed the mortality of epilepsy patients who had undergone epilepsy surgery. Finally, we suggest a further direction of studies about the mortality of people with epilepsy.

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The association of tissue doppler E/e' ratio with poor survival is modified by gender and is attenuated with advanced age

European Heart Journal ◽

10.1093/eurheartj/ehab724.012 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

Y Wasserstrum ◽

R Gilead ◽

R Kuperstein ◽

S Ben-Zekry ◽

O Vatury ◽

...

Keyword(s):

Cox Regression ◽

Mitral Annulus ◽

Tissue Doppler ◽

Outcome Data ◽

Poor Survival ◽

Age And Gender ◽

Risk Of Death ◽

Increased Risk ◽

And Gender

Abstract Introduction Contemporary guidelines recommend a universal cutoff of 14 for the ratio between early mitral flow wave and early diastolic mitral annulus velocity measured by tissue doppler (E/e' ratio). While age-dependent normal E/e' values have been suggested, outcome data is lacking. Purpose We sought to evaluate the modification effect of age and gender on the prognostic value of the E/e' ratio. Methods Consecutive patients who underwent echocardiographic evaluation between 2009 and 2021 (N=104,315) in a single tertiary cardiovascular center. Patients with left or right ventricular dysfunction, any significant valvular disease, structural heart disease or evidence of pulmonary hypertension were excluded. Cancer and mortality data were available for all subjects from national registries. Patients with a metastatic malignancy at baseline or during follow up were excluded. Cox regression models were applied. Results Overall, 44,541 patients were included in the final analysis. Mean age was 55±17, 59% were male and 63% of the exams were performed in an outpatient setting. An elevated E/e' ratio above 14 was documented in 2,598 (7%) patients. During a median follow-up of 5.7 (IQR 2.8–9.1) years, 5,015 (11.3%) patients died. Kaplan Meier survival analysis demonstrated that the cumulative probability of death at 6 years was 23.4% (21.6–25.3) among patients with elevated E/e' ratio compared with 9.7% (9.3–10.0) among patients with E/e'<14 (p Log rank <0.001). This difference was less significant as age progressed (figure 1). Multivariate cox-regression model yielded consistent results such that an elevated E/e' ratio was associated with 2.66-fold increased risk of death during follow up (95% CI 2.44–2.89, p<0.001), and there was a decline in the increased risk and significant as age advanced in both genders (figure 2). Interaction analysis was significant for both gender and age such the association of elevated E/e' ratio with poor survival was more significant among men compared with women and among young vs. older subjects. Among women, elevated E/e' was associated with 2.4-fold increased risk of death versus 2.7-fold increased risk among men. Similarly, the hazard ratio for death associated with elevated E/e' was 2.29 (95% CI 1.74–3.02), 1.8 (95% CI 1.5–2.1), 1.13 (95% CI 0.97–1.31) and 1.07 (95% CI 0.92–1.25) for the age groups of <60, 60–70, 70–80 and >80, respectively. In a sensitivity analysis, similar findings were seen in when excluding patients with mild hypertrophy (maximal wall thickness >12mm) and without any mitral annulus calcification. Conclusion In apparently normal hearts, an elevated E/e' ratio is independently associated with increased mortality. This association is more pronounced among men and is attenuated with increased age. This study supports the need for gender-specific and age-specified outcome data with respect to measures of diastolic dysfunction. FUNDunding Acknowledgement Type of funding sources: None. Survival by age and gender groups E/e' >14 and mortality by age and gender

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Unexpected Increase of Myocardial Extracellular Volume Fraction in Low Cardiovascular Risk HIV Patients

10.21203/rs.3.rs-64907/v1 ◽

2020 ◽

Author(s):

Cristian Borrazzo ◽

Gabriella d'Ettorre ◽

Giancarlo Ceccarelli ◽

Massimiliano Pacilio ◽

Letizia Santinelli ◽

...

Keyword(s):

Computed Tomography ◽

General Population ◽

Hiv Infection ◽

Volume Fraction ◽

Control Group ◽

People Living With Hiv ◽

Hiv Patients ◽

Age And Gender ◽

And Gender ◽

Asymptomatic Hiv

Abstract Background: People living with HIV (PLWH) are prone to develop sub-clinical Cardiovascular (CV) disease, despite the effectiveness of combined Antiretroviral Therapy (cART). Algorithms developed to predict CV risk in the general population could be inaccurate when applied to PLWH. Myocardial Extra-Cellular Matrix (ECM) expansion, measured by computed tomography, has been associated with an increased CV vulnerability in HIV-negative population. Measurement of Myocardial Extra-Cellular Volume (ECV) by computed tomography or magnetic resonance, is considered a useful surrogate for clinical evaluation of ECM expansion. In the present study, we aimed to determine the extent of cardiovascular involvement in asymptomatic HIV-infected patients with the use of a comprehensive cardiac computed tomography (CCT) approach.Materials and methods: In the present study, ECV in low atherosclerotic CV risk PLWH was compared with ECV of age and gender matched HIV- individuals. 53 asymptomatic HIV+ individuals (45 males, age 48 (42.5-48) years) on effective cART (CD4+ cell count: 450 cells/μL (IQR: 328-750); plasma HIV RNA: <37 copies/ml in all subjects) and 18 age and gender matched controls (14 males, age 55 (44.5-56) years) were retrospectively enrolled. All participants underwent CCT protocol to obtain native and postcontrast Hounsfield unit values of blood and myocardium, ECM was calculated accordingly.Results: The ECV was significantly higher in HIV+ patients than in the control group (ECV: 31% (IQR: 28%-31%) vs 27.4% (IQR: 25%-28%), p<0.001). The duration of cART (standardized β=0.56 (0.33-0.95), p=0.014) and the years of exposure to HIV infection (standardized β=0.53 (0.4-0.92), p<0.001), were positively and strongly associated with ECV values. Differences in ECV (p<0.001) were also observed regarding the duration of cART exposure (<5 years, 5-10 years and >10 years). Moreover, ECV was independently associated with age of participants (standardized β = 0.42 (0.33-0.89), p=0.084).Conclusions: HIV infection and exposure to antiretrovirals play a detrimental role on ECV expansion. An increase in ECV indicates ECM expansion, which has been associated to a higher CV risk in the general population. The non-invasive evaluation of ECM trough ECV could represent an important tool to further understand the relationship between HIV infection, cardiac pathophysiology and the increased CV risk observed in PLWH.

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