scholarly journals Development and validation of a predictive algorithm for risk of dementia in the community setting

2021 ◽  
pp. jech-2020-214797
Author(s):  
Stacey Fisher ◽  
Douglas G Manuel ◽  
Amy T Hsu ◽  
Carol Bennett ◽  
Meltem Tuna ◽  
...  

BackgroundMost dementia algorithms are unsuitable for population-level assessment and planning as they are designed for use in the clinical setting. A predictive risk algorithm to estimate 5-year dementia risk in the community setting was developed.MethodsThe Dementia Population Risk Tool (DemPoRT) was derived using Ontario respondents to the Canadian Community Health Survey (survey years 2001 to 2012). Five-year incidence of physician-diagnosed dementia was ascertained by individual linkage to administrative healthcare databases and using a validated case ascertainment definition with follow-up to March 2017. Sex-specific proportional hazards regression models considering competing risk of death were developed using self-reported risk factors including information on socio-demographic characteristics, general and chronic health conditions, health behaviours and physical function.ResultsAmong 75 460 respondents included in the combined derivation and validation cohorts, there were 8448 cases of incident dementia in 348 677 person-years of follow-up (5-year cumulative incidence, men: 0.044, 95% CI: 0.042 to 0.047; women: 0.057, 95% CI: 0.055 to 0.060). The final full models each include 90 df (65 main effects and 25 interactions) and 28 predictors (8 continuous). The DemPoRT algorithm is discriminating (C-statistic in validation data: men 0.83 (95% CI: 0.81 to 0.85); women 0.83 (95% CI: 0.81 to 0.85)) and well-calibrated in a wide range of subgroups including behavioural risk exposure categories, socio-demographic groups and by diabetes and hypertension status.ConclusionsThis algorithm will support the development and evaluation of population-level dementia prevention strategies, support decision-making for population health and can be used by individuals or their clinicians for individual risk assessment.

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Baback Roshanravan ◽  
Cassiane Robinson-Cohen ◽  
Kushang V Patel ◽  
Greg Levin ◽  
Ian H de Boer ◽  
...  

Objective: Skeletal muscle dysfunction (sarcopenia) is an under-recognized complication of chronic kidney disease (CKD) that may have important clinical consequences. Gait speed is associated with sarcopenia and comorbid disease burden among older adults; however, little is known about the prognostic significance of gait speed in CKD. We determined the association of gait speed with all-cause mortality in a prospective cohort of non-dialysis CKD patients. Methods: We measured usual gait speed over 4-meters in 309 participants from a prospective study of non-dialysis CKD. Included subjects had an estimated glomerular filtration rate (eGFR ckdepi ) <90mL/min/1.73m 2 , were stroke-free and did not require a wheelchair for ambulation. Study coordinators assessed mortality during follow-up by phone contacts, medical record review, and the social security death index. We evaluated gait speed continuously, and using a cut point of 0.8 m/s, consistent with previous studies. We used Cox's proportional hazards to estimate the association of gait speed with mortality after adjustment for age, sex, race, smoking, diabetes, pre-existing CAD, BMI, eGFR and hemoglobin. Results: Median follow-up time was 2.7 years; range 27 days to 4.8 years. The mean age was 58.9 ± 13 years and mean eGFR by cystatin C (eGFR cysc ) was 48.5 ± 23mL/min/1.73m 2 . There were a total of 31 deaths (10.4%) during follow-up. Unadjusted mortality rates were 23 and 80 deaths per 1,000 person-years among participants who had a gait speed of >0.8m/s versus ≤0.8m/s, respectively. After full adjustment, gait speed ≤0.8m/s was associated with a 2.8-fold greater risk of death compared to a gait speed >0.8 m/s. Gait speed was also strongly associated with mortality when analyzed as a continuous variable ( Table ) and a stronger predictor of death than age, history of CAD, or diabetes. No. Deaths (%) Model 1 + Model 2 # Hazard Ratio 95% CI Hazard Ratio 95% CI Gait speed * 32(10) 0.74 (0.64-0.86) 0.75 (0.64-0.87) >0.8m/s 13 (6) Reference Reference ≤0.8m/s 19(19) 3.49 (1.54-7.95) 2.84 (1.25-6.48) * Gait speed analyzed continuously per 10cm/s increase in speed. +Model 1: Adjusted for age, sex, race, study site #Model 2: adds smoking, BMI, eGFR cysc , diabetes, prevalent coronary disease. Conclusion: Gait speed is strongly associated with death in a cohort of middle-aged CKD patients.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Si-wei Pan ◽  
Peng-liang Wang ◽  
Han-wei Huang ◽  
Lei Luo ◽  
Xin Wang ◽  
...  

Background. In gastric cancer, various surveillance strategies are suggested in international guidelines. The current study is intended to evaluate the current strategies and provide more personalized proposals for personalized cancer medicine. Materials and Methods. In the aggregate, 9191 patients with gastric cancer after gastrectomy from 1998 to 2009 were selected from the Surveillance, Epidemiology, and End Results database. Disease-specific survival was analyzed by Kaplan-Meier method and the log-rank test. Cox proportional hazards regression analyses were used to confirm the independent prognostic factors. As well, hazard ratio (HR) curves were used to compare the risk of death over time. Conditional survival (CS) was applied to dynamically assess the prognosis after each follow-up. Results. Comparisons from HR curves on different stages showed that earlier stages had distinctly lower HR than advanced stages. The curve of stage IIA was flat and more likely the same as that of stage I while that of stage IIB is like that of stage III with an obvious peak. After estimating CS at intervals of three months, six months, and 12 months in different periods, stages I and IIA had high levels of CS all along, while there were visible differences among CS levels of stages IIB and III. Conclusions. The frequency of follow-up for early stages, like stages I and IIA, could be every six months or longer in the first three years and annually thereafter. And those with unfavorable conditions, such as stages IIB and III, could be followed up much more frequently and sufficiently than usual.


Author(s):  
Josje D. Schoufour ◽  
Alyt Oppewal ◽  
Hanne J.K. van der Maarl ◽  
Heidi Hermans ◽  
Heleen M. Evenhuis ◽  
...  

Abstract We studied the association between multimorbidity, polypharmacy, and mortality in 1,050 older adults (50+) with intellectual disability (ID). Multimorbidity (presence of ≥ 4 chronic health conditions) and polypharmacy (presence ≥ 5 chronic medication prescriptions) were collected at baseline. Multimorbidity included a wide range of disorders, including hearing impairment, thyroid dysfunction, autism, and cancer. Mortality data were collected during a 5-year follow-up period. Cox proportional hazards models were used to determine the independent association between multimorbidity and polypharmacy with survival. Models were adjusted for age, sex, level of ID, and the presence of Down syndrome. We observed that people classified as having multimorbidity or polypharmacy at baseline were 2.60 (95% CI = 1.86–3.66) and 2.32 (95% CI = 1.70–3.16) times more likely to decease during the follow-up period, respectively, independent of age, sex, level of ID, and the presence of Down syndrome. Although slightly attenuated, we found similar hazard ratios if the model for multimorbidity was adjusted for polypharmacy and vice versa. We showed for the first time that multimorbidity and polypharmacy are strong predictors for mortality in people with ID. Awareness and screening of these conditions is important to start existing treatments as soon as possible. Future research is required to develop interventions for older people with ID, aiming to reduce the incidence of polypharmacy and multimorbidity.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Wilkinson ◽  
O Todd ◽  
M Yadegarfar ◽  
A Clegg ◽  
C P Gale ◽  
...  

Abstract Background The prevalence of atrial fibrillation (AF) in older people is increasing, as is frailty. Frailty describes an increased vulnerability to adverse outcomes, whereby the balance of risk and benefit associated with an intervention may be more nuanced. However, there are limited data from a community setting on the prevalence of AF and frailty in older people. It is important to understand the burden of AF and frailty, and the associated impact on mortality and stroke disease in order to inform shared decision making with patients, and also inform guidelines for this increasing group of older people. Purpose To estimate the prevalence of AF and the burden of frailty in patients with AF, in a large primary care dataset. To report stroke and mortality by frailty group. Methods We used electronic health records of 537,051 patients in England aged 65 years or older on 31/12/2015, with follow-up for all-cause mortality and ischaemic or unclassified stroke to 11/04/2017. Patients with a history of AF were identified using Clinical Terms Version 3 (CTV-3) codes. Frailty was identified up to the point of study entry using the electronic frailty index (eFI, the proportion of deficits out of 36 possible deficits), and categorised into robust (0–0.12), mild (>0.12–0.24), moderate (>0.24–0.36) or severe (>0.36) frailty. Median CHA2DS2-VASc and ATRIA scores for patients with frailty were compared with the robust group using Mann-Whitney. The association between frailty status, all-cause mortality and stroke was calculated using Cox proportional hazards models, adjusted for age and sex. Results Of the cohort, 61,177 patients (11.4%) had AF. Of those with AF, 27,987 (45.8%) were female, and 54,734 (89.5%) had frailty. 6,443 (10.5%) were classified as robust; 20,352 (33.3%) mildly frail; 20,315 (33.2%) moderately frail; and 14,067 (23.0%) severely frail. The median number of eFI-defined deficits among patients with AF was 9 (interquartile range [IQR] 6–12). Median stroke and bleeding scores were higher in those with frailty compared with the robust group (CHA2DS2-VASc 4 [IQR 3–5] v 2 [2–3], p≤0.001; ATRIA 4 [2–6] v 1 [0–2], p≤0.001). During 73,338 patient-years of follow-up, there were 6,805 (11.1%) deaths and 945 (1.54%) strokes. Compared with the robust group, all-cause mortality and stroke were higher with increasing frailty. Mortality: mild frailty hazard ratio 1.53 (95% confidence interval 1.29–1.80); moderate frailty 2.50 (2.13–2.94); severe frailty 4.26 (3.63–5.01). Stroke: mild frailty 1.36 (0.99–1.85); moderate frailty 1.67 (1.23–2.28); severe 1.99 (1.45–2.73). Kaplan-Meier survival curves by frailty Conclusion The prevalence of AF among those aged over 65 years in primary care in England is high, the majority of whom are frail. Increasing severity of frailty was associated with higher mortality and stroke rates. The extent to which the judicious use of oral anticoagulation may improve clinical outcomes for patients with AF and frailty is currently unknown. Acknowledgement/Funding CPG: Bayer, BMS, AstraZeneca, Novartis Vifor Pharma, Menerini


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1-1
Author(s):  
Roberto Machado ◽  
Martin Steinberg ◽  
Duane Bonds ◽  
Samir Ballas ◽  
William Blackwelder ◽  
...  

Abstract Pulmonary hypertension [PH-tricuspid regurgitant jet velocity (TRV) ≥2.5 m/s] is a common complication of sickle cell disease associated with high mortality. Identification of biomarkers of PH and mortality could facilitate screening and risk stratification in this population. Validated biomarkers would provide methods for retrospective evaluation of the prevalence and prognosis of PH in large historical cohorts of patients such as the Multicenter Study of Hydroxyurea in Sickle Cell Anemia(MSH). Because brain natriuretic peptide(BNP) is released from the ventricles during pressure strain, we hypothesized that BNP levels would correlate with the severity of PH and prospective risk of death in patients with SCD. BNP was measured in 45 African-American control subjects and 230 patients with SCD. Median (interquartile range) BNP(pg/ml) was higher in patients with PH than patients without PH or controls[+PH: 206(81–701),-PH: 47(26–104), C: 29, P&lt;0.001]. BNP levels directly correlated with age (R=0.32, P&lt;0.001), creatinine (R=0.22, P&lt;0.001), LDH(R=0.31, P&lt;0.001), TRV (R=0.5, P&lt;0.001), pulmonary vascular resistance (R=0.5, P=0.001); and inversely with hemoglobin(R=0.41, P&lt;0.001), cardiac output(R=0.47, P= 0.003) and 6-minute walk distance(R=0.51, P=0.001). The area under the ROC for BNP and the diagnosis of pulmonary hypertension was 0.84 (P&lt;0.001). A cutoff value of 160 pg/ml (corresponding to the 75th percentile for the population) had 58% sensitivity and 98% specificity for the diagnosis of PH. Cox proportional hazards regression identified BNP as an independent predictor of mortality(RR 2.17,95% CI 1.2–3.8, P =0.001) with clear mortality break point at the 75th percentile(160 pg/ml). To independently explore the prevalence and associated risk of PH in patients with sickle cell disease, a BNP value of 160 pg/ml was used as an indicator of PH. BNP levels were then measured in plasma samples collected in 121 patients who were enrolled in the MSH patient’s follow-up study that started in 1996. These patients had received hydroxyurea or placebo for two years, had moderately severe disease based on study entry criteria, and had 9-years of comprehensive follow-up. An abnormal BNP level ≥160 pg/ml was present in 30% of patients in the MSH cohort. BNP levels correlated directly with age(R=0.35, P&lt;0.001) and creatinine (R=0.24, P&lt;0.001), and inversely with hemoglobin(R=−0.54, P&lt;0.001). There was no correlation between BNP and rate of painful episodes or acute chest syndrome, use of hydroxyurea or leukocyte count. A high BNP level in the MSH cohort was associated with mortality by logistic regression(OR 3.04,95% CI 1.2–7.6, P = 0.018) and Cox proportional hazards regression analysis(RR 2.87, P=0.017). The relationship remained significant for continuous log- transformed BNP values and after adjustment for other covariates. These studies confirm that PH is common, mechanistically linked to hemolytic anemia and the major risk factor for death in SCD. Provocatively, the MSH analysis suggests that rates of pain episodes in this small sample of seriously ill patients were unrelated to risk of death: this risk was largely determined by a high BNP level, which is probably explained by undiagnosed hemolysis-associated PH.


2017 ◽  
Vol 46 (4) ◽  
pp. 276-284 ◽  
Author(s):  
Pierre-Jean Saulnier ◽  
Brad P. Dieter ◽  
Stephanie K. Tanamas ◽  
Sterling M. McPherson ◽  
Kevin M. Wheelock ◽  
...  

Background: Serum amyloid A (SAA) induces inflammation and apoptosis in kidney cells and is found to be causing the pathologic changes that are associated with diabetic kidney disease (DKD). Higher serum SAA concentrations were previously associated with increased risk of end-stage renal disease (ESRD) and death in persons with type 2 diabetes and advanced DKD. We explored the prognostic value of SAA in American Indians with type 2 diabetes without DKD or with early DKD. Methods: SAA concentration was measured in serum samples obtained at the start of follow-up. Multivariate proportional hazards models were employed to examine the magnitude of the risk of ESRD or death across tertiles of SAA concentration after adjustment for traditional risk factors. The C statistic was used to assess the additional predictive value of SAA relative to traditional risk factors. Results: Of 256 participants (mean ± SD glomerular filtration rate [iothalamate] = 148 ± 45 mL/min, and median [interquartile range] urine albumin/creatinine = 39 [14-221] mg/g), 76 developed ESRD and 125 died during a median follow-up period of 15.2 and 15.7 years, respectively. After multivariable proportional hazards regression, participants in the 2 highest SAA tertiles together exhibited a 53% lower risk of ESRD (hazard ratio [HR] 0.47, 95% CI 0.29-0.78), and a 30% lower risk of death (HR 0.70, 95% CI 0.48-1.02), compared with participants in the lowest SAA tertile, although the lower risk of death was not statistically significant. Addition of SAA to the ESRD model increased the C statistic from 0.814 to 0.815 (p = 0.005). Conclusions: Higher circulating SAA concentration is associated with a reduced risk of ESRD in American Indians with type 2 diabetes.


Author(s):  
Claire R. Palmer ◽  
Jamie W. Bellinge ◽  
Frederik Dalgaard ◽  
Marc Sim ◽  
Kevin Murray ◽  
...  

AbstractReported associations between vitamin K1 and both all-cause and cause-specific mortality are conflicting. The 56,048 participants from the Danish Diet, Cancer, and Health prospective cohort study, with a median [IQR] age of 56 [52–60] years at entry and of whom 47.6% male, were followed for 23 years, with 14,083 reported deaths. Of these, 5015 deaths were CVD-related, and 6342 deaths were cancer-related. Intake of vitamin K1 (phylloquinone) was estimated from a food-frequency questionnaire (FFQ), and its relationship with mortality outcomes was investigated using Cox proportional hazards models. A moderate to high (87–192 µg/d) intake of vitamin K1 was associated with a lower risk of all-cause [HR (95%CI) for quintile 5 vs quintile 1: 0.76 (0.72, 0.79)], cardiovascular disease (CVD)-related [quintile 5 vs quintile 1: 0.72 (0.66, 0.79)], and cancer-related mortality [quintile 5 vs quintile 1: 0.80 (0.75, 0.86)], after adjusting for demographic and lifestyle confounders. The association between vitamin K1 intake and cardiovascular disease-related mortality was present in all subpopulations (categorised according to sex, smoking status, diabetes status, and hypertension status), while the association with cancer-related mortality was only present in current/former smokers (p for interaction = 0.002). These findings suggest that promoting adequate intakes of foods rich in vitamin K1 may help to reduce all-cause, CVD-related, and cancer-related mortality at the population level.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5068-5068
Author(s):  
Neeraj Agarwal ◽  
Simon Chowdhury ◽  
Anders Bjartell ◽  
Byung Ha Chung ◽  
Andrea Juliana Pereira de Santana Gomes ◽  
...  

5068 Background: The phase 3 TITAN study evaluated APA vs PBO in pts with mCSPC receiving ADT. At primary analysis with 22.7 mo median follow-up, APA significantly improved overall survival (OS) and radiographic progression-free survival vs PBO (Chi NEJM 2019) while preserving HRQoL (Agarwal Lancet Oncol 2019). The study was unblinded; pts on PBO were allowed to cross over to APA. At final analysis with 44 mo median follow-up, APA significantly improved OS vs PBO, reducing risk of death by 35% despite crossover (Chi ASCO GU 2021). We evaluated HRQoL and treatment bother at final analysis. Methods: mCSPC pts (N = 1052) were randomized 1:1 to APA (240 mg QD; n = 525) or PBO (n = 527). All pts received ADT. Patient-reported outcomes were assessed using Brief Pain Inventory-Short Form (BPI-SF) and Functional Assessment of Cancer Therapy-Prostate (FACT-P). BPI was completed for 7d consecutively (Days -6 to 1 of each 28-d cycle [C]) through end of treatment (EOT). FACT-P was completed at baseline (BL), C2-C7, then every other C through EOT. Mean scores were reported by treatment group and over time. Time to deterioration on BPI and FACT-P scores was calculated by Kaplan-Meier methods and compared between groups by fitting proportional hazards regression models. Results: Of eligible pts per C, > 62% completed BPI through C32 and > 50% completed FACT-P through C31. Pts were relatively asymptomatic with good BL HRQoL: on 0-10 worst pain severity scale (BPI), median scores were 1.1 (APA) and 1.0 (PBO); on 0-156 HRQoL scale (FACT-P total; higher score = better HRQoL), median scores were 113.0 (APA) and 113.3 (PBO). Low BL BPI scores remained stable over time in both groups. On average, favorable BL FACT-P scores did not notably worsen over time in APA or PBO groups. There were no significant differences between groups in median time to deterioration in any BPI or FACT-P scores (Table). At each C at least 86% (APA) and 85% (PBO) of pts were either “not at all” or “a little bit” bothered by side effects. At BL, 76% (APA) and 72% (PBO) had favorable energy levels (reporting lack of energy “not at all” or “a little bit”). Energy levels remained stable or improved at each C for > 78% (APA) and > 71% (PBO) of pts. Conclusions: In the final analysis of TITAN, survival benefit with addition of APA to ADT was achieved without significant patient-reported side effect burden or reduced HRQoL compared with PBO in pts with mCSPC. Clinical trial information: NCT02489318. [Table: see text]


Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Sheila M McNallan ◽  
Yariv Gerber ◽  
Susan A Weston ◽  
Jill Killian ◽  
Shannon M Dunlay ◽  
...  

Background: Contemporary data on survival after incident acute coronary syndrome (ACS), including both myocardial infarction (MI) and unstable angina (UA), are limited. Objective: To describe survival after incident ACS, to determine if it differs by ACS type (MI or UA) and to determine whether it has improved over time. Methods: Olmsted County, MN residents hospitalized between 1/1/2005-12/31/2010 were screened for incident ACS. ACS was defined as either MI validated by standard epidemiological criteria or UA validated by the Braunwald classification. Patients were followed for death from any cause. Cox proportional hazards regression was used to determine whether survival differed by ACS type, while adjusting for year of diagnosis, age, sex and comorbidities. Results: Among 1,160 incident ACS cases (mean±SD age 66.9±14.8, 60% male), 35% were UA and 65% were MI. After a mean (SD) follow up of 3.7 (2.1) years, 274 deaths occurred. The 3-year Kaplan-Meier survival estimate for MI was 79.6% (95% CI: 76.7%-82.6%) and for UA was 84.9% (95% CI: 81.3%-88.6%) (log-rank p=0.011). The association of ACS type with survival differed by age (p=0.056). After adjustment for year of diagnosis, sex and comorbidities, no difference in survival was observed between ACS types among those aged <60 (HR for MI vs. UA: 0.64, 95% 0.29-1.42). By contrast, among patients aged 60-79, those with an MI had 2 times the risk of death compared to those with UA (HR: 2.04, 95% CI: 1.24-3.37). Patients aged 80 or older who had an MI had a 40% increased risk of death compared to patients of the same age who had UA (HR: 1.42, 95% CI: 1.02-1.98). There was no difference in survival over time (HR for 2010 vs. 2005: 0.91, 95% CI: 0.61-1.36). Conclusions: Survival did not differ between UA and MI patients younger than 60, however among patients 60 or older, survival was worse among those with an MI. Survival after ACS did not change over the study period.


2020 ◽  
Author(s):  
Kai Cao ◽  
Bingsong Wang ◽  
David S. Friedman ◽  
Jie Hao ◽  
Ye Zhang ◽  
...  

Purpose: To explore the association between diabetic retinopathy (DR) and the risk of six-year death, as well as the association between visual impairment (VI) and the risk of six-year death, in a rural Chinese population of age≥30 years. Methods: This was a population-based cohort study. In 2006-2007, 6,830 subjects aged ≥30 years were recruited from 13 villages in northern China through clustered randomization. In 2012-2013, a six-year follow-up was further done. Six different proportional hazards models, with different confounders adjusted, were used to explore the association between baseline DR and risk of death. Results: 5,570 subjects were included in this study by our inclusion and exclusion criteria. 410 (7.36%) subjects died by follow-up. The median ages of the dead subjects and survived subjects were 67 (interquartile range, IQR: 58-72) years and 52 (IQR: 42-58) years (Z=21.979, p<0.001). Male accounted for 62.20% and 44.92% among the dead and survived subjects (p<0.001). Besides, compared with those survived, the dead were found to be with lower education (p<0.001), lower marriage rate (p<0.001), lower income (p<0.001), higher proportion of smoking (p=0.003), higher systolic blood pressure (Z=10.411, p<0.001), lower body mass index (Z=-3.302, p=0.001), larger spherical equivalent error (Z=4.248, p<0.001), lower intraocular pressure (Z=-4.912, p<0.001), smaller anterior chamber depth (Z=-9.186, p<0.001), larger length thickness (Z=11.069, p<0.001), higher fast blood glucose level (Z=5.650, p<0.001), higher total cholesterols (Z=2.015, p=0.044), higher low-density lipoprotein (Z=2.024, p=0.043), higher proportion of drug usage (p<0.001). Besides, the dead subjects were more likely to be with VI, glaucoma, cataract, age-related macular degeneration, diabetes and DR. 148 subjects were diagnosed with DR at baseline, 33 (22.30%) of them were dead before follow-up. By adjusting all relative confounders in a proportional hazards model, DR was found to be a risk factor of six-year death, the hazard ratio (HR) was 1.739 (95% confidence intervals: 1.080, 2.803). Another five different statistical models with different confounders adjusted also revealed a statistically significant association between DR and six-year death. The association between VI and six-year death was not statistically significant. Conclusions: DR increased the risk of six-year death in a rural Chinese population aged ≥30 years, while VI not.  


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