Highest Quintile Research Articles

Socioeconomic deprivation and 1 year clinical outcomes after cryablation for atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND Socioeconomic deprivation has previously been demonstrated to result in worse heart failure and myocardial infarction outcomes. Published studies shown lower socioeconomic group to associate with higher prevalence of atrial fibrillation (AF), increased mortality and morbidity. However, the impact of socioeconomic deprivation on clinical outcomes post AF cryoablation has yet to be investigated. AIM To assess the impact of socioeconomic deprivation (as categorised by Scottish Index of Multiple Deprivation, SIMD) on the medical management and clinical outcomes of patients with AF treated by cryoablation. METHODS A retrospective study of paroxysmal or persistent AF patients after cryoablation. The parameters included basic demographics, weight, past medical history (inclusive of hypertension, heart failure, diabetes, stroke or transient ischaemic attacks, prior myocardial infarction, obstructive sleep apnoea) and alcohol misuse. Medical treatment post AF ablation (Beta blocker, non-dihydropyridine calcium channel blocker, flecainide, amiodarone, dronaderone, sotolol, anticoagulant use) were also recorded. Individual’s socioeconomic deprivation index, as described SIMD was also recorded (1 – most deprived and 10 – least deprived), and accordingly placed into quintile (SIMD 1-2,3-4,5-6,7-8, 9-10). Follow-up for 12 months. Clinical outcome assessed was rate of readmission for symptomatic documented AF, rate of heart failure admission, stroke, bleeding diathesis and all-cause mortality. RESULTS 312 patients were identified: 65 from the lowest quintile (SIMD 1-2), 57 from SIMD 3-4, 54 from SIMD 5-6, 52 from SIMD 7-8, and 84 from the highest quintile (SIMD 9-10). No statistical difference exists between age, gender or weight. Lowest socioeconomic quintile has higher incidence of heart failure (p =0.018) but other past medical history was no different. No difference in incidence of alcohol misuse. Prescription rate/rhythm control agents and anticoagulant use post ablation was not statistically different between all groups. 12 months follow-up demonstrated readmission for symptomatic documented AF was statistically higher among patients of lowest socioeconomic quintile (Keplan Meier plot, p = 0.001). Stepwise multiple regression analysis also confirmed multiple socioeconomic deprivation as an independent predictor for more adverse clinical outcome (p = 0.02). Risk of readmission for AF in patients from the wealthiest socioeconomic group is almost a quarter as compared to those of most deprived social group (Odd-ratio 0.273 (95% CI 0.122 – 0.607)). Other clinical outcomes including risk of admissions for heart failure, stroke, bleeding diathesis and all-cause mortality was not statistically different across all groups. Summary After cryoablation for AF, patients from the lower socioeconomic group are still more likely to experience readmission for symptomatic AF at 12-month, despite similar post-procedure pharmaceutical agents utilised.

Association Between First-Line Immune Checkpoint Inhibition and Survival for Medicare-Insured Patients With Advanced Non–Small Cell Lung Cancer

Immunotherapy is now a cornerstone of treatment for advanced non-small cell lung cancer (NSCLC), but its uptake and effectiveness among older patients outside clinical trials remain poorly understood. To understand treatment patterns and evaluate the overall survival associated with checkpoint inhibitor immunotherapy, cytotoxic chemotherapy, and combined chemoimmunotherapy for older patients who have advanced NSCLC and Medicare coverage. This retrospective cohort study included Medicare-insured patients in the US aged 66 to 89 years who initiated first palliative-intent systemic therapy for lung cancer between January 1, 2016, and December 31, 2018. Survival follow-up continued through March 31, 2020. A total of 19 529 patients who had advanced lung cancer and were insured by a Medicare fee-for-service plan were included in the analysis. Regimens included pembrolizumab monotherapy (n = 3079), combined platinum-based drug (ie, cisplatin or carboplatin [hereinafter, platinum]) and pemetrexed disodium (n = 5159), combined platinum and a taxane (ie, paclitaxel, nab-paclitaxel, or docetaxel) (n = 9866), and combined platinum, pemetrexed, and pembrolizumab (n = 1425), as ascertained using Medicare claims from the Centers for Medicare & Medicaid Services. The primary outcome was overall survival, which was measured using the restricted mean survival time (RMST) with propensity score adjustment for clinical and sociodemographic characteristics. Median survival was also reported for comparison with outcomes from registrational trials. A total of 19 529 patients (54% male, 46% female; median age, 73.8 [interquartile range, 69.9-78.4] years) were identified for analysis. The uptake of pembrolizumab-containing regimens in the Medicare population was rapid, increasing from 0.7% of first-line treatments in the second quarter of 2016 to 42.4% in the third quarter of 2018. Patients who were older (≥70 years, 2484 [81%]), were female (1577 [51%]), and/or had higher Risk Stratification Index scores (highest quintile, 922 [30%]) were more likely to receive single-agent pembrolizumab than chemotherapy. After propensity score adjustment, pembrolizumab was associated with survival similar to platinum/pemetrexed (RMST difference, -0.2 [95% CI, -0.5 to 0.2] months) or platinum/taxane (RMST difference, -0.7 [95% CI, -1.0 to -0.4] months). Patients receiving platinum/pemetrexed/pembrolizumab chemoimmunotherapy also had adjusted survival similar to those receiving platinum/pemetrexed chemotherapy (RMST difference, 0.5 [95% CI, 0.1-0.9] months). The unadjusted median survival was 11.4 (95% CI, 10.5-12.3) months among patients receiving single-agent pembrolizumab, approximately 15 months shorter than observed among pembrolizumab-treated participants in the KEYNOTE-024 trial. The unadjusted median survival was 12.9 (95% CI, 11.8-14.0) months among patients receiving platinum/pemetrexed/pembrolizumab chemoimmunotherapy, approximately 10 months shorter than observed among platinum/pemetrexed/pembrolizumab-treated participants in the KEYNOTE-189 trial. Immunotherapy has been incorporated rapidly into treatment for patients with advanced NSCLC. However, survival estimates in the Medicare population are much shorter than those reported in registrational trials. These results provide contemporary estimates of survival for older patients with advanced NSCLC treated in routine practice, facilitating patient-centered decision-making.

The Global, Regional, and National Burden and Trends of Breast Cancer From 1990 to 2019: Results From the Global Burden of Disease Study 2019

BackgroundThe burden of breast cancer has been increasing globally. The epidemiology burden and trends need to be updated. This study aimed to update the burden and trends of breast cancer incidences, deaths, and disability-adjusted life-years (DALYs) from 1990 to 2019, using the Global Burden of Disease 2019 study.MethodsThe data of incidences, deaths, DALYs, and age-standardized rates were extracted. Estimated annual percentage changes were used to quantify the trends of age-standardized rates. Besides, the population attributable fractions of the risk factors of breast cancer were also estimated.ResultsGlobally, the incidences of breast cancer increased to 2,002,354 in 2019. High social-development index (SDI) quintiles had the highest incidence cases with a declining trend in age-standardized incidence rate. In 2019, the global deaths and DALYs of breast cancer increased to 700,660 and 20,625,313, respectively. From 1990 to 2019, the age-standardized mortality rates and age-standardized DALY rates declined globally, especially in high and high-middle SDI quintiles. Besides, the trends varied from different regions and countries. The proportion of the patients in the 70+ years age group increased globally. Deaths of breast cancer attributable to high fasting plasma glucose and high body mass index increased globally, and high fasting plasma glucose was the greatest contributor to the global breast cancer deaths.ConclusionThe burden of breast cancer in higher SDI quintiles had gone down while the burden was still on the rise in lower SDI quintiles. It is necessary to appeal to the public to decrease the exposure of the risk factors.

Influence of dietary insulin scores on survival in patients with metastatic colorectal cancer (mCRC): Findings from CALGB (Alliance) 80405.

3568 Background: Diets inducing an elevated insulin response have been associated with increased recurrence and mortality in patients with non-metastatic colorectal cancer, but it remains unknown if postprandial hyperinsulinemia also affects progression and mortality in mCRC patients. The goal of this study was to assess the influence of dietary insulin load (DIL) and dietary insulin index (DII) on survival of mCRC patients. Methods: This was a prospective cohort study of 1,177 patients with previously untreated mCRC enrolled in a phase III trial of systemic chemotherapy plus biologics who reported dietary intake within one month after chemotherapy initiation. DIL was calculated as a function of food insulin index and the energy content of individual foods reported on a food frequency questionnaire. DII was calculated by dividing DIL by total energy intake. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS) and treatment-related adverse events (TRAEs). The primary statistical test was a test for trend, which was performed using the median value for each quintile of dietary insulin score as a continuous variable. Cox proportional hazards regression was used to adjust for potential confounders including assigned treatment arm, known prognostic factors, comorbidities, body mass index, and physical activity. Results: Higher DIL was significantly associated with worse OS (ptrend = 0.04); patients in the highest quintile survived 34.1 months, compared to 27.7 months in the lowest quintile (Cox hazard ratio [HR] 1.22, 95% confidence interval [CI] 0.99 - 1.51). Higher DII was non-significantly associated with worse OS (HR 1.18, 95% CI 0.94 - 1.48, ptrend = 0.09). There was no significant association between dietary insulin scores and PFS. The influence of dietary insulin scores on survival did not differ significantly by various molecular markers involved in the insulin signaling pathway, including C-peptide, adiponectin, IGF-1, IGFBP-3, and IGFBP-7. Higher dietary insulin scores were significantly associated with greater risk of any TRAE. Those with a DIL greater than the median had a 75.4% rate of any TRAE, compared to 70.8% in those with a DIL less than or equal to the median (HR 1.19, 95% CI 1.03 - 1.38, p=0.02); the most significant associations were with neutropenia (HR 1.30, 95% CI 1.05 - 1.61, p=0.01) and diarrhea (HR 1.43, 95% CI 1.00 - 2.06, p=0.05). Conclusions: Higher DIL was significantly associated with worse OS, and both higher DIL and DII were significantly associated with increased TRAEs, in patients with previously untreated mCRC. These findings may inform future dietary recommendations for patients with mCRC. Further investigation into the molecular mechanisms underlying these associations is warranted. Clinical trial information: NCT00265850.

Associations of Osteocalcin Forms With Metabolic Syndrome and Its Individual Components in Older Men: The Health In Men Study.

The osteoblast-derived polypeptide, osteocalcin (OC), has been associated with lower risk of type 2 diabetes and metabolic syndrome (MetS) in several epidemiological studies. Animal studies have indicated the undercarboxylated form of OC (ucOC) drives its association with metabolic outcomes. We compared associations of ucOC and carboxylated OC (cOC) with MetS and its components in older men. A cross-sectional analysis of 2575 men aged ≥70 years and older resident in Perth, Western Australia. ucOC was assayed using a hydroxyapatite-binding method, and cOC calculated by subtracting ucOC from total OC. Main outcome measures were MetS and its components. Both lower serum ucOC and cOC levels, and the proportion of cOC (%cOC) were associated with less favorable metabolic parameters (higher waist circumference, triglyceride, glucose, blood pressure, and lower high-density lipoprotein cholesterol), whereas inverse associations were found with %ucOC. Men in the lowest quintile of ucOC had higher risk of MetS compared to men in the highest quintile (Q1 ≤ 7.7 vs Q5 > 13.8 ng/mL; OR = 2.4; 95% CI, 1.8-3.2). Men in the lowest quintile of cOC had higher risk of MetS compared to those in the highest quintile (≤ 5.8 vs > 13.0 ng/mL; OR = 2.4; 95% CI, 1.8-3.2). Lower concentrations of serum ucOC or cOC were associated with less favorable metabolic parameters and a higher risk of MetS. In contrast, a lower proportion of ucOC was associated with better metabolic parameters and lower MetS risk. Further research is warranted to determine whether ucOC and cOC are suitable biomarkers for cardiometabolic risk in men.

Impact of perceived stress into mortality among the elderly population

Abstract Funding Acknowledgements Type of funding sources: None. Introduction. According to the results of the recent studies, high levels of perceived stress were the potent risk factors for all-cause and cardiovascular mortality among the middle-aged population. However, there were few studies on the impact of this factor to mortality among the older males and females. Purpose. To investigate the association between perceived stress and all-cause and CVD mortality among the population of 75 years and older. Methods. This study was a part of the prospective cohort survey "Stress, aging and health." Data of 455 adults 75 years and older (287 males and 168 females) was used. We evaluated perceived stress Cohen"s Stress Scale. All items were scored on a 5-point scale, high scores indicated high levels of stress. Perceived Stress Scale sum scores were categorized into quintiles; we considered scores in the highest quintile (>19) as abnormal. The mean follow-up was 12 years, 292 deaths occurred, including 200 from cardiovascular diseases (CVD). Association between perceived stress and all-cause and CVD mortality was evaluated by Cox regression model after adjustment for age. Results. High levels of stress were significantly associated with all-cause and CVD mortality among elderly males (HR = 1,48 95% CI: 1,09-1,99; p = 0,01; HR = 1,65; 95% CI: 1,15-2,36; p = 0,007) after adjusting for age. At the same time, among females aged 75 years and older no significant associations of perceived stress scale high scores with all-cause and CVD mortality were found (HR = 1,28; 95% CI: 0,84-1,96; p = 0,25; HR = 1,19; 95% CI: 0,73-1,95; p = 0,48). Conclusions. Perceived stress contributed significantly to higher mortality rates among males aged 75 years and older. While among females of the same age, no significant associations between high stress levels and all-cause and CVD mortality were found.

The association of energy and macronutrient intake at dinner vs breakfast with the incidence of type 2 diabetes mellitus in a cohort study: The China Health and Nutrition Survey, 1997-2011.

This study aims to investigate the association of energy and macronutrient intake at dinner vs breakfast with the incidence of type 2 diabetes mellitus (T2DM). A total of 11 153 adults, including 811 with T2DM, completed a questionnaire about energy and macronutrient intake in the China Health and Nutrition Survey (1997-2011). The differences (Δ) in energy and macronutrient intake between dinner and breakfast (Δ=dinner- breakfast) were categorized into quintiles. Cox proportional hazards regression models were performed to explore the association between Δ and the risk of T2DM and to investigate the change of the risk when 5% total energy or energy provided by macronutrients at dinner was substituted with total energy or energy provided by macronutrients at breakfast by isocaloric substitution models. After adjustment for potential confounders, compared with participants in the lowest quintile, participants in the highest quintile were more likely to develop T2DM (hazard ratio [HR]Δenergy 1.46, 95% CI 1.13-1.87; HRΔfat 1.85, 95% CI 1.43-2.41; HRΔprotein 1.37, 95% CI 1.06-1.78). Isocalorically replacing 5% energy at dinner with energy at breakfast was associated with a 7% lower T2DM risk. Replacing 5% energy provided by fat at dinner with energy provided by carbohydrate, protein, and fat at breakfast was associated with a 9%, 5%, and 7% lower T2DM risk, respectively. Replacing 5% energy provided by protein at dinner with energy provided by carbohydrate or protein at breakfast was associated with a 5% lower T2DM risk. Higher intake of energy, protein, and fat at dinner than at breakfast increased the risk of T2DM.

High adherence to recommended diabetes follow-up procedures by general practitioners is associated with lower estimated cardiovascular risk.

To explore whether the general practitioners' (GPs') performance of recommended processes of care was associated with estimated risk of cardiovascular disease (CVD) and poor glycaemic control in patients with type 2 diabetes. A cross-sectional study from Norwegian general practice including 6015 people with type 2 diabetes <75years old, without CVD and their 275 GPs. The GPs were split into quintiles based on each GP's average performance of six recommended processes of care. The quintiles were the exposure variable in multilevel regression models with 10-year risk of cardiovascular events estimated by NORRISK 2 (total and modifiable fraction) and poor glycaemic control (HbA1c >69mmol/mol (>8.5%)) as outcome variables. The mean total and modifiable estimated 10-year CVD risk was 12.3% and 3.3%, respectively. Compared with patients of GPs in the highest-performing quintile, patients treated by GPs in the lowest quintile had an adjusted total and modifiable CVD risk that was 1.88 (95% CI 1.17-2.60) and 1.78 (1.14-2.41) percent point higher. This represents a relative mean difference of 16.6% higher total and 74.8% higher modifiable risk among patients of GPs in the lowest compared with the highest quintile. For patients with GPs in the lowest-performing quintile, the adjusted odds of poor glycaemic control was 1.77 (1.27-2.46) times higher than that for patients with a GP in the highest quintile. We found a pattern of lower CVD risk and better glycaemic control in patients of GPs performing more recommended diabetes processes of care.

A Longitudinal Case Study of Mathematics and Mathematical Literacy Achievement of Boys at a High Quintile School in South Africa

Little is known about longitudinal profiles of mathematics achievement spanning all phases of basic education of the same learners. This would be useful for identifying crucial points for intervention and informing learner subject choices. This research was aimed at establishing such a profile for boys attending a quintile 5 single gender school. Learners’ promotion marks across eight cohorts from Grades 1–12 were used to compare achievement trends for those who took mathematics (n = 302) or mathematical literacy (n = 160) to Grade 12. Additionally, we explored the effectiveness of mathematics marks from lower grades for predicting achievement in subsequent grades. Data were analysed fitting a Mixed Model for Repeated Measures and using regression analysis. Findings show consistently higher achievement by the mathematics set from Grade 1 to Grade 9. Relatively stable achievement was found in the primary grades up until Grade 6, where marks dropped noticeably but peaked in Grade 7, after which marks declined dramatically to Grade 9, particularly for the mathematical literacy set. After adoption of mathematical literacy, these learners’ marks improved noticeably to Grade 12 with more pronounced gains the lower the Grade 9 achievement. Those who opted for mathematics continued to achieve slightly lower marks than in Grade 9 throughout the further education and training phase, with their lowest marks attained in Grade 11. The moderate to strong correlations between most grades made it possible to predict subsequent marks based on marks achieved in earlier grades. Suggestions made from the observed trends could guide appropriate early intervention programmes and subject choice.

A cohort study on plasma uric acid levels and the risk of type 2 diabetes mellitus among the oldest old in longevity areas of China

Objective: To investigate the effect of plasma uric acid level on the incident risk of type 2 diabetes mellitus (T2DM) among the oldest old (those aged ≥80 years). Methods: Participants were recruited from the Healthy Aging and Biomarkers Cohort Study (HABCS), which conducted a baseline survey in 2008-2009 and follow-up of 3 times in 2011-2012, 2014, and 2017-2018, respectively. A total of 2 213 oldest old were enrolled in this study. The general demographic, socioeconomic, lifestyle and disease data of the oldest old were collected, and physical measurements were made for the oldest old. Fasting venous blood was collected for uric acid and blood glucose detection. Information on the incident and death of T2DM were collected through the follow-up. Cox proportional hazard regression model was used to explore the association of hyperuricemia and plasma uric acid level with the incidence of T2DM. Restricted cubic spline (RCS) function was used to explore the dose-response relationship of plasma uric acid levels with the risk of T2DM. Results: The age of participants was (93.2±7.6) years old, and 66.7% of the participants (1 475) were female. The plasma uric acid level at baseline was (289.1±88.0)μmol/L, and the prevalence of hyperuricemia was 13.3% (294 cases). During 9 years of cumulative follow-up of 7 471 person-years (average of 3.38 years for each), 122 new cases of T2DM occurred and the incidence density was 1 632.98/105 person year. Cox proportional hazards regression analysis showed that per 10μmol/L increase in plasma uric acid level, the risk of T2DM increased by 1.1% [HR (95%CI): 1.011 (1.004, 1.017)]. Compared with the participants with the lowest quintile of plasma uric acid (Q1), the risk of diabetes increased by 20.7 % among the oldest old with uric acid in the highest quintile (Q5) [HR (95%CI):1.207 (1.029, 1.416)]. The risk of T2DM was 19.2% higher in the hyperuricemia group than that in the oldest old with normal plasma uric acid [HR (95%CI): 1.192 (1.033, 1.377)]. RCS function showed that the risk of T2DM increased with the increase in plasma uric acid levels in a nonlinear dose-response relationship (P=0.016). Conclusion: The incident risk of T2DM increases with the elevates of plasma uric acid levels in the oldest old.

P094 Incidence of clinically diagnosed Paget’s disease of bone: evidence of a continuing decline

Abstract Background/Aims Evidence from the UK suggest that the incidence of Paget's disease of bone declined during the latter half of the last century with a decline also in the incidence of clinically apparent disease. We aimed to characterise the recent incidence of clinically diagnosed Paget’s disease of bone in the UK by age and sex among those aged &amp;gt;18 years and, to determine whether the incidence has changed from 1999-2015. Methods Incident cases of Paget’s disease during 1999-2015 were identified from the first recorded diagnostic code for Paget’s disease in the UK Clinical Practice Research Datalink (CPRD) database. Crude incidence was calculated for each year from 1999 to 2015 and, to account for changes in the distribution of age and sex over time within the CPRD, direct age- and sex-standardised incidence rates were calculated for each year. This was done by multiplying the crude incidence in each age-sex stratum by the age-sex stratum weight of the 1999 population of those at risk of developing Paget’s disease. We looked also at the incidence of disease by quintile of index of multiple deprivation and geographic region. Using Poisson regression, we looked at the influence of deprivation and geography on occurrence of the disease after adjustment for age and sex. Results In total 3,592 incident cases of Paget’s disease were identified between 1999 and 2015. Overall the incidence increased with age and at all ages was greater in men than women. In men, and women, respectively, incidence increased from 0.074 and 0.037 per 10,000 per year at the age of 45-49 years to 6.3 and 3.7 per 10,000 per year at age of 85 years and older. When stratified by year, the age- and sex-standardised incidence fell from 0.75/10,000 person years in 1999 to 0.20/10,000 person years in 2015. Crude incidence (1999-2015) was slightly higher in those living in the most deprived areas (0.53/10,000 person years) compared to those in least deprived areas (0.43/10,000 person years). After adjustment for age and sex, compared to those in the highest quintile of index of multiple deprivation, those in the lowest quintile of index of multiple deprivation had over a 30% increased risk of disease. There was evidence also of geographic variation in the occurrence of disease with the highest incidence in the North West of England. Conclusion The incidence of clinically diagnosed Paget’s disease has continued to decrease since 1999. The reason for the decline remains unknown, though the rapidity of change points to an alteration in one or more environmental determinants. Disclosure M.J. Cook: None. S.R. Pye: None. W.G. Dixon: None. T.W. O'Neill: None.

Associations between dietary patterns and the incidence of total and fatal cardiovascular disease and all-cause mortality in 116,806 individuals from the UK Biobank: a prospective cohort study

BackgroundTraditionally, studies investigating diet and health associations have focused on single nutrients. However, key nutrients co-exist in many common foods, and studies focusing solely on individual nutrients may obscure their combined effects on cardiovascular disease (CVD) and all-cause mortality. We aimed to identify food-based dietary patterns which operate through excess energy intake and explain high variability in energy density, free sugars, saturated fat, and fiber intakes and to investigate their association with total and fatal CVD and all-cause mortality.MethodsDetailed dietary data was collected using a 24-h online dietary assessment on two or more occasions (n = 116,806). We used reduced rank regression to derive dietary patterns explaining the maximum variance. Multivariable Cox-proportional hazards models were used to investigate prospective associations with all-cause mortality and fatal and non-fatal CVD.ResultsOver an average of 4.9 years of follow-up, 4245 cases of total CVD, 838 cases of fatal CVD, and 3629 cases of all-cause mortality occurred. Two dietary patterns were retained that jointly explained 63% of variation in energy density, free sugars, saturated fat, and fiber intakes in total. The main dietary pattern was characterized by high intakes of chocolate and confectionery, butter and low-fiber bread, and low intakes of fresh fruit and vegetables. There was a positive linear association between the dietary pattern and total CVD [hazard ratio (HR) per z-score 1.07, 95% confidence interval (CI) 1.04–1.09; HRtotal CVD 1.40, 95% CI 1.31–1.50, and HRall-cause mortality 1.37, 95% CI 1.27–1.47 in highest quintile]. A second dietary pattern was characterized by a higher intakes of sugar-sweetened beverages, fruit juice, and table sugar/preserves. There was a non-linear association with total CVD risk and all-cause mortality, with increased risk in the highest quintile [HRtotal CVD 1.14, 95% CI 1.07–1.22; HRall-cause mortality 1.11, 95% CI 1.03–1.19].ConclusionsWe identified dietary patterns which are associated with increased risk of CVD and all-cause mortality. These results help identify specific foods and beverages which are major contributors to unhealthy dietary patterns and provide evidence to underpin food-based dietary advice to reduce health risks.

Utility of cardiovascular implantable electronic device–derived patient activity to predict clinical outcomes

The role of cardiovascular implantable electronic device (CIED)-derived activity to predict implantable cardioverter-defibrillator (ICD) therapy or death is not known. We aimed to assess CIED-derived activity to predict clinical outcomes. In 1500 patients enrolled in MADIT-RIT, CIED-derived patient activity was acquired daily, then averaged for the first 30 days following randomization to predict inappropriate/appropriate therapy or death. Kaplan-Meier analysis and Cox proportional regression models were used to evaluate inappropriate/appropriate therapy, heart failure, or death by 30-day CIED-derived patient activity quintiles. There were 1463 patients with CIED activity data (98%). Patients in the highest quintile (Q5) of activity (more active) had the highest rate of inappropriate therapy, 21% at 2 years, as compared to 7%-11% in the other 4 quintiles (P < .001), a 1.75 times higher risk (95% confidence interval [CI]: 1.23-2.50, P = .002). However, patients in the lowest quintile of activity (Q1, 1 hour/day) had the highest risk of mortality, 15% in 2 years, as compared to Q2-3 (1-2 hours/day, 8%-7% mortality), and Q4-5 (>2 hours/day, 2%-3% mortality) (P < .001). Patients with the lowest level of activity (Q1) had a 2.02 times higher risk of mortality (95% CI: 1.21-3.38, P = .007), and they had an 82% higher risk of heart failure hospitalization (95% CI: 1.28-2.57, P = .001). High CIED-derived 30-day median patient activity predicted inappropriate therapy, while low patient activity predicted mortality and heart failure in ICD and cardiac resynchronization therapy with defibrillator patients enrolled in MADIT-RIT. Device-derived activity assessment could serve as a useful predictor of outcomes.

Plasma Concentrations of Magnesium and Risk of Dementia: A General Population Study of 102 648 Individuals.

Low and high concentrations of plasma magnesium are associated with increased risk of future all-cause dementia; however, the underlying reasons remain elusive. The magnesium ion is an important electrolyte serving as a cofactor in many enzymatic processes in the human organism. Magnesium affects both neuronal and vascular functions. We investigated the associations of plasma concentrations of magnesium associate with common subtypes of dementia as Alzheimer dementia and non-Alzheimer dementia, and potential pathways by which magnesium may affect risk of dementia. Plasma concentrations of magnesium were measured in 102 648 individuals from the Copenhagen General Population Study. Cox regression and natural effects mediation analyses evaluated associations with either Alzheimer dementia or non-Alzheimer dementia. Multifactorially adjusted hazard ratios for non-Alzheimer dementia were 1.50(95% confidence interval (CI):1.21-1.87) for the lowest and 1.34(1.07-1.69) for the highest vs the fourth quintile (reference) of plasma magnesium concentrations. Diabetes, cumulated smoking, stroke, and systolic blood pressure mediated 10.4%(3.1-22.8%), 6.8%(1.2-14.0%), 1.3%(0.1-3.6%), and 1.0%(0.2-2.6%), respectively, in the lowest quintile, whereas stroke mediated 3.2%(0.4-11.9%) in the highest quintile. No associations were observed for Alzheimer dementia. Low and high plasma magnesium concentrations were associated with high risk of vascular-related non-Alzheimer dementia, with the lowest risk observed at a concentration of 2.07 mg/dL (0.85 mmol/L). No association was observed for Alzheimer dementia. Mediation analysis suggested that diabetes may be in the causal pathway between low plasma magnesium concentrations and high risk of non-Alzheimer dementia, while cumulated smoking, stroke, and systolic blood pressure played minor mediating roles.

Diet Quality and Cognitive Performance in Australian Adults Aged 55-85 Years: A Cross-Sectional Analysis of the Hunter Community Study Cohort.

There is a lack of evidence to determine if diet quality is associated with cognitive performance in older adults. Therefore, the aim of this study was to examine whether diet quality is associated with cognitive performance among older adults. A cross-sectional, secondary analysis of baseline data from the Hunter Community Study (HCS), comparing diet quality, measured using the Australian Recommended Food Score (ARFS), along with validated cognitive performance instruments the Audio Recorded Cognitive Screen (ARCS) and the Mini-Mental State Examination (MMSE) were undertaken in adults aged 55–85 years, living in Newcastle, NSW, Australia. Adjusted linear regression analyses showed that, compared with the lowest ARFS quintile, those in the highest quintile had an ARCS score 5.883 units greater (p < 0.001; R2 = 0.0098). Furthermore, when quintiles of ARFS score were tested against each ARCS sub-scale score, statistically significant associations were observed with the greatest effect for the Memory (β = 4.055; p = 0.001; R2 = 0.0065) and Attention (β = 4.136; p = 0.002; R2 = 0.0047) domains. No statistically significant associations were observed between quintiles of ARFS and MMSE score in the adjusted linear regression analyses. In conclusion, a positive association was observed between diet quality and cognitive performance within this sample of older Australian adults. Further investigation of the above association over time, when follow-up data becomes available, in longitudinal analysis is recommended.

Socioeconomic disadvantage and sleep in early childhood: Real-world data from a mobile health application

ObjectivesTo examine whether increased socioeconomic disadvantage, indexed using a measure of community distress, was associated with variation in caregiver-reported early childhood sleep patterns and problems in a large US sample using a mobile health application (app). DesignCross-sectional. SettingData were collected using the free, publicly available Johnson's Bedtime© baby sleep app. ParticipantsA total of 14,980 caregivers (85.1% mothers) of children ages 6-35.9 months (M = 13.88 months; 52.6% boys) participated in this study. MeasuresCaregivers reported on child sleep using the Brief Infant Sleep Questionnaire-Revised. Socioeconomic disadvantage was indexed by zip code using the Distressed Communities Index (DCI), which combines seven US census indicators of socioeconomic disadvantage. DCI scores range from prosperous (lowest quintile) to distressed (highest quintile). ResultsSocioeconomic disadvantage was significantly associated with later bedtimes, longer sleep onset latency, and shorter nighttime and 24-hour (total) sleep duration, with children living in distressed communities showing the poorest sleep. However, caregivers living in distressed communities reported a significantly lower prevalence of overall child sleep problems (43% vs 58% in prosperous communities), and more confidence in managing child sleep (42% vs 34% in prosperous communities). ConclusionsChildren living in the most distressed communities have the poorest reported sleep patterns and bedtime behaviors; however, their caregivers are less likely to report problematic child sleep. These findings highlight the need for community-level sleep health promotion interventions, as well as further investigation of caregiver perceptions about child sleep and sleep health promotion among families living in socioeconomically disadvantaged contexts.

Abstract 16: IV TPA in the 0-3 Hour Window: Quantitative Fragility-Robustness Assessment of the Strength of the RCT Evidence

Background: After 3 decades, the era of RCTs of IV tPA as a standalone therapy in acute ischemic stroke has now likely closed, with the completion of TESPI, PRISMS, and late, imaging-selection RCTs, and the advent of endovascular thrombectomy. Some non-expert contrarians questioned the accumulating evidence regarding tPA; the recently formulated fragility-robustness index (FRI) enables quantification of the actual rigor of evidence throughout the era of IV tPA investigation. Methods: The FRI summarizing the strength of the statistical evidence for clinical trial findings is the minimum nonevent to event changes needed to turn a statistically significant to non-significant result. The FRI was applied to disability-free (mRS 0-1) and independence (mRS 0-2) outcomes; cumulative meta-analyses delineated evidence strength after each successive RCT. FRI scores were classified: Not Robust (FRI 0-4), Somewhat Robust (5-12), Robust (13-33), and Highly Robust (&gt;33). Results: Systematic search identified 8 RCTs (1960 patients) of IV tPA in the 0-3h window from 1995 - 2018. Study-level meta-analyses showed FRIs of 42 for mRS 0-1 and 40 for mRS 0-2; individual patient data meta-analyses showed FRIs of 40 for both mRS 0-1 and mRS 0-2, placing IV tPA in the highest quintile of FRIs among meta-analyses for all conditions. Evolution of RCT evidence over time is shown in Table 1. Strength of evidence for IV tPA superiority was already robust with publication of the initial 2 NINDS-tPA in 1995, remained robust through 2011 after 4 additional RCTs, increased to highly robust with the IST-3 mega-trial in 2012, and remains highly robust today after 1 additional trial. Conclusions: Intravenous tPA for acute ischemic stroke in 0-3h patients is one of the most robustly proven therapies in medicine. This therapy was already robustly supported with publication of the initial trials 25 years ago and advanced 9 years ago after additional trials to highly robust/non-fragile.

Low Level of Serum Cadmium in Relation to Blood Pressures Among Japanese General Population.

Hypertension (HT) is an important risk factor for mortality and morbidity. Previous studies showed that cadmium (Cd) was associated with increased blood pressures and the prevalence of HT. This study hypothesized that Cd, regardless of its level, may increase blood pressures/HT. The objective of this study was to examine the associations between alow level of serum Cd concentration and blood pressures/HT among a general population in the Iwaki area, Japan. This was a cross-sectional study, conducted in the Aomori prefecture with 1144 volunteers aged over 19 years old, who were participants of the Iwaki health check-up in 2014. The study assessed questionnaire survey, body composition, and serum Cd concentrations. Median serum Cd concentration was 0.06 ng/mL (interquartile range 0.05-0.08 ng/mL) among our study population. Compared to the lowest quintile of serum Cd concentration group, the highest quintile of serum Cd concentration group had 4.9 mmHg higher systolic blood pressure (SBP) (95% confidence interval [CI] 1.53-8.31, p < 0.01) and 2.4 mmHg higher diastolic blood pressure (DBP) (95% CI 0.36-4.34, p < 0.05), compared to the lowest quintile group. Similarly, the highest quintile of serum Cd concentration group had 1.7 times higher prevalence of HT (95% CI 1.10-2.51, p < 0.05) than the lowest quintile group. This study identified that higher serum Cd concentration was significantly, positively, associated with SBP and DBP and HT prevalence. This study provided evidence for the associations between environmental exposure to Cd and blood pressures/HT which should be considered for future preventive measures.

The association of prediagnostic circulating levels of cardiometabolic markers, testosterone and sex hormone-binding globulin with risk of breast cancer among normal weight postmenopausal women in the UK Biobank.

Emerging evidence suggests that normal weight postmenopausal women with a relative excess of body fat are at increased breast cancer risk. However, little is known about the associations between obesity-related blood markers and risk of breast cancer among these individuals. In this prospective study comprising 58 629 normal weight postmenopausal women (body mass index between 18.5 kg/m2 and 24.9 kg/m2 ) who were enrolled in the UK Biobank cohort between 2006 and 2010, we examined the associations of glycated hemoglobin, triglycerides, high-density lipoprotein cholesterol, C-reactive protein (CRP), testosterone and sex hormone-binding globulin (SHBG) with risk of breast cancer. A total of 1268 postmenopausal breast cancer cases were ascertained during a median follow-up period of 7 years. Women with CRP, total testosterone and free testosterone (FT) levels in the highest quintile had increased risk of breast cancer compared to those in the lowest quintile (HRQ5 vs Q1 : 1.35, 95% confidence interval [CI]: 1.12-1.63, HR Q5 vs Q1 : 1.47, 95% CI: 1.20-1.80 and HR Q5 vs Q1 : 1.53, 95% CI: 1.23-1.90, respectively), whereas those with SHBG in the highest quintile had reduced risk (HR Q5 vs Q1 : 0.70, 95% CI: 0.56-0.88). These associations were attenuated but persisted after additional adjustment for BMI, fat mass index (whole body fat mass [kg]/height [m2 ]) or waist circumference and after mutual adjustment for testosterone, CRP and/or SHBG. Our study suggests that the risk of postmenopausal breast cancer among normal weight women is increased in association with relatively high levels of CRP and testosterone and with relatively low levels of SHBG.

Differences in ambulatory care fragmentation by race

BackgroundMore fragmented ambulatory care (i.e., care spread across many providers without a dominant provider) has been associated with more subsequent healthcare utilization (such as more tests, procedures, emergency department visits, and hospitalizations) than less fragmented ambulatory care. It is not known if race and socioeconomic status are associated with fragmented ambulatory care.MethodsWe conducted a longitudinal analysis of data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, using the REGARDS baseline visit plus the first year of follow-up. We included participants ≥65 years old, who had linked fee-for-service Medicare claims, and ≥ 4 ambulatory visits in the first year of follow-up. We used Tobit regression to determine the associations between race, annual household income, and educational attainment at baseline and fragmentation score in the subsequent year (as measured with the reversed Bice-Boxerman Index). Covariates included other demographic characteristics, medical conditions, medication use, health behaviors, and psychosocial variables. Additional analyses categorized visits by the type of provider (primary care vs. specialist).ResultsThe study participants (N = 6799) had an average age of 73.0 years, 53% were female, and 30% were black. Nearly half had low annual household income (<$35,000) and 41% had a high school education or less. Overall, participants had a median of 10 ambulatory visits to 4 providers in the 12 months following their baseline study visit. Participants in the highest quintile of fragmentation scores had a median of 11 visits to 7 providers. Black race was associated with an absolute adjusted 3% lower fragmentation score compared to white race (95% confidence interval (2% lower to 4% lower; p < 0.001). This difference was explained by blacks seeing fewer specialists than whites. Income and education were not independent predictors of fragmentation scores.ConclusionsAmong Medicare beneficiaries, blacks had less fragmented ambulatory care than whites, due to lower utilization of specialty care. Future research is needed to determine the effect of fragmented care on health outcomes for blacks and whites.