Differences In Annual Rates Research Articles

Annual incidence and assessment of risk factors for early-onset deep surgical site infection following primary total knee arthroplasty in osteoarthritis.

This study aims to determine difference in annual rate of early-onset (≤ 90 days) deep surgical site infection (SSI) following primary total knee arthroplasty (TKA) for osteoarthritis, and to identify risk factors that may be associated with infection. This is a retrospective population-based cohort study using prospectively collected patient-level data between 1 January 2013 and 1 March 2020. The diagnosis of deep SSI was defined as per the Centers for Disease Control/National Healthcare Safety Network criteria. The Mann-Kendall Trend test was used to detect monotonic trends in annual rates of early-onset deep SSI over time. Multiple logistic regression was used to analyze the effect of different patient, surgical, and healthcare setting factors on the risk of developing a deep SSI within 90 days from surgery for patients with complete data. We also report 90-day mortality. A total of 39,038 patients underwent primary TKA for osteoarthritis during the study period. Of these, 275 patients developed a deep SSI within 90 days of surgery, representing a cumulative incidence of 0.7%. The annual infection rate did not significantly decrease over the seven-year study period (p = 0.162). Overall, 13,885 (35.5%) cases were excluded from the risk analysis due to missing data. Risk factors associated with early-onset deep SSI included male sex, American Society of Anesthesiologists grade ≥ 3, blood transfusion, acute length of stay, and surgeon volume < 30 TKAs/year. Early-onset deep SSI was not associated with increased 90-day mortality. This study establishes a reliable baseline infection rate for early-onset deep SSI after TKA for osteoarthritis using robust Infection Prevention and Control surveillance data, and identifies several potentially modifiable risk factors.

1864. Trends in Staphylococcus aureus Bacteremia Rates among U.S. Acute Care Hospitals, January 2017- June 2021

Abstract Background Previous estimates of methicillin-resistant and -sensitive Staphylococcus aureus (MRSA, MSSA) bacteremia rates in hospitalized patients showed decreases in hospital-onset (HO) MRSA, no changes in community-onset (CO) MRSA and HO MSSA, and slight increases in CO MSSA rates from 2012–2017; more recent trends have not been well characterized. Methods We calculated monthly S. aureus bacteremia rates using microbiology data from hospitals reporting antibiotic susceptibility results in the Premier Healthcare Database from January 2017- June 2021. S. aureus blood isolates resistant to methicillin, oxacillin, or cefoxitin were categorized as MRSA. Positive blood cultures collected on or before hospital day 3 were categorized as CO; those collected on day 4 or later were categorized as HO. Annual rate differences were assessed using generalized estimating equation models with a negative binomial distribution adjusting for hospital bed size, teaching status, urban/rural designation, discharge month, census division, distributions of patient age, sex and race and hospital-level clustering. Results Among 11 million discharges from 356 hospitals, we identified 5,627 HO S. aureus bacteremia events: 2,558 (45%) MRSA and 3,069 (55%) MSSA. In 2017, we observed HO MRSA bacteremia rates of 0.41 and HO MSSA rates of 0.49 per 10,000 patient-days. Compared with 2017, adjusted rates of HO MRSA and MSSA bacteremia were significantly higher in 2019, 2020, and 2021 (Figure 1). Of 42,587 CO S. aureus bacteremia events, 19,107 (45%) were MRSA and 23,480 (55%) MSSA. CO MRSA bacteremia rates were lowest in 2017 (1.52 per 1,000 discharges), and adjusted rates were significantly higher in all later years (Figure 2); we observed significant regional variability in annual differences (p=0.018). The observed CO MSSA bacteremia rate was 2.03 per 1,000 discharges in 2017, and adjusted rates were significantly higher in 2020 and 2021. Figure 1.Hospital-Onset MRSA and MSSA Bacteremia Incidence Rate Ratios* with 95% confidence intervals, 2017 – 2021**.*Reference year =2017.**2021 includes data during January – June.***Statistically significant at p&amp;lt;0.05.Figure 2.Community-Onset MRSA and MSSA Bacteremia Incidence Rate Ratios* with 95% confidence intervals, 2017 - 2021***Reference year =2017.**2021 includes data during January – June.***Statistically significant at p&amp;lt;0.05. Conclusion In contrast with previous trends, recent S. aureus bacteremia rates in this cohort have increased in comparison to 2017. Potential explanations warranting exploration include differences in regional trends and pandemic-associated changes in inpatient risk, severity of illness, length of stay, and hospital utilization Disclosures All Authors: No reported disclosures.

A longitudinal analysis of nosocomial bloodstream infections among preterm neonates

Nosocomial bloodstream infections (NBSIs), commonly due to central-line associated bloodstream infections (CLABSI), contribute substantially to neonatal morbidity and mortality. We aimed to identify longitudinal changes in incidence of NBSI, microbiological-spectrum, and antibiotic exposure in a large cohort of preterm neonates admitted to the neonatal intensive care unit. We retrospectively assessed differences in annual rates of NBSI (per 1000 patient-days), CLABSI (per 1000 central-line days), and antibiotic consumption (per 1000 patient-days) among preterm neonates (< 32 weeks’ gestation) hospitalized between January 2012 and December 2020. Multi-state Markov models were created to model states of progression of NBSI and infection risk given a central-line on days 0, 3, 7, and 10 of admission. Of 1547 preterm infants, 292 (19%) neonates acquired 310 NBSI episodes, 99 (32%) of which were attributed to a central-line. Over the years, a significant reduction in central-line use was observed (p < 0.001), although median dwell-time increased (p = 0.002). CLABSI incidence varied from 8.83 to 25.3 per 1000 central-line days, with no significant difference between years (p = 0.27). Coagulase-negative staphylococci accounted for 66% of infections. A significant decrease was found in antibiotic consumption (p < 0.001). Probability of NBSI decreased from 16% on day 3 to 6% on day 10. NBSI remains a common problem in preterm neonates. Overall antibiotic consumption decreased over time despite the absence of a significant reduction in infection rates. Further research aimed at reducing NBSI, in particular CLABSI, is warranted, particularly with regard to limiting central-line dwell-time and fine-tuning insertion and maintenance practices.

Marine n-3 fatty acids and cognitive change among older adults in the VITAL randomized trial.

Introduction: Few large, randomized trials have evaluated marine n‐3 supplements and cognition in healthy older adults.Methods: Healthy community‐dwelling participants aged 60+ years (mean [standard deviation] = 70.9 [5.8] years) in VITAL (randomized trial of n‐3 fats [1 g/day, including 840 mg of eicosapentaenoic acid + docosahexaenoic acid] and vitamin D) were included: 3424 whose cognition was assessed by phone (VITAL‐Cog; eight neuropsychological tests; 2.8 years) and 794 evaluated in person (CTSC‐Cog; nine tests; 2.0 years). The primary outcome was a global score (average of test z‐scores) of change over two assessments. We used multivariable‐adjusted linear mixed models; substudy‐specific results were meta‐analyzed.Results: We observed no significant effect of n‐3 supplementation: the mean difference in annual rate of cognitive change for the n‐3 versus placebo group was –0.01 standard units (95% confidence interval [CI]: –0.02, 0.003) in VITAL‐Cog and –0.002 (95% CI: –0.04, 0.03) in CTSC‐Cog; the pooled difference was –0.01 (95% CI: –0.02, 0.003; P = .15).Discussion: Marine n‐3 supplementation (1 g/day) did not confer cognitive benefits over 2 to 3 years in community‐dwelling older adults.

Real-world study in severe eosinophilic asthma patients refractory to anti-IL5 biological agents treated with benralizumab in Spain (ORBE study)

BackgroundBenralizumab, a monoclonal antibody targeting the human interleukin-5 (IL-5) receptor (IL-5R), was used before marketing authorisation in Spain in a real world setting as part of an early-access programme (EAP) to treat patients with severe eosinophilic asthma with prior insufficient response or intolerance to anti-IL5 treatment (mepolizumab or reslizumab). The objective of this study is to describe the patient profile candidate for treatment and to assess benralizumab effectiveness.MethodsThis is an observational, retrospective, multicentre study in severe eosinophilic asthma patients refractory to other biological agents targeting the IL-5 pathway. Baseline characteristics included closest data, from the previous 12 months, to benralizumab treatment onset (index date). Patients were followed until the last treatment dosage while EAP was active (March to December 2018). Effectiveness was evaluated versus baseline, in patients who received at least three doses, with asthma control test (ACT), Mini Asthma Quality of Life Questionnaire (MiniAQLQ), annual severe exacerbation rate, oral corticosteroids treatment (OCS) and asthma-related healthcare resources utilization.ResultsTwenty-seven patients treated with benralizumab were included in the analysis. Effectiveness was assessed in 19 patients. Both questionnaires showed clinically meaningful differences, i.e. ACT score ≥ 3 and MiniAQLQ score ≥ 0.5, compared with baseline [mean (SD), 3.3 (6.8) and 1.2 (1.9), respectively]. Patients treated with OCS decreased during follow-up from 88.9% (n = 24/27) at baseline to 78.9% (n = 15/19) and 31.6% (n = 6/19) had an OCS dose reduction ≥ 50%. The difference in annual severe exacerbation rate during follow-up showed a significant reduction vs. baseline (2.12 per patient-year, 95% CI 0.99–3.24, p = 0.002). The differences in annual rate of non-scheduled primary care and specialist visits during follow-up indicated a significant decrease [2.28 per patient-year (95% CI 1.55–3.01; p < 0.001) and 1.47 per patient-year (95% CI 0.65–2.30; p = 0.004), respectively], as well as the difference in annual rate of number of emergency department visits [1.18 per patient-year (95% CI 0.51–1.85; p = 0.007)].ConclusionsThese results suggest that severe eosinophilic asthma patients receiving benralizumab, presented clinically meaningful improvement in asthma control and asthma-related QoL as well as OCS dose reduction. Results also aim to significant reductions in annual severe exacerbation rates, non-scheduled primary care and specialist visits, and emergency department visits rates.

Marine n‐3 fatty acids and cognitive change among older adults in the VITAL randomized trial

AbstractBackgroundHigh intake of marine omega‐3 (n‐3) fatty acids has been associated with lower risk of cognitive decline; however, few large‐scale, long‐term randomized trials have been conducted. We evaluated n‐3 supplementation (1 gram/day, including 840 mg of EPA + DHA) and change in cognitive function over 2‐3 years.MethodCommunity‐dwelling participants aged 60+ years (mean[SD]=70.9[5.8]y) in the Vitamin D and Omega‐3 Trial (VITAL) were included: 3424 had cognitive function assessment by phone (VITAL‐Cog; 8 neuropsychological tests; mean follow‐up=2.8 years) and 794 were evaluated in‐person at the Harvard Clinical and Translational Science Center (CTSC‐Cog; 9 neuropsychological tests; mean follow‐up=2.0 years). The primary, pre‐specified outcome was a global composite score (average z‐scores across all tests) of change over two assessments. We used multivariable‐adjusted linear mixed models and meta‐analyzed the results for the two settings.ResultWe observed no significant effect of n‐3 supplementation on the global composite score: the mean difference in annual rate of change for the n‐3 versus placebo group was ‐0.01 standard units (95% CI:‐0.02,0.003) in VITAL‐Cog and ‐0.002 (95% CI:‐0.04,0.03) in CTSC‐Cog; the pooled mean difference was ‐0.01 (95%CI:‐0.02,0.003; p=0.15). For secondary outcomes of change in verbal memory, executive function/attention and general cognition, we observed null results to trends of adverse associations with n‐3 treatment versus placebo that were not statistically significant after multiple‐testing correction. In pre‐specified secondary analyses, we observed no significant interaction of the intervention with baseline plasma omega‐3 fatty acid levels for the global composite score (pooled p‐interaction=0.37).ConclusionMarine n‐3 supplementation (1 gram/day) did not confer cognitive benefits over 2‐3 years in community‐dwelling older adults.

Effect of vitamin D on cognitive decline: results from two ancillary studies of the VITAL randomized trial

Low vitamin D levels have been associated with cognitive decline; however, few randomized trials have been conducted. In a trial, we evaluated vitamin D3 supplementation on cognitive decline. We included participants aged 60+ years (mean[SD] = 70.9[5.8] years) free of cardiovascular disease and cancer in two substudies in the VITAL 2 × 2 randomized trial of vitamin D3 (2000 IU/day of cholecalciferol) and fish oil supplements: 3424 had cognitive assessments by phone (eight neuropsychologic tests; 2.8 years follow-up) and 794 had in-person assessments (nine tests; 2.0 years follow-up). The primary, pre-specified outcome was decline over two assessments in global composite score (average z-scores of all tests); substudy-specific results were meta-analyzed. The pooled mean difference in annual rate of decline (MD) for vitamin D3 versus placebo was 0.01 (95% CI − 0.01, 0.02; p = 0.39). We observed no interaction with baseline 25-hydroxyvitamin-D levels (p-interaction = 0.84) and a significant interaction with self-reported race (p-interaction = 0.01). Among Black participants (19%), those assigned vitamin D3 versus placebo had better cognitive maintenance (MD = 0.04, 95% CI 0.01, 0.08, similar to that observed for Black participants 1.2 years apart in age). Thus, vitamin D3 (2000 IU/day cholecalciferol) supplementation was not associated with cognitive decline over 2–3 years among community-dwelling older participants but may provide modest cognitive benefits in older Black adults, although these results need confirmation.Trial registration ClinicalTrials.gov; VITAL (NCT01169259), VITAL-DEP (NCT01696435) and VITAL-Cog (NCT01669915); the date the registration for the parent trial (NCT01169259) was submitted to the registry: 7/26/2010 and the date of first patient enrollment in either of the ancillary studies for cognitive function in a subset of eligible VITAL participants: 9/14/2011.

Impact of pregnancy on the trajectories of cardiovascular risk factors in women with and without gestational diabetes.

The elevated lifetime risk of cardiovascular disease in women who develop gestational diabetes mellitus (GDM) has been attributed to adverse life-course trajectories of cardiovascular risk factors that arise before pregnancy and continue thereafter. We hypothesized that pregnancy may differentially affect these trajectories in women who develop GDM and those who do not. With population-based administrative databases, we identified all nulliparous women in Ontario, Canada, who had singleton pregnancies between January 2011 and December 2016 and ≥2 measurements of the following analytes both before and after pregnancy: glycated haemoglobin (HbA1c), glucose, lipids and transaminases. In total, 39 581 women (4373 with GDM) had 3.9 ± 3.4 tests before and 4.6 ± 5.4 tests after pregnancy. Both before and after pregnancy, women who developed GDM had higher HbA1c, fasting glucose, low-density lipoprotein (LDL)-cholesterol and triglycerides than their peers, with lower high-density lipoprotein (HDL)-cholesterol (all p < .0001). Before pregnancy, women who went on to GDM had higher annual increases than their peers did in HbA1c, fasting glucose and triglycerides (all p ≤ .01); lesser annual decrease in LDL (p=.0003); and greater annual decrease in HDL (p=.0006). Compared with pre-pregnancy, the postpartum differences in annual rates of change in HbA1c and fasting glucose were 6.9- and 3.3-fold higher, respectively, in women with GDM. Conversely, the respective postpartum differences in annual rates of change in triglycerides, LDL and HDL were 1.2, 1.6 and 0.3 times lower than before pregnancy. After pregnancy, differences in pregravid trajectories of glycaemic measures are amplified between women with GDM and their peers. In contrast, pregravid differences in lipid measures persist but do not differentially worsen after pregnancy.

Incidence, predictors and outcomes of device-related thrombus after left atrial appendage closure with the WATCHMAN device-Insights from the EWOLUTION real world registry.

In this analysis of the EWOLUTION registry, we evaluated the incidence, relevance and predictors of device-related thrombus in a large multi-center real-world cohort undergoing LAAc with the WATCHMAN device. We analyzed the 835 patients who underwent percutaneous LAA closure with the WATCHMAN device in the EWOLUTION registry in whom at least one TEE follow up was performed. Patients were 74 ± 9 y/o and were at high risk for stroke and bleeding (CHA2DS2-VASC-Score 4.3± 1.7; HAS-BLED-Score 2.3± 1.2). Device-related thrombus was detected in 4.1% (34/835) after a median of 54 days (IQR 42-111 days) with 91.2% (31/34) being detected within 3months after the procedure or at the time of first TEE. Hereby DRT occurred irrespective of postprocedural anticoagulation. Patients with DRT more frequently had long-standing, non-paroxysmal atrial fibrillation (82.4 vs. 64.9%, p< .01), evidence of dense spontaneous echo contrast (26.5 vs. 11.9%, p= .03) and larger LAA diameters at the ostium (22.8± 3.5 vs. 21.1± 3.5 mm, p< .01) compared to patients without DRT. Left ventricular ejection fraction, device compression ratio and the incidence of renal dysfunction did not differ between the two groups. In a multivariate analysis, only non-paroxysmal atrial fibrillation identified as an independent predictor of developing DRT. Specific treatment of DRT was initiated in 62% (21/34) of patients whereas resolution was confirmed in 86% (18/21) of cases. Overall, no significant differences in annual rates of stroke/TIA or systemic embolism were observed in patients with or without DRT (DRT 1.7 vs. No-DRT 2.2%/year, p= .8). In real-world patients undergoing LAAc with the WATCHMAN device, DRT is rare. DRT was most frequently detected within the first 3months after LAAc regardless of post-procedural regimen and was not associated with an increased risk of stroke or SE. While long-standing atrial fibrillation was the only independent factor associated with DRT, medical treatment of DRT resulted in a resolution of thrombi in most cases.

Relationship of hearing impairment with MRI brain volumes and cognitive decline in the Atherosclerosis Risk in Communities study

AbstractBackgroundHearing impairment is associated with cognitive decline but whether it is a cause or marker is unknown. We investigated the association of hearing impairment with brain volumes and 8‐year cognitive decline. Because the superior temporal gyrus (STG) is the location of the primary auditory cortex, we stratified results by STG volume to investigate if the association of hearing and cognition differed among participants with and without evidence of possible hearing‐related brain atrophy.MethodWe used data from 1195 community‐dwelling adults (72‐94 years, 61% female, 36% black) from the Atherosclerosis Risk in Communities Study. A composite cognitive score was created from 10 neuropsychological tests administered at 3 study visits spanning 8 years (2011‐13 to 2018‐19). Brain volumes were calculated from structural magnetic resonance imaging scans for 6 regions of interest. Pure tone air conduction hearing thresholds (frequencies 0.5‐4 kHz) were obtained in 2016‐17 and averaged, with better‐ear hearing impairment defined as an average &gt;25 dB. Multivariable‐adjusted linear regression was used to estimate cross‐sectional differences in standardized brain volumes, adjusting for intracranial volume, demographic and clinical covariates. We estimated differences in annual rates of cognitive change by hearing impairment status adjusting for demographic and clinical covariates using linear mixed models; results were stratified by intracranial volume‐adjusted STG volume (below vs. equal to or greater than the median value).ResultThe mean STG volume difference comparing hearing impairment to normal hearing was ‐0.121 standard deviations (SD) (95% CI: ‐0.213, ‐0.028). Overall, the difference in the rate of cognitive decline associated with hearing impairment was ‐0.014 SD (‐0.023, ‐0.005). Hearing was more strongly associated with cognitive decline among participants with smaller STG volumes; rate difference, ‐0.014 SD (‐0.027, ‐0.002) compared to ‐0.008 (‐0.022, 0.006) for participants with larger STG volumes.ConclusionHearing impairment was associated with smaller brain volumes in the primary auditory region, but not with other regions. Our stratified analysis suggests that hearing treatment might be an important possible strategy to delay cognitive decline, even among participants with hearing‐related brain atrophy. Furthermore, the adverse cognitive effects of hearing impairment could potentially be mitigated if early hearing treatment can prevent STG atrophy.

Endocardial versus epicardial left atrial appendage exclusion for stroke prevention in patients with atrial fibrillation: Midterm follow-up.

Left atrial appendage closure (LAAC) became an alternative method for stroke prevention in patients with non-valvular atrial fibrillation (AF) intolerant to long term oral anticoagulation therapy. This study aimed to compare endocardial (Amulet and LAmbere occluders) and epicardial (Lariat) LAAC techniques. A retrospective, observational case-control study included 223 consecutive CHA2 DS2 -VAS score-matched patients with AF who underwent LAAC in two centers. There were 55 matched cases with the mean CHA2DS2-VASs score 4.4 ± 1.22 (p = 1). Overall follow-up was 308.2 patient-years. The Endocardial group patients were older and more often females with congestive heart failure and peripheral vascular disease. The epicardial group more frequently had a stroke/transient ischemic attack history. There were no differences in hypertension, diabetes mellitus, and indications for procedure between both groups. The mean HAS-BLED score was significantly higher in the endocardial group than in the epicardial group (4.3 ± 0.9 vs. 3.7 ± 1.3, p = .011). There were no differences in annual rates of thromboembolic events (2.6% vs 0.5%) and annual stroke (0.87% vs. 0%) between the endocardial and epicardial groups. Endocardial and Epicardial LAAC techniques show comparable implantation outcomes and safety profile and stroke prevention in patients with AF. Future randomized studies are needed to corroborate these initial results and assess long term mortality.

Branch atheromatous disease diagnosed as embolic stroke of undetermined source: A sub-analysis of NAVIGATE ESUS

Branch atheromatous disease (BAD) is distinctive from large and small arterial diseases, which is single subcortical infarction larger than lacunar stroke in the territories of deep perforators without relevant arterial stenosis. BAD meets the current criteria of embolic stroke of undetermined source. We performed an exploratory analysis of BAD in patients recruited to NAVIGATE embolic stroke of undetermined source, a randomized controlled trial to compare rivaroxaban and aspirin in embolic stroke of undetermined source patients. Among 3972 stroke patients in cerebral hemispheres with intracranial arterial imaging, 502 (12.6%) patients met the criteria for BAD. BAD was associated with younger age (years; OR: 0.97, 95% CI: 0.96-0.98), race (Asian; OR: 1.78, 95% CI: 1.44-2.21), region (Eastern Europe; OR: 2.49, 95% CI: 1.87-3.32), and higher National Institute of Health Stroke Scale (OR: 1.17, 95% CI: 1.12-1.22) at randomization. During follow-up, stroke or systemic embolism (2.5%/year vs. 6.2%/year, p = 0.0022), stroke (2.1%/year vs. 6.2%/year, p = 0.0008), and ischemic stroke (2.1%/year vs. 5.9%/year, p = 0.0013) occurred less frequently in BAD than non-BAD patients. There were no differences in annual rates of stroke or systemic embolism (2.5%/year vs. 2.5%/year, HR: 1.01, 95% CI: 0.33-3.14) or major bleeding (1.3%/year vs. 0.8%/year, HR: 1.51, 95% CI: 0.25-9.05) between rivaroxaban and aspirin groups among BAD patients. BAD was relatively common, especially in Asian and from Eastern Europe among embolic stroke of undetermined source patients. Stroke severity was higher at randomization but recurrence of stroke was fewer in BAD than non-BAD patients. The efficacy and safety of rivaroxaban and aspirin did not differ among BAD patients.

Segmented regression analysis of emergency departments patient visits from Septicemia in Taiwan

BackgroundThe protocol for early goal-directed therapy (EGDT) is effective for improving both the costs and outcomes of septicemia treatment, including a significant reduction in case fatality. However, this complicated protocol may have a downside. Furthermore, the Joint Taiwan Critical Care Medicine Committee has launched a nationwide educational program after the publication of the Surviving Sepsis Campaign (SSC) to improve the overall survival rate from septicemia in the emergency care system of Taiwan. ObjectivesTo assess the impact of the EGDT protocol and SSC education programs on island-wide septicemia-related emergency department (ED) visits. MethodsSegmented regression techniques were utilized to assess the differences in annual rates and changes in septicemia-related ED visits between 1998 and 2012. We considered annual incidence of two medical comorbidities as potential confounders: metastatic malignant neoplasms and malignant neoplasms of the lymphatic and hematopoietic tissues. ResultsThe EGDT protocol was associated with decreased septicemia-related ED visits in 2002 (level change; p < 0.001), while the SSC education program led to a slight increase in septicemia-related ED visits in 2007 (slope change; p < 0.001). For the EGDT protocol, the number of patient visits decreased by 32.9% after the protocol was implemented in 2002 compared with the expected number without the intervention. For the SSC education program, the number of patient visits increased by 20.2% (compared with the predicted number) in 2007 after the education program was implemented. ConclusionsThe EGDT protocol and SSC education program were associated with significant immediate changes and lagged intervention effects on island-wide septicemia-related ED visits.

County-level cumulative environmental quality associated with cancer incidence.

Individual environmental exposures are associated with cancer development; however, environmental exposures occur simultaneously. The Environmental Quality Index (EQI) is a county-level measure of cumulative environmental exposures that occur in 5 domains. The EQI was linked to county-level annual age-adjusted cancer incidence rates from the Surveillance, Epidemiology, and End Results (SEER) Program state cancer profiles. All-site cancer and the top 3 site-specific cancers for male and female subjects were considered. Incident rate differences (IRDs; annual rate difference per 100,000 persons) and 95% confidence intervals (CIs) were estimated using fixed-slope, random intercept multilevel linear regression models. Associations were assessed with domain-specific indices and analyses were stratified by rural/urban status. Comparing the highest quintile/poorest environmental quality with the lowest quintile/best environmental quality for overall EQI, all-site county-level cancer incidence rate was positively associated with poor environmental quality overall (IRD, 38.55; 95% CI, 29.57-47.53) and for male (IRD, 32.60; 95% CI, 16.28-48.91) and female (IRD, 30.34; 95% CI, 20.47-40.21) subjects, indicating a potential increase in cancer incidence with decreasing environmental quality. Rural/urban stratified models demonstrated positive associations comparing the highest with the lowest quintiles for all strata, except the thinly populated/rural stratum and in the metropolitan/urbanized stratum. Prostate and breast cancer demonstrated the strongest positive associations with poor environmental quality. We observed strong positive associations between the EQI and all-site cancer incidence rates, and associations differed by rural/urban status and environmental domain. Research focusing on single environmental exposures in cancer development may not address the broader environmental context in which cancers develop, and future research should address cumulative environmental exposures. Cancer 2017;123:2901-8. © 2017 American Cancer Society.

Association Between Vascular Pathology and Rate of Cognitive Decline Independent of Alzheimer's Disease Pathology.

To examine the association between vascular pathology and rate of cognitive decline in older adults independent of Alzheimer's disease (AD) pathology. Prospective cohort study. Community sample. Individuals from the Einstein Aging Study autopsy series (N=62). The Blessed Information-Memory-Concentration (BIMC) test was used to assess global cognitive status. AD pathology was quantified according to Braak stage (<3 vs ≥ 3). Vascular pathology was quantified using a previously reported macrovascular lesion (MVL) score. The association between vascular pathology and antemortem rates of cognitive decline adjusted for level of AD pathology was assessed using linear mixed-effects models. Mean age was 81.8 at enrollment and 89.0 at death. Participants with more than two MVLs had faster cognitive decline than those with no MVLs (difference in annual rate of change in BIMC 0.74 points/yr, P=.03). Braak stage was also associated with cognitive decline (difference 0.57 points/yr, P=.03). The difference in rate of cognitive decline between those with more than two MVLs and those free of vascular lesions persisted after adjustment for AD pathology (difference in rate of change in BIMC 0.68 points/yr, P=.04). The effect of vascular pathology on cognitive decline was not significantly different according to AD pathology. Vascular brain pathology is associated with rate of cognitive decline after adjusting for level of AD pathology.

Association of Adherence to a Healthy Diet with Cognitive Decline in European and American Older Adults: A Meta-Analysis within the CHANCES Consortium

Aim: To examine the association between a healthy diet, assessed by the Healthy Diet Indicator (HDI), and cognitive decline in older adults. Methods: Data from 21,837 participants aged ≥55 years from 3 cohorts (Survey in Europe on Nutrition and the Elderly, a Concerted Action [SENECA], Rotterdam Study [RS], Nurses' Health Study [NHS]) were analyzed. HDI scores were based on intakes of saturated fatty acids, polyunsaturated fatty acids, mono- and disaccharides, protein, cholesterol, fruits and vegetables, and fiber. The Telephone Interview for Cognitive Status in NHS and Mini-Mental State Examination in RS and SENECA were used to assess cognitive function from multiple repeated measures. Using multivariable-adjusted, mixed linear regression, mean differences in annual rates of cognitive decline by HDI quintiles were estimated. Results: Multivariable-adjusted differences in rates in the highest versus the lowest HDI quintile were 0.01 (95% CI -0.01, 0.02) in NHS, 0.00 (95% CI -0.02, 0.01) in RS, and 0.00 (95% CI -0.05, 0.05) in SENECA with a pooled estimate of 0.00 (95% CI -0.01, 0.01), I² = 0%. Conclusions: A higher HDI score was not related to reduced rates of cognitive decline in European and American older adults.

Common variant rs356182 near SNCA defines a Parkinson's disease endophenotype.

ObjectiveParkinson's disease (PD) presents clinically with several motor subtypes that exhibit variable treatment response and prognosis. Here, we investigated genetic variants for their potential association with PD motor phenotype and progression.MethodsWe screened 10 SNPs, previously associated with PD risk, for association with tremor‐dominant (TD) versus postural‐instability gait disorder (PIGD) motor subtypes. SNPs that correlated with the TD/PIGD ratio in a discovery cohort of 251 PD patients were then evaluated in a multi‐site replication cohort of 559 PD patients. SNPs associated with motor phenotype in both cross‐sectional cohorts were next evaluated for association with (1) rates of motor progression in a longitudinal subgroup of 230 PD patients and (2) brain alpha‐synuclein (SNCA) expression in the GTEx (Genotype‐Tissue Expression project) consortium database.ResultsGenotype at rs356182, near SNCA, correlated with the TD/PIGD ratio in both the discovery (Bonferroni‐corrected P = 0.04) and replication cohorts (P = 0.02). The rs356182 GG genotype was associated with a more tremor‐predominant phenotype and predicted a slower rate of motor progression (1‐point difference in annual rate of UPDRS‐III motor score change, P = 0.01). The rs356182 genotype was associated with SNCA expression in the cerebellum (P = 0.005).InterpretationOur study demonstrates that the GG genotype at rs356182 provides molecular definition for a clinically important endophenotype associated with (1) more tremor‐predominant motor phenomenology, (2) slower rates of motor progression, and (3) decreased brain expression of SNCA. Such molecularly defined endophenotyping in PD may benefit both clinical trial design and tailoring of clinical care as we enter the era of precision medicine.

Effect of tillage practices on net carbon flux and economic parameters from farmland on the Loess Plateau in China

It is important to evaluate the effect of tillage practices on carbon flow and economic parameters in order to better understand soil carbon sequestration and mitigation of carbon release into the atmosphere, and to increase income for farmers. A 2-year field experiment was conducted in a winter wheat-summer corn rotation system on dryland farmland on the Loess Plateau in Northwest China with four treatments; zero tillage with straw mulching (zero tillage), rotary tillage with straw incorporation (rotary tillage), chisel plow tillage with straw incorporation (chisel plow), and conventional mouldboard plow tillage without crop straw (conventional tillage). Results showed that zero tillage reduced carbon emissions, mainly through reduction of emissions from tillage practices, and served as a net carbon sink, as did rotary tillage and chisel plow, while conventional tillage served as a net carbon source. Specifically, zero tillage reduced carbon emissions from farm inputs by 168.8 and 75.0 kg C ha−1 yr−1 compared with conventional tillage and rotary tillage (or chisel plow), respectively. The difference in annual rate of carbon sequestration between 2013 and 2015 was 1.21-fold higher with zero tillage than with conventional tillage, suggesting zero tillage released less CO2 and was therefore better able to mitigate against global warming. Chisel plow significantly (P < 0.05) improved net return values by 10.7%–63.2% in the 2013-14 cropping year and by 12.8%–93.7% in the 2014–15 cropping year, respectively when compared to other tillage treatments. Zero tillage was the most effective method for reducing carbon inputs and increasing carbon sequestration, and chisel plow was the best option for provision of economic parameters on dryland farmland in this region. Therefore, the application of conservation (zero, rotary and chisel plow) tillage could be a C-smart and effective economic agricultural practice for winter wheat-summer corn ecosystems under rain fed condition.

Evaluation of Cardiovascular Disease Risk in Chronic Myelogenous Leukemia Patients Using Electronic Medical Records from Community-Based Oncology Practices in the United States

PURPOSE: Current guidelines (Version I.2015) from the National Cancer Comprehensive Network recommend that patient's comorbidities, including cardiovascular disease (CVD), be taken into consideration when evaluating tyrosine kinase inhibitor (TKI) therapy options for chronic myelogenous leukemia (CML). The guidelines also recommend using certain TKIs "with caution in patients with cardiovascular risk factors" and evaluating patients "for vascular risk factors prior to initiating and during treatment." Recent research has evaluated the prevalence of CVD in the CML patient population, but there is a lack of published data on the risk of developing CVD in this population. The study purpose was to assess the risk for CVD among CML patients using an oncology-based electronic medical record (EMR) database.METHODS: A retrospective cohort analysis was conducted using data from the International Oncology Network (ION) EMR Database (01/2005 to 01/2015) of patients treated by community-based oncologists in the U.S. The study population included patients with a diagnosis of CML (ICD-9 CM: 205.1) aged 18 years and older, having no other primary cancer or acute myeloid leukemia, and not enrolled in a clinical trial anytime during the study period. Study index was the date of the first observed CML diagnosis during 01/2005 to 10/2014. Prevalence of CVD and its risk factors were estimated for baseline and during a follow-up of up to 5 years. Baseline included all available medical information prior to and on the index date. CVD and its risk factors were defined as in the Framingham Heart Study, and were identified using diagnoses and/or treatment as applicable from pre-defined fields in standard EMR tables or through electronic text search of the physician progress notes available in the database. The Framingham risk score for CVD was computed at baseline using age, gender, smoking status, hypertension, dyslipidemia, and diabetes. To compare with annual estimates from the U.S. general population, all prevalence estimates at 1 year for the CML population were age and gender standardized to the U.S. 2010 census population aged 20 and older. Standardized rate ratios and z-tests were computed to assess the magnitude and significance, respectively, of the differences in annual rates between CML patients and the general U.S. population.RESULTS: A total of 1,639 CML patients were included with mean±SD and median follow-up time (in years) of 2.4±1.7 and 2.1, respectively. Average age was 59±16 and 52.2% were male. CVD was present in 18.7% of patients at baseline. On average, CML patients without CVD at baseline had a Framingham CVD risk score of 12.8% compared to 8.7% in the general US adult population without CVD and nearly 44% of CML patients without CVD were at intermediate to high risk (>10%). Among patients without CVD, in the 5-year follow-up period 77.7% had at least 1 CVD risk factor up from 52.7% at baseline. Relative to the general U.S. adult population, annual standardized prevalence rates in CML patients were 20%, 30%, and 40% higher for hypertension, diabetes and obesity, respectively, while being 20% and 60% lower for dyslipidemia and smoking. In the 5-year follow-up period, the prevalence of CVD in the study sample rose to 33.0% of the sample of patients available at 5 years. Annual standardized prevalence rates of myocardial infarction, atherosclerosis, and heart failure was 2.7 to 3.5 times higher (p<0.001) relative to the general U.S. adult population.CONCLUSION: This study suggests that CML patients may have both a higher risk and prevalence of CVD compared to the general U.S. adult population, likely due to several contributing factors which should be evaluated in further research. Given the chronic nature of CML and the need for long term TKI treatment, it is important to regularly evaluate and monitor patients for CVD and its risk factors. DisclosuresD'Souza:Xcenda: Research Funding. Makenbaeva:Bristol-Myers Squibb: Employment, Equity Ownership. Farrelly:Xcenda: Research Funding. Landsman-Blumberg:Xcenda: Research Funding. Bolinder:Bristol-Myers Squibb: Employment, Equity Ownership.

Physician health programmes and malpractice claims: reducing risk through monitoring

Physician health programmes (PHPs) are peer-assistance organizations that provide support to physicians struggling with addiction or with physical or mental health challenges. While the services they offer are setting new standards for recovery and care, they are not immune to public debate and criticism since some have concerns about those who are enrolled in, or have completed, such programmes and their subsequent ability to practice medicine safely. To examine whether medical malpractice claims were associated with monitoring by a PHP using a retrospective examination of administrative data. Data on PHP clients who were insured by the largest malpractice carrier in the state were examined. First, a business-model analysis of malpractice risk examined relative risk ratings between programme clients and a matched physician cohort. Second, Wilcoxon analysis examined differences in annual rates of pre- and post-monitoring claims for PHP clients only. Data on 818 clients was available for analysis. After monitoring, those enrolled in the programme showed a 20% lower malpractice risk than the matched cohort. Furthermore physicians' annual rate of claims were significantly lower after programme monitoring among PHP clients (P < 0.01). This is the only study examining this issue to date. While there are a variety of reasons why physicians present to PHPs, this study demonstrates that treatment and monitoring is associated with a lowered risk of malpractice claims and suggests that patient care may be improved by PHP monitoring.