Care Needs and Clinical Outcomes of Older People with Dementia: A Population-Based Propensity Score-Matched Cohort Study

Objective

To explore the healthcare resource utilization, psychotropic drug use and mortality of older people with dementia.

Design

A nationwide propensity score-matched cohort study.

Setting

National Health Insurance Research database.

Participants

A total of 32,649 elderly people with dementia and their propensity-score matched controls (n=32,649).

Measurements

Outpatient visits, inpatient care, psychotropic drug use, in-hospital mortality and all-cause mortality at 90 and 365 days.

Results

Compared to the non-dementia group, a higher proportion of patients with dementia used inpatient services (1 year after index date: 20.91% vs. 9.55%), and the dementia group had more outpatient visits (median [standard deviation]: 7.00 [8.87] vs. 3.00 [8.30]). Furthermore, dementia cases with acute admission had the highest psychotropic drug utilization both at baseline and at the post-index dates (difference-in-differences: all <0.001). Dementia was associated with an increased risk of all-cause mortality (90 days, Odds ratio (OR)=1.85 [95%CI 1.67-2.05], p<0.001; 365 days, OR=1.59 [1.50-1.69], p<0.001) and in-hospital mortality (90 days, OR=1.97 [1.71-2.27], p<0.001; 365 days, OR=1.82 [1.61-2.05], p<0.001) compared to matched controls.

Conclusions

When older people with dementia are admitted for acute illnesses, they may increase their use of psychotropic agents and their risk of death, particularly in-hospital mortality.     

Serum Trimethylamine-N-Oxide Is Strongly Related to Renal Function and Predicts Outcome in Chronic Kidney Disease

Background

The microbial metabolite Trimethylamine-N-oxide (TMAO) has been linked to adverse cardiovascular outcome and mortality in the general population.

Objective

To assess the contribution of TMAO to inflammation and mortality in chronic kidney disease (CKD) patients ranging from mild-moderate to end-stage disease and 1) associations with glomerular filtration rate (GFR) 2) effect of dialysis and renal transplantation (Rtx) 3) association with inflammatory biomarkers and 4) its predictive value for all-cause mortality.

Methods

Levels of metabolites were quantified by a novel liquid chromatography/tandem mass spectrometry-based method in fasting plasma samples from 80 controls and 179 CKD 3–5 patients. Comorbidities, nutritional status, biomarkers of inflammation and GFR were assessed.

Results

GFR was the dominant variable affecting TMAO (β = -0.41; p<0.001), choline (β = -0.38; p<0.001), and betaine (β = 0.45; p<0.001) levels. A longitudinal study of 74 CKD 5 patients starting renal replacement therapy demonstrated that whereas dialysis treatment did not affect TMAO, Rtx reduced levels of TMAO to that of controls (p<0.001). Following Rtx choline and betaine levels continued to increase. In CKD 3–5, TMAO levels were associated with IL-6 (Rho = 0.42; p<0.0001), fibrinogen (Rho = 0.43; p<0.0001) and hsCRP (Rho = 0.17; p = 0.022). Higher TMAO levels were associated with an increased risk for all-cause mortality that remained significant after multivariate adjustment (HR 4.32, 95% CI 1.32–14.2; p = 0.016).

Conclusion

Elevated TMAO levels are strongly associated with degree of renal function in CKD and normalize after renal transplantation. TMAO levels correlates with increased systemic inflammation and is an independent predictor of mortality in CKD 3–5 patients.     

Time Interval from Symptom Onset to Hospital Care in Patients with Acute Heart Failure: A Report from the Tokyo Cardiac Care Unit Network Emergency Medical Service Database

Aims

There seems to be two distinct patterns in the presentation of acute heart failure (AHF) patients; early- vs. gradual-onset. However, whether time-dependent relationship exists in outcomes of patients with AHF remains unclear.

Methods

The Tokyo Cardiac Care Unit Network Database prospectively collects information of emergency admissions via EMS service to acute cardiac care facilities from 67 participating hospitals in the Tokyo metropolitan area. Between 2009 and 2011, a total of 3811 AHF patients were registered. The documentation of symptom onset time was mandated by the on-site ambulance team. We divided the patients into two groups according to the median onset-to-hospitalization (OH) time for those patients (2h); early- (presenting ≤2h after symptom onset) vs. gradual-onset (late) group (>2h). The primary outcome was in-hospital mortality.

Results

The early OH group had more urgent presentation, as demonstrated by a higher systolic blood pressure (SBP), respiratory rate, and higher incidence of pulmonary congestion (48.6% vs. 41.6%; P<0.001); whereas medical comorbidities such as stroke (10.8% vs. 7.9%; P<0.001) and atrial fibrillation (30.0% vs. 26.0%; P<0.001) were more frequently seen in the late OH group. Overall, 242 (6.5%) patients died during hospitalization. Notably, a shorter OH time was associated with a better in-hospital mortality rate (odds ratio, 0.71; 95% confidence interval, 0.51−0.99; P = 0.043).

Conclusions

Early-onset patients had rather typical AHF presentations (e.g., higher SBP or pulmonary congestion) but had a better in-hospital outcome compared to gradual-onset patients.     

Disparities in Outcomes following Admission for Cholangitis

Introduction

Few have examined determinants of adverse outcomes in patients presenting with ascending cholangitis. The objective of this study was to examine factors associated with in-hospital mortality, prolonged length of stay (LOS) and increased hospital charges (HC) in patients presenting with acute cholangitis.

Methods

Within the Health Care Utilization Project Nationwide Inpatient Sample (NIS), we focused on patients, 18 years and older, admitted to the emergency department with cholangitis as primary diagnosis (1998–2009). Models were fitted to predict likelihood of in-hospital mortality, prolonged LOS and increased HC. Covariates included race, day of admission, insurance status, socio-economical status and other patient and hospital characteristics.

Results

Overall, weighted estimates of 248,942 patients were admitted with acute cholangitis between 1998 and 2009, of which 13,534 (5.4%) died during the admission. Multivariable analyses revealed that relative to Caucasian patients, African American, Hispanic and Asian and Pacific Islander patients were more likely to die (OR = 1.61, p<0.001, OR = 1.20, p = 0.01 and OR = 1.26, p = 0.008), to experience a prolonged LOS (OR = 1.77, p<0.001, OR = 1.30, p<0.001, 1.34, p<0.001), and to incur high HC (OR = 1.83, p<0.001, OR = 1.51, p<0.001, OR = 1.56, p<0.001). Moreover, Medicaid and Medicare patients were more likely to die (OR = 1.64, p<0.001, OR = 1.24, p<0.001), to experience a prolonged LOS (1.74, p<0.001, OR = 1.25, p<0.001) and to incur high HC (OR = 1.23, p = 0.002, OR = 1.12, p = 0.002) compared to privately insured patients. In subgroup analysis, there were no differences for Medicare patients age 65 years and over. However, those under 65, most of whom have disability or end stage renal disease, were more likely to experience the negative outcomes.

Conclusion

Race and insurance status represent independent predictors of in-hospital mortality and adverse outcomes in patients presenting with cholangitis. Whether these disparities are due to biological predisposition or unequal quality of care requires further investigation. Regardless, efforts should be made to reduce these outcome disparities.     

Impact of Body Mass Index on In-Hospital Complications in Patients Undergoing Percutaneous Coronary Intervention in a Japanese Real-World Multicenter Registry

Background

Obesity is associated with advanced cardiovascular disease. However, some studies have reported the “obesity paradox” after percutaneous coronary intervention (PCI). The relationship between body mass index (BMI) and clinical outcomes after PCI has not been thoroughly investigated, especially in Asian populations.

Methods

We studied 10,142 patients who underwent PCI at 15 Japanese hospitals participating in the JCD-KICS registry from September 2008 to April 2013. Patients were divided into four groups according to BMI: underweight, BMI <18.5 (n=462); normal, BMI ≥18.5 and <25.0 (n=5,945); overweight, BMI ≥25.0 and <30.0 (n=3,100); and obese, BMI ≥30.0 (n=635).

Results

Patients with a high BMI were significantly younger (p<0.001) and had a higher incidence of coronary risk factors such as hypertension (p<0.001), hyperlipidemia (p<0.001), diabetes mellitus (p<0.001), and current smoking (p<0.001), than those with a low BMI. Importantly, patients in the underweight group had the worst in-hospital outcomes, including overall complications (underweight, normal, overweight, and obese groups: 20.4%, 11.5%, 8.4%, and 10.2%, p<0.001), in-hospital mortality (5.8%, 2.1%, 1.2%, and 2.7%, p<0.001), cardiogenic shock (3.5%, 2.0%, 1.5%, and 1.6%, p=0.018), bleeding complications (10.0%, 4.5%, 2.6%, and 2.8%, p<0.001), and receiving blood transfusion (7.6%, 2.7%, 1.6%, and 1.7%, p<0.001). BMI was inversely associated with bleeding complications after adjustment by multivariate logistic regression analysis (odds ratio, 0.95; 95% confidence interval, 0.92–0.98; p=0.002). In subgroup multivariate analysis of patients without cardiogenic shock, BMI was inversely associated with overall complications (OR, 0.98; 95% CI, 0.95–0.99; p=0.033) and bleeding complications (OR, 0.95; 95% CI, 0.91–0.98; p=0.006). Furthermore, there was a trend that BMI was moderately associated with in-hospital mortality (OR, 0.94; 95% CI, 0.88–1.01; p=0.091).

Conclusions

Lean patients, rather than obese patients are at greater risk for in-hospital complications during and after PCI, particularly for bleeding complications.     

In Nonagenarians,Acute Kidney Injury Predicts In-Hospital Mortality,while Heart Failure Predicts Hospital Length of Stay

Background/Aims

The elderly constitute an increasing proportion of admitted patients worldwide. We investigate the determinants of hospital length of stay and outcomes in patients aged 90 years and older.

Methods

We retrospectively analyzed all admitted patients aged >90 years from the general medical wards in a tertiary referral medical center between August 31, 2009 and August 31, 2012. Patients’ clinical characteristics, admission diagnosis, concomitant illnesses at admission, and discharge diagnosis were collected. Each patient was followed until discharge or death. Multivariate logistic regression analysis was utilized to study factors associated with longer hospital length of stay (>7 days) and in-hospital mortality.

Results

A total of 283 nonagenarian in-patients were recruited, with 118 (41.7%) hospitalized longer than one week. Nonagenarians admitted with pneumonia (p = 0.04) and those with lower Barthel Index (p = 0.012) were more likely to be hospitalized longer than one week. Multivariate logistic regression analysis revealed that patients with lower Barthel Index (odds ratio [OR] 0.98; p = 0.021) and those with heart failure (OR 3.05; p = 0.046) had hospital stays >7 days, while patients with lower Barthel Index (OR 0.93; p = 0.005), main admission nephrologic diagnosis (OR 4.83; p = 0.016) or acute kidney injury (OR 30.7; p = 0.007) had higher in-hospital mortality.

Conclusion

In nonagenarians, presence of heart failure at admission was associated with longer hospital length of stay, while acute kidney injury at admission predicted higher hospitalization mortality. Poorer functional status was associated with both prolonged admission and higher in-hospital mortality.     

The Economic Crisis and Acute Myocardial Infarction: New Evidence Using Hospital-Level Data

Objective

This research sought to assess whether and to what extent the ongoing economic crisis in Italy impacted hospitalizations, in-hospital mortality and expenditures associated with acute myocardial infarction (AMI).

Methods

The data were obtained from the hospital discharge database of the Italian Health Ministry and aggregated at the hospital level. Each hospital (n = 549) was observed for 4 years and was geographically located within a “Sistema Locale del Lavoro” (SLL, i.e., clusters of neighboring towns with a common economic structure). For each SLL, the intensity of the crisis was determined, defined as the 2012–2008 increase in the area-specific unemployment rate. A difference-in-differences (DiD) approach was employed to compare the increases in AMI-related outcomes across different quintiles of crisis intensity.

Results

Hospitals located in areas with the highest intensity of crisis (in the fifth quintile) had an increase of approximately 30 AMI cases annually (approximately 13%) compared with hospitals in area with lower crisis intensities (p<0.001). A significant increase in total hospital days was observed (13%, p<0.001) in addition to in-hospital mortality (17%, p<0.001). As a consequence, an increase of around €350.000 was incurred in annual hospital expenditures for AMI (approximately 36%, p<0.001).

Conclusions

More attention should be given to the increase in health needs associated with the financial crisis. Policies aimed to contrast unemployment in the community by keeping and reintegrating workers in jobs could also have positive impacts on adverse health outcomes, especially in areas of high crisis intensity.     

Altered Osteocyte-Specific Protein Expression in Bone after Childhood Solid Organ Transplantation

Background

Bone fragility is common post solid organ transplantation but little is known about bone pathology on a tissue level. Abnormal osteocytic protein expression has been linked to compromised bone health in chronic kidney disease (CKD) and immunosuppressant medications may impact osteocyte function.

Methods

Transiliac bone biopsies were obtained from 22 pediatric solid organ allograft recipients (average age 15.6 years) an average of 6.3 ± 1.2 years after transplantation and from 12 pediatric pre-dialysis CKD patients (average age 13.2 years). Histomorphometry and immunohistochemistry for FGF23, DMP1, sclerostin, and osteopontin were performed on all biopsies.

Results

FGF23 and sclerostin were increased in transplant recipients relative to non-transplant CKD, regardless of the type of allograft received and despite, in the case of liver and heart recipients, a higher GFR. Bone DMP1 expression was higher in liver or heart than in kidney recipients, concomitant with higher serum phosphate values. Osteopontin expression was higher in CKD than in transplant recipients (p<0.01). Bone FGF23 and sclerostin correlated directly (r = 0.38, p<0.05); bone FGF23 expression and osteoid thickness correlated inversely (r = - 0.46, p<0.01).

Conclusions

Solid-organ transplantation is associated with increased FGF23 and sclerostin expression. The contribution of these findings to compromised bone health post transplantation warrants further evaluation.     

A New Data Analysis System to Quantify Associations between Biochemical Parameters of Chronic Kidney Disease-Mineral Bone Disease

Background

In hemodialysis patients, deviations from KDIGO recommended values of individual parameters, phosphate, calcium or parathyroid hormone (PTH), are associated with increased mortality. However, it is widely accepted that these parameters are not regulated independently of each other and that therapy aimed to correct one parameter often modifies the others. The aim of the present study is to quantify the degree of association between parameters of chronic kidney disease and mineral bone disease (CKD-MBD).

Methods

Data was extracted from a cohort of 1758 adult HD patients between January 2000 and June 2013 obtaining a total of 46.141 records (10 year follow-up). We used an advanced data analysis system called Random Forest (RF) which is based on self-learning procedure with similar axioms to those utilized for the development of artificial intelligence. This new approach is particularly useful when the variables analyzed are closely dependent to each other.

Results

The analysis revealed a strong association between PTH and phosphate that was superior to that of PTH and Calcium. The classical linear regression analysis between PTH and phosphate shows a correlation coefficient is 0.27, p<0.001, the possibility to predict PTH changes from phosphate modification is marginal. Alternatively, RF assumes that changes in phosphate will cause modifications in other associated variables (calcium and others) that may also affect PTH values. Using RF the correlation coefficient between changes in serum PTH and phosphate is 0.77, p<0.001; thus, the power of prediction is markedly increased. The effect of therapy on biochemical variables was also analyzed using this RF.

Conclusion

Our results suggest that the analysis of the complex interactions between mineral metabolism parameters in CKD-MBD may demand a more advanced data analysis system such as RF.     

Delta Neutrophil Index as a Promising Prognostic Marker in Out of Hospital Cardiac Arrest

Background

The post-resuscitation phase after out-of-hospital cardiac arrest (OHCA) is characterised by a systemic inflammatory response (e.g., severe sepsis), for which the immature granulocyte count is a diagnostic marker. In this study we evaluated the prognostic significance of the delta neutrophil index (DNI), which is the difference in leukocyte subfractions as assessed by an automated blood cell analyser, for early mortality after OHCA.

Materials and Methods

OHCA records from the emergency department cardiac arrest registry were retrospectively analysed. Patients who survived at least 24 h after return of spontaneous circulation were included in the analysis. We evaluated mortality and cerebral performance category scores at 30 days.

Results

A total of 83 patients with OHCA were included in the study. Our results showed that DNI >8.4% on day 1 (hazard ratio [HR], 3.227; 95% CI, 1.485–6.967; p = 0.001) and DNI >10.5% on day 2 (HR, 3.292; 95% CI, 1.662–6.519; p<0.001) were associated with increased 30-day mortality in patients with OHCA. Additionally, DNI >8.4% on day 1 (HR, 2.718; 95% CI, 1.508–4.899; p<0.001) and DNI >10.5% on day 2 (HR, 1.709; 95% CI, 1.051–2.778; p = 0.02) were associated with worse neurologic outcomes 30 days after OHCA.

Conclusion

A higher DNI is a promising prognostic marker for 30-day mortality and neurologic outcomes after OHCA. Our findings indicate that patients with elevated DNI values after OHCA might be closely monitored so that appropriate treatment strategies can be implemented.     

Nucleated Red Blood Cells as Predictors of All-Cause Mortality in Cardiac Intensive Care Unit Patients: A Prospective Cohort Study

Background

The presence of nucleated red blood cells (NRBCs) in the peripheral blood of critically ill patients is associated with a poorer prognosis, though data on cardiovascular critical care patients is lacking. The aim of the present study was to assess the role of NRBCs as a predictor of intensive care unit (ICU) and in hospital all-cause mortality among cardiologic patients.

Methods

NRBCs were measured daily in consecutive cardiac ICU patients, including individuals with both coronary and non-coronary acute cardiac care. We excluded patients younger than 18 years, with cancer or hematological disease, on glucocorticoid therapy, those that were readmitted after hospital discharge and patients who died in the first 24 hours after admission. We performed a multiple logistic analysis to identify independent predictors of mortality.

Results

We included 152 patients (60.6 ± 16.8 years, 51.8% female, median ICU stay of 7 [4–11] days). The prevalence of NRBCs was 54.6% (83/152). The presence of NRBC was associated with a higher ICU mortality (49.4% vs 21.7%, P<0.001) as well as in-hospital mortality (61.4% vs 33.3%, p = 0.001). NRBC were equally associated with mortality among coronary disease (64.71% vs 32.5% [OR 3.80; 95%CI: 1.45–10.0; p = 0.007]) and non-coronary disease patients (61.45% vs 33.3% [OR 3.19; 95%CI: 1.63–6.21; p<0.001]). In a multivariable model, the inclusion of NRBC to the APACHE II score resulted in a significant improvement in the discrimination (p = 0.01).

Conclusions

NRBC are predictors of all-cause in-hospital mortality in patients admitted to a cardiac ICU. This predictive value is independent and complementary to the well validated APACHE II score.     

Performance of Three Prognostic Models in Patients with Cancer in Need of Intensive Care in a Medical Center in China

Objective

The aim of this study was to evaluate the performance of Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score 3 (SAPS 3), and Acute Physiology and Chronic Health Evaluation IV (APACHE IV) in patients with cancer admitted to intensive care unit (ICU) in a single medical center in China.

Materials and Methods

This is a retrospective observational cohort study including nine hundred and eighty one consecutive patients over a 2-year period.

Results

The hospital mortality rate was 4.5%. When all 981 patients were evaluated, the area under the receiver operating characteristic curve (AUROC, 95% Confidential Intervals) of the three models in predicting hospital mortality were 0.948 (0.914–0.982), 0.863 (0.804–0.923), and 0.873 (0.813–0.934) for SAPS 3, APACHE II and APACHE IV respectively. The p values of Hosmer-Lemeshow statistics for the models were 0.759, 0.900 and 0.878 for SAPS 3, APACHE II and APACHE IV respectively. However, SAPS 3 and APACHE IV underestimated the in-hospital mortality with standardized mortality ratio (SMR) of 1.5 and 1.17 respectively, while APACHE II overestimated the in-hospital mortality with SMR of 0.72. Further analysis showed that discrimination power was better with SAPS 3 than with APACHE II and APACHE IV whether for emergency surgical and medical patients (AUROC of 0.912 vs 0.866 and 0.857) or for scheduled surgical patients (AUROC of 0.945 vs 0.834 and 0.851). Calibration was good for all models (all p > 0.05) whether for scheduled surgical patients or emergency surgical and medical patients. However, in terms of SMR, SAPS 3 was both accurate in predicting the in-hospital mortality for emergency surgical and medical patients and for scheduled surgical patients, while APACHE IV and APACHE II were not.

Conclusion

In this cohort, we found that APACHE II, APACHE IV and SAPS 3 models had good discrimination and calibration ability in predicting in-hospital mortality of critically ill patients with cancer in need of intensive care. Of these three severity scores, SAPS 3 was superior to APACHE II and APACHE IV, whether in terms of discrimination and calibration power, or standardized mortality ratios.     

Angiographic Lesion Complexity Score and In-Hospital Outcomes after Percutaneous Coronary Intervention

Objective

We devised a percutaneous coronary intervention (PCI) scoring system based on angiographic lesion complexity and assessed its association with in-hospital complications.

Background

Although PCI is finding increasing application in patients with coronary artery disease, lesion complexity can lead to in-hospital complications.

Methods

Data from 3692 PCI patients were scored based on lesion complexity, defined by bifurcation, chronic total occlusion, type C, and left main lesion, along with acute thrombus in the presence of ST-segment elevation myocardial infarction (1 point assigned for each variable).

Results

The patients’ mean age was 67.5 +/- 10.8 years; 79.8% were male. About half of the patients (50.3%) presented with an acute coronary syndrome, and 2218 (60.1%) underwent PCI for at least one complex lesion. The patients in the higher-risk score groups were older (p < 0.001) and had present or previous heart failure (p = 0.02 and p = 0.01, respectively). Higher-risk score groups had significantly higher in-hospital event rates for death, heart failure, and cardiogenic shock (from 0 to 4 risk score; 1.7%, 4.5%, 6.3%, 7.1%, 40%, p < 0.001); bleeding with a hemoglobin decrease of >3.0 g/dL (3.1%, 11.0%, 13.1%, 10.3%, 28.6%, p < 0.001); and postoperative myocardial infarction (1.5%, 3.1%, 3.8%, 3.8%, 10%, p = 0.004), respectively. The association with adverse outcomes persisted after adjustment for known clinical predictors (odds ratio 1.72, p < 0.001).

Conclusion

The complexity score was cumulatively associated with in-hospital mortality and complication rate and could be used for event prediction in PCI patients.     

Free Levels of Selected Organic Solutes and Cardiovascular Morbidity and Mortality in Hemodialysis Patients: Results from the Retained Organic Solutes and Clinical Outcomes (ROSCO) Investigators

Background and Objectives

Numerous substances accumulate in the body in uremia but those contributing to cardiovascular morbidity and mortality in dialysis patients are still undefined. We examined the association of baseline free levels of four organic solutes that are secreted in the native kidney — p-cresol sulfate, indoxyl sulfate, hippurate and phenylacetylglutamine — with outcomes in hemodialysis patients.

Design, Setting, Participants and Measurements

We measured these solutes in stored specimens from 394 participants of a US national prospective cohort study of incident dialysis patients. We examined the relation of each solute and a combined solute index to cardiovascular mortality and morbidity (first cardiovascular event) using Cox proportional hazards regression adjusted for demographics, comorbidities, clinical factors and laboratory tests including Kt/V_UREA.

Results

Mean age of the patients was 57 years, 65% were white and 55% were male. In fully adjusted models, a higher p-cresol sulfate level was associated with a greater risk (HR per SD increase; 95% CI) of cardiovascular mortality (1.62; 1.17–2.25; p=0.004) and first cardiovascular event (1.60; 1.23–2.08; p<0.001). A higher phenylacetylglutamine level was associated with a greater risk of first cardiovascular event (1.37; 1.18–1.58; p<0.001). Patients in the highest quintile of the combined solute index had a 96% greater risk of cardiovascular mortality (1.96; 1.05–3.68; p=0.04) and 62% greater risk of first cardiovascular event (1.62; 1.12–2.35; p=0.01) compared with patients in the lowest quintile. Results were robust in sensitivity analyses.

Conclusions

Free levels of uremic solutes that are secreted by the native kidney are associated with a higher risk of cardiovascular morbidity and mortality in incident hemodialysis patients.     

Association between Inflammation and Cardiac Geometry in Chronic Kidney Disease: Findings from the CRIC Study

Background

Left ventricular hypertrophy (LVH) and myocardial contractile dysfunction are independent predictors of mortality in patients with chronic kidney disease (CKD). The association between inflammatory biomarkers and cardiac geometry has not yet been studied in a large cohort of CKD patients with a wide range of kidney function.

Methods

Plasma levels of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, high-sensitivity C-Reactive protein (hs-CRP), fibrinogen and serum albumin were measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Echocardiography was performed according to the recommendations of the American Society of Echocardiography and interpreted at a centralized core laboratory.

Results

LVH, systolic dysfunction and diastolic dysfunction were present in 52.3%, 11.8% and 76.3% of the study subjects, respectively. In logistic regression analysis adjusted for age, sex, race/ethnicity, diabetic status, current smoking status, systolic blood pressure, urinary albumin- creatinine ratio and estimated glomerular filtration rate, hs-CRP (OR 1.26 [95% CI 1.16, 1.37], p<0.001), IL-1RA (1.23 [1.13, 1.34], p<0.0001), IL-6 (1.25 [1.14, 1.36], p<0.001) and TNF-α (1.14 [1.04, 1.25], p = 0.004) were associated with LVH. The odds for systolic dysfunction were greater for subjects with elevated levels of hs-CRP (1.32 [1.18, 1.48], p<0.001) and IL-6 (1.34 [1.21, 1.49], p<0.001). Only hs-CRP was associated with diastolic dysfunction (1.14 [1.04, 1.26], p = 0.005).

Conclusion

In patients with CKD, elevated plasma levels of hs-CRP and IL-6 are associated with LVH and systolic dysfunction.     

Systemic Inflammation Predicts All-Cause Mortality: A Glasgow Inflammation Outcome Study

Introduction

Markers of the systemic inflammatory response, including C-reactive protein and albumin (combined to form the modified Glasgow Prognostic Score), as well as neutrophil, lymphocyte and platelet counts have been shown to be prognostic of survival in patients with cancer. The aim of the present study was to examine the prognostic relationship between these markers of the systemic inflammatory response and all-cause, cancer, cardiovascular and cerebrovascular mortality in a large incidentally sampled cohort.

Methods

Patients (n = 160 481) who had an incidental blood sample taken between 2000 and 2008 were studied for the prognostic value of C-reactive protein (>10mg/l, albumin (>35mg/l), neutrophil (>7.5×10⁹/l) lymphocyte and platelet counts. Also, patients (n = 52 091) sampled following the introduction of high sensitivity C-reactive protein (>3mg/l) measurements were studied. A combination of these markers, to make cumulative inflammation-based scores, were investigated.

Results

In all patients (n = 160 481) C-reactive protein (>10mg/l) (HR 2.71, p<0.001), albumin (>35mg/l) (HR 3.68, p<0.001) and neutrophil counts (HR 2.18, p<0.001) were independently predictive of all-cause mortality. These associations were also observed in cancer, cardiovascular and cerebrovascular mortality before and after the introduction of high sensitivity C-reactive protein measurements (>3mg/l) (n = 52 091). A combination of high sensitivity C-reactive protein (>3mg/l), albumin and neutrophil count predicted all-cause (HR 7.37, p<0.001, AUC 0.723), cancer (HR 9.32, p<0.001, AUC 0.731), cardiovascular (HR 4.03, p<0.001, AUC 0.650) and cerebrovascular (HR 3.10, p<0.001, AUC 0.623) mortality.

Conclusion

The results of the present study showed that an inflammation-based prognostic score, combining high sensitivity C-reactive protein, albumin and neutrophil count is prognostic of all-cause mortality.     

Hepcidin-25 in Diabetic Chronic Kidney Disease Is Predictive for Mortality and Progression to End Stage Renal Disease

Background

Anemia is common and is associated with impaired clinical outcomes in diabetic chronic kidney disease (CKD). It may be explained by reduced erythropoietin (EPO) synthesis, but recent data suggest that EPO-resistance and diminished iron availability due to inflammation contribute significantly. In this cohort study, we evaluated the impact of hepcidin-25—the key hormone of iron-metabolism—on clinical outcomes in diabetic patients with CKD along with endogenous EPO levels.

Methods

249 diabetic patients with CKD of any stage, excluding end-stage renal disease (ESRD), were enrolled (2003–2005), if they were not on EPO-stimulating agent and iron therapy. Hepcidin-25 levels were measured by radioimmunoassay. The association of hepcidin-25 at baseline with clinical variables was investigated using linear regression models. All-cause mortality and a composite endpoint of CKD progression (ESRD or doubling of serum creatinine) were analyzed by Cox proportional hazards models.

Results

Patients (age 67 yrs, 53% male, GFR 51 ml/min, hemoglobin 131 g/L, EPO 13.5 U/L, hepcidin-25 62.0 ng/ml) were followed for a median time of 4.2 yrs. Forty-nine patients died (19.7%) and forty (16.1%) patients reached the composite endpoint. Elevated hepcidin levels were independently associated with higher ferritin-levels, lower EPO-levels and impaired kidney function (all p<0.05). Hepcidin was related to mortality, along with its interaction with EPO, older age, greater proteinuria and elevated CRP (all p<0.05). Hepcidin was also predictive for progression of CKD, aside from baseline GFR, proteinuria, low albumin- and hemoglobin-levels and a history of CVD (all p<0.05).

Conclusions

We found hepcidin-25 to be associated with EPO and impaired kidney function in diabetic CKD. Elevated hepcidin-25 and EPO-levels were independent predictors of mortality, while hepcidin-25 was also predictive for progression of CKD. Both hepcidin-25 and EPO may represent important prognostic factors of clinical outcome and have the potential to further define “high risk” populations in CKD.     

Risk of Post-Discharge Venous Thromboembolism and Associated Mortality in General Surgery: A Population-Based Cohort Study Using Linked Hospital and Primary Care Data in England

Background

Trends towards day case surgery and enhanced recovery mean that postoperative venous thromboembolism (VTE) may increasingly arise after hospital discharge. However, hospital data alone are unable to capture adverse events that occur outside of the hospital setting. The National Institute for Health and Care Excellence has suggested the use of primary care data to quantify hospital care-related VTE. Data in surgical patients using these resources is lacking. The aim of this study was to measure VTE risk and associated mortality in general surgery using linked primary care and hospital databases, to improve our understanding of harm from VTE that arises beyond hospital stay.

Methods

This was a longitudinal cohort study using nationally linked primary care (Clinical Practice Research Datalink, CPRD), hospital administrative (Hospital Episodes Statistics, HES), population statistics (Office of National Statistics, ONS) and National Cancer Intelligence Network databases. Routinely collected information was used to quantify 90-day in-hospital VTE, 90-day post-discharge VTE and 90-day mortality in adults undergoing one of twelve general surgical procedures between 1st April 1997 and 31st March 2012. The earliest postoperative recording of deep vein thrombosis or pulmonary embolism in CPRD, HES and ONS was counted in each patient. Covariates from multiple datasets were combined to derive detailed prediction models for VTE and mortality. Limitation included the capture of VTE presenting to healthcare only and the lack of information on adherence to pharmacological thromboprophylaxis as there was no data linkage to hospital pharmacy records.

Results

There were 981 VTE events captured within 90 days of surgery in 168005 procedures (23.7/1000 patient-years). Overall, primary care data increased the detection of postoperative VTE by a factor of 1.38 (981/710) when compared with using HES and ONS only. Total VTE rates ranged between 3.2/1000 patient-years in haemorrhoidectomy to 118.3/1000 patient-years in esophagogastric resection. Predictors of VTE included emergency surgery (OR = 1.91 95%CI 1.60–2.28, p<0.001), age (OR = 1.02 95%CI 1.02–1.03, p<0.001), body mass index (OR = 1.03 95%CI 1.01–1.04, p<0.001), previous VTE (OR = 8.07 95%CI 6.61–9.83, p<0.001), length of stay (OR = 1.00 95%CI 1.00–1.00, p = 0.007) and cancer stages II (OR = 1.38 95%CI 1.03–1.87, p = 0.033), III (OR = 1.50 95%CI 1.11–2.01, p = 0.008) and IV (OR = 1.63 95%CI 1.03–2.59, p = 0.038). Major organ resections had the greatest odds of VTE when adjusted for other risk factors including length of hospital stay. Post-discharge VTE accounted for 64.8% (636/981) of all recorded VTE. In-hospital VTE (165.4/1000 patient-years) was recorded more frequently than post-discharge VTE (16.2/1000 patient-years). Both in-hospital (OR = 2.07 95%CI 1.51–2.85, p<0.001) and post-discharge (OR = 4.03 95%CI 2.95–5.51, p<0.001) VTE independently predicted 90-day mortality. In patients who died and VTE was recorded on HES or CPRD (n = 56), VTE was one of the causes of death in 37.5% (21/56) of cases.

Conclusions

A large proportion of postoperative VTE was detected in primary care. Evaluation of linked databases was a useful way of measuring postoperative VTE at population level. These resources identified a significant association between post-discharge VTE and mortality in general surgery.     

Age-Related Disparity in Immediate Prognosis of Patients with Triple-Negative Breast Cancer: A Population-Based Study from SEER Cancer Registries

Background

Triple-negative breast cancer (TNBC) has been demonstrated to carry poor prognosis, but whether or not there exists any age-related variation in TNBC outcomes has yet to be elucidated. The current population-based study investigated the early survival pattern of elderly women with TNBC and identified outcome-correlated factors.

Patients and Methods

We searched the Surveillance, Epidemiology, and End Results (SEER) database and enrolled female primary non-metastatic TNBC cases. The patients were subdivided into elderly (≥70 years) and young groups (<70 years). The survival status of elderly patients was compared to that of the younger women. The primary and secondary endpoints were cancer-specific survival (CSS) and overall survival (OS) respectively.

Results

9908 female TNBC patients diagnosed from 2010 to 2011 were included in the current study (20.4% elderly). Elderly patients with relatively advanced diseases exhibited distinctly worse cancer-specific (log-rank, p<0.001) and overall survival (log-rank, p<0.001) than their young counterparts. Advanced age at diagnosis (≥70 years) was significantly predictive of poor outcome in terms of CSS (hazard ratio (HR), 2.125; 95% confidence interval (CI), 1.664 to 2.713; p<0.001) and OS (HR, 3.042; 95%CI, 2.474 to 3.740; p<0.001). Underuse of curative treatment especially radiotherapy was more prevalent in elderly women with stage II or III diseases than in younger patients.

Conclusion

Elderly patients with TNBC displayed elevated early mortality within the first two years of diagnosis compared to the younger individuals. The observed lower rate of loco-regional treatment might be associated with worse cancer-specific outcome for these patients.