David Yanez

Weight Change in Old Age and its Association with Mortality

Previous studies of weight change and mortality in older adults have relied on self‐reported weight loss, have not evaluated weight gain, or have had limited information on health status. Our objective was to determine whether 5% weight gain or loss in 3 years was predictive of mortality in a large sample of older adults.

Importance of perioperative glycemic control in general surgery: A report from the surgical care and outcomes assessment program

Objective:To determine the relationship of perioperative hyperglycemia and insulin administration on outcomes in elective colon/rectal and bariatric operations. Background:There is limited evidence to characterize the impact of perioperative hyperglycemia and insulin on adverse outcomes in patients, with and without diabetes, undergoing general surgical procedures. Methods:The Surgical Care and Outcomes Assessment Program is a Washington State quality improvement benchmarking-based initiative. We evaluated the relationship of perioperative hyperglycemia (>180 mg/dL) and insulin administration on mortality, reoperative interventions, and infections for patients undergoing elective colorectal and bariatric surgery at 47 participating hospitals between fourth quarter of 2005 and fourth quarter of 2010. Results:Of the 11,633 patients (55.4 ± 15.3 years; 65.7% women) with a serum glucose determination on the day of surgery, postoperative day 1, or postoperative day 2, 29.1% of patients were hyperglycemic. After controlling for clinical factors, those with hyperglycemia had a significantly increased risk of infection [odds ratio (OR) 2.0; 95% confidence interval (CI), 1.63–2.44], reoperative interventions (OR, 1.8; 95% CI, 1.41–2.3), and death (OR, 2.71; 95% CI, 1.72–4.28). Increased risk of poor outcomes was observed both for patients with and without diabetes. Those with hyperglycemia on the day of surgery who received insulin had no significant increase in infections (OR, 1.01; 95% CI, 0.72–1.42), reoperative interventions (OR, 1.29; 95% CI, 0.89–1.89), or deaths (OR, 1.21; 95% CI, 0.61–2.42). A dose-effect relationship was found between the effectiveness of insulin-related glucose control (worst 180–250 mg/dL, best <130 mg/dL) and adverse outcomes. Conclusions:Perioperative hyperglycemia was associated with adverse outcomes in general surgery patients with and without diabetes. However, patients with hyperglycemia who received insulin were at no greater risk than those with normal blood glucoses. Perioperative glucose evaluation and insulin administration in patients with hyperglycemia are important quality targets.

Fibrinogen and Factor VIII, but Not Factor VII, Are Associated With Measures of Subclinical Cardiovascular Disease in the Elderly Results From the Cardiovascular Health Study

No studies have examined the associations of coagulation factor levels with measures of subclinical cardiovascular disease (CVD) in the elderly. The Cardiovascular Health Study (CHS) is a prospective, population-based cohort study of CVD in persons older than 65 years. At the baseline examination, we measured fibrinogen, factor VII, and factor VIII levels in 5024 of the 5201 participants of the CHS and examined the associations of these coagulation factors with measures of subclinical CVD in a cross-sectional analysis. Subclinical CVD measures were based on electrocardiography, carotid ultrasonography, echocardiography, and ankle-arm blood pressure measurements (AAI). For analyses, we used the full cohort as well as two mutually exclusive subgroups: those with prevalent clinical CVD at baseline and those without. Fibrinogen and to a lesser extent factor VIII showed positive associations with a variety of subclinical CVD measures. In age-adjusted analyses, fibrinogen and factor VIII were significantly associated with 8 of 10 measures. In multivariate analyses, fibrinogen was significantly associated with carotid artery stenosis, internal (but not common) carotid artery wall thickness, and AAI. Factor VIII was associated with abnormal wall motion and AAI in the full cohort only. Factor VII was not consistently associated with subclinical disease measures. In bivariate analyses that included data from all three groups, there were 5 positive subclinical disease associations and 5 negative associations for factor VII. In multivariate analyses, there were no significant associations between factor VII and subclinical CVD in the full cohort or in either subgroup. We conclude that in these cross-sectional analyses, fibrinogen and to a lesser extent factor VIII are associated with subclinical CVD in the elderly, even in those without symptoms or a history of clinical CVD. Factor VII, however, was not associated with subclinical CVD in the elderly.

Individual progression of carotid intima media thickness as a surrogate for vascular risk (PROG-IMT): Rationale and design of a meta-analysis project

Carotid intima media thickness (IMT) progression is increasingly used as a surrogate for vascular risk. This use is supported by data from a few clinical trials investigating statins, but established criteria of surrogacy are only partially fulfilled. To provide a valid basis for the use of IMT progression as a study end point, we are performing a 3-step meta-analysis project based on individual participant data. Objectives of the 3 successive stages are to investigate (1) whether IMT progression prospectively predicts myocardial infarction, stroke, or death in population-based samples; (2) whether it does so in prevalent disease cohorts; and (3) whether interventions affecting IMT progression predict a therapeutic effect on clinical end points. Recruitment strategies, inclusion criteria, and estimates of the expected numbers of eligible studies are presented along with a detailed analysis plan.

Inflammatory markers and extent and progression of early atherosclerosis: Meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration

Background Large-scale epidemiological evidence on the role of inflammation in early atherosclerosis, assessed by carotid ultrasound, is lacking. We aimed to quantify cross-sectional and longitudinal associations of inflammatory markers with common-carotid-artery intima-media thickness (CCA-IMT) in the general population. Methods Information on high-sensitivity C-reactive protein, fibrinogen, leucocyte count and CCA-IMT was available in 20 prospective cohort studies of the PROG-IMT collaboration involving 49,097 participants free of pre-existing cardiovascular disease. Estimates of associations were calculated within each study and then combined using random-effects meta-analyses. Results Mean baseline CCA-IMT amounted to 0.74 mm (SD = 0.18) and mean CCA-IMT progression over a mean of 3.9 years to 0.011 mm/year (SD = 0.039). Cross-sectional analyses showed positive linear associations between inflammatory markers and baseline CCA-IMT. After adjustment for traditional cardiovascular risk factors, mean differences in baseline CCA-IMT per one-SD higher inflammatory marker were: 0.0082 mm for high-sensitivity C-reactive protein (p < 0.001); 0.0072 mm for fibrinogen (p < 0.001); and 0.0025 mm for leucocyte count (p = 0.033). ‘Inflammatory load’, defined as the number of elevated inflammatory markers (i.e. in upper two quintiles), showed a positive linear association with baseline CCA-IMT (p < 0.001). Longitudinal associations of baseline inflammatory markers and changes therein with CCA-IMT progression were null or at most weak. Participants with the highest ‘inflammatory load’ had a greater CCA-IMT progression (p = 0.015). Conclusion Inflammation was independently associated with CCA-IMT cross-sectionally. The lack of clear associations with CCA-IMT progression may be explained by imprecision in its assessment within a limited time period. Our findings for ‘inflammatory load’ suggest important combined effects of the three inflammatory markers on early atherosclerosis.

Temporal Trends in the Management of Potentially Resectable Lung Cancer

BACKGROUND Standardized, evidence-based guidelines recommend lung resection for patients with stage I or II nonsmall-cell lung cancer (NSCLC), and select patients with stage IIIA disease. We hypothesized that the proportion of patients operated on would increase over time coincident with increasing adherence to practice guidelines and improved patient/provider education over time. METHODS This investigation was a cohort study of tumor-registry data linked to Medicare claims. RESULTS Between 1992 and 2002, 24,030 patients--mean age 75 +/- 6 years, 55% men--were diagnosed with NSCLC. In each stage, the proportion of patients undergoing resection was lower in 2002 compared with 1992: stage I (68% versus 80%, p < 0.001), II (59% versus 74%, p < 0.001), and IIIA (23% versus 35%, p < 0.001). The mean age and comorbidity index of the cohort was higher in 2002 compared with 1992 (76 versus 74 years, p < 0.001; and 0.47 and 0.82, p < 0.001, respectively). The unadjusted odds of resection decreased by 6% per year (odds ratio 0.94, 99% confidence interval: 0.93 to 0.95), and adjustment for age, comorbidity index, race, and stage resulted in a slightly smaller (4% per year) but significantly decreasing trend in operative management over time (odds ratio 0.96, 99% confidence interval: 0.95 to 0.97). CONCLUSIONS Unexpectedly, the use of resection for lung cancer has decreased dramatically over time, and this decline is not fully accounted for by an older cohort with more comorbid conditions. Future investigations should determine whether increasing unmeasured contraindications to resection, barriers to accessing specialty care, an inadequate supply of thoracic surgeons, or bias against operative therapy are responsible.

ACE-inhibition increases podocyte number in experimental glomerular disease independent of proliferation

Objective: The objective of this article is to test the effects of angiotensin-converting enzyme (ACE)-inhibition on glomerular epithelial cell number in an inducible experimental model of focal segmental glomerulosclerosis (FSGS). Background: Although ACE-inhibition has been shown to limit podocyte loss by enhancing survival, little is known about its effect on podocyte number following an abrupt decline in disease. Methods: Experimental FSGS was induced with cytotoxic antipodocyte antibody. Following induction, groups were randomized to receive the ACE-inhibitor enalapril, the smooth muscle relaxant hydralazine (blood pressure control) or drinking water. Blood pressure, kidney function and histology were measured seven and 14 days following disease induction. Results: Both glomerulosclerosis and urinary albumin-to-creatinine ratio were less in the ACE-inhibition arm at day 14. At day 7 of disease, mean podocyte numbers were 26% and 29% lower in the enalapril and hydralazine arms, respectively, compared to normal mice in which no antibody was injected. At day 14, the mean podocyte number was only 18% lower in the enalapril arm, but was 39% lower in the hydralazine arm compared to normal mice. Podocyte proliferation did not occur at any time in any group. Compared to water- or hydralazine-treated mice with FSGS, the enalapril arm had a higher mean number of glomerular parietal epithelial cells that co-expressed the podocyte proteins WT-1 and synaptopodin, as well as phospho-ERK. Conclusion: The results show following an abrupt decline in podocyte number, the initiation of ACE-inhibition but not hydralazine, was accompanied by higher podocyte number in the absence of proliferation. This was accompanied by a higher number of parietal epithelial cells that co-express podocyte proteins. Increasing podocyte number appears to be accompanied by reduced glomerulosclerosis.

The Association Between Time Since Last Meal and Blood Pressure in Older Adults: The Cardiovascular Health Study

OBJECTIVES: To demonstrate a postprandial hypotensive (PPH) phenomenon in older adults.

Daytime Sleepiness, Poor Sleep Quality, Eveningness Chronotype, and Common Mental Disorders among Chilean College Students.

Abstract Objectives: To evaluate whether daytime sleepiness, poor sleep quality, and morningness and eveningness preferences are associated with common mental disorders (CMDs) among college students. Methods: A total of 963 college students completed self-administered questionnaires that collected information about sociodemographic characteristics, sleep quality characteristics, CMDs, and other lifestyle behaviors. Results: The prevalence of CMDs was 24.3% (95% confidence interval [CI] [21.5%, 27.1%]) among all students. Prevalence estimates of both excessive daytime sleepiness and poor sleep quality were higher among females (35.4% and 54.4%) than males (22.0% and 45.8%). Cigarette smoking was statistically significantly and positively associated with having CMDs (p = .034). Excessive daytime sleepiness (odds ratio [OR] = 3.65; 95% CI [2.56, 4.91]) and poor sleep quality (OR = 4.76; 95% CI [3.11, 7.29]) were associated with increased odds of CMDs. Conclusion: Given the adverse health consequences associated with both sleep disorders and CMDs, improving sleep hygiene among college students is imperative to public health.

Antenatal haemoglobin A1c and risk of large-for-gestational-age infants in a multi-ethnic cohort of women with gestational diabetes.

Gestational diabetes mellitus (GDM) is a risk factor for delivering a large-for-gestational-age (LGA) infant. Haemoglobin A1c (A1C) is an indicator of glycaemic control. The objective of this study was to test whether higher A1C quartile at the time of diagnosis of GDM is associated with increased risk of delivering a LGA or macrosomic infant. Women with singleton pregnancies treated for GDM at a large diabetes and pregnancy programme located in Charlotte, North Carolina, were eligible for inclusion in this retrospective cohort study. Clinical information, including A1C at diagnosis, treatment, prior medical and obstetric history, and birth data were abstracted from medical records. LGA was defined as birthweight >90th percentile for gestational age and sex and macrosomia as birthweight >4000 g. Logistic regression was used to analyse the association of A1C at GDM diagnosis with risk of delivering LGA or macrosomic infants. This study included 502 women. Prevalences of LGA and macrosomia were 4% and 6% respectively. After adjustment there was no detectable trend of increased risk for LGA (P for trend = 0.12) or macrosomia (P for trend = 0.20) across increasing quartiles of A1C at GDM diagnosis. A1C at GDM diagnosis may not be linearly associated with LGA or macrosomia, possibly because of the mediating effect of strict glycaemic control in this clinical setting.