Sliding Scale Insulin vs Basal-Bolus Insulin Therapy in Long-Term Care: A 21-Day Randomized Controlled Trial Comparing Efficacy, Safety and Feasibility.

INTRODUCTION: Sliding scale insulin (SSI) therapy remains a common means of insulin therapy in long-term care (LTC) for the management of type 2 diabetes mellitus, despite current recommendations not supportive of the form of therapy today. Lack of randomized trial data on the efficacy and safety of basal-bolus insulin (B-BI) therapy in nursing home residents may have precluded this form of insulin administration in the LTC setting. Our study is a comparison of the efficacy of SSI (control) and B-BI (intervention) therapies during a 21-day intervention trial in older nursing home residents. METHODS: Fourteen LTC facilities in the US participated; 110 residents with type 2 diabetes volunteered to participate; 35 failed inclusion criteria, 75 signed informed written consent, and 11 were discharged to home/hospital or withdrew consent; data from 64 participants are reported. Recent fasting blood glucose (FBG), hemoglobin A1c, and chemistries were obtained. Four glucose readings (prior to breakfast, lunch, dinner, and bedtime), oral antiglycemic drug, and insulin doses and changes, and all adverse events/serious adverse events, both those related to glucose control [hypoglycemic (<70 mg/dL) and hyperglycemic (>200 mg/dL) episodes] and those unrelated, were recorded daily. Patients were randomized to either remain on SSI or be shifted to the B-BI group. RESULTS: Nursing home residents 80 ± 8 (standard deviation) years, 66% female participated; Control and Intervention participants had similar age, gender, race distributions, comorbidity, and 3-day average pretrial FBG levels (all P > .05). At study end, B-BI volunteers had significantly lower 3-day average FBG levels vs pretrial (P = .0231) while SSI participants had no change in 3-day average FBG (P > .05). During the trial, participants from both groups had similar rates of hypoglycemia, hyperglycemia, other adverse events, and hospitalizations (serious adverse events) unrelated to glucose control (all P > .05). CONCLUSIONS: B-BI therapy produced significantly lower average FBG levels after 21 days compared with SSI therapy; both groups had similar rates of hypo- and hyperglycemia. Switching to B-BI therapy is feasible, safe, and effective in the LTC setting.

Prevention of venous thromboembolism in long term care: results of a multicenter educational intervention using clinical practice guidelines: part 2 of 2 (an AMDA Foundation project).

INTRODUCTION: Implementation of prophylaxis for venous thomboembolism (VTE) through risk assessment based on clinical practice guidelines (CPGs) is variably adopted in long term care facilities (LTCF). Current guidelines recommend venous thromboembolism prophylaxis (VTE-P) following risk assessment, individualized to patient status. In LTCF, differing comorbidity, life-expectancy, ethical, and quality-of-life issues may warrant a unique approach. This article examines VTE-P practices in LTCF before and after educational intervention to bring practice patterns consistent with CPGs. METHODS: Phase 1 (preceding article in this issue) identified current practice to assess risk and implement VTE-P (17 geographically diverse LTCFs, 3260 total beds). Phase 2 (educational intervention using CPGs) and Phase 3 (outcomes) reexamined VTE-P at the same 17 centers. RESULTS: The frequency of indications for VTE-P and contraindications to anticoagulation were similar during Phases 1 and 3 (all P > .05). In Phase 3, use of aspirin alone decreased more than 50% (P < .0005), whereas use of compression devices increased (P < .0005). Regression models predicted no relationship between any indication or contraindication and VTE-P in Phase 1 (all P > .05) but identified significant relationships between indication and contraindications and VTE-P in Phase 3 (P = .022 to P < .0005), suggesting adequate understanding of current CPGs following education as the basis for improved VTE-P. CONCLUSIONS: The study confirms the presence of significant comorbidity in LTC residents, many with indications for VTE-P, some with contraindications for anticoagulation. Following educational intervention, more residents received VTE-P, influenced by risk-benefit ratio favoring treatment. These findings suggest that even a modest educational intervention significantly improves provider knowledge pertinent to risk assessment consistent with CPG and more appropriate VTE-P.

Prevention of venous thromboembolism: practice patterns in 17 geographically diverse long term care facilities in the United States: part 1 of 2 (an AMDA Foundation project).

INTRODUCTION: Current guidelines recommend antithrombotic prophylaxis for venous thromboembolism (VTE) using risk assessment, factoring contraindications. This report represents a summary of current practice patterns to prevent VTE in long term care as Phase 1 of a 3-phase educational intervention study. PHASE 1 PARTICIPANTS: Participants were 376 new admissions/readmissions (77 ± 12 [SD] years; 67% female) from 17 geographically diverse long term care facilities (3260 total beds). MEASUREMENTS: The process describes current VTE prophylaxis (VTE-P) practices; a companion article describes the educational intervention (Phase 2) and outcome (Phase 3). Phase 1 data were collected on use of nonpharmacological measures and antithrombotic drugs for VTE-P between July and September 2009. RESULTS: Indications for VTE-P were evident in 85% of new admissions, of which two-thirds received VTE-P. Contraindications for anticoagulation were observed in 54.8% of admissions, including quality of life or patient/caregiver wishes. Logistic regression analysis predicted no relationship between any indication for or any contraindication to VTE-P and use of VTE-P, suggesting an inadequate understanding of current clinical practice guidelines. CONCLUSIONS: Residents of long term care have significant comorbidity that poses risk for VTE; although many received VTE-P, contraindications were common, warranting individualized considerations. The likelihood of VTE-P was greatest following orthopedic surgery, severe trauma, and medical illness.

Chronic kidney disease staging in nursing home and community older adults: does the choice of cockcroft-gault, modification of diet in renal disease study, or the chronic kidney disease epidemiology collaboration initiative equations matter?

OBJECTIVE: To compare the chronic kidney disease (CKD) stages derived from GFR estimates using 3 different formulae in a sample of older adults from the community and long term care settings. PARTICIPANTS: Data from 1535 older, hospitalized patients (2000-2008) were collected; individuals were hospitalized for acute illness unrelated to renal function. MEASUREMENTS: Patient demographics, pertinent medical history, and routine laboratory test results were collected. Estimate of glomerular filtration rate and creatinine clearance values were determined by the Cockcroft-Gault, Modification of Diet in Renal Disease Study, and Chronic Kidney Disease Epidemiology Collaboration equations. RESULTS: The Cockcroft-Gault equation generated significantly lower mean estimate of glomerular filtration rate values than either Modification of Diet in Renal Disease Study or Chronic Kidney Disease Epidemiology Collaboration equations in the total sample (P < .0005) and in a subset of patients diagnosed as renal insufficiency (P < .00005). Using the 3 formulae produced a significant disconnect in CKD staging resulting in the potential for different recommendations for monitoring and management across formulae (National Kidney Foundation Guidelines) (P < .0005). When stratified by age, the 3 equations produce nearly identical glomerular filtration rate estimates in patients younger than 70 years (P = .989) but significantly different glomerular filtration rate estimates in patients from 70 to 104 years (P < .0005). CONCLUSIONS: The Cockcroft-Gault equation systematically provides lower (more severe) estimates of renal function than the Modification of Diet in Renal Disease Study and Chronic Kidney Disease Epidemiology Collaboration equation in patients older than 70 years. However, significant differences in CKD staging derived from estimate of glomerular filtration rate or creatinine clearance were not observed in adults from 59 to 69 years of age. These findings do not validate one formula over the others, but demonstrate that disparities exist; it may be prudent to use the same formula over time in a given patient to monitor changes in renal function.

Warfarin: implementing its safe use in hospitalized patients from nursing homes and community through a performance improvement initiative.

INTRODUCTION: Warfarin is increasingly used to prevent thromboembolism but adverse drug events (ADEs) are common. The National Safety Goals (3E) 2008 recommend that institutions develop processes to monitor the safe use of warfarin. Despite these guidelines, adverse events (bleeding) are common. This initiative, in an academic hospital, tracked warfarin use before and after using a PI process aimed at improving safe use of warfarin in hospitalized adults. METHODS: Retrospective (PRE-initiative, September-December 2007) and prospective (POST-initiative, January-December 2008) data were collected on in-hospital and prior warfarin use, demographics, medical history, initial and in-hospital warfarin maintenance dosing, hematocrit, International Normalized Ratio (INR), hepatic and renal function and adverse events related to warfarin use. Education on the appropriate use of warfarin was provided through formal and informal sessions and during daily hand-off sessions. RESULTS: A total of 308 patients receiving oral warfarin were examined (mean age 70 ± 17(SD) years, 47% males, 36% from nursing homes). Age, sex ratios, and place of residence were similar PRE- versus POST-initiative. Overall initial and maintenance warfarin doses were significantly lower POST-initiative (P = .0129 and P = .0319, respectively) and these decreases occurred exclusively in patients with supratherapeutic INR levels (>3.0). During the POST-period, the prevalence of high INR levels and bleeding events during hospitalization also decreased significantly (P = .015 and P < .0005, respectively). Finally, concomitant use of anticoagulant and/or antiplatelet drugs was significantly decreased POST-initiative (P = .028). CONCLUSIONS: Most hospitalized patients (PRE- and POST-) presented with INRs in the sub- or supratherapeutic ranges (<2 and >3, respectively), requiring warfarin dose adjustments. Education through this initiative resulted in significantly lower average maintenance doses of warfarin, less use of concomitant anticoagulant or antiplatelet drugs, fewer supratherapeutic range INRs, and fewer adverse events during warfarin therapy. Education through a PI initiative is a simple and effective means to implement safer use of warfarin in the in-hospital setting.

Serum lutein response is greater from free lutein than from esterified lutein during 4 weeks of supplementation in healthy adults.

BACKGROUND: Current data suggest great variability in serum response following lutein ingestion from various sources. OBJECTIVE: To compare the relative serum response during supplementation with free lutein (fL) and lutein esters (Le). METHODS: 72 volunteers (23-52 years; body mass index [BMI] >20 and <30 kg/m2; baseline serum lutein <20 µg/dL [<352 nmol/L]) were identified. Subjects, matched for gender, age, and BMI, were randomly assigned to the fL or Le group. fL and Le capsules contained 12.2 mg of free lutein or 27 mg of lutein ester (equivalent to 13.5 mg free lutein), respectively. Fasting blood was obtained at baseline and after 7, 14, 21, and 28 days of supplementation. Supplements were consumed with standard portions of dry, ready-to-eat cereal and 2% cow's milk. RESULTS: Absolute changes in serum lutein, per mg daily dose, were significantly greater in fL vs. Le after 21 days (p  =  0.0012) and remained so after 28 days (p  =  0.0011) of supplementation. Serum lutein Area Under the Curve [AUC((day 0-28))] response was 17% greater for fL vs. Le (p  =  0.0187). Regression models were used and determined that (1) baseline serum lutein levels and (2) the form of lutein ingested (fL > Le) influence the serum lutein response during supplementation, while subject age, gender, BMI, and serum lipids do not affect serum response. CONCLUSIONS: These results suggest that the relative serum lutein response will be significantly greater from supplements containing free lutein than from supplements containing lutein esters. These findings should be useful for future clinical trials exploring the effectiveness of lutein supplementation in the prevention of or protection against age-related macular degeneration and/or cataracts.

Vitamin C treatment reduces elevated C-reactive protein.

Plasma C-reactive protein (CRP) is an inflammatory biomarker that predicts cardiovascular disease. Lowering elevated CRP with statins has reduced the incidence of cardiovascular disease. We investigated whether vitamin C or E could reduce CRP. Healthy nonsmokers (N=396) were randomized to three groups, 1000 mg/day vitamin C, 800 IU/day vitamin E, or placebo, for 2 months. Median baseline CRP was low, 0.85 mg/L. No treatment effect was seen when all participants were included. However, a significant interaction was found, indicating that treatment effect depends on baseline CRP concentration. Among participants with CRP indicative of elevated cardiovascular risk (> or =1.0 mg/L), vitamin C reduced the median CRP by 25.3% vs placebo (p=0.02) (median reduction in the vitamin C group, 0.25 mg/L, 16.7%). These effects are similar to those of statins. The vitamin E effect was not significant. In summary, treatment with vitamin C but not vitamin E significantly reduced CRP among individuals with CRP > or =1.0 mg/L. Among the obese, 75% had CRP > or =1.0 mg/L. Research is needed to determine whether reducing this inflammatory biomarker with vitamin C could reduce diseases associated with obesity. But research on clinical benefits of antioxidants should limit participants to persons with elevations in the target biomarkers.

Vitamin C in plasma is inversely related to blood pressure and change in blood pressure during the previous year in young Black and White women.

BACKGROUND: The prevalence of hypertension and its contribution to cardiovascular disease risk makes it imperative to identify factors that may help prevent this disorder. Extensive biological and biochemical data suggest that plasma ascorbic acid may be such a factor. In this study we examined the association between plasma ascorbic acid concentration and blood pressure (BP) in young-adult women. METHODS: Participants were 242 Black and White women aged 18-21 yr from the Richmond, CA, cohort of the National Heart, Lung and Blood Institute Growth and Health Study. We examined the associations of plasma ascorbic acid with BP at follow-up year 10, and with change in BP during the previous year. RESULTS: In cross-sectional analysis, plasma ascorbic acid at year 10 was inversely associated with systolic BP and diastolic BP after adjusting for race, body mass index, education, and dietary intake of fat and sodium. Persons in the highest one-fourth of the plasma ascorbic acid distribution had 4.66 mmHg lower systolic BP (95% CI 1.10 to 8.22 mmHg, p = 0.005) and 6.04 mmHg lower diastolic BP (95% CI 2.70 to 9.38 mmHg, p = 0.0002) than those in the lowest one-fourth of the distribution. In analysis of the change in BP, plasma ascorbic acid was also inversely associated with change in systolic BP and diastolic BP during the previous year. While diastolic blood pressure among persons in the lowest quartile of plasma ascorbic acid increased by 5.97 mmHg (95% CI 3.82 to 8.13 mmHg) from year 9 to year 10, those in the highest quartile of plasma vitamin C increased by only 0.23 mmHg (95% CI -1.90 to +2.36 mmHg) (test for linear trend: p < 0.0001). A similar effect was seen for change in systolic BP, p = 0.005. CONCLUSION: Plasma ascorbic acid was found to be inversely associated with BP and change in BP during the prior year. The findings suggest the possibility that vitamin C may influence BP in healthy young adults. Since lower BP in young adulthood may lead to lower BP and decreased incidence of age-associated vascular events in older adults, further investigation of treatment effects of vitamin C on BP regulation in young adults is warranted.

The risk of developing lung cancer associated with antioxidants in the blood: ascorbic acids, carotenoids, alpha-tocopherol, selenium, and total peroxyl radical absorbing capacity.

Lung cancer cases diagnosed during the period 1975 through 1993 and matched controls were identified in the rosters of Washington County, Maryland residents who had donated blood for a serum bank in 1974 or 1989. Plasma from participants in the 1989 project was assayed for ascorbic acid; serum or plasma was assayed for participants in either project for alpha- and beta-carotene, cryptoxanthin, lutein/zeaxanthin, lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity. Among the total group of 258 cases and 515 controls, serum/plasma concentrations were significantly lower among cases than controls for cryptoxanthin, beta-carotene, and lutein/zeaxanthin with case-control differences of -25.5, -17.1, and -10.1%, respectively. Modest nonsignificant case-control differences in a protective direction were noted for alpha-carotene and ascorbic acid. There were only trivial differences for lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity. Findings are reported for males and females and for persons who had never smoked cigarettes, former smokers, and current smokers at baseline. These results and those from previous studies suggest that beta-carotene is a marker for some protective factor(s) against lung cancer; that cryptoxanthin, alpha-carotene, and ascorbic acid need to be investigated further as potentially protective factors or associates of a protective factor; and that lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity are unlikely to be associated with lung cancer risk. Until specific preventive factors are identified, the best protection against lung cancer is still the avoidance of airborne carcinogens, especially tobacco smoke; second best is the consumption of a diet rich in fruits and vegetables.

Associations of plasma carotenoids with risk factors and biomarkers related to cardiovascular disease in middle-aged and older women.

BACKGROUND: Cardiovascular disease (CVD) risk factors may potentially influence plasma concentrations of carotenoids. However, data on the association of plasma carotenoids with CVD related biomarkers are only limited. OBJECTIVE: We examined the cross-sectional association of plasma carotenoids with blood lipids, glycated hemoglobin (Hb A(1c)), and C-reactive protein (CRP) in middle-aged and older women initially free of CVD and cancer. DESIGN: Participants from 3 nested case-control studies in the Women's Health Study were pooled. Baseline plasma carotenoids, including alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein-zeaxanthin, blood lipids, Hb A(1c), and CRP were available for 2895 women. RESULTS: Women who were current smokers or obese had lower plasma concentrations of most carotenoids expect for lycopene. After adjusting for age, race, lifestyle factors, clinical factors, plasma total cholesterol, and dietary carotenoids, an increase of 30 mg/dL in LDL cholesterol was associated with a 17% increase in alpha-carotene, a 16% increase in beta-carotene, and an 8.5% increase in lycopene; an increase of 10 mg/dL in HDL cholesterol was associated with a 5.3% decrease in lycopene; an increase of 0.3% in Hb A(1c) was associated with a 1.4% increase in lycopene; and an increase of 2 mg/L in CRP was associated with a 1.3% decrease in beta-carotene (all P < 0.01). CONCLUSIONS: In middle-aged and older women free of CVD and cancer, plasma carotenoids were associated with smoking, obesity, LDL cholesterol, HDL cholesterol, Hb A(1c), and CRP. The associations differ among individual carotenoids, possibly reflecting metabolic effects of lifestyle and physiologic factors on plasma carotenoids, and may partially explain the inverse association of plasma carotenoids with CVD outcomes observed in epidemiologic studies.

Anemia: its impact on hospitalizations and length of hospital stay in nursing home and community older adults.

OBJECTIVE: To examine the association between anemia and its severity on hospitalizations and length of stay (LOS) in hospital in older adults. PARTICIPANTS: A cross-sectional sample of 590 adults from long term care facilities (NH) and community ambulatory care (C) in the Bronx, NY. MEASUREMENTS: Patient demographics, medical history, hospitalizations during an 18-month period, LOS per hospitalization, and laboratory parameters including hemoglobin (Hb) at enrollment and during hospitalization. RESULTS: Anemia and hospitalization occurred in 62% and 64% of the sample, respectively. NH residents were older (P = .0013), had fewer hospitalizations (P = .001) but similar rates of anemia, anemia severity, gender ratios and LOS per hospitalization as C subjects (all P > .05). Females were older (P = .0455), had fewer hospitalizations (P = .001) and more severe anemia than males (P < .0005). The likelihood of hospitalization increased 1) as anemia severity increased (P < .00005), 2) in African Americans (P = .002), 3) in males (P = .006), and 4) as anemia duration increased (P < .0005). Anemic patients had significantly longer total LOS days than non-anemic individuals (P < .00005); total LOS also increased as severity of anemia increased (P = .0022). CONCLUSIONS: Our findings suggest anemia, in particular chronic and severe anemia in older Americans is associated with an increased likelihood of hospitalizations and an increased LOS when hospitalized. The recognition and treatment of anemia in older adults has the potential to reduce hospitalizations and LOS and decrease overall health care costs to individuals and third party providers.

The effect of vitamins C and E on biomarkers of oxidative stress depends on baseline level.

Oxidative stress is elevated in obesity, and may be a major mechanism for obesity-related diseases. Nonsmokers (n=396) were randomized to 1000 mg/day vitamin C, 800 IU/day vitamin E, or placebo, for 2 months. Treatment effect was examined in multiple regression analyses using an intention-to-treat approach. Vitamin C (P=0.001) and vitamin E (P=0.043) reduced plasma F2-isoprostanes. In the overall sample, changes from baseline were +6.8, -10.6, and -3.9% for placebo, vitamin C, and vitamin E groups, respectively. However, a significant interaction with baseline F2-isoprostane was found. When baseline F2-isoprostane was >50 microg/mL, vitamin C reduced F2-isoprostane by 22% (P=0.01). Vitamin E reduced it by 9.8% (P=0.46). Below that cut point, neither treatment produced further reductions. F2-isoprostane>50 microg/mL was strongly associated with obesity, and was present in 42% of the sample. Change in malondialdehyde concentration was minimal. These findings suggest a role for vitamin C in reducing lipid peroxidation. Future research on effects of vitamins C or E on plasma F2-isoprostane should limit participants to those with baseline levels >50 mug/mL. Further studies are needed to establish whether treatment with vitamins C or E in persons with concentrations above that cut point could slow the development of cardiovascular disease.

The relationship between total plasma carotenoids and risk factors for chronic disease among middle-aged and older men.

Individual plasma carotenoids have been associated with various chronic diseases but little is known about the relationship between total plasma carotenoids and risk factors for chronic diseases. In the Physicians' Health Study, we examined 492 men free of CVD and cancer for the relationship between total plasma carotenoids (the sum of alpha-carotene, beta-carotene, lycopene, zeaxanthin, lutein and beta-cryptoxanthin) and a wide variety of factors that predict chronic disease. Multivariate linear and logistic regression was performed to calculate parameter estimates (95% CI) and OR (95% CI) for total plasma carotenoids. In linear regression models, BMI, hypertension, alcohol intake and plasma levels of each lipid parameter and a-tocopherol significantly predicted levels of total plasma carotenoids. Upon adjustment for multiple chronic disease risk factors, the OR for levels of total plasma carotenoids greater than or equal to the median (> or=1.301 micromol/l) was statistically significant for current smoking (OR 0.21; 95% CI 0.06, 0.77), weekly alcohol ingestion (OR 2.30; 95% CI 1.06, 4.99), daily alcohol ingestion (OR 2.46; 95% CI 1.29, 4.67), each 100 mg/l increase in total cholesterol (OR 0.73; 95% CI 0.58, 0.91), LDL-cholesterol (OR 1.48; 95% CI 1.17, 1.89) and HDL-cholesterol (OR 1.58; 95% CI 1.26, 1.99), each 100 mg/ml increase in intercellular adhesion molecule-1 (OR 0.70; 95% CI 0.53, 0.93) and each 10 micromol/l increase in alpha-tocopherol (OR 1.33; 95% CI 1.12, 1.57), using logistic regression. Few lifestyle and clinical risk factors appear to be related to levels of total plasma carotenoids; however, levels of biomarkers such as plasma lipids and alpha-tocopherol may be strongly related.

Do acid-lowering agents affect vitamin B12 status in older adults?

OBJECTIVE: To examine the relationship between serum vitamin B12 levels in older adults on histamine(2) receptor antagonists (H2 blockers) or proton-pump inhibitors (PPI) over 6 years. PARTICIPANTS: A cross-sectional sample of 659 adults, 60 to 102 years, from long-term care facilities and community ambulatory care (C) in the Bronx. MEASUREMENTS: Patient demographics, serum B12 levels, use and duration of use of H2 blockers, PPIs, antacids, multivitamin/minerals, liquid dietary supplements, oral vitamin B12 supplementation, oral or intramuscular B12 therapy, and recent lab chemistries. RESULTS: Acid-lowering agents (ALA) were used by 54% (PPIs by 26% and H2 blockers by 28%), duration averaged 18.2 +/- 16.0 (SD) months. NH and C subjects had similar ages (P = .9971), gender distributions (P = .625), durations of ALA use (P = .1227), and rates of PPI use (P = .130); NH subjects used more H2 blockers (P < .0005) and had less low B12 status (P = .037). H2 blocker use did not influence serum B12 status (P = .1036) while PPI use was associated with diminished serum B12 levels (P < .00005). Concomitant oral B12 supplementation slowed but did not prevent the decline in B12 status during prolonged PPI use (P = .0125). CONCLUSIONS: B12 status declines during prolonged PPI use in older adults, but not with prolonged H2 blocker use; supplementation with RDA amounts of B12 do not prevent this decline. This report reinforces that B12 deficiency is common in the elderly and suggests that it appears prudent to monitor periodically B12 status while on prolonged PPI use, to enable correction before complications ensue.