Prevalence of apolipoprotein E4 genotype and homozygotes (APOE e4/4) among patients diagnosed with Alzheimer's disease: a systematic review and meta-analysis.

BACKGROUND: Population allele frequencies of apolipoprotein E (APOE) vary by geographic region. The purpose of this study is to summarize and evaluate published estimates for the prevalence of APOE e4 carrier status among the population diagnosed with Alzheimer's disease (AD) by geographic region and country. METHODS: A systematic review of English-language publications from January 1, 1985, through May 31, 2010, was conducted. Studies reporting APOE e4 status for patients diagnosed with AD were included in the analysis; trials and autopsies were excluded. APOE e4 data were pooled, and prevalence and 95% confidence intervals (CIs) were calculated. RESULTS: Pooled estimates for APOE e4 carrier prevalence data were derived from 142 independent samples: 48.7% (95% CI: 46.5-51.0), and from 73 samples for e4/4 (homozygotes): 9.6% (95% CI: 8.4-10.8). The highest estimates were in Northern Europe: 61.3% (95% CI: 55.9-66.7), e4/4 prevalence: 14.1% (95% CI: 12.2-16.0). The lowest estimates were in Asia and Southern Europe. Substantial heterogeneity of these prevalence estimates was observed. CONCLUSIONS: APOE e4 genotype prevalence varies among AD patients by region and within each country. Further exploration is warranted to better understand the substantial heterogeneity of these prevalence estimates.

Cost efficiency of anticoagulation with warfarin to prevent stroke in medicare beneficiaries with nonvalvular atrial fibrillation.

BACKGROUND AND PURPOSE: in controlled trials, anticoagulation with warfarin reduces stroke risk by nearly two thirds, but the benefit has been less pronounced in clinical practice. This report describes the extent of warfarin use, its effectiveness, and its impact on medical costs among Medicare patients with nonvalvular atrial fibrillation. METHODS: using claims from >2 million beneficiaries in the Centers for Medicare and Medicaid Services 5% Sample Standard Analytic Files, we identified patients with nonvalvular atrial fibrillation from 2004 to 2005. Warfarin use was inferred from 3 or more tests of the international normalized ratio within 1 year. Incidence of ischemic/hemorrhagic stroke and major bleeding was evaluated. Adjusted risk was calculated by Cox proportional-hazards regression. Medical costs (reimbursed amounts in 2006 US dollars) were estimated by multivariate linear regression. RESULTS: of patients with nonvalvular atrial fibrillation (N=119 764, mean age=79.3 years), 58.5% were categorized as warfarin users based on the study definition. During an average of 2.1 years' follow-up, the rate of ischemic stroke was 3.9 per 100 patient-years. After multivariate adjustment, ischemic stroke incidence was 27% lower in patients taking warfarin than in patients not taking warfarin (P<0.0001), with no increase in hemorrhagic stroke and a slightly elevated risk of a major bleed. Use of warfarin was independently associated with lower total medical costs, averaging $9836 per patient per year. CONCLUSIONS: these results indicate that 41.5% of Medicare patients with nonvalvular atrial fibrillation are not anticoagulated with warfarin. The incidence of stroke and overall medical costs were significantly lower in patients treated with warfarin.

Apolipoprotein E ε4 prevalence in Alzheimer's disease patients varies across global populations: a systematic literature review and meta-analysis.

BACKGROUND: The ε4 allele of apolipoprotein E (APOE) is associated with Alzheimer's disease (AD). However, attributable risk due to APOE4 varies by region and by race/ethnicity. METHODS: A literature review and meta-analysis were conducted to estimate the prevalence of APOE4 by geographic area among AD patients. RESULTS: Although estimates varied significantly by study design and case definition, AD patients recruited in Asian and southern European/Mediterranean communities seemed to have significantly lower E4 carrier status estimates (37 and 43%) than those recruited in North America (58%) or northern Europe (64%; all: p < 0.05). CONCLUSIONS: APOE4 genotype frequency varies among AD patients in regional patterns similar to that of the general population. Study level differences may also contribute to the heterogeneity of published estimates of APOE4 in AD cases.

Comparative risk of bloodstream infection in hospitalized patients receiving intravenous medication by open, point-of-care, or closed delivery systems.

PURPOSE: The impact of i.v. drug delivery via point-of-care (POC)-activated and closed systems versus traditional manual admixture systems on the risk of hospital-acquired bloodstream infection (BSI) is examined. METHODS: Using data from a proprietary hospital database, a retrospective observational cohort study of patients receiving one or more i.v. drug administrations via POC-activated or closed systems during a three-year period (2007-09) was conducted. Cases of hospital-acquired BSI were identified using diagnosis codes and billing charges for blood cultures and antibiotic use. The risk of BSI in patients with exposure to POC-activated systems, closed systems, or both relative to that of patients exposed to open systems was estimated by odds ratios (ORs) calculated by multivariate logistic regression analysis. RESULTS: The evaluated data indicated that of the 4,073,864 patients included in the study cohort, 0.5% (n = 20,251) experienced hospital-acquired BSI. After adjusting for selected confounding variables, the use of POC-activated systems was associated with a 16% reduction in BSI risk relative to the use of open systems (OR, 0.84; 95% confidence interval [CI], 0.76-0.93), and the use of closed systems correlated with a 12% risk reduction (OR, 0.88; 95% CI, 0.82-0.96). Patients who received i.v. drugs via both POC-activated and closed systems appeared to derive the greatest relative risk reduction benefit (OR, 0.12; 95% CI, 0.06-0.23). CONCLUSION: Use of POC-activated and closed systems for i.v. drug delivery was associated with a significantly reduced risk of hospital-acquired BSI compared with exclusive use of open systems in a large population of hospitalized patients.

Ultrasound guidance decreases complications and improves the cost of care among patients undergoing thoracentesis and paracentesis.

Ultrasound guidance enables visualization of the needle insertion site for thoracentesis and paracentesis. The improved accuracy of needle placement using ultrasound may reduce risk of complications and their costs associated with these procedures. Using claims data from the Premier Perspective hospital database from January 1, 2007, through December 31, 2008, we conducted an observational cohort study examining the effect of ultrasound guidance on risk of pneumothorax among patients undergoing thoracentesis and on risk of bleeding complications after paracentesis. Patients at elevated risk of these outcomes for reasons beyond the procedure of interest were excluded. Adjusted risk of events was assessed using multivariate logistic regression controlling for patient and hospitalization characteristics. Hospitalization cost and length of stay (LOS) were estimated using multivariate ordinary least squares regression of log-transformed values. We analyzed 61,261 thoracentesis and 69,859 paracentesis patient records. Approximately 45% of these procedures were ultrasound guided. Pneumothorax occurred in 2.7% (n = 1,670) of patients undergoing thoracentesis. Of patients undergoing paracentesis, 0.8% (n = 565) experienced bleeding complications. After adjustment, ultrasound guidance reduced the risk of pneumothorax after thoracentesis by 19% (OR, 0.81; 95% CI, 0.74-0.90) and by 68% for bleeding complications after paracentesis (OR, 0.32; 95% CI, 0.25-0.41). Pneumothorax increased the total cost of hospitalization by $2,801 (P < .001) and LOS by 1.5 days (P < .001). Bleeding complications increased cost by $19,066 (P < .0001) and LOS by 4.3 days (P < .0001). The data indicate that ultrasound guidance is associated with decreased risk of pneumothorax with thoracentesis and of bleeding complications with paracentesis. These complications resulted in measurable increases in hospitalization costs and LOS.

Methods to identify and compare parenteral nutrition administered from hospital-compounded and premixed multichamber bags in a retrospective hospital claims database.

PURPOSE: Use of parenteral nutrition (PN) is indicated for patients who are unable to meet their needs enterally. PN may be administered via custom-compounded mix or commercially available ready-to-use multichamber bags (MCB), but little is known about potential differences in clinical outcomes between these delivery systems. This study was undertaken to assess the feasibility of comparing custom-compounded and MCB PN in a large hospital claims database. METHODS: Hospital claims data from the Premier Perspective Comparative Hospital Database (PCD) reported from 2005 through 2007 were analyzed. The authors searched the data for patients who received any PN products, including compounded PN and MCB PN. Coding algorithms for identifying patient characteristics, risk factors, and outcomes of interest were explored. RESULTS: Using hospital billing claims, the authors identified patients in the database treated with premixed PN from multichamber bags ("MCB only," n = 4699) and patients treated with custom-compounded PN solution ("compounded PN," n = 64,315). Methods of identifying PN administration groups, patient characteristics and risk factors, outcomes of interest, and data limitations are described. CONCLUSIONS: Exploratory analysis suggests that comparisons of PN administered via compounding and MCB are possible using the Premier data. The ability to control for many identifiable risk factors allows data to be presented for the use of PN and related outcomes in both a clinically sensible and relevant manner, albeit with some limitations.

Long-Term Costs of Ischemic Stroke and Major Bleeding Events among Medicare Patients with Nonvalvular Atrial Fibrillation.

Purpose. Acute healthcare utilization of stroke and bleeding has been previously examined among patients with nonvalvular atrial fibrillation (NVAF). The long-term cost of such outcomes over several years is not well understood. Methods. Using 1999-2009 Medicare medical and enrollment data, we identified incident NVAF patients without history of stroke or bleeding. Patients were followed from the first occurrence of ischemic stroke, major bleeding, or intracranial hemorrhage (ICH) resulting in hospitalization. Those with events were matched with 1-5 NVAF patients without events. Total incremental costs of events were calculated as the difference between costs for patients with events and matched controls for up to 3 years. Results. Among the 25,465 patients who experienced events, 94.5% were successfully matched. In the first year after event, average incremental costs were $32,900 for ischemic stroke, $23,414 for major bleeding, and $47,640 for ICH. At 3 years after these events, costs remained elevated by $3,156-$5,400 per annum. Conclusion. While the costs of stroke and bleeding among patients with NVAF are most dramatic in the first year, utilization remained elevated at 3 years. Cost consequences extend beyond the initial year after these events and should be accounted for when assessing the cost-effectiveness of treatment regimens for stroke prevention.

Bloodstream infections in patients receiving manufactured parenteral nutrition with vs without lipids: is the use of lipids really deleterious?

BACKGROUND: This study compared overall bacterial and bloodstream infection rates in patients receiving premixed parenteral nutrition (PN) with vs without lipid emulsion. METHODS: Data from hospitalized patients who were ≥18 years of age and receiving premixed PN between 2005 and 2007 were extracted from the Premier Perspective database. Data were categorized into 2 groups: patients who received premixed PN only and those receiving premixed PN with lipids. Multiple logistic regression was used to adjust for risk factors and potential confounders, reporting the probability of risk for an infection. RESULTS: The group without lipids was observed to have lower rates of both overall bacterial infection (43.5% vs 53.5%) and bloodstream infection (14.5% vs 18.9%). However, after adjusting for baseline characteristics, there were no significant differences in overall risk of bacterial infections (51.4% vs 53.5%; odds ratio [OR] = 1.11; 95% confidence interval [CI], 0.96-1.27) or bloodstream infections (19.6% vs 19.2%; 0.97; 0.81-1.16). In a subset of patients in the intensive care unit for ≥3 days, lower overall bacterial infection rates (58.3% vs 67.3%) and bloodstream infection rates (31.0% vs 37.0%) were observed in the group without lipids. After adjustment, there were no significant differences in risk of overall bacterial infection (OR = 0.95; 95% CI, 0.75-1.22) or bloodstream infection (0.92; 0.71-1.19) between the 2 groups. CONCLUSIONS: When administered with premixed PN, lipid emulsion was not significantly associated with an increase in the risk of infectious morbidity when compared to omitting lipids from therapy.

Bloodstream infections associated with parenteral nutrition preparation methods in the United States: a retrospective, large database analysis.

BACKGROUND: The incidence of bloodstream infection (BSI) among patients receiving parenteral nutrition (PN) is reported to vary widely from 1.3%-39%. BSI rates in a large inpatient population were compared in this study to determine if PN prepared by different methods was associated with BSI. METHODS: Data from Premier Perspective, the largest inpatient cost-based clinical and financial claims database in the United States, were analyzed. Included were all hospitalized patients age ≥18 years who received any PN from January 1, 2005, to December 31, 2007. BSI rates, the primary dependent variable, were defined as the occurrence ICD-9 codes of 038.x (septicemia), 995.91 (sepsis), 995.92 (severe sepsis), and 790.7 (bacteremia). The exposure cohort received PN in a commercial multichamber bag (MCB) (n = 4669), whereas the comparator group received PN prepared by a pharmacy (either hospital compounded or outsourced; n = 64,315). Observed data were adjusted using multivariate logistic regression for baseline differences, risk factors, and potential confounders, with propensity score matching as a sensitivity analysis. RESULTS: The observed and adjusted BSI rates indicate that MCB is associated with fewer infections than pharmacy-prepared PN (observed 17.5% vs 26.6%; adjusted 19.6% vs 25.9%, both P < .001). Propensity-matched scores found similar results with observed BSI rates of 18.9% in patients receiving MCB and 24.6% in patients receiving a compounded PN. CONCLUSION: Both the observed rate of BSI and adjusted probability of developing a BSI remained significantly lower for the MCB than the compounded PN group.

Comparison of hand-assisted laparoscopy versus open and laparoscopic techniques in urology procedures: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Hand-assisted laparoscopic surgery (HALS) is an integral part of the urologist's armamentarium. We aimed to perform a comprehensive meta-analysis comparing HALS renal surgery with open and laparoscopic techniques. METHODS: A systematic review and meta-analysis of HALS renal procedures (donor nephrectomy, nephrectomy, or nephroureterectomy) from 1996 to 2007 was performed. RESULTS: Sixty-two studies of 30 donor nephrectomy, 21 radical nephrectomy, and 14 nephroureterectomy procedures in 5446 patients were included in the analysis. In donor nephrectomy, estimated blood loss (EBL) was statistically significant for HALS vs the open and laparoscopic cohorts, -69.0 mL (95% confidence interval [CI], -129.7, -8.2) and -40.1 mL (95% CI, -68.2, -12.0), respectively. Length of stay (LOS) was shorter compared with the open group, -1.7 days (95% CI, -2.3, -1.1). For nephroureterectomy, EBL (-29.9 mL (95% CI, -242.3, 182.5)), and LOS (-1.5 d [95% CI, -2.8, -0.3]) again favored HALS vs open procedures. Operating room (OR) time and warm ischemia time (WIT) were statistically significant in favor of HALS donor nephrectomy vs the laparoscopic cohort; -36.8 minutes (95% CI, -61.3, -12.3) and -1.3 minutes (95% CI, -1.8, -0.7), respectively. For radical nephrectomy, both EBL -232.9 mL (95% CI, -383.6, -82.2) and LOS -2.4 days (95% CI, -3.5, -1.3) were statistically significant, favoring HALS vs the open group. CONCLUSION: We report the largest meta-analysis of HALS renal surgery to date. When compared with open surgery, HALS allows for a significant decrease in EBL and LOS. Compared with laparoscopic donor nephrectomy, HALS resulted in a significant decrease in blood loss, OR time, and WIT.

Nutrition therapy cost analysis in the US: pre-mixed multi-chamber bag vs compounded parenteral nutrition.

BACKGROUND: Bloodstream infections (BSI) occur in up to 350 000 inpatient admissions each year in the US, with BSI rates among patients receiving parenteral nutrition (PN) varying from 1.3% to 39%. BSI-attributable costs were estimated to approximate $US12 000 per episode in 2000. While previous studies have compared the cost of different PN preparation methods, this analysis evaluates both the direct costs of PN and the treatment costs for BSI associated with different PN delivery methods to determine whether compounded or manufactured pre-mixed PN has lower overall costs. OBJECTIVE: The purpose of this study was to compare costs in the US associated with compounded PN versus pre-mixed multi-chamber bag (MCB) PN based on underlying infection risk. METHODS: Using claims information from the Premier Perspective™ database, multivariate logistic regression was used to estimate the risk of infection. A total of 44 358 hospitalized patients aged ≥18 years who received PN between 1 January 2005 and 31 December 2007 were included in the analyses. A total of 3256 patients received MCB PN and 41 102 received compounded PN. The PN-associated costs and length of stay were analysed using multivariate ordinary least squares regression models constructed to measure the impact of infectious events on total hospital costs after controlling for baseline and clinical patient characteristics. RESULTS: There were 7.3 additional hospital days attributable to BSI. After adjustment for baseline variables, the probability of developing a BSI was 30% higher in patients receiving compounded PN than in those receiving MCB PN (16.1% vs 11.3%; odds ratio = 1.56; 95% CI 1.37, 1.79; p < 0.0001), demonstrating 2172 potentially avoidable infections. The observed daily mean PN acquisition cost for patients receiving MCB PN was $US164 (including all additives and fees) compared with $US239 for patients receiving compounded PN (all differences p < 0.001). With a mean cost attributable to BSI of $US16 141, the total per-patient savings (including avoided BSI and PN costs) was $US1545. CONCLUSION: In this analysis of real-world PN use, MCB PN is associated with lower costs than compounded PN with regards to both PN acquisition and potential avoidance of BSI. Our base case indicates that $US1545 per PN patient may be saved; even if as few as 50% of PN patients are candidates for standardized pre-mix formulations, a potential savings of $US773 per patient may be realized.