Comparative Effectiveness and Safety of New-Generation Versus Early-Generation Drug-Eluting Stents According to Complexity of Coronary Artery Disease: A Patient-Level Pooled Analysis of 6,081 Patients.

OBJECTIVES The purpose of this study was to compare the 2-year safety and effectiveness of new- versus early-generation drug-eluting stents (DES) according to the severity of coronary artery disease (CAD) as assessed by the SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score. BACKGROUND New-generation DES are considered the standard-of-care in patients with CAD undergoing percutaneous coronary intervention. However, there are few data investigating the effects of new- over early-generation DES according to the anatomic complexity of CAD. METHODS Patient-level data from 4 contemporary, all-comers trials were pooled. The primary device-oriented clinical endpoint was the composite of cardiac death, myocardial infarction, or ischemia-driven target-lesion revascularization (TLR). The principal effectiveness and safety endpoints were TLR and definite stent thrombosis (ST), respectively. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated at 2 years for overall comparisons, as well as stratified for patients with lower (SYNTAX score ≤11) and higher complexity (SYNTAX score >11). RESULTS A total of 6,081 patients were included in the study. New-generation DES (n = 4,554) compared with early-generation DES (n = 1,527) reduced the primary endpoint (HR: 0.75 [95% CI: 0.63 to 0.89]; p = 0.001) without interaction (p = 0.219) between patients with lower (HR: 0.86 [95% CI: 0.64 to 1.16]; p = 0.322) versus higher CAD complexity (HR: 0.68 [95% CI: 0.54 to 0.85]; p = 0.001). In patients with SYNTAX score >11, new-generation DES significantly reduced TLR (HR: 0.36 [95% CI: 0.26 to 0.51]; p < 0.001) and definite ST (HR: 0.28 [95% CI: 0.15 to 0.55]; p < 0.001) to a greater extent than in the low-complexity group (TLR pint = 0.059; ST pint = 0.013). New-generation DES decreased the risk of cardiac mortality in patients with SYNTAX score >11 (HR: 0.45 [95% CI: 0.27 to 0.76]; p = 0.003) but not in patients with SYNTAX score ≤11 (pint = 0.042). CONCLUSIONS New-generation DES improve clinical outcomes compared with early-generation DES, with a greater safety and effectiveness in patients with SYNTAX score >11.

Anatomic characteristics and clinical implications of angiographic coronary thrombus: insights from a patient-level pooled analysis of SYNTAX, RESOLUTE, and LEADERS Trials.

BACKGROUND The distribution of thrombus-containing lesions (TCLs) in an all-comer population admitted with a heterogeneous clinical presentation (stable, ustable angina, or an acute coronary syndrome) and treated with percutaneous coronary intervention is yet unclear, and the long-term prognostic implications are still disputed. This study sought to assess the distribution and prognostic implications of coronary thrombus, detected by coronary angiography, in a population recruited in all-comer percutaneous coronary intervention trials. METHODS AND RESULTS Patient-level data from 3 contemporary coronary stent trials were pooled by an independent academic research organization (Cardialysis, Rotterdam, the Netherlands). Clinical outcomes in terms of major adverse cardiac events (major adverse cardiac events, a composite of death, myocardial infarction, and repeat revascularization), death, myocardial infarction, and repeated revascularization were compared between patients with and without angiographic TCL. Preprocedural TCL was present in 257 patients (5.8%) and absent in 4193 (94.2%) patients. At 3-year follow-up, there was no difference for major adverse cardiac events (25.3 versus 25.4%; P=0.683); all-cause death (7.4 versus 6.8%; P=0.683); myocardial infarction (5.8 versus 6.0%; P=0.962), and any revascularizations (17.5 versus 17.7%; P=0.822) between patients with and without TCL. The comparison of outcomes in groups weighing the jeopardized myocardial by TCL also did not show a significant difference. TCL were seen more often in the first 2 segments of the right (43.6%) and left anterior descending (36.8%) coronary arteries. The association of TCL and bifurcation lesions was present in 40.1% of the prespecified segments. CONCLUSIONS TCL involved mainly the proximal coronary segments and did not have any effect on clinical outcomes. A more detailed thrombus burden quantification is required to investigate its prognostic implications. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00114972, NCT01443104, NCT00617084.

"Attacks" or "Whistling": Impact of Questionnaire Wording on Wheeze Prevalence Estimates.

BACKGROUND Estimates of prevalence of wheeze depend on questionnaires. However, wording of questions may vary between studies. We investigated effects of alternative wording on estimates of prevalence and severity of wheeze, and associations with risk factors. METHODS White and South Asian children from a population-based cohort (UK) were randomly assigned to two groups and followed up at one, four and six years (1998, 2001, 2003). Parents were asked either if their child ever had "attacks of wheeze" (attack group, N=535), or "wheezing or whistling in the chest" (whistling group, N=2859). All other study aspects were identical, including questions about other respiratory symptoms. RESULTS Prevalence of wheeze ever was lower in the attack group than in the whistling group for all surveys (32 vs. 40% in white children aged one year, p<0.001). Prevalence of other respiratory symptoms did not differ between groups. Wheeze tended to be more severe in the attack group. The strength of association with risk factors was comparable in the two groups. CONCLUSIONS The wording of questions on wheeze can affect estimates of prevalence, but has less impact on measured associations with risk factors. Question wording is a potential source of between-study-heterogeneity in meta-analyses.

Reference values for digital X-ray radiogrammetry parameters in children and adolescents in comparison to estimates in patients with distal radius fractures.

The first objective of this study was to determine normative digital X-ray radiogrammetry (DXR) values, based on original digital images, in a pediatric population (aged 6-18 years). The second aim was to compare these reference data with patients suffering from distal radius fractures, whereas both cohorts originated from the same geographical region and were evaluated using the same technical parameters as well as inclusion and exclusion criteria. DXR-BMD and DXR-MCI of the metacarpal bones II-IV were assessed on standardized digital hand radiographs, without printing or scanning procedures. DXR parameters were estimated separately by gender and among six age groups; values in the fracture group were compared to age- and gender-matched normative data using Student's t tests and Z scores. In the reference cohort (150 boys, 138 girls), gender differences were found in bone mineral density (DXR-BMD), with higher values for girls from 11 to 14 years and for boys from 15 to 18 years (p < 0.05). Girls had higher normative metacarpal index (DXR-MCI) values than boys, with significant differences at 11-14 years (p < 0.05). In the case-control investigation, the fracture group (95 boys, 69 girls) presented lower DXR-BMD at 15-18 years in boys and 13-16 years in girls vs. the reference cohort (p < 0.05); DXR-MCI was lower at 11-18 years in boys and 11-16 years in girls (p < 0.05). Mean Z scores in the fracture group for DXR-BMD were -0.42 (boys) and -0.46 (girls), and for DXR-MCI were -0.51 (boys) and -0.53 (girls). These findings indicate that the fully digital DXR technique can be accurately applied in pediatric populations ≥ 6 years of age. The lower DXR-BMD and DXR-MCI values in the fracture group suggest promising early identification of individuals with increased fracture risk, without the need for additional radiation exposure, enabling the initiation of prevention strategies to possibly reduce the incidence of osteoporosis later in life.

Global Estimates of the Prevalence and Incidence of Four Curable Sexually Transmitted Infections in 2012 Based on Systematic Review and Global Reporting.

BACKGROUND Quantifying sexually transmitted infection (STI) prevalence and incidence is important for planning interventions and advocating for resources. The World Health Organization (WHO) periodically estimates global and regional prevalence and incidence of four curable STIs: chlamydia, gonorrhoea, trichomoniasis and syphilis. METHODS AND FINDINGS WHO's 2012 estimates were based upon literature reviews of prevalence data from 2005 through 2012 among general populations for genitourinary infection with chlamydia, gonorrhoea, and trichomoniasis, and nationally reported data on syphilis seroprevalence among antenatal care attendees. Data were standardized for laboratory test type, geography, age, and high risk subpopulations, and combined using a Bayesian meta-analytic approach. Regional incidence estimates were generated from prevalence estimates by adjusting for average duration of infection. In 2012, among women aged 15-49 years, the estimated global prevalence of chlamydia was 4.2% (95% uncertainty interval (UI): 3.7-4.7%), gonorrhoea 0.8% (0.6-1.0%), trichomoniasis 5.0% (4.0-6.4%), and syphilis 0.5% (0.4-0.6%); among men, estimated chlamydia prevalence was 2.7% (2.0-3.6%), gonorrhoea 0.6% (0.4-0.9%), trichomoniasis 0.6% (0.4-0.8%), and syphilis 0.48% (0.3-0.7%). These figures correspond to an estimated 131 million new cases of chlamydia (100-166 million), 78 million of gonorrhoea (53-110 million), 143 million of trichomoniasis (98-202 million), and 6 million of syphilis (4-8 million). Prevalence and incidence estimates varied by region and sex. CONCLUSIONS Estimates of the global prevalence and incidence of chlamydia, gonorrhoea, trichomoniasis, and syphilis in adult women and men remain high, with nearly one million new infections with curable STI each day. The estimates highlight the urgent need for the public health community to ensure that well-recognized effective interventions for STI prevention, screening, diagnosis, and treatment are made more widely available. Improved estimation methods are needed to allow use of more varied data and generation of estimates at the national level.

Effect of Chronic Kidney Disease in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents: A Patient-Level Pooled Analysis of Randomized Controlled Trials.

OBJECTIVES This study sought to evaluate: 1) the effect of impaired renal function on long-term clinical outcomes in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stent (DES); and 2) the safety and efficacy of new-generation compared with early-generation DES in women with chronic kidney disease (CKD). BACKGROUND The prevalence and effect of CKD in women undergoing PCI with DES is unclear. METHODS We pooled patient-level data for women enrolled in 26 randomized trials. The study population was categorized by creatinine clearance (CrCl) <45 ml/min, 45 to 59 ml/min, and ≥60 ml/min. The primary endpoint was the 3-year rate of major adverse cardiovascular events (MACE). Participants for whom baseline creatinine was missing were excluded from the analysis. RESULTS Of 4,217 women included in the pooled cohort treated with DES and for whom serum creatinine was available, 603 (14%) had a CrCl <45 ml/min, 811 (19%) had a CrCl 45 to 59 ml/min, and 2,803 (66%) had a CrCl ≥60 ml/min. A significant stepwise gradient in risk for MACE was observed with worsening renal function (26.6% vs. 15.8% vs. 12.9%; p < 0.01). Following multivariable adjustment, CrCl <45 ml/min was independently associated with a higher risk of MACE (adjusted hazard ratio: 1.56; 95% confidence interval: 1.23 to 1.98) and all-cause mortality (adjusted hazard ratio: 2.67; 95% confidence interval: 1.85 to 3.85). Compared with older-generation DES, the use of newer-generation DES was associated with a reduction in the risk of cardiac death, myocardial infarction, or stent thrombosis in women with CKD. The effect of new-generation DES on outcomes was uniform, between women with or without CKD, without evidence of interaction. CONCLUSIONS Among women undergoing PCI with DES, CKD is a common comorbidity associated with a strong and independent risk for MACE that is durable over 3 years. The benefits of newer-generation DES are uniform in women with or without CKD.

Safety and Efficacy of New-Generation Drug-Eluting Stents in Women at High Risk for Atherothrombosis: From the Women in Innovation and Drug-Eluting Stents Collaborative Patient-Level Pooled Analysis

BACKGROUND The safety and efficacy of new-generation drug-eluting stents (DES) in women with multiple atherothrombotic risk (ATR) factors is unclear. METHODS AND RESULTS We pooled patient-level data for women enrolled in 26 randomized trials. Study population was categorized based on the presence or absence of high ATR, which was defined as having history of diabetes mellitus, prior percutaneous or surgical coronary revascularization, or prior myocardial infarction. The primary end point was major adverse cardiovascular events defined as a composite of all-cause mortality, myocardial infarction, or target lesion revascularization at 3 years of follow-up. Out of 10 449 women included in the pooled database, 5333 (51%) were at high ATR. Compared with women not at high ATR, those at high ATR had significantly higher risk of major adverse cardiovascular events (15.8% versus 10.6%; adjusted hazard ratio: 1.53; 95% confidence interval: 1.34-1.75; P=0.006) and all-cause mortality. In high-ATR risk women, the use of new-generation DES was associated with significantly lower risk of 3-year major adverse cardiovascular events (adjusted hazard ratio: 0.69; 95% confidence interval: 0.52-0.92) compared with early-generation DES. The benefit of new-generation DES on major adverse cardiovascular events was uniform between high-ATR and non-high-ATR women, without evidence of interaction (Pinteraction=0.14). At landmark analysis, in high-ATR women, stent thrombosis rates were comparable between DES generations in the first year, whereas between 1 and 3 years, stent thrombosis risk was lower with new-generation devices. CONCLUSIONS Use of new-generation DES even in women at high ATR is associated with a benefit consistent over 3 years of follow-up and a substantial improvement in very-late thrombotic safety.

Impact of Diabetic Status on Outcomes After Revascularization With Drug-Eluting Stents in Relation to Coronary Artery Disease Complexity: Patient-Level Pooled Analysis of 6081 Patients.

BACKGROUND Diabetes mellitus and angiographic coronary artery disease complexity are intertwined and unfavorably affect prognosis after percutaneous coronary interventions, but their relative impact on long-term outcomes after percutaneous coronary intervention with drug-eluting stents remains controversial. This study determined drug-eluting stents outcomes in relation to diabetic status and coronary artery disease complexity as assessed by the Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score. METHODS AND RESULTS In a patient-level pooled analysis from 4 all-comers trials, 6081 patients were stratified according to diabetic status and according to the median SYNTAX score ≤11 or >11. The primary end point was major adverse cardiac events, a composite of cardiac death, myocardial infarction, and clinically indicated target lesion revascularization within 2 years. Diabetes mellitus was present in 1310 patients (22%), and new-generation drug-eluting stents were used in 4554 patients (75%). Major adverse cardiac events occurred in 173 diabetics (14.5%) and 436 nondiabetic patients (9.9%; P<0.001). In adjusted Cox regression analyses, SYNTAX score and diabetes mellitus were both associated with the primary end point (P<0.001 and P=0.028, respectively; P for interaction, 0.07). In multivariable analyses, diabetic versus nondiabetic patients had higher risks of major adverse cardiac events (hazard ratio, 1.25; 95% confidence interval, 1.03-1.53; P=0.026) and target lesion revascularization (hazard ratio, 1.54; 95% confidence interval, 1.18-2.01; P=0.002) but similar risks of cardiac death (hazard ratio, 1.41; 95% confidence interval, 0.96-2.07; P=0.08) and myocardial infarction (hazard ratio, 0.89; 95% confidence interval, 0.64-1.22; P=0.45), without significant interaction with SYNTAX score ≤11 or >11 for any of the end points. CONCLUSIONS In this population treated with predominantly new-generation drug-eluting stents, diabetic patients were at increased risk for repeat target-lesion revascularization consistently across the spectrum of disease complexity. The SYNTAX score was an independent predictor of 2-year outcomes but did not modify the respective effect of diabetes mellitus. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00297661, NCT00389220, NCT00617084, and NCT01443104.

Estimates of in situ Larval Development Time for the Lobster, Homarus Americanus

Larval development time is a critical factor in assessing the potential for larval transport, mortality. and subsequently, the connectivity of marine populations through larval exchange. Most estimates of larval duration are based on laboratory studies and may not reflect development times in nature. For larvae of the American lobster (Homarus americanus), temperature-dependent development times have been established in previous laboratory studies. Here, we used the timing of seasonal abundance curves for newly hatched larvae (stage 1) and the final plankonic instar (postlarva), coupled with a model of temperature-dependent development to assess development time in the field. We were unable to reproduce the timing of the seasonal abundance curves using laboratory development rates in our model. Our results suggest that larval development in situ may be twice as fast as reported laboratory rates. This will result in reduced estimates of larval transport potential, and increased estimates of instantaneous mortality rate and production.

HIV incidence estimates and HIV/AIDS concurrent diagnosis in Houston/Harris County

The purpose of this dissertation was to estimate HIV incidence among the individuals who had HIV tests performed at the Houston Department of Health and Human Services (HDHHS) public health laboratory, and to examine the prevalence of HIV and AIDS concurrent diagnoses among HIV cases reported between 2000 and 2007 in Houston/Harris County. ^ The first study in this dissertation estimated the cumulative HIV incidence among the individuals testing at Houston public health laboratory using Serologic Testing Algorithms for Recent HIV Seroconversion (STARHS) during the two year study period (June 1, 2005 to May 31, 2007). The HIV incidence was estimated using two independently developed statistical imputation methods, one developed by the Centers for Disease Control and Prevention (CDC), and the other developed by HDHHS. Among the 54,394 persons who tested for HIV during the study period, 942 tested HIV positive (positivity rate=1.7%). Of these HIV positives, 448 (48%) were newly reported to the Houston HIV/AIDS Reporting System (HARS) and 417 of these 448 blood specimens (93%) were available for STARHS testing. The STARHS results showed 139 (33%) out of the 417 specimens were newly infected with HIV. Using both the CDC and HDHHS methods, the estimated cumulative HIV incidences over the two-year study period were similar: 862 per 100,000 persons (95% CI: 655-1,070) by CDC method, and 925 per 100,000 persons (95% CI: 908-943) by HDHHS method. Consistent with the national finding, this study found African Americans, and men who have sex with men (MSM) accounted for most of the new HIV infections among the individuals testing at Houston public health laboratory. Using CDC statistical method, this study also found the highest cumulative HIV incidence (2,176 per 100,000 persons [95%CI: 1,536-2,798]) was among those who tested in the HIV counseling and testing sites, compared to the sexually transmitted disease clinics (1,242 per 100,000 persons [95%CI: 871-1,608]) and city health clinics (215 per 100,000 persons [95%CI: 80-353]. This finding suggested the HIV counseling and testing sites in Houston were successful in reaching high risk populations and testing them early for HIV. In addition, older age groups had higher cumulative HIV incidence, but accounted for smaller proportions of new HIV infections. The incidence in the 30-39 age group (994 per 100,000 persons [95%CI: 625-1,363]) was 1.5 times the incidence in 13-29 age group (645 per 100,000 persons [95%CI: 447-840]); the incidences in 40-49 age group (1,371 per 100,000 persons [95%CI: 765-1,977]) and 50 or above age groups (1,369 per 100,000 persons [95%CI: 318-2,415]) were 2.1 times compared to the youngest 13-29 age group. The increased HIV incidence in older age groups suggested that persons 40 or above were still at risk to contract HIV infections. HIV prevention programs should encourage more people who are age 40 and above to test for HIV. ^ The second study investigated concurrent diagnoses of HIV and AIDS in Houston. Concurrent HIV/AIDS diagnosis is defined as AIDS diagnosis within three months of HIV diagnosis. This study found about one-third of the HIV cases were diagnosed with HIV and AIDS concurrently (within three months) in Houston/Harris County. Using multivariable logistic regression analysis, this study found being male, Hispanic, older, and diagnosed in the private sector of care were positively associated with concurrent HIV and AIDS diagnoses. By contrast, men who had sex with men and also used injection drugs (MSM/IDU) were 0.64 times (95% CI: 0.44-0.93) less likely to have concurrent HIV and AIDS diagnoses. A sensitivity analysis comparing difference durations of elapsed time for concurrent HIV and AIDS diagnosis definitions (1-month, 3-month, and 12-month cut-offs) affected the effect size of the odds ratios, but not the direction. ^ The results of these two studies, one describing characteristics of the individuals who were newly infected with HIV, and the other study describing persons who were diagnosed with HIV and AIDS concurrently, can be used as a reference for HIV prevention program planning in Houston/Harris County. ^

Estimates of life expectancy gains from reducing/eliminating major causes of death in the USA: An update analysis for population in 2001--2008

Evaluation of the impact of a disease on life expectancy is an important part of public health. Potential gains in life expectancy (PGLE) that can properly take into account the competing risks are an effective indicator for measuring the impact of the multiple causes of death. This study aimed to measure the PGLEs from reducing/eliminating the major causes of death in the USA from 2001 to 2008. To calculate the PGLEs due to the elimination of specific causes of death, the age-specific mortality rates for heart disease, malignant neoplasms, Alzheimer disease, kidney diseases and HIV/AIDS and life table constructing data were obtained from the National Center for Health Statistics, and the multiple decremental life tables were constructed. The PGLEs by elimination of heart disease, malignant neoplasms or HIV/AIDS continued decreasing from 2001 to 2008, but the PGLE by elimination of Alzheimer's disease or kidney diseases revealed increased trends. The PGLEs (by years) for all race, male, female, white, white male, white female, black, black male and black female at birth by complete elimination of heart disease 2001–2008 were 0.336–0.299, 0.327–0.301, 0.344–0.295, 0.360–0.315, 0.349–0.317, 0.371–0.316,0.278–0.251, 0.272–0.255, and 0.282–0.246 respectively. Similarly, the PGLEs (by years) for all race, male, female, white, white male, white female, black, black male and black female at birth by complete elimination of malignant neoplasms, Alzheimer's disease, kidney disease or HIV/AIDS 2001–2008 were also uncovered, respectively. Most diseases affect specific population, such as, HIV/AIDS tends to have a greater impact on people of working age, heart disease and malignant neoplasms have a greater impact on people over 65 years of age, but Alzheimer's disease and kidney diseases have a greater impact on people over 75 years of age. To measure the impact of these diseases on life expectancy in people of working age, partial multiple decremental life tables were constructed and the PGLEs were computed by partial or complete elimination of various causes of death during the working years. Thus, the results of the study outlined a picture of how each single disease could affect the life expectancy in age-, race-, or sex-specific population in USA. Therefore, the findings would not only assist to evaluate current public health improvements, but also provide useful information for future research and disease control programs.^

Effects of overweight and obesity on economic outcomes among U.S. adults with kidney disease

Background. Kidney disease is a growing public health phenomenon in the U.S. and in the world. Downstream interventions, dialysis and renal transplants covered by Medicare's renal disease entitlement policy in those who are 65 years and over have been expensive treatments that have been not foolproof. The shortage of kidney donors in the U.S. has grown in the last two decades. Therefore study of upstream events in kidney disease development and progression is justified to prevent the rising prevalence of kidney disease. Previous studies have documented the biological route by which obesity can progress and accelerate kidney disease, but health services literature on quantifying the effects of overweight and obesity on economic outcomes in the context of renal disease were lacking. Objectives . The specific aims of this study were (1) to determine the likelihood of overweight and obesity in renal disease and in three specific adult renal disease sub-populations, hypertensive, diabetic and both hypertensive and diabetic (2) to determine the incremental health service use and spending in overweight and obese renal disease populations and (3) to determine who financed the cost of healthcare for renal disease in overweight and obese adult populations less than 65 years of age. Methods. This study was a retrospective cross-sectional study of renal disease cases pooled for years 2002 to 2009 from the Medical Expenditure Panel Survey. The likelihood of overweight and obesity was estimated using chi-square test. Negative binomial regression and generalized gamma model with log link were used to estimate healthcare utilization and healthcare expenditures for six health event categories. Payments by self/family, public and private insurance were described for overweight and obese kidney disease sub-populations. Results. The likelihood of overweight and obesity was 0.29 and 0.46 among renal disease and obesity was common in hypertensive and diabetic renal disease population. Among obese renal disease population, negative binomial regression estimates of healthcare utilization per person per year as compared to normal weight renal disease persons were significant for office-based provider visits and agency home health visits respectively (p=0.001; p=0.005). Among overweight kidney disease population health service use was significant for inpatient hospital discharges (p=0.027). Over years 2002 to 2009, overweight and obese renal disease sub-populations had 53% and 63% higher inpatient facility and doctor expenditures as compared to normal weight renal disease population and these result were statistically significant (p=0.007; p=0.026). Overweigh renal disease population had significant total expenses per person per year for office-based and outpatient associated care. Overweight and obese renal disease persons paid less from out-of-pocket overall compared to normal weight renal disease population. Medicare and Medicaid had the highest mean annual payments for obese renal disease persons, while mean annual payments per year were highest for private insurance among normal weight renal disease population. Conclusion. Overweight and obesity were common in those with acute and chronic kidney disease and resulted in higher healthcare spending and increased utilization of office-based providers, hospital inpatient department and agency home healthcare. Healthcare for overweight and obese renal disease persons younger than 65 years of age was financed more by private and public insurance and less by out of pocket payments. With the increasing epidemic of obesity in the U.S. and the aging of the baby boomer population, the findings of the present study have implications for public health and for greater dissemination of healthcare resources to prevent, manage and delay the onset of overweight and obesity that can progress and accelerate the course of the kidney disease.^

Estimates of hospital and physician costs of epilepsy in the United States for 1995 comparing the provider -based survey method and a patient -based medical charts and billing method

This investigation compares two different methodologies for calculating the national cost of epilepsy: provider-based survey method (PBSM) and the patient-based medical charts and billing method (PBMC&BM). The PBSM uses the National Hospital Discharge Survey (NHDS), the National Hospital Ambulatory Medical Care Survey (NHAMCS) and the National Ambulatory Medical Care Survey (NAMCS) as the sources of utilization. The PBMC&BM uses patient data, charts and billings, to determine utilization rates for specific components of hospital, physician and drug prescriptions. ^ The 1995 hospital and physician cost of epilepsy is estimated to be $722 million using the PBSM and $1,058 million using the PBMC&BM. The difference of $336 million results from $136 million difference in utilization and $200 million difference in unit cost. ^ Utilization. The utilization difference of $136 million is composed of an inpatient variation of $129 million, $100 million hospital and $29 million physician, and an ambulatory variation of $7 million. The $100 million hospital variance is attributed to inclusion of febrile seizures in the PBSM, $−79 million, and the exclusion of admissions attributed to epilepsy, $179 million. The former suggests that the diagnostic codes used in the NHDS may not properly match the current definition of epilepsy as used in the PBMC&BM. The latter suggests NHDS errors in the attribution of an admission to the principal diagnosis. ^ The $29 million variance in inpatient physician utilization is the result of different per-day-of-care physician visit rates, 1.3 for the PBMC&BM versus 1.0 for the PBSM. The absence of visit frequency measures in the NHDS affects the internal validity of the PBSM estimate and requires the investigator to make conservative assumptions. ^ The remaining ambulatory resource utilization variance is $7 million. Of this amount, $22 million is the result of an underestimate of ancillaries in the NHAMCS and NAMCS extrapolations using the patient visit weight. ^ Unit cost. The resource cost variation is $200 million, inpatient is $22 million and ambulatory is $178 million. The inpatient variation of $22 million is composed of $19 million in hospital per day rates, due to a higher cost per day in the PBMC&BM, and $3 million in physician visit rates, due to a higher cost per visit in the PBMC&BM. ^ The ambulatory cost variance is $178 million, composed of higher per-physician-visit costs of $97 million and higher per-ancillary costs of $81 million. Both are attributed to the PBMC&BM's precise identification of resource utilization that permits accurate valuation. ^ Conclusion. Both methods have specific limitations. The PBSM strengths are its sample designs that lead to nationally representative estimates and permit statistical point and confidence interval estimation for the nation for certain variables under investigation. However, the findings of this investigation suggest the internal validity of the estimates derived is questionable and important additional information required to precisely estimate the cost of an illness is absent. ^ The PBMC&BM is a superior method in identifying resources utilized in the physician encounter with the patient permitting more accurate valuation. However, the PBMC&BM does not have the statistical reliability of the PBSM; it relies on synthesized national prevalence estimates to extrapolate a national cost estimate. While precision is important, the ability to generalize to the nation may be limited due to the small number of patients that are followed. ^

Dinoflagellate cyst assemblages, oxygen isotope records of foraminifera, and alkenone and Mg/Ca-based SST estimates for the time interval 3.40-3.18 Ma (Late Pliocene) from five North Atlantic and Caribbean sediment cores

The early Late Pliocene (3.6 to ~3.0 million years ago) is the last extended interval in Earth's history when atmospheric CO2 concentrations were comparable to today's and global climate was warmer. Yet a severe global glaciation during marine isotope stage (MIS) M2 interrupted this phase of global warmth ~3.30 million years ago, and is seen as a premature attempt of the climate system to establish an ice-age world. Our geochemical and palynological records from five marine sediment cores along a Caribbean to eastern North Atlantic transect show that increased Pacific-to-Atlantic flow via the Central American Seaway weakened the North Atlantic Current (NAC) and attendant northward heat transport prior to MIS M2. The consequent cooling of the northern high latitude oceans permitted expansion of the Greenland ice sheet during MIS M2, despite near-modern atmospheric CO2 concentrations. Before and after MIS M2, heat transport via the NAC was crucial in maintaining warm climates comparable to those predicted for the end of this century.