Circulating vitamin D levels are associated with the presence and severity of coronary artery disease but not peripheral arterial disease in patients undergoing coronary angiography.

BACKGROUND AND AIMS: To investigate the association between vitamin D levels, angiographic severity of coronary artery disease, arterial stiffness and degree of peripheral arterial disease (PAD) as assessed by ankle brachial index (ABI). METHODS AND RESULTS: 375 patients undergoing coronary angiography from November 2012 to September 2013 were recruited. Serum 25-hydroxyvitamin D (25OHD) levels were measured as were ABI and pulse wave velocity (PWV). Based on the findings of the coronary angiogram, patients were divided into subgroups: Absent, Single, Double and Triple Vessel Disease (as defined by >50% stenosis in each major coronary artery) 0.275 patients not taking vitamin D supplements were included in the analysis. Mean age was 66.0 ± 11.2 (mean ± SD) years. Levels of 25(OH)D were significantly lower in patients with CAD when compared to patients without CAD (57.0 ± 1.73 versus 70.1 ± 2.46 nmol/L; p < 0.01). One way ANOVA revealed triple vessel disease patients had significantly lower 25(OH)D levels when compared to single vessel disease patients (50.6 ± 2.84 nmol/L versus 61.3 ± 3.16 p < 0.01) and trended to be lower when compared to double vessel disease patients (50.6 ± 2.84 versus 59.0 ± 2.99 nmol/L; p = 0.07). Stepwise regression revealed that age, gender (male), hypertension, hyperlipidemia and 25(OH)D were significant predictors of CAD (p < 0.05). Vitamin D was the most significant predictor for CAD (p < 0.001) There was no correlation between 25(OH)D levels, ABI and PWV. CONCLUSION: Among patients presenting for coronary angiography, low serum 25-hydroxyvitamin D levels are associated with the presence and extent of angiographic CAD but not arterial stiffness or PAD.

Risk of cardiovascular adverse events from trastuzumab (Herceptin(®)) in elderly persons with breast cancer: a population-based study.

Randomized controlled trials have reported a 4-5 times increased risk of heart failure (HF) in breast cancer patients receiving trastuzumab (Herceptin (®) ) compared to patients who do not receive trastuzumab. However, data regarding the cardiac effects of trastuzumab on elderly patients treated in general practice remain very limited. Using the US surveillance, epidemiology, and end results (SEER)-Medicare database, we conducted a retrospective cohort study on the cardiac effects of trastuzumab use in all incident breast cancer patients diagnosed from 1998 to 2007 who were 66 years and older, had no prior recent claims for cardiomyopathy (CM) or HF, and were followed through 2009. We defined our outcome as the first CM/HF event after diagnosis. We performed Cox-proportional hazard models with propensity score adjustment to estimate CM/HF risk associated with trastuzumab use. A total of 6,829 out of 68,536 breast cancer patients (median age: 75) had an incident CM/HF event. Patients who received trastuzumab tended to be younger, non-white, diagnosed more recently, and had a stage IV diagnosis. Trastuzumab use was associated with an increased risk of CM/HF (HR = 2.08, 95 % CI 1.77-2.44, p < 0.001). The trastuzumab-associated CM/HF risk was stronger in patients who were younger (HR = 2.52 for 66-75 years and HR = 1.44 for 76 years and older, p < 0.001) and diagnosed in recent years (HR = 2.58 for 2006-2007 vs. 1.86 for 1998-2005, p = 0.01). The twofold risk of CM/HF associated with trastuzumab remained regardless of patients' diagnosis stage, presence of hypertension, cardiovascular comorbidities, or receipt of anthracyclines, taxanes, or radiation. Trastuzumab may double CM/HF risk among elderly breast cancer patients. Our findings reinforce the need to prevent and manage cardiac risk among elderly breast cancer patients receiving trastuzumab.

Bevacizumab use and risk of cardiovascular adverse events among elderly patients with colorectal cancer receiving chemotherapy: a population-based study.

BACKGROUND: Cardiovascular risk attributable to bevacizumab (Avastin(®), BEV) for treatment of metastatic colorectal cancer (CRC) remains unclear. We conducted a population-based cohort study to assess the safety of BEV use among patients aged ≥ 65. PATIENTS AND METHODS: We identified CRC patients diagnosed from 2005 to 2007 who received chemotherapy and were followed until 31 December 2009. Outcomes were 3-year risk of arterial thromboembolic events (ATEs), cardiomyopathy or congestive heart failure (CM/CHF), and cardiac death (CD) after chemotherapy initiation. We fitted Cox-proportional hazards (PHs) models with inverse-probability-of-treatment-weights and calculated hazard ratios (HRs) for the risk of adverse events. RESULTS: We identified 6803 CRC patients (median age: 73 years). Those with cardiac comorbidity were less likely to receive BEV (P < 0.0001). BEV is associated with an elevated risk of ATEs (HR = 1.82, 95% CI = 1.20-2.76, P < 0.001; rate difference: 3.5 additional cases/1000 person-years). We observed no association between BEV and CD or CM/CHF. CONCLUSIONS: In general practice, the cardiovascular risk of BEV in elderly CRC is modest. The observed ATEs risk is lower than reported in clinical trials, which may be due to careful patient selection. Our findings may facilitate clinical decision-making of BEV use in elderly patients.

Topography dependence of the metamagnetic phase transition in FeRh thin films.

The equiatomic alloy FeRh is of great scientific and technological interest due its highly unusual first-order antiferromagnetic (AF) to ferromagnetic (FM) phase transition. Here we report an exploration of the interplay between topography and phase evolution with a comprehensive magnetic force microscopy study of nominal 50 nm thick FeRh thin films and subtractively patterned wires of width 0.2 µm-2 µm. In continuous films where the surface morphology had not been optimised for smoothness, the topographical variation was observed to dominate the distribution of the magnetic transition temperatures and dictates the nucleation and growth of the magnetic phases. This observation was repeated for patterned elements, where the effects of surface morphology were more significant than those of spatial confinement. These results have clear implications for future studies of low-dimensional FeRh films, as surface topography must be considered when analysing and comparing the transition behaviour of FeRh thin films.

Iodothyronamines are oxidatively deaminated to iodothyroacetic acids in vivo.

3-Iodothyronamine (T(1)AM) and 3,3',5-triiodothyroacetic acid (Triac) are bioactive metabolites of the hormone thyroxine (T(4)). In the present study, the ability of T(1)AM and 3,3',5-triiodothyronamine (T(3)AM) to be metabolized to 3-iodothyroacetic acid (TA(1)) and Triac, respectively, was investigated. Both T(1)AM and T(3)AM were converted to their respective iodinated thyroacetic acid analogues in both cell and tissue extracts. This conversion could be significantly inhibited with the monamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO) inhibitor iproniazid. TA(1) was found to be present in trace quantities in human serum and in substantial levels in serum from T(1)AM-treated rats. These results demonstrate that iodothyronamines are substrates for amine oxidases and that this metabolism may be the source of the corresponding endogenous arylacetic acid products Triac and TA(1).

Early views of the martian surface from the Mars Orbiter Camera of Mars Global Surveyor.

High-resolution images of the martian surface at scales of a few meters show ubiquitous erosional and depositional eolian landforms. Dunes, sandsheets, and drifts are prevalent and exhibit a range of morphology, composition (inferred from albedo), and age (as seen in occurrences of different dune orientations at the same location). Steep walls of topographic depressions such as canyons, valleys, and impact craters show the martian crust to be stratified at scales of a few tens of meters. The south polar layered terrain and superposed permanent ice cap display diverse surface textures that may reflect the complex interplay of volatile and non-volatile components. Low resolution regional views of the planet provide synoptic observations of polar cap retreat, condensate clouds, and the lifecycle of local and regional dust storms.

Identification of selective, nonpeptidic nitrile inhibitors of cathepsin s using the substrate activity screening method.

The substrate activity screening method, a substrate-based fragment identification and optimization method for the development of enzyme inhibitors, was previously applied to cathepsin S to obtain low nanomolar 1,4-disubstituted-1,2,3-triazole-based aldehyde inhibitors (Wood, W. J. L.; Patterson, A. W.; Tsuruoka, H.; Jain, R. K.; Ellman, J. A. J. Am. Chem. Soc. 2005, 127, 15521-15527). Replacement of the metabolically labile aldehyde pharmacophore with the nitrile pharmacophore provided inhibitors with moderate potency for cathepsin S. The inhibitors showed good selectivity over cathepsins B and L but no selectivity over cathepsin K. X-ray structures of two crystal forms (1.5 and 1.9 A) of a complex between cathepsin S and a triazole inhibitor incorporating a chloromethyl ketone pharmacophore guided the design of triazole substrates with increased cleavage efficiency and selectivity for cathepsin S over cathepsins B, L, and K. Conversion of select substrates to nitrile inhibitors yielded a low molecular weight (414 Da) and potent (15 nM) cathepsin S inhibitor that showed >1000-fold selectivity over cathepsins B, L, and K.

Trends and outcomes of outpatient mastectomy in elderly women.

BACKGROUND: Considerable public attention has focused on the use of outpatient mastectomy and has resulted in numerous legislative proposals to mandate a minimum hospital stay following mastectomy. To date, only limited scientific data are available regarding the use and the outcomes of outpatient mastectomy. The purpose of this study was to provide population-based information on trends and outcomes for outpatient mastectomy in elderly women. METHODS: Medicare data for elderly women with fee-for-service coverage were examined for trends and regional variation in the use of outpatient mastectomy. Logistic regression was used to identify patient and provider characteristics associated with having an outpatient mastectomy, and outcomes were assessed by calculating the risk of being rehospitalized and the reasons for rehospitalization. RESULTS: From 1986 through 1995, the proportion of mastectomies performed on an outpatient basis increased from virtually 0% to 10.8%. Outpatient mastectomies were more likely to be performed on women with no coexisting health problems in hospitals that were for-profit or non-teaching or in large metropolitan statistical areas. Women undergoing outpatient mastectomy had substantially higher rates of rehospitalization within 30 days than women with a 1-day stay in the hospital. Both groups had comparable rates of rehospitalization for complications definitely related to their surgery. The percentage of women who required rehospitalization was low, and the actual number of women rehospitalized was relatively small. CONCLUSIONS: We conclude that the risks from outpatient mastectomy are modest, although ongoing monitoring of outcomes and assessment of patient satisfaction are needed.

Cancer surveillance series [corrected]: brain and other central nervous system cancers: recent trends in incidence and mortality.

BACKGROUND: During the 1980s, the incidence of primary malignant brain and other central nervous system tumors (hereafter called brain cancer) was reported to be increasing among all age groups in the United States, while mortality was declining for persons younger than 65 years. We analyzed these data to provide updates on incidence and mortality trends for brain cancer in the United States and to examine these patterns in search of their causes. METHODS: Data on incidence, overall and according to histology and anatomic site, and on relative survival were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute for 1975 through 1995. Mortality data were obtained from the National Center for Health Statistics. Medicare procedure claims from the National Cancer Institute's SEER-Medicare database were used for imaging trends. Statistically significant changes in incidence trends were identified, and annual percent changes were computed for log linear models. RESULTS/CONCLUSIONS: Rates stabilized for all age groups during the most recent period for which SEER data were available, except for the group containing individuals 85 years of age or older. Mortality trends continued to decline for the younger age groups, and the steep increases in mortality seen in the past for the elderly slowed substantially. Patterns differed by age group according to the site and grade of tumors between younger and older patients. During the last decade, use of computed tomography scans was relatively stable for those 65-74 years old but increased among those 85 years old or older. IMPLICATIONS: Improvements in diagnosis and changes in the diagnosis and treatment of elderly patients provide likely explanations for the observed patterns in brain cancer trends.

The impact and cost of influenza in the elderly.

BACKGROUND: Traditional methods of measuring the impact and cost of influenza virus have focused on epidemic years and morbidity and mortality due to pneumonia and influenza. METHODS: Annualized age-sex-race adjusted rates of hospitalization for pneumonia and influenza and other diagnoses among elderly Medicare beneficiaries during the epidemic influenza season of 1989 to 1990 and the nonepidemic season of 1990 to 1991 were compared with an interim period in 1990 without influenza virus circulation. RESULTS: The rates of hospitalization for pneumonia and influenza, acute bronchitis, chronic respiratory disease, and congestive heart failure were significantly greater during each influenza period compared with the interim period. The highest rates were found in the epidemic season of 1989 to 1990. The amount reimbursed by Medicare to hospitals to 1990. The amount reimbursed by Medicare to hospitals for the treatment of excess hospitalizations during periods of influenza activity was more than $1 billion in 1989 to 1990 and almost $750 million in 1990 to 1991. CONCLUSIONS: Measures of the impact and cost of influenza in elderly Americans should include all of the diagnoses listed above and should recognize that the impact of influenza virus is significant even in nonepidemic years. There are great opportunities for cost savings if effective control programs are implemented.

Hospitalizations with adverse events caused by digitalis therapy among elderly Medicare beneficiaries.

BACKGROUND: Digitalis products are among the agents most frequently prescribed to the elderly, yet previous studies have not provided age-, race-, and sex-specific rates of utilization of digitalis by this population. Estimates of the rate of hospitalization with an adverse reaction from digitalis therapy have varied considerably between systems relying on passive reports and those using active surveillance. METHODS: Medicare data from 1985 through 1991 and data from the 1987 National Medical Expenditure Survey were used to determine population-based estimates of the use of digitalis in elderly beneficiaries by age group, sex, and race. Hospitalization rates with an adverse event caused by digitalis therapy were calculated for those persons estimated to be using digitalis. Medicare data were used to identify the frequency of selected comorbidities among persons with an adverse event caused by digitalis therapy as well as the frequency of clinical manifestations associated with digitalis intoxication. RESULTS: Over 3 million Medicare beneficiaries were estimated to be using digitalis in 1987. A total of 202,011 hospitalizations with a coded adverse event caused by digitalis therapy were reported during the 7-year study period. Of persons estimated to be using digitalis, 8.53 per 1000 were hospitalized annually with an adverse event caused by digitalis therapy. Women, individuals with increasing age, and persons of black race, especially those with impaired renal function, were significantly (P < .05) more likely to experience hospitalization with an adverse event caused by digitalis therapy. CONCLUSION: This information may help identify categories of elderly patients who require more frequent monitoring to prevent adverse effects of digitalis therapy. Changes in the format of the hospital bill to include more diagnoses along with increased mandatory reporting of adverse drug events will improve the sensitivity of Medicare data for surveillance of adverse drug events.

Development of a comorbidity index using physician claims data.

Important comorbidities recorded on outpatient claims in administrative datasets may be missed in analyses when only inpatient care is considered. Using the comorbid conditions identified by Charlson and colleagues, we developed a comorbidity index that incorporates the diagnostic and procedure data contained in Medicare physician (Part B) claims. In the national cohorts of elderly prostate (n = 28,868) and breast cancer (n = 14,943) patients assessed in this study, less than 10% of patients had comorbid conditions identified when only Medicare hospital (Part A) claims were examined. By incorporating physician claims, the proportion of patients with comorbid conditions increased to 25%. The new physician claims comorbidity index significantly contributes to models of 2-year noncancer mortality and treatment received in both patient cohorts. We demonstrate the utility of a disease-specific index using an alternative method of construction employing study-specific weights. The physician claims index can be used in conjunction with a comorbidity index derived from inpatient hospital claims, or employed as a stand-alone measure.

Detection of small radiation sources: the effect of mode of count-rate presentation.

We used an observer-performance study to compare four different modes of presenting count-rate data from a radiation detector. Observers searched for small, concealed radioactive sources using a hand-held radiation-detector probe. The modes of count-rate presentation were a ratemeter, howler, multichannel scaler, and HRM III. The HRM III calculates the statistical significance of the difference between current and previous count rates and presents the result as an audio signal. We tested six observers with each mode of count-rate presentation, calculated receiver operating characteristic (ROC) curves, and used the areas under the ROC curves to compare the different modes. Observer performance was better with the multichannel scaler and HRM III than with either the ratemeter or the howler. The results suggest that observer performance with devices that use ratemeters or howlers can be enhanced by improving the mode of count-rate presentation.

Use of Medicare data to identify incident breast cancer cases.

Surveillance, Epidemiology and End Results (SEER) data from the National Cancer Institute (NCI) provide reliable information about cancer incidence. However, because SEER data are geographically limited and have a 2-year time lag, we evaluated whether Medicare data could provide timely information on cancer incidence. Comparing Medicare women hospitalized for breast cancer with women reported to SEER, Medicare data had high specificity (96.6 percent), yet low sensitivity (59.4 percent). We conclude that Medicare hospitalization data can identify incident cases for cancers that usually require inpatient hospitalization. For cancers that often only receive outpatient treatment, such as breast cancer, additional Medicare data, such as physician bills, are needed to understand the entirety of treatment practices.

Medicare Part A utilization and expenditures for psychiatric services: 1995.

This study provides an overview of Medicare's current coverage and payment policies regarding hospitalization for psychiatric disorders, and presents new information on demographic, diagnostic, utilization, and expenditure characteristics associated with inpatient psychiatric care among 1995 Medicare beneficiaries. Results suggest that utilization and expenditure patterns for Medicare beneficiaries hospitalized for psychiatric illness in 1995 differ across demographic (e.g., age, sex, race) and diagnostic categories. The implications of these findings for current management of the Medicare program as well as the evolution of Medicare managed care systems for behavioral health services are discussed.