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It is not known whether women who develop venous thromboembolism (VTE) during pregnancy have a higher or lower incidence of recurrent VTE than women with unprovoked VTE. The aim of the study was to compare the risk of recurrent VTE among women with pregnancy-associated VTE to women with unprovoked VTE. Hospital discharge data identified women age 18-46 years old with pregnancy-associated or unprovoked index VTE between 1994 and 2005. Risk of recurrent VTE was compared between six and 60 months after the index event using both age-matched comparison of disease-free survival and proportional hazard modelling, adjusting for age and other risk factors. The Kaplan-Meier incidence of recurrent VTE in 1085 women with pregnancy-associated VTE was 5.8% versus 10.4% in 7625 women with unprovoked VTE (p = 0.02). Twelve of 34 (35%) recurrent events in the pregnancy-associated group occurred during a subsequent pregnancy compared with 29 of 331 (8.7%) events in the unprovoked group (p0.001). In the risk-adjusted multivariate model, women with pregnancy-associated VTE had a significantly lower risk of recurrent VTE (HR = 0.6, 95%CI = 0.4-0.9). Overall, the incidence of recurrent VTE during subsequent pregnancies was higher in the pregnancy group, 21 of 465 (4.5%), than in the unprovoked group, 37 of 1353 (2.7%, RR = 1.7, CI: 1.0-2.8). Compared to women with unprovoked VTE, women with pregnancy-associated VTE had a significantly lower long-term risk of recurrent VTE but a higher risk of recurrent VTE during a subsequent pregnancy. These findings should be considered when decisions are made about VTE prophylaxis in women with a history of pregnancy-associated VTE.

Lower activated partial thromboplastin times are associated with higher levels of some coagulation factors and may represent a procoagulant tendency.In the Atherosclerosis Risk in Communities study, we studied the 13-year risk of venous thromboembolism in relation to baseline activated partial thromboplastin time in 13,880 individuals. We also studied 258 venous thromboembolism cases and 589 matched controls with measurements of additional coagulation factors.After adjustment for demographics and procoagulant factors reflected in the activated partial thromboplastin time (fibrinogen, factors VIII, IX, and XI, and von Willebrand factor), participants in the lowest 2 quartiles of activated partial thromboplastin time compared with the fourth quartile had 2.4-fold (95% confidence interval [CI], 1.4-4.2) and 1.9-fold (95% CI, 1.1-3.2) higher risks of venous thromboembolism. The risk associated with activated partial thromboplastin times below the median was higher for idiopathic (odds ratio 5.5; 95% CI, 2.0-15.5) than secondary venous thromboembolism (odds ratio 1.74; 95% CI, 0.88-3.43). Subjects with both activated partial thromboplastin times below the median and factor V Leiden were 12.6-fold (95% CI, 5.7-28.0) more likely to develop venous thromboembolism compared with those with neither risk factor (P interaction.01). A lower activated partial thromboplastin time also added to the thrombosis risk associated with obesity and elevated D-dimer.A single determination of the activated partial thromboplastin time below the median increased the risk of future venous thromboembolism. Findings were independent of coagulation factor levels, and a low activated partial thromboplastin time added to the risk associated with other risk factors.

Sixty patients who had had a major fracture of the pelvis and were in stable condition on the orthopaedic ward three to five days after the injury were tested serially with duplex ultrasound, beginning approximately seven days after the injury, in order to determine the incidence of deep-vein thrombosis. Contrast venography was performed to confirm all positive non-invasive studies. Deep-vein thrombosis developed in eight patients (approximately 15 per cent). The thrombosis was in the popliteal or a more proximal vein in six of the eight patients, whereas in two it was distal to the popliteal vein. In four patients, evidence of thrombosis developed after one or more normal duplex-ultrasound studies. In one patient, symptoms that were suggestive of deep-vein thrombosis developed fifty-two days after the injury (four days after the fourth normal duplex-ultrasound examination), and ascending venography was entirely normal. Another patient had a pulmonary embolus fifteen days after the injury, and on the same day a duplex-ultrasound study was positive for thrombosis. During six weeks of follow-up after discharge from the hospital, symptoms of deep-vein thrombosis or pulmonary embolism did not develop in any patient in whom serial duplex-ultrasound studies had been negative.

Field research was conducted to determine the effects of N, Fe, and benzyladenine (BA) on fall perform- ance, post-dormancy recovery, and storage nonstructural carbohydrate composition of 'Midiron' bermudagrass (Cy - nodon dactylon (L.) Pers.). Fall green color retention and turf quality were superior for 48 than for 24 kg N/ha per month. Nitrogen level did not affect post-dormancy recovery or nonstructural carbohydrate levels in stolons and rhizomes measured in Sept. and Nov. 1983 and 1984. Iron level did not influence turf color and quality during summer months. Biweekly application of 0.6 kg Fe/ha produced better retention of greenness and turf quality during Fall 1983 and 1984 and superior turf color in Spring 1985 than the 0 kg Fe/ha treatment. Better green turf coverage was obtained with the biweekly than the monthly Fe (1.2 kg-ha-l) treatment during Fall 1983. In contrast, monthly Fe produced color and turf quality similar to that of the biweekly Fe treatment during Fall 1984. Nonstructural carbohydrates were similar among Fe levels in 1983 and 1984. The effects of Fe on turf color and quality were similar at each level of N and BA. BA level did not consistently influence turf color or quality and did not affect storage carbohydrate levels. When used in conjunction with moderate summer N fertilization, foliar-applied Fe can extend bermudagrass quality during fall without adversely affecting postdormancy recovery. Chemical name used: N- (phen- ylmethyl)-lH-purin-6-amine (benzyladenine, BA). Bermudagrass ceases growth and becomes discolored when exposed to chilling temperatures (3-5). Chilling stress occurs in grasses of tropical and subtropical origin at temperatures of 15 to 0C (12). Chilling injury of bermudagrass is characterized by the presence of necrotic lesions, chlorophyll loss, and sub- sequent leaf discoloration, and cessation of growth (4, 10, 23). Disruption, of photosynthesi s, respiration, and carbohydrate par- titioning at chilling temperatures (21) contribute to reduced ber- mudagrass growth. Pretreatment of 'Tifgreen' and 'Midiron' bermudagrass with 120 mg Fe/m 2 maintained a 23% higher average daytime C02 exchange rate (CER) than within 0 mg Fe/m 2 after 4 days at a 10/7C chilling regime and following a 2-hr recovery period at 30C after exposure to chilling (21). Nighttime CER before and after the chilling regime was not significantly affected by Fe. However, average nighttime CER was 28% higher for the 120 than the 0 mg Fe/m 2 treatment after recovery from chilling. Darker green turf color was observed for the 120 than for the 0 mg Fe/m 2 treatment after the chilling period, although no difference in chlorophyll content was detected among Fe treat- ments.

Introduction It is not clear which cancer patients are at highest risk for developing venous thromboembolism (VTE). Materials and Methods: The epidemiology of VTE in cancer patients was investigated by linking the California Cancer Registry database to the discharge records of all patients hospitalized in California public hospitals between 1993–1999. Nineteen types of cancer were studied, four in detail. Results and Conclusions The incidence of VTE was highest in patients who presented with metastatic cancer, particularly clinically aggressive cancers associate with a high one-year mortality rate, such as pancreatic cancer. The incidence of VTE increased as the number of chronic medical co-morbid conditions increased. The incidence of VTE was highest in the first few months after diagnosis, and decreased over time, even when the death rate due to cancer remained constant. Patients with glioma had a very high incidence of VTE after invasive neurosurgery, whereas patients with solid cancers who underwent major surgery had a lower risk of developing VTE compared to patients who did not undergo major surgery. Development of VTE was associated with significantly shortened survival compared to cancer patients without VTE matched for age, race, sex, initial cancer stage and time after cancer diagnosis. This effect of VTE on survival was greatest in patients initially diagnosed with local or regional stage solid cancer as VTE was associated with emergence of metastatic disease. If primary thromboprophylaxis of cancer patients is considered, treatment should begin immediately after cancer diagnosis, and it should be targeted toward patients who have a biologically aggressive cancer that is initially metastatic and/or toward patients who have several chronic co-morbid conditions. Secondary thromboprophylaxis should be targeted toward patients who have evidence of an ongoing active malignancy. Glioma patients are at very high risk in the 3 month period immediately after invasive neurosurgery.

We conducted a retrospective cohort study to examine cancer risk in a large cohort of systemic lupus erythematosus (SLE) patients in California.The cohort consisted of individuals with SLE derived from statewide patient discharge data during the period 1991-2002. SLE patients were followed using cancer registry data to examine patterns of cancer development. Standardized incidence ratios (SIRs) and 95% CI were calculated to compare the observed to expected numbers of cancers based on age-, race-, and sex-specific incidence rates in the California population.The 30,478 SLE patients were observed for 157,969 person-years. A total of 1,273 cancers occurred within the observation interval. Overall cancer risk was significantly elevated (SIR = 1.14, 95% CI = 1.07-1.20). SLE patients had higher risks of vagina/vulva (SIR = 3.27, 95% CI = 2.41-4.31) and liver cancers (SIR = 2.70, 95% CI = 1.54-4.24). Elevated risks of lung, kidney, and thyroid cancers and several hematopoietic malignancies were also observed. Individuals had significantly lower risks of several screenable cancers, including breast, cervix, and prostate.These data suggest that risks of several cancer types are elevated among SLE patients. Detailed studies of endogenous and exogenous factors that drive these associations are needed.

To construct a semi-Markov model to compare health outcomes and medical costs associated with warfarin and a second anticoagulant over 1- and 5-year periods.We posited a hypothetical cohort of 10,000 identical 70-year-old patients with atrial fibrillation. We posited 20 scenarios for events that included four possibilities for ischemic strokes (mild, moderate, severe, death) and 16 possibilities for hemorrhages. The model allowed for four levels of International Normalized Ratio. Event rates were based on outcomes in clinical trials and observational studies. Costs were estimated from the perspective of the third-party payer.The greatest cost-generating events were virtually the same for the two drugs and included severe stroke ($1,758,548 for 1 year for both drugs), moderate stroke ($380,355 for 1 year for both drugs), and severe lower gastrointestinal (GI) hemorrhage ($193,804 for 1 year for warfarin and $193,474 for second drug). The least costly events for both drugs were mild intracranial or intracerebral hemorrhage ($7584 for warfarin and $4314 for second drug) and fatal upper GI hemorrhage ($16,781 and $16,752). Total costs for adverse events over 5 years were similar: $18,330,662 for warfarin and $17,102,847 for the second drug. Fatalities for 5 years were 123 for warfarin and 101 for the non-warfarin drug. Varying assumptions for nursing home care and numbers of ischemic strokes and hemorrhages generated the widest variation in costs.We did not account for out-of-pocket expenses, 'pain and suffering' costs, or variation across practice settings.There was substantial variation in numbers and costs of adverse events across 20 scenarios, and for fatalities between the two drugs, but variation in costs between the two drugs was modest.

Municipal programs for turfgrass establishment recommend large volume-based application rates of composted municipal biosolids (CMB). This study compared runoff water quality among combinations of two common turfgrass establishment practices and two CMB sources. Bryan- or Austin-CMB were incorporated into 5 cm of soil at a rate of 12.5 or 25% by volume (v/v) on an 8.5% slope. Tifway bermudagrass [Cynodon dactylon (L.) Pers. × C. transvaalensis Burtt-Davy, var. Tifway] sprigs were planted and established; sod, produced at a separate site using either CMB amendment at the 25% v/v rate, was transplanted to the runoff plots on the same day. A mature stand of bermudagrass was used as a control. Runoff water was collected after each of eight natural rain events during the sampling period. Total runoff water loss (mm) was similar for the CMB-amended sprigged and transplanted sod stands. The concentration of total dissolved P (TDP) in runoff water was greatest from the transplanted sod in the first seven rain events (4.1 to 7.5 mg L -1 ). The concentration of TDP in runoff water was similar at both the 12.5 and 25% v/v incorporation rates. Regression analysis indicated Mehlich-3-extractable soil test P concentrations in soil amended with CMB were positively correlated to concentration and mass loss of dissolved P in runoff. At similar application rates, dissolved P loss in runoff water was reduced by incorporating CMB into the soil on site rather than transplanting sod produced with CMB.

Land application of large, volume-based rates of municipal biosolids (MB) enhances soil physical properties and provides an alternative to disposal in landfills. Yet, topdressing or incorporation of the volume-based rates can increase non-point source losses of sediment and nutrients from excavated soils to surface waters. Cycling of MB through turfgrass sod produced on agricultural fields and transplanted back to urban landscapes could reduce non-point source losses of sediment compared to excavated soils amended with MB. Three research objectives were developed to evaluate the options for minimizing sediment and nutrient loss during cycling of MB through turfgrass sod. The first objective was to compare Tifway bermudagrass sod production between fields grown with and without MB under increasing rates of supplemental fertilizer N. The percent turfgrass cover of the MB-amended soil remained consistently greater (P=0.05) than the un-amended treatment throughout establishment and resulted in lighter sod weights with greater water content. The second objective was to compare runoff losses between excavated soils planted to sprigs or transplanted sod, with and without MB amendments. Runoff concentrations and mass loss of total dissolved P (TDP) were significantly greater (P=0.001) for MB-amended compared to un-amended sod. In addition, TDP concentration in runoff from MB-amended sod was greater (P=0.05) than excavated soil mixed with MB and bermudagrass sprigs. The third objective was to relate runoff loss of TDP to extractable soil P concentrations. A linear relationship was observed between water extractable P of soil and concentrations and mass loss of TDP in runoff.

Source Citation Sharma M, Cornelius VR, Patel JP, Davies JG, Molokhia M. Efficacy and harms of direct oral anticoagulants in the elderly for stroke prevention in atrial fibrillation and secondary p...

Purpose The incidence of venous thromboembolism (VTE) and the risk factors associated with development of VTE have not been reported in a large population-based study of breast cancer patients. Patients and Methods The California Cancer Registry was merged with the Patient Discharge Data Set, and the number of VTE events determined among patients diagnosed between 1993 and 1999. Results Among 108,255 patients with breast cancer, the 2-year cumulative VTE incidence was 1.2%, with a rate of 1.2 and 0.6 events/100 patient-years during the first and second half-year, respectively. The 1-year incidence of VTE was significantly increased compared with the general population (standardized incidence ratio of VTE, 4.2; 95% CI, 3.9 to 4.4). In a multivariate model, significant predictors of developing VTE within 2 years were: age (hazard ratio [HR], 2.0 if > 75 years v < 45; 95% CI, 1.6 to 2.6), the number of chronic medical comorbidities (HR, 2.9 if 3 v 0; 95% CI, 2.4 to 3.5), and advancing cancer stage (HR, 6.3; 95% CI, 5.3 to 7.5 for metastatic v local disease). In multivariate models, VTE was a significant predictor of decreased 2-year survival (HR, 2.3; 95% CI, 2.1 to 2.6) and when stratified by initial cancer stage, the effect was highest in patients with localized (HR, 5.1; 95% CI, 3.6 to 7.1) or regional stage (HR, 3.5; 95% CI, 2.5 to 4.8) cancer compared with patients with metastatic disease (HR, 1.9; 95% CI, 1.5 to 2.4). Conclusion Approximately 1% of breast cancer patients developed VTE within 2 years, with the highest incidence in the first 6 months after diagnosis. Metastatic disease and comorbidities were the strongest predictors. The diagnosis of VTE was associated with a higher risk of death within 2 years.

Objective To better define the epidemiology of acute pancreatitis in a racially diverse population. Methods Analysis of all patients hospitalized in California with first-time acute pancreatitis for the period between January 1994 and September 2001. Subtypes were classified based on the presence or absence of predisposing conditions. Results There were 70,231 patients hospitalized for first-time acute pancreatitis; 32.6% had biliary tract disease alone, 20.3% had alcohol abuse alone, and 36.6% were idiopathic. The age-standardized incidence increased by 32% from 33.2 to 43.8 cases per 100,000 adults for the period between 1994 and 2001, with the largest increase in the biliary group (52%). The standardized incidence rate of alcoholic and idiopathic pancreatitis was highest in African Americans, whereas biliary pancreatitis was highest in Hispanics. There was no change over time in the percentage of patients dying in the first 14 or 91 days; and in a risk-adjusted model, patients with alcoholic pancreatitis had the highest risk of dying. Conclusions The incidence rate of acute pancreatitis rose for the period between 1994 and 2001. However, there was no reduction in the 14- or 91-day case-fatality rate. Further research is needed to explain both the rise in the incidence rate of pancreatitis and the absence of any improvement in the early case-fatality rate.

Compost application to turfgrasses can increase plant-available nutrient concentrations in soil and improve growth, but may alter micronutrient dynamics and increase leaching and runoff losses. The objectives of this study were to investigate the influence of compost on the seasonal dynamics of plant-available Mn, Fe, Cu, and Zn in soil after a single application to bermudagrass [ Cynodon dactylon (L.) Pers.] turf. Extractable Mn increased from 270 to 670 mg kg −1 and Cu from 0.36 to 9.89 mg kg −1 from 0 to 29 months. In contrast, extractable Fe and Zn decreased by 52% and 57% during the same time period. Seasonal trends in extractable Mn and Cu were closely related to dissolved organic C (DOC), and appeared influenced by bermudagrass growth and dormancy patterns and subsequent impacts on DOC. Losses of Mn and Cu from the soil surface occurred after high levels of precipitation during winter dormancy but not during the growing season, while Fe and Zn exhibited an opposite pattern. Thus, seasonal variation of soil micronutrients was likely related to seasonal patterns of bermudagrass growth and dormancy and their effects on DOC, and precipitation events which probably leached DOC and complexed nutrients from surface soil. Composts only influenced the magnitude of changes in micronutrient concentrations, as similar seasonal trends occurred for both compost-amended and unamended soils.

Background: The incidence of venous thromboembolism after diagnosis of specific cancers and the effect of thromboembolism on survival are not well defined. Methods: The California Cancer Registry was linked to the California Patient Discharge Data Set to determine the incidence of venous thromboembolism among cancer cases diagnosed between 1993 and 1995. The incidence and timing of thromboembolism within 1 and 2 years of cancer diagnosis and the risk factors associated with thromboembolism and death were determined. Results: Among 235 149 cancer cases, 3775 (1.6%) were diagnosed with venous thromboembolism within 2 years, 463 (12%) at the time cancer was diagnosed and 3312 (88%) subsequently. In risk-adjusted models, metastatic disease at the time of diagnosis was the strongest predictor of thromboembolism. Expressed as events per 100 patient-years, the highest incidence of thromboembolism occurred during the first year of follow-up among cases with metastatic-stage pancreatic (20.0), stomach (10.7), bladder (7.9), uterine (6.4), renal (6.0), and lung (5.0) cancer. Adjusting for age, race, and stage, diagnosis of thromboembolism was a significant predictor of decreased survival during the first year for all cancer types (hazard ratios, 1.6-4.2; P Conclusions: The incidence of venous thromboembolism varied with cancer type and was highest among patients initially diagnosed with metastatic-stage disease. The incidence rate of thromboembolism decreased over time. Diagnosis of thromboembolism during the first year of follow-up was a significant predictor of death for most cancer types and stages analyzed. For some types of cancer, the incidence of thromboembolism was sufficiently high to warrant prospective clinical trials of primary thromboprophylaxis.

Postoperative deep venous thrombosis and pulmonary embolism are serious and potentially life-threatening complications that frequently occur after major surgery. Most guidelines for thromboprophylaxis use advancing age as a key component to estimate thromboembolic risk. The reported effect of age on postoperative venous thromboembolism varies widely, making it unclear whether age alone is a significant risk factor. This article reviews the recent literature on the effect of age on the incidence of postoperative venous thromboembolism.Between 2003 and 2005, several cohort studies assessed the risk factors for postoperative venous thromboembolism, showing a variable effect of age on its incidence in the 2- to 3-month period after major surgery. Studies also revealed a significant difference in the effect of age on the incidence of venous thromboembolism depending on the type of surgery. Obesity, postoperative immobilization, the use of thromboprophylaxis, the nature of the surgery, and underlying comorbid conditions such as heart failure seem to have a greater influence on the risk of venous thromboembolism than does age.The variation in the effect of age on postoperative venous thromboembolism likely depends on whether or not other comorbid conditions or age-related changes in functional status are considered as risk factors. When these other risk factors are taken into account, the effect of advanced age decreases. More research is needed to develop validated venous thromboembolism risk-prediction tools for specific types of surgery. By use of this information, the intensity and duration of postoperative thromboprophylaxis can be tailored to the level of risk, not just age alone.

More than six million patients worldwide are being treated with an oral anticoagulant. Dosing of the anticoagulant is usually managed by a primary care physician, cardiologist, or a specialized anticoagulation clinic. With the introduction of point-of-care testing devices, it is possible for patients to monitor their coagulation time, the international normalized ratio, at home. Selected patients, when properly trained, are capable of managing their oral anticoagulation treatment from home, so-called patient self-management (PSM). PSM has been practiced for many years in Europe, where training centers and reimbursement are well established. Because the US Center for Medicare and Medicaid Services recently decided to cover PSM, the practice will likely become more common in the United States. This article reviews the evidence behind the efficacy, safety, and cost effectiveness of PSM.

Summary. Background: Most guidelines for administration of thromboprophylaxis after major surgery use age as a major predictor of postoperative venous thromboembolism (VTE). We sought to quantify the effect of age on the risk of symptomatic VTE after a spectrum of surgical procedures. Methods: Using the California Patient Discharge Data Set and specific ICD-9-CM surgical procedure codes, we retrospectively determined the incidence of VTE diagnosed within 91 days after 40 different urgent or elective surgeries performed in the hospital between 1992 and 1996. Logistic regression was used to quantify the effect of age on the incidence of postoperative VTE and to adjust for other risk factors. Results: 1 464 452 cases underwent one of 40 different procedures (mean cases per procedure = 35 718, range 4500–145 500). There was a significant interaction between age and the type of surgery performed (P

Adult stemmata are distinctive insect photoreceptors located on the posterior surfaces of the optic lobes. They originate as larval eyes that migrate inward during metamorphosis. We used a combination of light microscopy and in situ hybridization to examine their anatomical organization in the butterfly Vanessa cardui and to test for the presence of visual pigments, the light sensitive components of the visual transduction pathway. The bilateral cluster of six internal stemmata is located near the ventral edge of the lamina. They retain the dark screening pigment and overlying crystalline cones of the larval stemmata. We found two opsin mRNAs expressed in the stemmata that are also expressed, respectively, in UV-sensitive and green-sensitive photoreceptor cells in the compound eye. A third mRNA that is expressed in blue-sensitive photoreceptor cells of the compound eye was not expressed in the stemmata. Our results reinforce the idea that the adult stemmata are not merely developmental remnants of larval eyes, but remain functional, possibly as components of the circadian input channel.

SUMMARYSpectral sensitivities of individual photoreceptors in the compound eye of Manduca sexta were verified by immunocytochemistry, and the retinal mosaic was mapped, using polyclonal antisera raised against amino-terminal sequences of three identified rhodopsins: P520, P450 and P357. Retinulae are composed of a small proximal cell and seven or eight elongate cells extending across the retina. In each retinula, one or two elongate dv cells oriented in the dorsal-ventral axis of the retinal lattice express either P450 or P357. Six elongate ap and ob cells in the anterior-posterior and oblique axes express P520. The small proximal pr cell also appears to express P520. The retinal mosaic is regionalized into three distinct domains: ventral and dorsal domains that divide the main retina, and a large dorsal rim area. The immunocytochemical data provide a high-resolution map of the Manduca retina that confirms and refines earlier low-resolution ERG spectral sensitivity measurements. The dorsal and ventral domains, separated at a well-defined equatorial border, are distinguished by differences in the proportion of blue-sensitive dv cells: these cells dominate the ventral retina but are less abundant in the dorsal retina. Green-sensitive ap and ob receptors are uniformly distributed across the dorsal and ventral domains, and UV-sensitive dv cells are fairly uniformly distributed because many retinulae in the dorsal domain contain only one dv cell. Similarly, dorsal rim retinulae contain only the ventral member of the dv pair of receptors, two-thirds of which express P357. Otherwise,dorsal rim receptors express none of the three sequenced Manducaopsins; they must express rhodopsins that have yet to be cloned.

Purpose: This prospective, randomized, controlled phase III trial assessed high-dose bolus interleukin-2 (IL-2) postoperatively in patients with high-risk renal cell carcinoma (RCC). Patients and Methods: Eligibility requirements were resected locally advanced (LA; T3b-4 or N1–3) or metastatic (M1) RCC, no prior systemic therapy, and excellent organ function. Randomized assignment was to one course of IL-2 (600,000 U/kg every 8 hours on days 1 to 5 and days 15 to 19 [maximum 28 doses]) or observation. The study was designed and powered to show an improvement in predicted 2-year disease-free survival (DFS) from 40% for the observation group to 70% for the treatment group. The accrual goal was 68 patients with LA disease, with 34 patients per treatment arm. Metastasectomy patients were to be analyzed separately because of their unpredictable natural history. Results: Sixty-nine patients were enrolled onto the study (44 LA and 25 M1 patients). Toxic effects of IL-2 were as anticipated; no unexpected serious adverse events or treatment-related deaths occurred. Early closure occurred when an interim analysis determined that the 30% improvement in 2-year DFS could not be achieved despite full accrual. Sixteen of 21 LA patients receiving IL-2 experienced relapse, compared with 15 of 23 patients in the observation arm (P = .73); in the LA group, three deaths occurred in the IL-2 arm, and five deaths occurred in the observation arm (P = .38). Analysis including metastasectomy patients made no difference in DFS or overall survival. Conclusion: One course of high-dose bolus IL-2, though feasible, did not produce the ambitious clinically meaningful benefit anticipated when administered postoperatively to patients with resected high-risk RCC.

Venous thromboembolism (VTE) occurs for the first time in approximately 100 persons per 100,000 each year in the United States, and rises exponentially from5 cases per 100,000 persons15 years old to approximately 500 cases (0.5%) per 100,000 persons at age 80 years. Approximately one third of patients with symptomatic VTE manifest pulmonary embolism (PE), whereas two thirds manifest deep vein thrombosis (DVT) alone. Despite anticoagulant therapy, VTE recurs frequently in the first few months after the initial event, with a recurrence rate of approximately 7% at 6 months. Death occurs in approximately 6% of DVT cases and 12% of PE cases within 1 month of diagnosis. The time of year may affect the occurrence of VTE, with a higher incidence in the winter than in the summer. One major risk factor for VTE is ethnicity, with a significantly higher incidence among Caucasians and African Americans than among Hispanic persons and Asian-Pacific Islanders. Overall, approximately 25% to 50% of patient with first-time VTE have an idiopathic condition, without a readily identifiable risk factor. Early mortality after VTE is strongly associated with presentation as PE, advanced age, cancer, and underlying cardiovascular disease.

Although deficiencies of protein C and antithrombin, 2 natural plasma anticoagulants, are known risk factors for venous thrombosis, population-based prospective incidence data on these associations are lacking. Venous thromboembolic events have been identified in adults in 2 longitudinal cohort studies, the Atherosclerosis Risk in Communities (ARIC) Study and the Cardiovascular Health Study (CHS). Incidence was examined in relation to prediagnostic plasma levels of protein C (ARIC Study only) and antithrombin. Over a mean of 8.1 years of follow-up, there were 130 incident venous thromboembolic events that were not due to cancer in the ARIC Study. The age-adjusted incidence was elevated 3.36-fold (95% CI 1.24 to 9.11) in the 1.1% of subjects with protein C values

To validate the predictive value of the Canadian clinical probability model for acute venous thrombosis, which, to the best of the authors' knowledge, has not been done in emergency department (ED) settings outside of Canada.Demographic and clinical information, rapid D-dimer testing, and venous ultrasound imaging were obtained among patients presenting with clinically suspected venous thrombosis at a university-affiliated ED. A diagnosis of deep venous thrombosis (DVT) was made based on venous ultrasound test results or objectively documented venous thromboembolism during a 12-week follow-up period. The probability of venous thrombosis was calculated using the Canadian clinical probability model.Among 102 patients, 17 (17%) were diagnosed as having venous thrombosis initially or during the three-month follow-up period. The frequency of venous thrombosis among patients categorized as having high probability was 10 of 17 [59%, 95% confidence interval (95% CI) = 35% to 82%], 6 of 44 (14%, 95% CI = 4% to 24%) with intermediate probability, and 1 of 41 (2%, 95% CI = 0.1% to 11%) with low probability. This compares with respective values of 49%, 14%, and 3%, reported by Canadian researchers in an ED study. Forty-one of 102 (40%) patients had an alternate diagnosis as likely or more likely than venous thrombosis, but only three (7%, 95% CI = 2% to 18%) of these had venous thrombosis.Use of the Canadian probability model for DVT in this ED resulted in effective risk stratification, comparable to previously published results.

OBJECTIVE: To describe heparin-induced thrombocytopenia (HIT or HIT-2), an immune-mediated adverse reaction to heparin or low-molecular-weight heparin. Available treatment options and considerations in developing a therapy approach are discussed. DATA SOURCES: A search of the National Library of Medicine (1992–June 2001) was done to identify pertinent literature. Additional references were reviewed from selected articles. STUDY SELECTION: Articles related to laboratory recognition and treatment options of HIT, including the use of agents in selected clinical conditions, were reviewed and included. CONCLUSIONS: HIT is a rare but potentially severe adverse reaction to heparin that was, until recently, poorly understood and had limited treatment options. Recent advances describing the recognition and clinical manifestations of immune-mediated HIT, including recently available antithrombotic treatment options, have dramatically changed outcomes for patients having this syndrome.

Background: Patients (pts) with non-Hodgkins lymphoma (NHL) are at increased risk of venous thromboembolism (VTE). We and others have demonstrated increased risk of death among NHL pts with incident VTE; however, these studies were largely conducted in the pre-rituximab era. We therefore analyzed a large cohort of NHL pts in the California Cancer Registry (CCR), determined the incidence of VTE, and evaluated its effect on survival in the rituximab era. Methods: Using the CCR linked with hospital discharge and emergency department records, we identified adult NHL pts diagnosed in 2005 – 2010, excluding cases ascertained via autopsy or death certificate, and those diagnosed with acute VTE in the 2 months preceding NHL diagnosis. VTE was defined by specific ICD-9-CM codes, and Elixhauser comorbidity score, excluding lymphoma, was calculated. Cumulative incidence was calculated using the Kaplan-Meier (KM) method. Adjusted hazard ratios (aHR) of VTE and death were estimated using Cox proportional hazard models, stratified by indolent vs aggressive NHL subtype, adjusting for age, race, stage, treatment, comorbidity and prior VTE. Analyses of VTE incidence treated death as a competing risk. Cox models for death incorporated VTE as a time-dependent covariate to account for immortal time bias. Results: NHL was identified in 18,424 pts. Most (n=12,963) had aggressive NHL (1,017 mantle cell, 11,246 diffuse large B-cell or follicular grade 3, 170 lymphoblastic, 530 Burkitt), while 5,461 had indolent NHL (2,809 follicular grade 1/2, 2,652 marginal zone). Median age was 64 years (yrs) and was similar in aggressive and indolent cohorts. Men accounted for 54% (n=9926) of cases, and were more common in aggressive compared to indolent NHL (7,317 (56%) vs 2,609 (48%) respectively). Most cases (62% n=11,451) were non-Hispanic White, 4% (n=795) were African American, 21% (n=3866) Hispanic, 11% Asian (n=2013) and 1.6% unknown (n=299). The ethnic distribution was similar in aggressive and indolent NHL. Median number of reported comorbid conditions was 2. Chemotherapy was initiated in 76% (n=9791) of aggressive NHL pts and 41% (n=2250) of indolent pts. The KM cumulative incidence of first time, acute VTE in NHL pts was 4.7% (95% CI 4.4 – 5.0) and 5.3% (95% CI 4.9- 5.6) at 1 and 2 years respectively. The incidence of VTE was higher in patients with aggressive versus indolent NHL (6.5% (95% CI 6.1 - 6.9) vs 2.3% (95% CI 2.0 - 2.8) at 2 yrs respectively P Conclusions: This large, population based study, which captured essentially all patients diagnosed with NHL in California between 2005-2010, confirms prior reports of VTE incidence in NHL patients. Pts are at highest risk early in their course, and pts undergoing chemotherapy were at increased risk. Moreover, VTE subsequent to NHL diagnosis independently increases the risk of death adjusting for other important covariates. Whereas chemoimmunotherapy has negated the effect of some previous negative prognostic factors, the adverse effect of incident VTE persists in this recent cohort. Table:Association of VTE and Death* Aggressive NHL Indolent NHLTime from NHL dx to VTEaHR95% CIaHR95% CI0 – 6 months1.411.3 – 1.62.071.4 – 3.06 – 12 months1.401.1 – 1.82.591.4 – 4.712 – 24 months1.631.3 – 2.13.201.9 – 5.4>24 months0.940.7 – 1.22.371.6 – 3.6 *Cox models adjusted for Age, Sex, Race, Stage, Treatment, Prior VTE and Comorbidity Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

OBJECTIVE: To report two cases of successful lepirudin use in two patients with heparin-induced thrombocytopenia (HIT) and renal failure. CASE SUMMARY: Two patients with renal failure requiring hemodialysis developed HIT syndrome during intravenous heparin therapy. Anticoagulation was necessary to prevent recurrent, acute venous thrombosis in one patient and to prevent arterial thrombosis associated with the use of an intraaortic balloon pump in the second. Intravenous lepirudin was initiated at doses of 0.01 mg/kg/h and 0.005 mg/kg/h, respectively, and titrated based on the activated partial thromboplastin time (aPTT). Steady-state doses were 0.015 mg/kg/h to maintain aPTT values of approximately 60 seconds in one patient, and 0.005–0.008 mg/kg/h to achieve an aPTT of approximately 45 seconds in the other patient. DISCUSSION: Lepirudin is one of few anticoagulants that can be safely used in patients with HIT. Because it is eliminated through the kidneys, great care must be taken when administering lepirudin to patients with renal failure; in fact, its use is currently not recommended in patients requiring hemodialysis. Lepirudin effectively prevented acute thrombosis in both of our patients with documented HIT, with no bleeding complications. We describe how we selected the initial doses and report results of aPTT monitoring. CONCLUSIONS: In patients with renal failure who develop HIT, lepirudin is one available alternative to heparin despite its poor renal elimination pattern and subsequently prolonged half-life.

In North America, atrial fibrillation is associated with at least 75 000 ischemic strokes each year. Most of these strokes occur in patients older than 75 years of age. The high incidence of stroke in very elderly persons reflects the increasing prevalence of atrial fibrillation that occurs with advanced age, the high incidence of stroke in elderly patients, and the failure of physicians to prescribe antithrombotic therapy in most of these patients. This failure is related to the increased risk for major hemorrhage with advanced age, obfuscating the decision to institute stroke prophylaxis with antithrombotic therapy. This case-based review describes the risk and benefits of prescribing antithrombotic therapy for a hypothetical 80-year-old man who has atrial fibrillation and hypertension, and it offers practical advice on managing warfarin therapy. After concluding that the benefits of warfarin outweigh its risks in this patient, we describe how to initiate warfarin therapy cautiously and how to monitor and dose the drug. We then review five recent randomized, controlled trials that document the increased risk for stroke when an international normalized ratio (INR) of less than 2.0 is targeted among patients with atrial fibrillation. Next, we make the case that cardioversion is not needed for this asymptomatic patient with chronic atrial fibrillation. Instead, we choose to leave the patient in atrial fibrillation and to control his ventricular rate with atenolol. Later, when the INR increases to 4.9, we advocate withholding one dose of warfarin and repeating the INR test. Finally, when the patient develops dental pain, we review the analgesic agents that are safe to take with warfarin and explain why warfarin therapy does not have to be interrupted during a subsequent dental extraction.

When initiating warfarin therapy, clinicians should avoid loading doses that can raise the International Normalized Ratio (INR) excessively; instead, warfarin should be initiated with a 5-mg dose (or 2 to 4 mg in the very elderly). With a 5-mg initial dose, the INR will not rise appreciably in the first 24 hours, except in rare patients who will ultimately require a very small daily dose (0.5 to 2.0 mg). Adjusting a steady-state warfarin dose depends on the measured INR values and clinical factors: the dose does not need to be adjusted for a single INR that is slightly out of range, and most changes should alter the total weekly dose by 5% to 20%. The INR should be monitored frequently (eg, 2 to 4 times per week) immediately after initiation of warfarin; subsequently, the interval between INR tests can be lengthened gradually (up to a maximum of 4 to 6 weeks) in patients with stable INR values. Patients who have an elevated INR will need more frequent testing and may also require vitamin K1. For example, a nonbleeding patient with an INR of 9 can be given low-dose vitamin K1 (eg, 2.5 mg phytonadione, by mouth). Patients who have an excessive INR with clinically important bleeding require clotting factors (eg, fresh-frozen plasma) as well as vitamin K1.

There are few population-based data regarding the effectiveness of inferior vena cava filter use in the prevention of symptomatic pulmonary embolism.To determine the 1-year cumulative incidence of rehospitalization for venous thrombosis or pulmonary embolism among patients with thromboembolism treated with a vena cava filter compared with the incidence in a control population with thromboembolism.Population-based retrospective analysis of linked hospital discharge abstracts in California. From January 1, 1991, through December 30, 1995, 3632 patients were treated with a filter and 64,333 controls were admitted with a principal diagnosis of venous thromboembolism.Filter-treated patients had significantly greater comorbidity, with a higher frequency of previous pulmonary embolism, recent major bleeding, malignant neoplasm, and stroke. Patients who initially manifested pulmonary embolism were significantly more likely to be rehospitalized for pulmonary embolism than patients with an initial diagnosis of venous thrombosis alone, among filter-treated patients (relative risk, 6.72; 95% confidence interval, 3.61-12.49) and controls (relative risk, 5.30; 95% confidence interval, 4.61-6.10). Risk-adjusted proportional hazards modeling showed no significant difference between filter-treated patients and controls in the relative hazard of rehospitalization for pulmonary embolism. However, filter placement was associated with a significantly higher relative hazard of rehospitalization for venous thrombosis among patients who initially manifested pulmonary embolism (relative hazard, 2.62; 95% confidence interval, 2.09-3.29), but not among those who presented with venous thrombosis (relative hazard, 1.14; 95% confidence interval, 0.92-1.43).Insertion of a vena cava filter was not associated with a significant reduction in the 1-year incidence of rehospitalization for pulmonary embolism. Use of a filter was associated with a higher incidence of rehospitalization for venous thrombosis, but only among patients who initially manifested pulmonary embolism. A prospective clinical study is needed to determine the efficacy of filter use among patients with pulmonary embolism who do not meet strict guidelines for insertion of a vena cava filter.

OBJECTIVE: To determine the effect of daily consultation by a team of hospital pharmacists on the accuracy and rapidity of optimizing warfarin therapy. DESIGN: Comparison of a historical control cohort with a prospective cohort matched for treatment indication. SETTING: A 400-bed university teaching hospital. PATIENTS: Sixty consecutive patients hospitalized in 1992 and starting warfarin for the first time, with anticoagulation therapy managed by physicians, were compared with 60 patients matched for warfarin indication hospitalized in 1995, but with anticoagulation therapy managed with pharmacy consultation. RESULTS: Pharmacist management of initial warfarin therapy resulted in a significant reduction in the length of hospitalization compared with physician dosing, from 9.5 ± 5.6 days to 6.8 ± 4.4 days (p = 0.009). The number of patients and patient-days with international normalized ratio (INR) values >3.5 were reduced by pharmacist dosing from 37 patients and 142 days to 16 patients and 29 days, respectively (p < 0.001). Similarly, the number of patients and patient-days with INR >6.0 were reduced from 20 patients and 50 days to two patients and six days, respectively (p < 0.001). There were six documented bleeding complications in 1992 compared with one in 1995 (p = 0.11). The mean INR at discharge was significantly lower in the pharmacy surveillance group, 2.6 ± 0.58, compared with the physician cohort, 3.3 ± 2.1 (p = 0.07). Readmissions after discharge due to bleeding or recurrent thrombosis were reduced from five (at 1 mo) and 10 (at 3 mo) to two and five readmissions, respectively, by pharmacist intervention (p = 0.43). The number of patients with concurrently prescribed drugs known to significantly interact with warfarin was significantly lower (6 vs. 13; p = 0.02) in the pharmacy surveillance group. CONCLUSIONS: Among patients starting warfarin for the first time, daily consultation by a pharmacist significantly decreased the length of hospital stay and the number of patients who received excessive anticoagulation therapy. These findings translate into improved quality of care and potentially significant cost savings.

PURPOSE: Most studies of oral anticoagulant-related bleeding have analyzed the incidence of adverse outcomes among patients with a variety of different conditions and without any comparison with a control group. We determined the incidence, time course, and risk factors associated with major bleeding after hospital discharge among patients with deep-vein thrombosis, and estimated the excess risk of bleeding associated with oral anticoagulant therapy. METHODS: A total of 22,000 adults were hospitalized in California for 3 or more days with a diagnosis of deep-venous thrombosis between January 1, 1992, and September 30, 1994. We determined the risk factors associated with readmission for bleeding. We compared the incidence of readmission for bleeding with comparison cohorts of patients with pneumonia or cellulitis who were matched for age, gender, race, and length of hospital stay. RESULTS: Of 21,250 patients with deep-venous thrombosis who were discharged without bleeding, 1.4% were readmitted for bleeding within 91 days; the rate was 2.7 times greater in the first 30 days than in the next 61 days. Risk factors for bleeding included hospitalization with gastrointestinal bleeding during the previous 18 months (relative hazard [RH] = 2.6, 95% confidence interval [CI]: 1.6 to 4.1), hospitalization with an alcohol-related diagnosis during the previous 18 months (RH = 2.6, 95% CI: 1.4 to 4.8), chronic renal disease (RH = 2.4, 95% CI: 1.4 to 4.2), female gender (RH = 1.7, 95% CI: 1.3 to 2.2), presence of a malignancy (RH = 1.6, 95% CI: 1.2 to 2.2), nonwhite race (RH = 1.6, 95% CI: 1.2 to 2.1), and age over 65 years (RH = 1.3, 95% CI: 1.0 to 1.7). Significantly more women (n = 40) had intracranial bleeding than men (n = 18, P = 0.02). In the comparison cohorts, the incidence of readmission for bleeding within 3 months of discharge was 0.7%, and the relative risk (RR) of readmission was greater in those with deep-venous thrombosis than in those with cellulitis (RR = 2.0, 95% CI: 1.6 to 2.5) or pneumonia (RR = 2.0, 95% CI: 1.7 to 2.5). CONCLUSIONS: The incidence of rehospitalization for bleeding was greatest in the first 30 days after discharge, and was approximately twice that seen in patients hospitalized for cellulitis or pneumonia. Further studies are needed to determine why women and nonwhite patients are at increased risk for anticoagulant-related bleeding.

Background: Several recent randomized clinical trials have demonstrated that warfarin sodium treatment, and to a lesser extent aspirin, reduces risk of stroke and death compared with placebo in persons with atrial fibrillation. Insufficient documentation exists on the extent to which the use of these therapies following trial publications has continued to increase in the elderly with atrial fibrillation. Methods: We used data from the Cardiovascular Health Study, a study of 5888 community-dwelling adults aged 65 years or older, to determine the prevalence of warfarin and aspirin use in persons with electrocardiogram-identified atrial fibrillation. Electrocardiogram examinations were conducted at baseline from 1989 through 1990, and at 6 subsequent annual examinations through 1995-1996. Medication data were collected by inventory methods at each examination. Temporal change in use of anticoagulants was analyzed by comparing percentage use in 1990 to use in each year through 1996. Results: The use of warfarin increased 4-fold from 13% in 1990 to 50% in 1996 among participants with prevalent atrial fibrillation (P,.001). Daily use of aspirin did not increase over time. Participants younger than 80 years were 4 times more likely to use warfarin in 1996 (P,.001) than those 80 years and older. Use of aspirin did not vary significantly with age. Conclusions: Warfarin use in community-dwelling elderly persons with electrocardiogram-documented atrial fibrillation increased steadily following the first publication of its treatment benefit, reaching 50% by 1996. In contrast, use of aspirin was unchanged during this same period. Continued efforts to promote appropriate anticoagulation therapy to physicians and their patients may still be needed. Arch Intern Med. 1999;159:1574-1578

To determine adherence with practice guidelines in a population-based cohort of elderly persons aged 70 years or older with atrial fibrillation.This was a cross-sectional analysis of a subgroup of participants in the Cardiovascular Health Study, a prospective observational study involving four communities in the United States. Subjects were participants with atrial fibrillation on electrocardiogram at one or more yearly examinations from 1993 to 1995. The outcome measure was self-reported use of warfarin in 1995.In 1995, 172 (4.1%) participants had atrial fibrillation together with information regarding warfarin use and no preexisting indication for its use. Warfarin was used by 63 (37%) of these participants. Of the 109 participants not reporting warfarin use, 92 (84%) had at least one of the clinical risk factors (aside from age) associated with stroke in patients with atrial fibrillation. Among participants not taking warfarin, 47% were taking aspirin. Several characteristics were independently associated with warfarin use, including age [odds ratio (OR) = 0.6 per 5-year increment, 95% CI 0.5-0.9], a modified mini-mental examination score85 points [OR = 0.3, 95% confidence interval (CI) 0.1-0.9], and among patients without prior stroke, female sex (OR = 0.5, 95% CI 0.2-1.0).Despite widely publicized practice guidelines to treat patients who have atrial fibrillation with warfarin, most participants who had atrial fibrillation were at high risk for stroke but were not treated with warfarin. More studies are needed to determine why elderly patients with atrial fibrillation are not being treated with warfarin.

Laboratory studies were conducted to determine the effects of Acremonium endophytes on four species of billbug (Coleoptera:Curculionidae: Sphenophorus parvulus Gyllenhal, S. venatus (Say), S. inaequalis Say, and S. minimus Hart) found damaging cool-season turfgrasses in New Jersey. Billbug adults feeding on potted tall fescue (Festuca arundinacea Schreb.) plants infected with Acremonium coenophialum Morgan-Jones and Gams showed significantly greater mortality than billbugs feeding on endophyte-free tall fescue. Little difference was observed in amount of feeding. In petri dish preference tests, billbug adults were given a choice and, again, no significant difference was observed in the amount of feeding on endophyte-free versus endophyte-infected tall fescue tillers. In a third experiment, billbug adults were placed in petri dishes with either tall fescue with or without A. coenophialum or perennial ryegrass (Lolium perenne L.) with or without Acremonium lolii Latch, Christensen, and Samuels. Only small differences were seen in number of eggs laid and amount of feeding. Mortality of all four billbug species, however, was greater on both grasses when endophyte-infected.

We have previously reported experimental studies of the magnetic aftereffect in CoCr films. In that work data were compared to phenomenological models, and it was recognized that the decay of the magnetization was driven by the demagnetizing field. The difficulty of incorporating such fields into phenomenological models, which rely on a broad distribution of relaxation times or activation energies to account for the quasilogarithmic decays, motivated the present study. Here we present a simple alternate model which does not assume a distribution of energies. Instead, we focus on the time dependence of the local magnetic field h which drives the magnetization. We approximate h by the average internal field Hi =Ha−4πM, where Ha is the applied field, M is the magnetization averaged over regions large compared to domains, and 4π is the demagnetizing factor appropriate for a planar geometry. The magnetization is found to relax quasilogarithmically with time in this model. We have also made a more detailed comp...

Background Current guidelines suggest that all patients with acute deep venous thrombosis should be treated with intravenous heparin for at least 5 days, overlapping with warfarin sodium for 4 to 5 days. Methods Using linked state of California hospital discharge records from 1991 to 1994 we identified patients with acute deep venous thrombosis without pulmonary embolism, and determined the 6-month cumulative incidence of rehospitalization for recurrent thromboembolism. Coding was validated by reviewing the charts of 218 patients matched with the statewide data from 4 local hospitals. Results A total of 36924 linked records met study criteria. In the validation group, objectively confirmed thrombosis that was treated with intravenous heparin followed by warfarin was noted in 20%, 65%, 94%, and 95% of the patients who were hospitalized for 2 or fewer days or 3, 4, or 5 or more days, respectively. Statewide, among patients hospitalized for 3, 4, 5, and 6 days, the 6-month cumulative incidence of hospitalization for recurrent thromboembolism was 5.4%, 5.1%, 5.4%, and 6.0%, respectively. Multivariate modeling of patients hospitalized for 3 to 10 days revealed that recurrent thromboembolism was associated with the length of hospitalization (odds ratio [OR], 1.06 each additional day; 95% confidence interval [CI], 1.04-1.08), presence of malignancy (OR, 1.58; 95% CI, 1.46-1.68), age (OR, 0.85 each 10 years; 95% CI, 0.84-0.86), dementia (OR, 0.38; 95% CI, 0.26-0.49), hospitalization for multiple injuries within 3 months (OR, 0.46; 95% CI, 0.32-0.60), and surgery within 3 months (OR, 0.84; 95% CI, 0.78-0.90). Conclusions We found no evidence that a stay of 4 days for treatment of deep venous thrombosis was associated with a higher rate of recurrent thromboembolism compared with hospitalization for 5 or more days. Although the evidence was not as strong, the incidence of recurrent thromboembolism after a stay of 3 days appeared comparable with that after a stay of 5 days. These findings suggest that fewer than 5 days of intravenous heparin overlapping with warfarin may provide effective initial treatment for deep venous thrombosis among patients deemed ready for hospital discharge.

Publisher Summary The optical properties of crystalline synthetic beryllium oxide, BeO, are reported for a very limited number of samples. The main reasons for this lack of data are the toxic properties of the material and the difficulty of growing large optical-quality crystals. BeO is considered a useful new optical material for the vacuum ultraviolet because of its high transmittance down to about 9.4 eV and its apparent resistance to UV radiation damage.Calculations by White, Edwards, and Rathkopf predict that overlayers of BeO on metallic reflectors can significantly enhance their hardness to X-ray radiation. Natural bromellite (BeO) and synthetically grown BeO crystals are uniaxially positive. Newkirk et al. using the angle-of-minimum deviation technique, measured the ordinary and extraordinary refractive indices and their dependence on temperature from 0.430 μm to0.690 μm. Loh evaluated the ordinary and extraordinary infrared refractive indices and extinction coefficients for BeO from their polarized reflectance spectra. The refractive index n and extinction coefficient k values are derived from parameters used to fit the classical oscillator dispersion formula to the reflectance spectra.

Publisher Summary This chapter analyzes the optical properties of aluminum antimonide (AlSb). The refractive index, n, and the extinction coefficient, k, of AlSb have been measured for a limited number of samples. The two main reasons for this are that large high-quality single crystals are difficult to grow and the surface of AlSb reacts rapidly with the atmosphere to produce a relatively thick contaminated layer. One method for measuring the optical properties of semiconductors—especially for the ultraviolet (UV) and visible regions—is spectroscopic ellipsometry. However, contamination-free surfaces are needed for precise ellipsometric measurements. The chapter reviews the measurements of the dependence of energy-gap absorptance of AlSb at room temperature for hydrostatic pressures from atmospheric up to the phase change at about 8 GPa; the reflectance of room-temperature AlSb between 16 m and 40 m, which includes the infrared lattice reflectance band; and the fundamental reflection band of six III–V compound semiconductors at liquid helium-temperature.

In this issue of Arthritis Care & Research, we inaugurate an occasional series of commentaries entitled Policy Matters. In all of clinical research, our goal is to improve patient outcomes. Usually, that means focusing on the medical, demographic, and socioeconomic factors at the level of individuals with rheumatic diseases; sometimes, our scope of inquiry expands to encompass the impact of the communities in which they live. However, increasingly, the welfare of persons with rheumatic conditions is also affected by health policies through such diverse mechanisms as reimbursement decisions for specific treatments, insurance coverage, manpower, and NIH budgets (the foregoing list is hardly exhaustive).Recently, a piece of legislation was introduced in California (SB913) that has the potential to alter the availability of biologic response modifying agents (BRMs) by mandating that health plans that provide coverage for one such agent include all on their formularies (a revised version would preclude a trial of another disease-modifying antirheumatic drug before use of a BRM). In this state, the California Health Benefits Review Program (CHBRP) provides evidence reviews of the medical effectiveness, cost, and public health impact of proposed health insurance mandates for the legislature. The analysts from the University of California who conducted the medical effectiveness review of SB913 for CHBRP provide a legislative history of the proposed law in this article. We hope that the readership of Arthritis Care & Research find this article informative as an exemplar of the policies that could dramatically alter the welfare of our patients.

There is a significant direct relationship between steady-state intravenous heparin dose requirements and total body weight. Less is known about whether sex, age, clinical diagnosis, and the thromboplastin used to measure the activated partial thromboplastin time (aPTT) affect heparin dose requirements.Four cohorts of patients treated with intravenous heparin were gathered from 3 hospitals: 2 cohorts with deep vein thrombosis (DVT) and 2 cohorts with coronary artery disease (CAD). For each clinical diagnosis, half the patients were monitored using one aPTT reagent and the remainder were monitored using a second reagent. Heparin doses and aPTT measurements were recorded, and the dose necessary to achieve an aPTT ratio of 2.0 was calculated using a computer software program.We analyzed the records of 340 patients: 165 with DVT and 175 with CAD. Using analysis of variance, there was a significant difference in the steady-state heparin requirements among patients with DVT compared with patients with CAD (P.001). For each clinical diagnosis, the use of a different thromboplastin reagent did not affect heparin dose requirements (P.42). Linear regression modeling disclosed that the steady-state heparin dose for patients with DVT was a function of weight plus an effect modifier involving weight and age, whereas for patients with CAD there was only a weak relationship with weight.Steady-state heparin dose requirements were significantly different in patients with DVT compared with patients with CAD, suggesting that different dosing nomograms are needed for each condition. For patients with DVT, the accuracy of the initial heparin dose estimate may be improved by considering the patient's age and weight.

Three distinct opsin-encoding cDNAs, designated MANOP1, MANOP2 and MANOP3, were isolated from the retina of the sphingid moth Manduca sexta. MANOP1 codes for a protein with 377 amino acid residues. It is similar in sequence to members of a phylogenetic group of long-wavelength-sensitive arthropod photopigments, most closely resembling the opsins of ants, a praying mantis, a locust and the honeybee. MANOP2 and MANOP3 opsins have 377 and 384 residues respectively. They belong to a related group of insect visual pigments that include the ultraviolet-sensitive rhodopsins of flies as well as other insect rhodopsins that are also thought to absorb at short wavelengths. The retina of Manduca sexta contains three rhodopsins, P520, P450 and P357, with absorbance peaks, respectively, at green, blue and ultraviolet wavelengths. There is evidence that MANOP1 encodes the opsin of P520. We suggest that MANOP2 encodes P357 and that MANOP3, representing a class of blue-sensitive insect photopigments, encodes P450.

A previous paper presented long term bleaching data on various glasses exposed to 10.6 krad of ionizing radiation. All the glasses reported except FK 51 have readily available `G` glass equivalents that are stabilized to the natural space environment. Yet, FK 51, because of its location on the Abbe diagram is extremely useful in certain lens design applications. To more fully explore the bleaching of FK 51, after the initial dose of 10.6 krad at 11.8 krad/hour, we irradiated three more samples at a similar dose rate but to different total doses. Since the dose rate for this study was significantly higher than the dose rate anticipated for glasses in as shielded space-based lens system (tilde 3 rad/day), additional data were obtained at a lower rate of 7 rad/hour. While this dose rate is still higher than the anticipated operational rate, it is more than 1000 times lower than the dose 011 011 011 rate used for our initial studies. The bleaching rate for the samples exposed at the lower dose rate is considerably less than for the samples exposed at the higher rate.

Typical camera designs include optical glass elements that may be affected by the ionizing radiation present in the natural space environment. Ordinary optical glasses darken at low (10(to the 3rd power) rad) dose levels when exposed to ionizing radiation. This darkening decreases the sensitivity of optical sensors. Optical glass flats of FK 51, LaK 0, PK 51A, and ZK Ny were exposed to a 10.6 krad dose of ionizing radiation. Spectrophotometer traces determined the transmittance of the samples as a function of wavelength in the range 350 to 850 nm before and at various time intervals after the irradiation. These measured values were then use to evaluate the rate of recovery or ``bleaching`` of the exposed samples. To prevent accelerated bleaching, the samples were kept at room temperature and away from light, except during measurement. Tables of the measured data and plots of the transmissivity vs. wavelength at various times after irradiation are presented.

Publisher Summary Potassium Dihydrogen Phosphate (KDP) is the best known; most extensively studied, and most widely used crystal in laser technology. Crystals of KDP are used for frequency up conversion operation in high-power laser systems. KDP is also the primary nonlinear optical material used at the major laser facilities. It is noted that for each application of these nonlinear crystals, a precise knowledge is required of the crystal's refractive index as a function of wavelength. In addition, crystal temperature has a sensitive effect on the indices within the precision range of interest. Kirby and DeShazer exhibit that the index values vary from about 6 x 10-5 to 60 x 10-5 in the visible region for KDP crystals from different crystal growers. These differences are correlated with deviations in the crystal lattice parameters and it is speculated that crystalline defects incorporated during the crystal-growth process are the cause of the lattice-parameter variations. The measured values of Zernike and Kirby and DeShazer are fit separately to both a Herzberger-type and a modified Sellmeier-type dispersion formula.