Optimizing a microwave gas ion source for continuous-flow accelerator mass spectrometry.

A 2.45 GHz microwave ion source coupled with a magnesium charge exchange canal (C × C) has been successfully adapted to a large acceptance radiocarbon accelerator mass spectrometry system at the National Ocean Sciences Accelerator Mass Spectrometry (AMS) Facility, Woods Hole Oceanographic Institution. CO(2) samples from various preparation sources are injected into the source through a glass capillary at 370 µl∕min. Routine system parameters are about 120-140 µA of negative (12)C current after the C × C, leading to about 400 (14)C counts per second for a modern sample and implying a system efficiency of 0.2%. While these parameters already allow us to perform high-quality AMS analyses on large samples, we are working on ways to improve the output of the ion source regarding emittance and efficiency. Modeling calculations suggest modifications in the extraction triode geometry, shape, and size of the plasma chamber could improve emittance and, hence, ion transport efficiency. Results of experimental tests of these modifications are presented.

Medullary thyroid cancer and pseudocirrhosis: case report and literature review.

Pseudocirrhosis is a rare form of liver disease that can cause clinical symptoms and radiographic signs of cirrhosis; however, its histologic features suggest a distinct pathologic process. In the setting of cancer, hepatic metastases and systemic chemotherapy are suspected causes of pseudocirrhosis. Here, we present a patient with medullary thyroid carcinoma metastatic to the liver who developed pseudocirrhosis while on maintenance sunitinib after receiving 5-fluorouracil, leucovorin, and oxaliplatin (folfox) in combination with sunitinib. Cirrhotic change in liver morphology was accompanied by diffusely infiltrative carcinomatous disease resembling the primary tumor. We discuss the diagnosis of pseudocirrhosis in this case and review the literature regarding pseudocirrhosis in cancer.

Review article: the treatment of hepatitis C virus recurrence after liver transplantation.

BACKGROUND: Recurrent hepatitis C represents a major challenge for the liver transplant community. Given the potentially significant impact that hepatitis C recurrence has on graft and patient survival, several treatment strategies have been utilized to prevent/slow the progression to hepatitis C-related graft failure. AIM: To review the efficacy and applicability of treatment strategies for managing recurrent hepatitis C. METHODS: Search of MEDLINE (1990 to December 2006) and national meeting abstracts. Search terms included hepatitis C, liver transplantation, treatment, sustained virological response (SVR), and end of treatment virological response. An emphasis was placed on randomized trials. RESULTS: The largest study of treatment prior to liver transplantation (n = 124) achieved SVR in 24%. Eight randomized trials (n = 383) examined the efficacy of preemptive therapy with SVR ranging from 0-33%. Eligibility for treatment was low and dose reduction common. Four randomized trials (n = 245; all abstracts) have reported SVR from 33-42% for treating those with histological evidence of recurrent disease. CONCLUSIONS: Therapies for treating hepatitis C recurrence have limited applicability and tolerability, and they have a low SVR. Based on available results, preemptive therapy is not recommended. Pegylated interferon and ribavirin is currently the preferred choice for treating established recurrence. There is an urgent need for safer and more effective anti-viral therapy in this situation.

First experience with direct, selective factor Xa inhibition in patients with non-ST-elevation acute coronary syndromes: results of the XaNADU-ACS Trial.

BACKGROUND: Unfractionated heparin is widely used in patients with non-ST-elevation acute coronary syndromes but has important limitations. Anticoagulants with predictable kinetics and anticoagulant effects, better efficacy, and greater safety are needed. OBJECTIVE: To investigate the efficacy and safety of a direct, selective factor Xa inhibitor, DX-9065a (Daiichi Pharmaceuticals LTD, Inc.) compared with heparin, in patients with non-ST-elevation acute coronary syndromes. PATIENTS AND METHODS: Patients (n = 402) from the USA, Canada, and Japan were randomized to blinded, weight-adjusted heparin, low-dose DX-9065a, or high-dose DX-9065a. RESULTS: The primary efficacy endpoint of death, myocardial infarction, urgent revascularization, or ischemia on continuous ST-segment monitoring occurred in 33.6%, 34.3%, and 31.3% of patients assigned to heparin, low-dose DX-9065a, and high-dose DX-9065a (P = 0.91 for heparin vs. combined DX-9065a). The composite of death, myocardial infarction, or urgent revascularization occurred in 19.5%, 19.3%, and 11.9% (P = 0.125 for heparin vs. high-dose DX-9065a) of patients; major or minor bleeding occurred in 7.7%, 4.2%, and 7.0% of patients; and major bleeding in 3.3%, 0.8%, and 0.9% of patients. Higher concentrations of DX-9065a were associated with a lower likelihood of ischemic events (P = 0.03) and a non-significant tendency toward a higher likelihood of major bleeding (P = 0.32). CONCLUSIONS: In this small phase II trial, there was a non-significant tendency toward a reduction in ischemic events and bleeding with DX-9065a compared with heparin in patients with acute coronary syndromes. The absence of an effect on ST-monitor ischemia warrants further investigation. These data provide the rationale for adequately powered studies of DX-9065a in acute coronary syndromes or percutaneous intervention.

Initial experience with factor-Xa inhibition in percutaneous coronary intervention: the XaNADU-PCI Pilot.

BACKGROUND: Direct factor (F)Xa inhibition is an attractive method to limit thrombotic complications during percutaneous coronary intervention (PCI). OBJECTIVES: To investigate drug levels achieved, effect on coagulation markers, and preliminary efficacy and safety of several doses of DX-9065a, an intravenous, small molecule, direct, reversible FXa inhibitor during PCI. PATIENTS AND METHODS: Patients undergoing elective, native-vessel PCI (n = 175) were randomized 4 : 1 to open-label DX-9065a or heparin in one of four sequential stages. DX-9065a regimens in stages I-III were designed to achieve concentrations of > 100 ng mL-1, > 75 ng mL-1, and > 150 ng mL-1. Stage IV used the stage III regimen but included patients recently given heparin. RESULTS: At 15 min median (minimum) DX-9065a plasma levels were 192 (176), 122 (117), 334 (221), and 429 (231) ng mL-1 in stages I-IV, respectively. Median whole-blood international normalized ratios (INRs) were 2.6 (interquartile range 2.5, 2.7), 1.9 (1.8, 2.0), 3.2 (3.0, 4.1), and 3.8 (3.4, 4.6), and anti-FXa levels were 0.36 (0.32, 0.38), 0.33 (0.26, 0.39), 0.45 (0.41, 0.51), and 0.62 (0.52, 0.65) U mL-1, respectively. Stage II enrollment was stopped (n = 7) after one serious thrombotic event. Ischemic and bleeding events were rare and, in this small population, showed no clear relation to DX-9065a dose. CONCLUSIONS: Elective PCI is feasible using a direct FXa inhibitor for anticoagulation. Predictable plasma drug levels can be rapidly obtained with double-bolus and infusion DX-9065a dosing. Monitoring of DX-9065a may be possible using whole-blood INR. Direct FXa inhibition is a novel and potentially promising approach to anticoagulation during PCI that deserves further study.

The future history of home care and physician house calls in the United States.

Over the last 20 years, home care has experienced significant change. The home care industry developed into big business and a number of innovative models of home care were developed and evaluated. Although physicians perform many fewer house calls than a half-century ago, there has been a recent revival in house-call training, education, and practice. In addition, telemedicine and other technologies hold great promise for the future of home care. However, the future history of home care will depend mostly on the ability of various stakeholders in the health care system to recognize the value of home care and develop and implement the appropriate incentives to encourage its proper place in the U.S. health care system.

Long-term effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT).

BACKGROUND: This long-term, multicenter, randomized, double-blind, placebo-controlled, 2 x 2 factorial, angiographic trial evaluated the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis in normocholesterolemic patients. METHODS AND RESULTS: There were a total of 460 patients: 230 received simvastatin and 230, a simvastatin placebo, and 229 received enalapril and 231, an enalapril placebo (some subjects received both drugs and some received a double placebo). Mean baseline measurements were as follows: cholesterol level, 5.20 mmol/L; triglyceride level, 1.82 mmol/L; HDL, 0.99 mmol/L; and LDL, 3.36 mmol/L. Average follow-up was 47.8 months. Changes in quantitative coronary angiographic measures between simvastatin and placebo, respectively, were as follows: mean diameters, -0.07 versus -0.14 mm (P:=0.004); minimum diameters, -0.09 versus -0.16 mm (P:=0. 0001); and percent diameter stenosis, 1.67% versus 3.83% (P:=0.0003). These benefits were not observed in patients on enalapril when compared with placebo. No additional benefits were seen in the group receiving both drugs. Simvastatin patients had less need for percutaneous transluminal coronary angioplasty (8 versus 21 events; P:=0.020), and fewer enalapril patients experienced the combined end point of death/myocardial infarction/stroke (16 versus 30; P:=0.043) than their respective placebo patients. CONCLUSIONS: This trial extends the observation of the beneficial angiographic effects of lipid-lowering therapy to normocholesterolemic patients. The implications of the neutral angiographic effects of angiotensin-converting enzyme inhibition are uncertain, but they deserve further investigation in light of the positive clinical benefits suggested here and seen elsewhere.

Collaborative angiographic patency trial of recombinant staphylokinase (CAPTORS).

BACKGROUND: We undertook an angiographic, dose-finding study of staphylokinase (SAK42D variant) to evaluate its efficacy and safety in patients with acute ST-segment myocardial infarction. METHODS AND RESULTS: Patients were studied within 6 hours of symptom onset and received SAK42D as a 30-minute infusion with 20% of the total dose given as a bolus. Eighty-two patients with a median age of 60 years (interquartile range 52 to 69 years), 84% male and 43% with an anterior myocardial infarction, were studied at a median time from symptom onset of 2.7 hours. There was a high degree of Thrombolysis in Myocardial Infarction (TIMI) 3 flow achieved with 15 mg of SAK42D, that is, 62%. Therefore after 21 patients had been studied at this dose the next dose of 30 mg was used and 65% TIMI 3 patency was achieved. At the peak dose of 45 mg, TIMI 3 90-minute patency was 63%. There were no allergic reactions, and no patient had intracranial hemorrhage. Four patients had major and 9 moderate bleeding during the study; 2 of the major and 5 of the moderate bleeding events occurred within 48 hours of commencement of treatment. The majority (62%) of these were related to vascular instrumentation, and there was no relation between the extent of bleeding and dose of SAK42D used. Forty-five minutes after cessation of SAK42D, there were small percent decrements in plasma fibrinogen and plasminogen levels that did not reach statistical significance. However, there were dose-related changes in alpha(2) anti-plasmin that revealed a borderline significant reduction that was dose related (P =.053). CONCLUSION: These data revealed similar fibrinolytic efficacy across a 3-fold increment in dose, indicating that this study operated on a flat portion of the dose-response curve. The favorable efficacy/safety profile achieved with staphylokinase is encouraging, and further investigation is warranted.

Home hospital program: a pilot study.

OBJECTIVE: To evaluate the basic safety and feasibility of hospital care at home (Home Hospital (HH)) for treating acutely ill older persons requiring hospitalization. DESIGN: Prospective case series SETTINGS AND PARTICIPANTS: Community-dwelling persons aged 65 and older requiring acute hospital admission for community-acquired pneumonia, chronic heart failure, chronic obstructive airways disease, or cellulitis. RESULTS: Seventeen subjects were treated in HH. One hundred twenty-two could not be enrolled because they presented for admission at times when HH was not operational. Six patients refused to enroll in HH. Subjects treated in HH had comparable clinical outcomes to those treated in the acute hospital and were highly satisfied with HH. Charges for HH care were 60% of those for the acute hospital care. CONCLUSIONS: In this pilot study, HH was safe, feasible, highly satisfactory, and cost-effective for certain acutely ill older persons who required acute hospitalization.

Future directions: alternative approaches to traditional hospital care-home hospital.

The acute hospital may be a difficult environment for many older patients and is an expensive site of care for payers. Home hospital is an emerging model of care that allows an older person with acute medical illness to avoid an inpatient hospital admission by bringing the critical elements of hospital care to the home. Challenges associated with the development and study of home hospitals as well as several specific home hospital models are reviewed. The need for continued study and the potential of home hospital are discussed.

Myocardial infarction complicated by ventricular septal rupture in a patient with polycythemia vera and minimal coronary ectasia.

Although it is known that patients with polycythemia vera (PV) are at increased risk of myocardial infarction (MI) secondary to thrombosis, ventricular septal rupture in this setting has never been reported. Ventricular septal rupture complicating a small anteroseptal MI is reported in a patient with PV and with only minimal ectasia of the left anterior descending coronary artery. Despite small infarct size these patients may be predisposed to myocardial hemorrhage, increasing the likelihood of myocardial rupture.

Changing practice patterns in the management of acute myocardial infarction complicated by cardiogenic shock: elderly compared with younger patients.

BACKGROUND: Cardiogenic shock continues to be an ominous complication of acute myocardial infarction (AMI). Evidence from retrospective analyses, registries and observational studies suggests that aggressive management using emergent revascularization strategies can bring about significant improvement in survival in this setting. Several studies have identified age as an independent predictor of survival. OBJECTIVE: To study retrospectively the possible changes in practice patterns in the management of patients with AMI complicated by cardiogenic shock in a tertiary care referral centre, and to determine what effect these changes may have had on survival of the patients, stratified by age. METHODS: From 1989 to 1995, 115 patients fulfilled the study criteria of cardiogenic shock based on pump failure and of presenting within 48 h of onset of shock. Prespecified data were extracted from medical records. All available coronary angiograms (n = 72) were analyzed by two experienced angiographers and consensus of findings was obtained. RESULTS: The study revealed a significant increase in the use of cardiac catheterization, interventional procedures and intra-aortic balloon pump (IABP) support in patients in the age groups 65 years or less, 66 to 75 years, and older than 75 years in 1989 to 1990, through 1991 to 1992, to 1993 to 1995. Significantly fewer patients aged older than 75 years received cardiac catheterization, coronary intervention and IABP support throughout the study period and even in the final period analyzed. In-hospital survival improved from 4% in 1989-90 to 33% in 1991-92, and 44% in 1993-95 (P = 0.001). Patients aged 65 years or less improved from 10% in 1989-90 to 59% in 1993-95 (P = 0.032). Only 20% of patients aged older than 75 years survived in the 1993-95 period. By univariate analysis, use of coronary angiography (catheterization 46% versus no catheterization 5%; P < 0.0001), coronary intervention procedures (percutaneous transluminal coronary angioplasty or coronary artery bypass grafting) (intervention 48% versus no intervention 9%; P < 0.0001) and IABP support (IABP 41% versus no IABP 18%; P = 0.0096) were all associated with improved in-hospital survival. Use of thrombolytic therapy showed possible survival benefit only in patients aged older than 75 years (thrombolysis 33% versus no thrombolysis 5%; P = 0.10). Patients who underwent coronary intervention were younger (P = 0.002), had a lower incidence of previous myocardial infarction (P = 0.0002), lower heart rate (P = 0.04), higher peak creatine phosphokinase (P = 0.04) and fewer vessels with at least 70% stenosis (P < 0.0001). On multivariate analysis only lower age, lower heart rate and presence of coronary intervention procedures were found to have an independent effect on survival. CONCLUSIONS: Use of invasive treatment strategies has increased significantly since 1989-90 in the management of patients with AMI complicated by cardiogenic shock. This increase has been associated with improved in-hospital survival in all age groups except possibly the very elderly. Patients undergoing coronary interventional procedures are significantly different in baseline clinical characteristics from patients not undergoing these procedures. These observations underscore the need for randomized trials to define the optimal treatment strategies in these patients. Efficacy of invasive treatment strategies in elderly patients aged older than 75 years-deserves special attention.

Acceptability to patients of a home hospital.

OBJECTIVE: To examine the acceptability to older patients of receiving care in the home for acute medical conditions that require hospital level care by current standards. DESIGN: Interviews with patients during hospitalization regarding their views of a hypothetical "home hospital." PARTICIPANTS: Patients (n = 87) admitted to a community-based academic medical center with a primary diagnosis of pneumonia, congestive heart failure, or chronic obstructive airway disease, their nurses (n = 111), and resident physicians (67). MEASUREMENTS: A questionnaire was developed to measure several domains of acceptability and expectations for care. RESULTS: A majority of patients agreed that treatment in a home hospital would be more comfortable compared with treatment in a hospital (78.5%), would be less likely to result in an infection (62.5%), and would not be a burden to their family (71.8%). There was less certainty that medical care at home can be as good as in the hospital (56.9%). Nearly three-quarters (72.3%) of patients would choose home hospital if it were available. CONCLUSION: Patients may be ready to accept home hospital as an alternative for acute care. The acceptability of home hospital to acutely ill older patients is a critical factor in the development of this alternative for care and has the potential for improving satisfaction with care, reducing complications, hastening return to function, and, possibly, of lowering costs of care.

Project REACH: a program to train community-based lay health educators.

The major purpose of this project was to test the feasibility of recruiting and training volunteers as lay health educators who could coordinate and reinforce the educational efforts of health care providers. A committee of health care professionals designed a 16-hour program. Twenty-five volunteers from T1 religious institutions and 4 retirement communities completed the 8-week program. The program was successful in identifying, recruiting, and training volunteers from racially and religiously diverse institutions. Favorable outcomes included participants' satisfaction and success in organizing numerous educational and screening programs in their communities.

Prospective evaluation of clinical criteria to select older persons with acute medical illness for care in a hypothetical home hospital.

OBJECTIVE: To evaluate criteria to select older persons who need hospitalization for common acute medical illnesses for care in a hypothetical home hospital. DESIGN: Prospective record review. SETTING AND PARTICIPANTS: Patients aged 65 and older admitted to the general medical service of a community-based university hospital. MEASUREMENTS: We developed illness-specific selection criteria to identify older persons with certain acute medical conditions for treatment in a hypothetical home hospital. The selection criteria were reviewed prospectively against all community-dwelling older patients admitted to the general medical service of a community-based university hospital over a 2-month period. We determined eligibility for home hospital admission based on information available at the time of admission and then tracked the patient's hospital course. RESULTS: One hundred fifty-seven admissions of 143 patients were reviewed. The selection criteria identified 33% of patients admitted to the acute hospital with one of the three target diagnoses as eligible for a home hospital model of care had it been available. Eligible patients experienced shorter lengths of stay (3.7 vs 5.4 days, P = .012), fewer mean number of procedures performed (0.98 vs 1.70, P = .001), fewer mean number of complications (0.17 vs 0.56, P = .010), and fewer events that could be handled only in the acute hospital setting (P = .036). In addition, in logistic regression analysis, three criteria for home hospital ineligibility, pulmonary congestion associated with ischemic chest pain (odds ratio 6.85, 95% CI 2.64, 17.81), the presence of an acute coexisting illness requiring hospitalization independent of the target conditions (odds ratio 2.66, 95% CI 1.11, 6.41), and significant pulmonary congestion after initial treatment (odds ratio 14.4, 95% CI 1.77, 117.41) were significantly associated with items difficult to accomplish at home. CONCLUSIONS: Criteria can be delineated that identify older persons with acute medical illnesses who may be suitable for treatment in a home hospital.