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Purpose Cancer accounts for $60.9 billion in direct medical costs and $15.5 billion for indirect morbidity costs. These estimates are derived primarily from national surveys or Federal databases. We derive estimates of the costs of cancer using administrative databases, which include claims and employment-related information on individuals insured by private or Medicare supplemental health plans. Methods A retrospective matched-cohort control analysis was performed using 1998 to 2000 databases with information on insurance claims, benefits, and health productivity for 3 million privately insured employees, their dependents, and early retirees. Study patients had new diagnoses of one of seven types of cancer (n = 12,709). Controls without cancer were matched at a 3:1 ratio by demographics. A variable follow-up length was used (maximum of 2 years). Direct costs included health care costs for patients and deductibles and copayments for caregivers. Indirect costs of work absence and short-term disability (STD) were calculated for a subgroup of cancer patients and caregivers. Results Mean monthly health care costs ranged from $2,187 for prostate cancer to $7,616 for pancreatic cancer, most often driven by hospitalization. Costs for controls were $329 per month. Indirect morbidity costs to employees with cancer averaged $945, a result of a mean monthly loss of 2.0 workdays and 5.0 STD days. Conclusion The economic burden of cancer is substantial. It is feasible to derive tumor-specific estimates of direct and indirect costs for large numbers of cancer patients using administrative databases. Policy makers charged with providing annual cost-of-cancer estimates should incorporate data obtained from a broad range of sources.

Background: Due to the rarity of TTP (approximately 4 cases per million), epidemiologic data and correlative laboratory samples from a prospectively identified incident cohort of TTP patients are needed. Methods: SERF TTP is a NHLBI-funded 15-site study targeted to identify 300 incident TTP patients and 600 age-/gender-matched community controls. Results: From nine IRB-approved collaborating sites, 22 incident TTP cases and 17 controls have been interviewed. Data and plasma (acute and convalescent samples) are available for 19 TTP patients (Table 1). Their mean age is 42.5 years (range, 20 – 80 years), and 90% are female. Using the Rose-Eldor TTP Scoring system based on platelets, creatinine, hemoglobin, and neurologic function, 37% would be classified as severely ill (score > 4 of a maximum 8 points). Mean time from symptom onset to diagnosis was 9.2 days, median 5.5 days (range, 0 to 33 days). Severity of TTP was poorer for the 5 patients whose treatment did not begin for at least 16 days (16–33 days) versus the other 14 patients (mean Rose-Eldor score of 4.6 versus 4). Medications which had been prescribed to the patients prior to TTP onset included herbal supplements (n= 5) and hormone replacement therapy or oral contraceptives (n= 6). All patients received at least daily therapeutic plasma exchange (TPE). A platelet count >150,000 was reached at a mean of 9.4 days following TPE initiation. At 30-days follow-up, all patients were alive, although 3 had an exacerbation requiring daily TPE reinstitution. Fourteen patients (78%) experienced an adverse event, including allergic reactions to plasma (n=9), citrate-related toxicity (n=9) and venous access complications (n=2) including one with major hemorrhage requiring transfer to the intensive care unit. Conclusion: The clinical characteristics of the SERF-TTP cohort are similar to those reported from large single-site studies, although the survival rate (100% versus 71% and 83%) is higher. Only a minority of incident TTP cases in the modern era present with renal insufficiency or neurologic findings - highlighting the importance of developing reliable diagnostic laboratory testing. Clinical Characteristics at Presentation Study Platelets 2mg/dl Fever Neurologic symptoms Mortality (1) Zheng XL, Kaufman RM et al. Blood.2004; 103: 4043; (2)Vesely SK, George JN et al. Blood.2003; 102: 60. HSCT: Hematopoetic stem cell transplantation, FK-506: Tacrolimus. SERF-TTP n=19 95% 79% 32% 11% 47% 0% Washington University (1) (excluding HSCT/FK506 cases) n= 28 96% 82% 29% 32% 50% 29% Oklahoma TTP-HUS Registry (2) (ADAMTS13 < 5%) n=18 100% 100% 22% NA (Not Available) 56% 17%

Introduction: The antiplatelet agents ticlopidine and clopidogrel are thienopyridine derivatives that are commonly used for secondary prevention of cerebrovascular events, prevention of coronary artery stent thrombosis, and for treatment of acute coronary syndrome. While these chemically related agents are the first and third most common causes of drug-associated TTP respectively, clinical presentations, laboratory findings, and outcomes suggest that there may be two distinct mechanistic pathways. Methods: Clinical and laboratory data for 60 cases of ticlopidine-associated TTP and 35 cases of clopidogrel associated TTP were reviewed. Results: Type 1 thienopyridine-associated TTP, characterized by onset of disease > 5 days after drug initiation, occurred in 98% of the ticlopidine patients versus 63% of the clopidogrel patients. Laboratory studies identified severe deficiency of ADAMTS13 activity and the presence of IgG inhibitors in 7 ticlopidine (Tsai, et al.; Annals of Internal Medicine, 2000) and 2 clopidogrel (Bennett, et al.; NEJM, 2000) patients. Survival was 68% in the ticlopidine patients versus 91% in the clopidogrel patients. Type 2 thienopyridine-associated TTP, consisting of TTP onset within 5 days of drug initiation, occurred in 2% of the ticlopidine patients versus 37% of the clopidogrel patients. Laboratory studies failed to identify deficient ADAMTS13 activity or the presence of IgG inhibitors in 1 clopidogrel patient (Zheng, et al.; Blood, 2004). Survival was 0% in the ticlopidine patients versus 38% in the clopidogrel patients. Conclusion: The proposed type 1 and type 2 thienopyridine-associated TTP may be distinguished on the basis of clinical presentation, ADAMTS13 levels, and outcome. Type 1 thienopyridine-associated TTP—characterized as occurring after > 5 days of thienopyridine treatment, severely deficient ADAMTS13 activity and presence of IgG inhibitors, and high survival rates with plasmapheresis—is more likely to occur in patients receiving ticlopidine. Type 2 thienopyridine-associated TTP—characterized as occurring within 5 days of thienopyridine therapy initiation, normal ADAMTS13 activity and undetectable IgG inhibitors, and poor survival rates despite plasmapheresis—is more likely to occur in patients receiving clopidogrel. Additional confirmatory studies on larger numbers of patients are needed.

6020 Background: Prior studies have found that women with cancer are especially likely to suffer financial hardships, as many women in these studies had limited financial resources and/or poor fami...

The pharmacodynamic effects of single oral doses of atenolol (100 mg), labetalol (300 mg), and propranolol (80 mg) were compared with those of placebo in a randomized, double-blind, Latin square design in 12 patients with hypertension. Atenolol and propranolol both significantly reduced cardiac output (-0.55 vs. -0.31 L/min) and heart rate (-8.0 vs. -6.6 bpm), whereas labetalol had no effect on either parameter (-0.08 L/min; + 1.0 bpm). Labetalol significantly reduced vascular resistance (-339 dynes X cm/sec5), but atenolol and propranolol did not (147 vs. 62 dynes X cm/sec5). Only labetalol significantly reduced the systolic (-15.3 mm Hg), diastolic (-11.5 mm Hg), and mean blood pressures (-12.8 mm Hg). Atenolol significantly reduced only diastolic blood pressure (-5.20 mm Hg), whereas propranolol failed to lower these parameters significantly. These data indicate that the hemodynamic profile of labetalol differs from that of selective and nonselective beta-blockers. Labetalol lowered blood pressure primarily by reducing vascular resistance, whereas reductions in heart rate and cardiac output were the predominant effects of atenolol and propranolol.

We examined in normal men and women the effects of chronic ethanol consumption and the coadministration of cimetidine and ranitidine on the kinetics of ethanol. We found that the consumption of 45 gm ethanol per day for 3 weeks increased the apparent volume of distribution of ethanol in men from 732 to 884 ml/kg (P < 0.01) but had no such effect in women (697 ml/kg before ethanol and 746 ml/kg after chronic ethanol consumption). This combined therapy had no effect on the rate of ethanol disappearance in either sex. In men the rate of disappearance was 165 mg/L/hr before and 168 mg/L/hr after chronic consumption, while in women the respective values were 209 and 203 mg/L/hr. The addition of either cimetidine or ranitidine had no effect on either parameter compared with values observed on day 22 of the study. In view of the known inhibitory effects of cimetidine on cytochrome P-450–dependent enzymes, our data suggest that this enzyme system does not metabolize a significant fraction of ingested ethanol in subjects who have consumed moderate doses of alcohol for several weeks. Clinical Pharmacology and Therapeutics (1985) 38, 157–163; doi:10.1038/clpt.1985.152

Flecainide and verapamil are antiarrhythmic agents that may be used in combination. We have examined their pharmacodynamic interaction by M-mode echocardiography and electrocardiography in eight normal male volunteers (24 +/- 1.8 years of age). Flecainide decreased the left ventricular ejection fraction (LVEF) (-4.4 +/- 1.2%, p less than 0.008), but verapamil did not. Neither drug affected cardiac output or vascular resistance. Both drugs increased the PR interval (12 +/- 4 msec, p less than 0.01 for flecainide; 12 +/- 5, p less than 0.04 for verapamil). Flecainide, but not verapamil, increased the QTc interval (23 +/- 8 msec, p less than 0.02). Both drugs also increased the systolic time interval ratio (PEPc/LVETc) (0.074 +/- 0.012, p less than 0.0004 for flecainide; 0.029 +/- 0.008, p less than 0.007 for verapamil). The combination of flecainide and verapamil had additive effects on myocardial contractility and on atrioventricular conduction. Verapamil slightly decreased the plasma clearance of flecainide (7.78 +/- 0.60 ml/kg/min for flecainide alone, 7.34 +/- 0.48 ml/kg/min for flecainide and verapamil together, p less than 0.05). On the other hand, flecainide had no effect on the plasma clearance of verapamil, which suggests that there was little interaction between the two drugs on their pharmacokinetic parameters.