Thomas E. Kearney

Locoregional Relapse and Distant Metastasis in Conservatively Managed Triple Negative Early-Stage Breast Cancer

PURPOSE To determine the prognostic significance of triple negative breast cancers with respect to locoregional relapse and distant metastasis in conservatively managed breast cancer patients. PATIENTS AND METHODS A database of conservative managed (conservative surgery followed by radiation) patients, in whom all three markers (estrogen receptor, progesterone receptor, and HER2/neu) were available, was reviewed. Patients were classified as triple negative if they tested negative for all three markers. Of 482 patients with all three markers available, 117 were classified as triple negative. RESULTS As of September 2005, with a median follow-up time of 7.9 years, of the 482 patients in the study, there have been 53 in-breast relapses, 10 nodal relapses, 77 distant relapses, and 69 deaths. At 5 years, the triple negative cohort had a poorer distant metastasis-free rate compared with the other subtypes (67% v 82%, respectively; P = .002). Triple negative subtype was an independent predictor of distant metastasis (hazard ratio = 2.14; 95% CI, 1.31 to 3.53; P = .002) and cause-specific survival (hazard ratio = 1.79; 95% CI, 1.03 to 3.22; P = .047). There was no significant difference in local control between the triple negative and other subtypes (83% v 83%, respectively). Of 99 BRCA-tested patients in this cohort, 10 had deleterious mutations in BRCA1, and seven had mutations in BRCA2. Of 10 BRCA1 patients, eight were triple negative, whereas only one of seven BRCA2 patients was triple negative (P < .001). CONCLUSION Patients classified as triple negative have a poor prognosis. However, there was no evidence that these patients are at higher risk for local relapse after conservative surgery and radiation. Patients with BRCA1 mutations develop predominantly triple negative tumors.

Seizures associated with poisoning and drug overdose.

A retrospective review of cases consulted by the San Francisco Bay Area Regional Poison Control Center during a 2-year period was performed to determine the causes and consequences of seizures associated with poisoning and drug intoxication. Of 233 charts coded as involving seizures, 191 occurred in humans and were available for analysis. The leading causes of seizures reported to the Poison Control Center were cyclic antidepressants (55 cases, 29%); cocaine and other stimulants (55 cases, 29%); diphenhydramine and other antihistamines (14 cases, 7%); theophylline (10 cases, 5%); and isoniazid (10 cases, 5%). Stimulants and diphenhydramine were more likely than other drugs to produce brief, self-limited seizures. In contrast, poisoning by cyclic antidepressants, cardiodepressant antiarrhythmic agents, or theophylline was more likely to be associated with death. Seizures in elderly patients were more likely to result in complications and death. The frequency of seizure-related cases by substance type was also compared with the results of an earlier survey performed in 1981, and found a striking increase in the proportion of seizures caused by cocaine and (23% in 1988 to 1989 compared with 4% in 1981). Poison Control Center data can provide valuable information about the causes and consequences of drug-related medical complications, as well as highlight changing trends in drug-related injury.

Evolving epidemiology of drug-induced seizures reported to a poison control center system

IntroductionWe sought to determine whether or not the causes and consequences of drug-induced seizures have changed in the last decade.MethodsWe conducted a retrospective review of all calls to the California Poison Control System in 2003 in which seizures occurred in association with poisoning or drug intoxication. We reviewed the poison center chart of each case to determine the drug(s) involved, the type of seizures, and the medical outcome. We compared the cause of reported seizures to that found in previous investigations.Results386 cases were evaluated and related to poisoning or drug intoxication. The leading causes of seizures were bupropion (89 cases, 23%), diphenhydramine (32 cases, 8.3%), tricyclic antidepressants (30 cases,7.7%), tramadol (29 cases, 7.5%), amphetamines (27 cases, 6.9%), isoniazid (23 cases, 5.9%), and venlafaxine (23 cases, 5.9%). Since 1993, there was a statistically significant increase in antidepressant related seizures but a decrease in TCA and cocaine related seizures. In 265 patients (68.6%) only a single seizure was reported, while 3.6% (14 cases) reported status epilepticus. Two-thirds (65.5%) of the cases involved suicide attempts and 14.8% the direct result of drug abuse. There were 7 deaths. Of the 7 deaths, 4 people had significant hyperthermia. There was a statistically significant increased risk of death associated with stimulant exposure.ConclusionWhile tricyclic antidepressants, antihistamines, stimulants, and isoniazid remain common causes of drug induced seizures, bupropion, tramadol, and venlafaxine have emerged as common causes of drug-induced seizures for which poison center consultation is requested.

Theophylline Toxicity and the Beta-Adrenergic System

After ingestion of 12 g of theophylline caused severe toxicity in a young woman, we developed an experimental canine model to study human theophylline toxicity. Our study involved four anesthetized dogs given theophylline in a continuous intravenous drip for 180 minutes in one of four protocols. The protocols included a low-dose infusion (400 mg/h), a high-dose infusion (1000 mg/h), a high-dose infusion with beta-blockade induced by propranolol at 125 minutes after infusion, and a high-dose infusion while maintaining beta-blockade with propranolol throughout the experiment. Toxic levels of theophylline were associated with hypokalemia, hypophosphatemia, hyperglycemia, metabolic acidosis, and hypotension in both the patient and the experimental series. These effects were either prevented or partially reversed after induction of beta-blockade with propranolol. Very high levels of theophylline were associated with elevated levels of norepinephrine and epinephrine in the animals.

WILLINGNESS TO PAY FOR POISON CONTROL CENTERS

We used the willingness-to-pay (WTP) method to value the benefits of poison control centers when direct access was blocked, comparing WTP among: (1) blocked callers (n = 396), (2) callers after access was restored (n = 418), and (3) the general population (n = 119). Mean monthly WTP was

The Costs and Outcomes of Restricting Public Access to Poison Control Centers Results from a Natural Experiment

6.70 (blocked callers),

Adverse Drug Events Associated with Yohimbine-Containing Products: A Retrospective Review of the California Poison Control System Reported Cases

6.11 (non-blocked callers), and

Poison control centers: Is there an antidote for budget cuts?

2.55 (general population). Blocked and non-blocked callers had a significantly higher WTP than general population respondents (p < 0.001). We conclude that the WTP method measured benefits that are difficult to quantify; however, WTP surveys need to be carefully conducted to minimize bias. We discuss how this approach could be useful for other health care services.

Comparative Toxicity of Tapentadol and Tramadol Utilizing Data Reported to the National Poison Data System

OBJECTIVES The authors examined the costs and outcomes resulting from a natural experiment during which direct public access to poison control centers was restricted and then restored. METHODS Both societal and health care purchaser perspectives were used. Probability data were obtained from a natural experiment during which public callers from a large county in California were electronically blocked from directly accessing the poison control center. Callers were referred to 911, which had direct access to the poison control center, if they thought they had a poisoning emergency. We conducted telephone interviews of: (a) persons who attempted to call the poison control center for a childs poisoning exposure but who did not have direct access (n = 270) and (b) persons who called the poison control center after direct access was restored (n = 279). Cost data were obtained from primary data collection and from other sources. The outcome measure was the appropriateness of the treatment location (at home or at a health care facility). Caller-reported outcomes were also examined. RESULTS The average additional cost per blocked call was

Pepper Spray Injury Severity: Ten-year Case Experience of a Poison Control System

10.89 from a societal perspective, or