Evaluation of cardiovascular risk factors, events, and costs across four BMI categories.

OBJECTIVE: The purpose of this study was to analyze the 1-year cost of cardiovascular (CV) events by body mass index (BMI) subgroups from a US employer health plan perspective. DESIGN AND METHODS: Patients aged 20-64 years from the GE Centricity Electronic Medical Record, National Health and Nutrition Examination Survey, and MarketScan databases were used to determine prevalence of risk factors (RFs) and CV events and 1-year costs. Risk factors included hypertension (HTN), diabetes, and hyperlipidemia (HLD) and CV events included myocardial infarction, angina, heart failure, and stroke. CV event costs were determined from claims by ICD-9 code in patients with overweight/obesity. RESULTS: Of 220,136 patients identified in GE, BMI was 25-26.9 in 19.4%, 27-29.9 in 30.4%, 30-34.9 in 27.9%, and ≥35 in 22.3%. Patients with diabetes, HTN, and HLD increased with BMI from 1.8% (25-26.9) to 11.4% (≥35) in males and 1.1% to 6.8% in females. Prevalence of CV events increased from 0.1% with no RFs up to 10.2% with multiple RFs. The average 1-year cost per patient increased from $1122 to $2383 as BMI increased. CONCLUSIONS: Patients with higher BMI values had an increased prevalence of RFs and CV events, which lead to higher average 1-year costs.

Creating a team approach to hospital and college of pharmacy relationships: a strategy to integrate missions to enhance education and patient care.

Academic medical centers continue to bear the burden of the additional costs of professional education. Such institutions and their affiliated colleges of pharmacy are challenged to sustain the degree of professional staffing required to deliver quality education and patient care services. Historically, these relationships have not always proven to be cooperative and mutually beneficial. As managers and deans attempt to maximize the productivity of their financial and human resources, they will need to creatively structure relationships that effectively meet those diverse professional missions that sometimes seem to exist in conflict or that each seem to be successful only at the expense of the other. Pharmacists who act as both faculty, delivering experiential education, and clinical staff providing patient care, are significantly stressed in their attempts to meet the sometimes conflicting objectives of these multiple missions. The survival of precepted experiential education in pharmacy and of pharmaceutical care in academic medical center hospitals will likely depend upon a model of cooperative relationship, such as the venture described by Jorgenson, et al.

Use of activated charcoal in a simulated poisoning with acetaminophen: a new loading dose for N-acetylcysteine?

STUDY OBJECTIVES: To investigate the ability of a supranormal dose of N-acetylcysteine to overcome the effects of activated charcoal on N-acetylcysteine bioavailability and to determine the effects of activated charcoal on serum acetaminophen levels. DESIGN, SETTING, AND PARTICIPANTS: Ten healthy adult volunteers participated in a controlled cross-over experiment. During phase I (control), subjects ingested 3 g acetaminophen, followed one hour later by the normal loading dose of N-acetylcysteine (140 mg/kg). During phase II (charcoal), subjects ingested 3 g acetaminophen, followed one hour later by 60 g activated charcoal and a supranormal loading dose of N-acetylcysteine (235 mg/kg). MAIN OUTCOME MEASURES: Serum levels of N-acetylcysteine were measured every 30 minutes for six hours. A serum acetaminophen level was measured at four hours. RESULTS: The area under the curve for N-acetylcysteine was significantly higher for phase II than phase I (P < .05, two-tailed paired t-test). Peak N-acetylcysteine and time to peak were not significantly different. The four-hour serum acetaminophen level was significantly lower for phase II than phase I (P < .05, two-tailed paired t-test). Diarrhea occurred during both phases, but N-acetylcysteine was otherwise well tolerated. CONCLUSION: These results suggest that activated charcoal can be used safely for victims of acetaminophen overdose. A beneficial effect in preventing acetaminophen absorption can be expected if it is given within one hour after ingestion. If N-acetylcysteine is needed because of a toxic serum acetaminophen level, bioavailability can be ensured by increasing the N-acetylcysteine loading dose from 140 mg/kg to 235 mg/kg.

Initial symptoms as predictors of esophageal injury in alkaline corrosive ingestions.

The predictive value of initial clinical evaluation in the management of alkaline corrosive ingestion remains unclear. This multicenter study was designed to determine if specific clinical signs and symptoms following ingestion of alkaline corrosives could predict significant esophageal injury. Alkaline corrosives were defined by a pH greater than or equal to 12. Signs and symptoms previously suggested as predictive of significant esophageal injury were documented on a standardized data form. Esophagoscopy reports were reviewed blinded to initial symptoms. Three hundred thirty-six alkaline-corrosive ingestions were analyzed. The mean number of symptoms reported in patients who did not have esophagoscopy was 1.2, in patients who had esophagoscopy was 3.0, and in patients that had visualized second or third degree esophageal burns was 4.8. Of 88 patients who had esophagoscopy, 63 (72%) had both the esophagoscopy report and initial symptom assessment available. Esophagoscopy was positive, defined as second or third degree esophageal burns, in 18 of 63 cases (29%). All patients with significant burns were symptomatic. No single or group of initially reported signs and symptoms could identify all patients with potentially serious esophageal burns.

Simulated acetaminophen overdose: pharmacokinetics and effectiveness of activated charcoal.

STUDY OBJECTIVE: To determine the absorption rate of a supratherapeutic dose of acetaminophen elixir and compare the effect of activated charcoal (AC) given at different time intervals on preventing acetaminophen absorption. DESIGN: Randomized, nonblinded, crossover controlled study. SETTING: A certified regional poison control center. PARTICIPANTS: Ten healthy, adult male volunteers from 21 to 39 years old. INTERVENTIONS: Each subject received 5 g acetaminophen (elixir) on four occasions: a control phase plus 30 g of AC administered 15, 30, or 120 minutes after acetaminophen. Serum acetaminophen levels were obtained during the control phase only, and 24-hour urine collections were obtained during all four phases. MEASUREMENTS AND MAIN RESULTS: The highest serum acetaminophen levels were measured 1.4 +/- 0.52 hours after ingestion, and absorption was 97% complete by a mean of 2.05 hours. The administration of AC at 15, 30, and 120 minutes after acetaminophen reduced urinary recovery of acetaminophen and metabolites by 48%, 44%, and 33%, respectively. CONCLUSION: AC significantly reduces urinary recovery but not absorption of acetaminophen when administered two hours after acetaminophen elixir.

Poisoning in the elderly. Epidemiological, clinical and management considerations.

Poisoning is a significant problem in the elderly. The majority of poisonings in older people are unintentional and may result from dementia and confusion, improper use of the product, improper storage or mistaken identities. Depression is also common in the elderly and suicide attempts are more likely to be successful in this age group. The elderly patient's recuperative abilities may be inadequate as a result of numerous factors including impaired hepatic or renal function as well as chronic disease processes. General management of poisoning in the elderly parallels management of younger adults, but it is especially important to ascertain underlying medical conditions and concurrent medications. In most poisonings, activated charcoal and cathartic are sufficient. Haemodialysis or haemoperfusion may be required at lower plasma drug concentrations in elderly patients. While the specific indications for antidotes are the same for all age groups, dosage alterations and precautions may need to be considered in the elderly. Drugs most often implicated in poisonings in the elderly include psychotherapeutic drugs, cardiovascular drugs, analgesics and anti-inflammatory drugs, oral hypoglycaemics and theophylline. Cardiovascular and neurological toxicities occur with overdoses of neuroleptic drugs and, more frequently and severely, with cyclic antidepressants. Patients with pre-existing cardiovascular disease are at particular risk of worsening ischaemic heart disease and congestive heart failure. Benzodiazepines only appear to produce significant toxicity during long term administration or in combination with other CNS depressants. Digoxin can cause both chronic and acute intoxication, most seriously cardiac toxicity including severe ventricular arrhythmias, second or third degree heart block or severe refractory hyperkalaemia. Immune Fab antibody is indicated for the management of digoxin toxicity, although patients dependent on the inotropic effect of digoxin may develop heart failure after digoxin Fab antibody administration. Nitrates can cause toxicity including headache, vomiting, hypotension and tachycardia from excessive sublingual, transdermal or intravenous doses. Conduction disturbances and hypotension occur with overdoses of antihypertensive drugs; these effects are mild with angiotensin converting enzyme (ACE) inhibitors, occasionally severe with beta-blockers and of significant concern with calcium channel antagonists. The elderly commonly use aspirin and other salicylates, are more likely to develop chronic intoxications to these agents, and are more susceptible to severe complications such as pulmonary oedema. Salicylate poisoning, recognition of which is often delayed, should be considered in elderly patients with neurological abnormalities or breathing difficulties, especially in the setting of acid-base abnormalities. The clinical effects of NSAID overdose are mild and usually involve the central nervous system and gastrointestinal tract.(ABSTRACT TRUNCATED AT 400 WORDS)

The effect of milk on ipecac-induced emesis.

A prospective study at two regional poison centers was undertaken in 500 children under six years of age (mean age 2.3 y) to resolve the question of whether milk has an effect on ipecac-induced emesis. When home administration of ipecac was recommended, parents were asked to select either milk or clear fluids. The mean volume of fluid +/- standard deviation administered was 159 +/- 72 mL in the milk group and 161 +/- 77 mL in the clear fluid group (p = 0.79). There was no difference in the onset of vomiting (23.4 +/- 18.5 vs. 23.3 +/- 12.9 min, p = 0.92), number of vomiting episodes (3.5 +/- 1.9 vs. 3.4 +/- 1.8, p = 0.65), or duration of vomiting (45 +/- 73 vs. 39 +/- 54 min, p = 0.31) for the milk group compared with the clear fluid group. Side effects including lethargy and diarrhea occurred with similar frequency in both groups. The substance ingested had no effect on onset of vomiting, vomiting duration or number of vomiting episodes. These findings again demonstrate that milk does not interfere with ipecac-induced emesis.

Publication of presented abstracts at annual scientific meetings: a measure of quality?

One measure of the quality of research presented at the annual scientific meeting is publication of the data presented in a peer review journal. This allows for a more rigorous review of design, methodology and conclusions. To determine the rate of subsequent publication, MEDLARS searches were performed on the 269 presented abstracts at the 1984 and 1986 meetings of the American Association of Poison Control Centers, The American Academy of Clinical Toxicology, The American Board of Medical Toxicology and the Canadian Association of Poison Control Centers. Of the 296 presented abstracts, 134 (49.8%) were published. There was no difference in the eventual publication rate between the 1984 and 1986 meeting. There were 38 non-reviewed symposia publications and 96 peer-reviewed articles. Publications of 35.7% of presented abstracts in peer review journals compares poorly with the percentage of peer-reviewed publication from other scientific meetings. If publication in a peer-review journal is important, steps should be taken to improve the percentage of presented abstracts that are accepted by peer-review journals.

Assessment of management guidelines. Acute iron ingestion.

A review of 339 treated acute iron ingestions was conducted to define treatment guidelines better. According to the poison center protocol, ingestions of 20-40 mg/kg of elemental iron required only home treatment, and ingestions of greater than or equal to 40 mg/kg required hospital referral. Gastrointestinal symptoms developed in 23% of patients. There were no seriously ill patients. No serious toxicity developed in patients ingesting 40-60 mg/kg. In 199 cases in which the dose ingested was known, the mean dose was 39.5 mg/kg. The peak measured serum iron levels ranged from 12 to 539 micrograms/dl. In 129 cases with serum iron levels reported, increasing serum iron levels were associated with vomiting (p = 0.006). Of 88 patients who received deferoxamine, 14 had urine color change. Urine color change was associated with symptoms (p = 0.005) but not with iron dose or peak serum iron level. The poison center protocol was changed to home management for ingestions of 20-60 mg/kg unless significant symptoms developed and hospital referral for ingestions greater than or equal to 60 mg/kg.

Three fatal sodium azide poisonings.

We report 3 cases and review the published literature on sodium azide ingestion. A 38-year-old man intentionally ingested 2 tablespoonsful of sodium azide in water and developed seizures, coma, hypotension and fatal ventricular arrhythmias within 2 hours. A 33-year-old male ingested an unknown quantity of sodium azide. In the emergency department he was unconscious and underwent immediate intubation and gastric lavage. Nitrite therapy was instituted without improvement. He remained acidotic despite bicarbonate therapy and developed hypotension which was unresponsive to pressor agents. He died approximately 8 hours after admission despite resuscitative efforts. A 52-year-old male ingested 1.5 to 2g of sodium azide and survived for 40 hours. Nitrite therapy was ineffective. The role of sodium nitrite in treating sodium azide toxicity by producing methaemoglobin which complexes with azide is discussed.

Effects of magnesium citrate and clidinium bromide on the excretion of activated charcoal in normal subjects.

The efficacy of cathartics in shortening the gastrointestinal transit time of activate charcoal (AC) in the presence of drugs that alter gastrointestinal motility has not been determined. We evaluated the effects of magnesium citrate (MC) on the excretion of activated charcoal in healthy volunteers alone and with concurrent administration of the anticholinergic drug clidinium bromide. Forty subjects were randomized to clidinium bromide 5 mg or placebo capsule (PC), followed by activated charcoal 15 g and magnesium citrate or a placebo liquid (PL). The onset and duration of excretion of activated charcoal were noted. Mean onset times for activated charcoal were: group I (CB, MC) 4.5 +/- 2.1 h; group II (CB, PL) 17.0 +/- 10.0 h; group III (PC, MC) 6.3 +/- 5.8 h; and group IV (PC, PL) 20.6 +/- 8.4 h. The onset of excretion of activated charcoal was statistically different in both magnesium citrate groups as compared with the placebo liquid groups. The duration of activated charcoal in the stool was similar among the groups. The addition of clidinium bromide did not appear to affect gastrointestinal transit time. These results support previous studies of the effects of cathartics on the excretion of activated charcoal, and suggest that cathartic efficacy is not inhibited by anticholinergic drugs when used in therapeutic doses.

Lithium intoxication with acute renal failure and death.

A 65-year-old female presented with only gastrointestinal symptoms eight to ten hours after an acute ingestion of an unknown amount of lithium carbonate. The serum lithium concentration was 8.5 mEq/L. Forty-eight hours postingestion she developed acute renal failure, deteriorating mental status, and cardiovascular collapse. Despite both hemodialysis and peritoneal dialysis the patient died approximately four and one-half days after ingestion. A direct nephrotoxic effect of lithium is proposed.

Clinical manifestations of toxicity in a series of 784 boric acid ingestions.

A retrospective chart review was conducted at two regional poison centers to determine the clinical outcome of boric acid ingestions and to assess the relationship between serum boric acid levels and clinical presentation. A total of 784 cases were studied; all but 2 were acute ingestions. No patients developed severe manifestations of toxicity, and 88.3% were entirely asymptomatic. The most common symptoms were vomiting, abdominal pain, and diarrhea. Lethargy, headache, lightheadedness, and atypical rash were seen less frequently. Boric acid levels were obtained in 51 patients and ranged from 0 to 340 micrograms/mL. Blood levels were 70 micrograms/mL or more in 7 patients; 4 remained asymptomatic, whereas the other 3 had nausea or vomiting. Dialysis was performed in 4 of these 7 patients, only 1 of whom had symptoms (vomiting). On the basis of data from 9 patients, the mean half-life of boric acid was determined to be 13.4 hours (range, 4.0 to 27.8). Hemodialysis in 3 patients significantly shortened the half-life compared with pre- and postdialysis half-lives. Our results suggest that acute boric acid ingestions produce minimal or no toxicity and that aggressive treatment is not necessary in most patients.

In vitro study of lithium carbonate adsorption by activated charcoal.

The purpose of this study was to determine whether lithium carbonate (Li2CO3) is effectively adsorbed by activated charcoal (AC). Either 0 (control), 1.5, 3.0 or 9.0 grams of AC were added to Li2CO3 (300 mg) in distilled deionized water or simulated gastric fluid USP, filtered and and the filtrate analyzed for lithium by flame photometry. Adsorption of lithium was dependent on AC concentration and pH. In water, lithium was 14.7%, 26.5% and 40.4% adsorbed at AC:Li2CO3 ratios of 5:1, 10:1 and 30:1, respectively (p less than 0.05). In simulated gastric fluid, there was no significant adsorption at any of the AC concentrations studied. Since simulated gastric fluid more closely resembles in vivo conditions, the efficacy of AC in lithium carbonate overdoses is questionable but in vivo studies are needed to confirm these findings.

In vitro study of boric acid and activated charcoal.

An in-vitro study utilizing a titration assay was performed to evaluate the degree of adsorption of one gram of boric acid by 7.5 g, 15.0 g and 30.0 g of activated charcoal. The mean percentage adsorbed was 5.7 +/- 1.6% for 7.5 g of activated charcoal, 17.6 +/- 3.5% for 15.0 g of activated charcoal and 38.6 +/- 6.3% for 30.0 g of activated charcoal. Analysis of variance showed a significant difference from the control (no activated charcoal) for the 15.0 and 30.0 g samples (p less than 0.05). Although binding of boric acid by activated charcoal increased as the proportion of activated charcoal to boric acid increased, this finding is not clinically significant since the amount of activated charcoal required for 38% adsorption is 30 times the amount of boric acid ingested. Considering the toxic and potentially fatal doses of boric acid in children (5 g) and adults (20 g), doses of activated charcoal of greater than 150 g in children or 600 g in adults would be impractical for the clinical situation.

Relative toxicity of cyclic antidepressants.

To compare the relative central nervous system and cardiac toxicity of amoxapine, maprotiline, and trazodone with the older tricyclic antidepressants, a three-year (1981 through 1983) retrospective review was performed on 1,313 cases involving cyclic antidepressant exposures reported to the Maryland Poison Center. Seizures were more common in the amoxapine (24.5%) and maprotiline (12.2%) groups, compared with either the tricyclic antidepressants (3.0%) or trazodone (0%) (P less than .01). A higher incidence of seizures also was observed in desipramine ingestors (17.9%) compared with other tricyclic antidepressants. No significant differences in the incidence of central nervous system depression or cardiotoxicity was found between the groups. These findings support reports of an increased incidence of seizures in overdoses of amoxapine and maprotiline, but do not substantiate claims of less cardiotoxicity.

Ipecac administration in children younger than 1 year of age.

The efficacy of ipecac syrup in the induction of emesis and safety of its administration was studied in 105 poison-exposed infants 6 through 11 months of age (study subjects) and compared prospectively with 302 poison-exposed infants and children 12 through 35 months of age who served as age controls. Of the 105 study subjects 101 (96.2%) vomited. The failure of ipecac to induce emesis in six patients (four of 105 study subjects two of 302 age control subjects) is comparable with ipecac failure rates reported elsewhere. The frequency of side effects caused by ipecac syrup did not differ between study and control subjects. There were no serious medical complications resulting from the administration of ipecac syrup. When not readily available at home, ipecac administration was delayed an additional 21.8 minutes if obtained from a pharmacy and 38.4 minutes if obtained from an emergency department. Because of the time delay and the increased health care cost, home rather than emergency department administration of ipecac should be advised. These data demonstrate that ipecac syrup effectively induces emesis and is safe for home administration to poisoned infants 6 to 11 months old.