Toxic Exposure Surveillance System Research Articles

A 10-Year Retrospective Analysis of Medication Errors among Adult Patients: Characteristics and Outcomes.

Medication errors (MEs) are a global health problem. We conducted this study to clarify the clinical characteristics, outcomes, and factors associated with MEs that caused harm to adult patients (>15 years of age) who were managed in hospitals or healthcare facilities. We performed a 10-year retrospective study (2011-2020) by analyzing data from the Ramathibodi Poison Center (RPC) database (RPC Toxic Exposure Surveillance System). There were a total of 112 patients included in this study. Most were women (59.8%) and had underlying diseases (53.6%). The mean patient age was 50.5 years. Most MEs occurred during the afternoon shift (51.8%) and in the outpatient department (65.2%). The most common type of ME was a dose error (40.2%). Local anesthetic was the most common class of ME-related drug. Five patients died due to MEs. We analyzed the factors associated with MEs that caused patient harm, including death (categories E-I). The presence of underlying diseases was the single factor that was statistically significantly different between groups. Clinical characteristics showed no significant difference between patients aged 15-65 years and those aged >65 years. In conclusion, our findings emphasized that MEs can cause harm and even death in some adult patients. Local anesthetics were the most commonly involved in MEs. Having an underlying disease might contribute to severe consequences from MEs. Preventive measures and safety systems must be highlighted and applied to prevent or minimize the occurrence of MEs.

Poisoning of Butanol-Containing Products: Clinical Characteristics and Outcomes.

BackgroundButanol (butyl alcohol) is a chemical which occurs naturally in some foods and is used in the manufacture of other chemicals. Current data on butanol poisoning in humans are limited.ObjectiveThis study describes clinical characteristics and outcomes of patients exposed to products containing butanol.MethodsWe performed a 5-year retrospective cross-sectional study by analyzing data from the Ramathibodi Poison Center Toxic Exposure Surveillance System for 2013–2017.ResultsThere were 163 patients included in the study. All products containing butanol reported were agricultural adjuvant products. Most (67.5%) patients were males and had ingested butanol accidentally (75.5%). The median age was 42 years. Almost all patients had oral exposure to butanol. At presentation, most of our patients had normal vital signs and were conscious. Clinical presentations mostly included gastrointestinal symptoms (65%) and local irritation (28.8%). Fifty-four patients (33.1%) had no obvious clinical effects at presentation. Most patients had normal laboratory tests at presentation, although eight developed systemic effects including high anion gap metabolic acidosis (n=8), acute kidney injury (AKI; n=5), depression of consciousness (n=5), and hypotension (n=3). Of these eight patients, two with intentional ingestion developed altered consciousness, hypotension, AKI, severe metabolic acidosis, and eventually died. One of these died within 1 day after ingestion, while the other died later through complications during admission. Therefore, the mortality rate was 1.23%. Sixty-six patients (40.5%) were admitted to hospitals, with a median length of stay of 1 day. Most patients received only supportive treatment and fully recovered.ConclusionAgricultural adjuvant products containing butanol or butanol itself caused only mild effects in most patients, but systemic effects occurred in some. The mortality from this poisoning was very low, and both fatalities were from intentional ingestion. Supportive care and proper management of complications should be the main treatment for this form of poisoning.

Toad Poisoning: Clinical Characteristics and Outcomes.

ObjectiveThis study was performed to describe the clinical characteristics and outcomes of patients with toad poisoning in Thailand.MethodsWe carried out a retrospective study of patients with toad poisoning from the Ramathibodi Poison Center Toxic Exposure Surveillance System during a 5-year period (2012–2016).ResultsWe studied 36 patients poisoned by toad toxin. The median age was 31 years. Most patients were male (66.7%) and had ingested toad meat (50%). The most common presentation was gastrointestinal (GI) symptoms with a median onset of 2 h after ingestion. Twelve patients presented with bradycardia; seven presented with shock and one with cardiac arrest. In the initial EKGs of all patients, the most common abnormality was sinus bradycardia.Two patients developed cardiac arrest early during management in the emergency room (within 15 minutes after ER arrival or within 4.5 h after ingestion). During admission, one patient developed sinus bradycardia, and two developed bradyarrhythmia; however, all three were stable. No tachyarrhythmias such as ventricular tachycardia were detected in any patient. Some patients (11.1%) presented with hyperkalemia. Serum digoxin was detected in five of seven patients tested, ranging from 0.43 to >8 ng/mL. Most patients (75%) were admitted to the hospital; the median duration of hospitalization was 2 d (range 0.5–5 d). The overall mortality rate was 8.3%, and all three patients that died ate toad meat and/or eggs and developed cardiac arrest. All patients received supportive with/without symptomatic care including GI decontamination, inotropic drugs, cardiac pacing, and management of hyperkalemia. One patient received intravenous calcium for hyperkalemia but did not develop dysrhythmia after calcium administration. One patient received digoxin-specific antibody fragments (DsFab), after which he clinically improved and was discharged.ConclusionToad poisoning commonly caused GI symptoms and bradycardia. However, in severe cases, death occurred. Tachyarrhythmia was not observed. Supportive, symptomatic care might be the main therapies for this poisoning, especially if DsFab is not available.

Myotoxic Mushroom Poisoning in Thailand: Clinical Characteristics and Outcomes.

PurposeTo describe the clinical characteristics and outcomes of myotoxic mushroom poisoning in Thailand.Patients and MethodsWe performed a retrospective cohort study of cases of myotoxic mushroom poisoning from the Ramathibodi Poison Center Toxic Exposure Surveillance System during a 5-year period (2012–2016).ResultsForty-one cases were included. Most (53.7%) were male with the average age of 49 years. In three cases, the mushrooms were identified as Russula species by an experienced mycologist. Common presenting symptoms were gastrointestinal (GI) symptoms and myalgia. The median onset of GI symptoms and symptoms suggesting rhabdomyolysis after consuming mushrooms was 2 hours (0.17–24 hours) and 24–48 hours (2–120 hours), respectively. Eight patients who ate the mushrooms together with other patients with rhabdomyolysis had GI symptoms but did not develop rhabdomyolysis. For patients with rhabdomyolysis, acute kidney injury (AKI) and hyperkalaemia occurred in 51.5% and 33.3% of cases, respectively. Median initial and maximum creatine phosphokinase (CPK) levels in patients with rhabdomyolysis were 31,145 and 47,861 U/L, respectively. Fifteen of 17 patients who were investigated for troponin levels had elevated troponin. Three patients had a low ejection fraction. Most patients (95.1%) were admitted to hospital, with a median stay of 5 days. The mortality rate was 26.8%. Treatments included intravenous fluid, urine alkalinization, haemodialysis and peritoneal dialysis. Among patients with rhabdomyolysis, AKI, hyperkalaemia during hospitalisation, maximum CPK level, maximum creatinine level and initial and maximum potassium levels were the factors found to be significantly different between patients who died and those who survived.ConclusionMyotoxic mushroom poisoning had a high mortality rate. Most patients had early or delayed onset of clinical symptoms after mushroom ingestion. Some patients developed severe cardiovascular effects. Early detection, close monitoring (especially serum potassium, creatinine, CPK and cardiac effect) and good supportive care were the main treatment modalities.

Clinical outcome of paraquat poisoning during pregnancy

Objectives: We aimed to describe clinical characteristics and outcomes of paraquat poisoning in pregnant patients, their fetuses, and newborns.Methods: We performed a retrospective study of pregnant patients who were exposed to paraquat, from the Ramathibodi Poison Center Toxic Exposure Surveillance System, during a 5-year period.Results: Thirty-six patients, representing every trimester, were included. All experienced oral exposure with a mean age of 22.7 years and mean gestational age (GA) of 23.1 weeks. Most had gastrointestinal symptoms and signs. Systemic effects, which mainly comprised of acute kidney injury (AKI), were found in 13 patients (36.1%); obstetric complications were noted in five patients (13.9%). Medical treatment included intravenous dexamethasone and cyclophosphamide. Some patients received hemodialysis and endotracheal intubation. Nine patients delivered during hospitalization; four newborns (maternal GAs of 30–36 weeks with systemic effects) died after delivery. One patient with GA 26 weeks delivered and died, but her newborn survived. Mortality rates of pregnant patients and their offspring delivered in-hospital were 25% and 44.4%, respectively; all deaths occurred in patients with systemic toxicity. The median length of hospital stay was 6 days. Notably, AKI, hepatotoxicity, and maximum white blood cell count significantly differed between dead and surviving patients. We followed-up 15 surviving patients who were discharged before delivery to assess delivery outcomes. All 15 patients and newborns survived without reports of congenital anomalies.Conclusions: Paraquat poisoning during pregnancy caused high fatalities in pregnant patients, fetuses, and newborns who were delivered during hospitalization, especially among patients with systemic effects. The GA of the pregnancy affected fetal outcomes, both in utero and at birth. Selective, appropriate management is warranted and might be guided by poisoning severity and the GA of the pregnancy.

Krait envenomation in Thailand.

PurposeThree species in the genus Bungarus inhabit Thailand. Among these, Bungarus candidus (Malayan krait) is the most common and deadliest. Currently, the clinical manifestations of patients envenomed by kraits, especially Bungarus fasciatus (banded krait), have not been thoroughly investigated. This study was performed to elucidate the clinical manifestations and outcomes of patients bitten by kraits in Thailand.Materials and methodsThe data of krait envenomation cases that occurred during a 9-year period were obtained from the Ramathibodi Poison Center Toxic Exposure Surveillance System and retrospectively analyzed.ResultsIn total, 78 cases of krait envenomation were included. Most patients were male (59.0%) and the median age was 28 years. All had minimal local effects. The median duration from the bite to the onset of neurological manifestations was 3 hours (range, 0.5–8 hours). Besides neurological effects, the patients also developed high blood pressure (67.4%), tachycardia (61.7%), hypokalemia (55.3%), and hyponatremia (17.6%). Severe hyponatremia (<120 mEq/L) was noted in four pediatric patients. Other clinical manifestations were bradycardia, abdominal pain, and rhabdomyolysis. The mortality rate was 6.4%, and all deaths occurred from B. candidus bites. Eighty-six percent of patients received antivenom. Most patients (75.6%) were intubated and underwent assisted ventilation for a median of 6 days (range, 1–37 days). The median length of hospital stay was 7 days. Some patients developed complications during hospitalization; the most common was pneumonia. These in-hospital complications were significantly associated with death.ConclusionAlthough krait bites caused only minimal local effects, the mortality rate was still high, particularly from Malayan krait bites. Besides neurological effects, other clinical manifestations were high blood pressure, tachycardia, hypokalemia, and hyponatremia. Thus, vital signs and electrolytes should be frequently and closely monitored in these patients. Apart from antivenom treatment, adequate supportive care including management of complications might help to decrease the mortality rate.

Clinical characteristics and outcome of toxicity from Amanita mushroom poisoning.

ObjectiveTo describe and analyze the clinical characteristics and outcome of amatoxin poisoning cases.MethodsWe performed a retrospective cohort study of amatoxin poisoning cases from Ramathibodi Poison Center Toxic Exposure Surveillance System, from May 2013 to August 2015.ResultsThere were 30 consultations with a total of 55 poisoning cases. Most cases were male and from the north-east region. Hepatitis, acute kidney injury, jaundice, and coagulopathy accounted for 74%, 46.3%, 44.7%, and 52.8% of the cases, respectively. Almost all of the patients were admitted to the hospital, and the median duration of hospital stay was found to be 4 days. Mortality rate was found to be 27.3%. Most patients (73%) received the treatment including multiple-dose activated charcoal (67.5%), intravenous N-acetylcysteine (87.5%), and benzylpenicillin (45%). In 60% of the cases, the treatment was initiated within 24 h after eating mushrooms. Exchange transfusion and liver transplantation were performed in one severe case. However, this patient died eventually. Because intravenous silybinin is not available in Thailand during the study period, 8 patients received oral silymarin instead. All 8 patients had hepatitis and were treated with high dosage of oral silymarin (5 patients with 4.48 g/day, 2 patients with 1.68 g/day, and 1 patient with 1.4 g/day) for a couple of days. One of these patients died as she received treatment very late; she was treated with silymarin at 1.68 g/day dosage. Thus, the fatality in oral silymarin treatment group was 12.5%. We performed the analysis between the dead and survival groups. We found that in hepatitis, initial and maximum serum aspartate transaminase, initial and maximum serum alanine transaminase, and acute kidney injury were significantly different between the two groups.ConclusionAmanita mushroom poisoning caused high fatalities. Serum transaminase and creatinine were the factors associated with death. Treatment with oral high dose silymarin should be investigated further as one of the principal therapies in amatoxin poisoning.

Using Poison Center Data for National Public Health Surveillance for Chemical and Poison Exposure and Associated Illness

The National Poison Data System (NPDS) is a national near-real-time surveillance system that improves situational awareness for chemical and poison exposures, according to data from US poison centers. NPDS is the successor to the Toxic Exposure Surveillance System. The Centers for Disease Control and Prevention (CDC) use these data, which are owned and managed by the American Association of Poison Control Centers, to improve public health surveillance for chemical and poison exposures and associated illness, identify early markers of chemical events, and enhance situational awareness during outbreaks. Information recorded in this database is from self-reported calls from the public or health care professionals. In 2009, NPDS detected 22 events of public health significance and CDC used the system to monitor several multistate outbreaks. One of the limitations of the system is that exposures do not necessarily represent a poisoning. Incorporating NPDS data into the public health surveillance network and subsequently using NPDS to rapidly identify chemical and poison exposures exemplifies the importance of the poison centers and NPDS to public health surveillance. This integration provides the opportunity to improve the public health response to chemical and poison exposures, minimizes morbidity and mortality, and serves as an important step forward in surveillance technology and integration.

Recognizing and Treating Valproic Acid Toxicity: A Case Report

Valproic Acid (VPA) toxicity has been steadily increasing in frequency since the FDA approved the drug for acute mania in 1995. According to the 2005 Annual Report of the American Association of Poison Control Center's Toxic Exposure Surveillance System (TESS), 8705 acute exposures to valproic acid occurred with major adverse outcomes reported in 404 patients of this cohort. Recognizing VPA toxicity is the first step in properly managing the patient. Key signs and symptoms of VPA toxicity include: CNS depression, lethargy and potential encephalopathy, respiratory depression, nausea/vomiting, and myoclonus. Lab abnormalities often include, in addition to elevated serum VPA levels, hypernatremia, elevated anion gap metabolic acidosis, hyperosmolality, hypocalcemia, and hyperammonemia with a transaminitis. A non-contrast head CT may demonstrate cerebral edema, the peak occurrence of which is between 12 hours and 4 days after ingestion. Activated charcoal can be given early if the timing of overdose is known. Serial head CT scans should be ordered to monitor the possible delayed side effect of cerebral edema. Other areas of treatment deal with correcting the ill effects of the metabolic abnormalities (e.g. replace calcium if hypocalcemia). Specifically, lactulose is used to decrease serum ammonia levels and reduce the risk of encephalopathy. Another mainstay of treatment, L-carnitine, increases levels of free carnitine to participate in mitochondrial fatty acid synthesis. In extreme cases, hemodialysis may be required to reduce the levels of VPA and the associated metabolites. Of note our patient presented with virtually all the lab abnormalities and symptoms typical of VPA toxicity. He improved with hemodialysis and was discharged to a mental health facility in stable condition. Though VPA toxicity occurs rarely, it has a consistent presentation, symptomotology and defined treatment regimen. Awareness of a typical patient’s presentation would assist in early diagnosis and a successful treatment. J Med Cases. 2011;2(5):185-187 doi: https://doi.org/10.4021/jmc234w

Dysgeusia following consumption of pine nuts: More than 3000 cases in France

Introduction. In March 2008, French poison centres (PCs) recorded the first calls reporting persistent bitterness following the ingestion of pine nuts. Methods. The French toxic exposure surveillance system (French-Tess) was searched and a descriptive analysis of cases was performed on data recorded from 13 March 2008 to 31 January 2010. Results. Some 3111 cases of bitterness were reported to PCs. The number of cases rose sharply from May 2009 to reach a peak in August 2009 with 697 cases. The median time to onset of dysgeusia was 24 hours and it lasted less than 14 days in 95% of cases. Raw as well as cooked or processed pine nuts were implicated. Discussion. The delayed onset and persistence of dysgeusia suggest that the toxin may act via an unknown toxic mechanism on the receptor. The aetiological agent could be an unidentified toxin present in some varieties of non-edible pine nuts. Conclusion. The high incidence of the event and the lack of understanding of the nature of the toxin and its pathophysiological mechanism require continued monitoring of poison cases, botanical and biochemical analysis, and experimental studies.

Recognizing and Treating Valproic Acid Toxicity: A Case Report

Valproic Acid (VPA) toxicity has been steadily increasing in frequency since the FDA approved the drug for acute mania in 1995. According to the 2005 Annual Report of the American Association of Poison Control Center's Toxic Exposure Surveillance System (TESS), 8705 acute exposures to valproic acid occurred with major adverse outcomes reported in 404 patients of this cohort. Recognizing VPA toxicity is the first step in properly managing the patient. Key signs and symptoms of VPA toxicity include: CNS depression, lethargy and potential encephalopathy, respiratory depression, nausea/vomiting, and myoclonus. Lab abnormalities often include, in addition to elevated serum VPA levels, hypernatremia, elevated anion gap metabolic acidosis, hyperosmolality, hypocalcemia, and hyperammonemia with a transaminitis. A non-contrast head CT may demonstrate cerebral edema, the peak occurrence of which is between 12 hours and 4 days after ingestion. Activated charcoal can be given early if the timing of overdose is known. Serial head CT scans should be ordered to monitor the possible delayed side effect of cerebral edema. Other areas of treatment deal with correcting the ill effects of the metabolic abnormalities (e.g. replace calcium if hypocalcemia). Specifically, lactulose is used to decrease serum ammonia levels and reduce the risk of encephalopathy. Another mainstay of treatment, L-carnitine, increases levels of free carnitine to participate in mitochondrial fatty acid synthesis. In extreme cases, hemodialysis may be required to reduce the levels of VPA and the associated metabolites. Of note our patient presented with virtually all the lab abnormalities and symptoms typical of VPA toxicity. He improved with hemodialysis and was discharged to a mental health facility in stable condition. Though VPA toxicity occurs rarely, it has a consistent presentation, symptomotology and defined treatment regimen. Awareness of a typical patient’s presentation would assist in early diagnosis and a successful treatment. J Med Cases. 2011;2(5):185-187 doi: https://doi.org/10.4021/jmc234w

Human exposure to insecticide products containing pyrethrins and piperonyl butoxide (2001–2003)

Pyrethrum, used as an insecticide for centuries, is derived from dried and ground flowers of Chrysanthemum cinerariaefolium. Its current major use is in insecticide products to the control insects in the home and food handling establishments. We investigated human incidents reported through the American Association of Poison Control Centers (AAPCC) Toxic Exposure Surveillance System (TESS ©) associated with regulated insecticides containing pyrethrins and piperonyl butoxide (PY/PBO) from 2001 to 2003. Special attention was paid to dermal and respiratory effects. Although there are limitations associated with TESS data, we observed that ■ Despite extensive use, incidents with reports of moderate or major adverse effects were relatively rare (717 moderate and 23 major outcomes out of 17,873 calls). ■ Following label-directed use of the products, adverse dermal or respiratory reactions were very rare; (dermal – 17 moderate, 1 major; respiratory – 18 moderate, 0 major). ■ The data suggest that asthmatics and people sensitive to ragweed ( Ambrosia artisifolia) are not unusually sensitive to PY/PBO. In view of their widespread use, the data indicates that PY/PBO products can be used with a relatively low risk of adverse effects. Moreover, the data suggest that they are not likely to cause reactions in people with asthma or allergies.

Brimonidine Tartrate Poisoning in Children: Frequency, Trends, and Use of Naloxone as an Antidote

Brimonidine tartrate, a centrally acting selective alpha-2 adrenergic agonist with a toxicity that is often compared with that of clonidine, is used as eye drops to lower intraocular pressure in glaucoma. We investigated characteristics of childhood exposures to brimonidine-containing products. All brimonidine exposures in children 0 to 5 years of age between 1997 and 2005 were retrieved from the American Association of Poison Control Centers' Toxic Exposure Surveillance System database and the US Food and Drug Administration's Medwatch Adverse Events Reporting System. The design of the study was retrospective, and the main outcome measures were frequency of exposures over time, reason, symptoms/signs of toxicity, dose, management site, treatment, and outcome. There were 413 brimonidine reports in the Toxic Exposure Surveillance System and 340 in the Adverse Events Reporting System during the 9 years under study, of which 185 Toxic Exposure Surveillance System reports involved children < or =5 years of age versus 15 cases in the Adverse Events Reporting System. There were no deaths. The peak age of poisoning in the Toxic Exposure Surveillance System pediatric cases was 2 years of age, and circumstances were unintentional poisoning in 176 cases, usually by ingestion (84.3%). Common symptoms in 176 children included drowsiness (40.9%), ataxia (4.5%), pallor (4.5%), irritability (4.0%), hypotension (4.0%), bradycardia (4.0%), miosis (3.4%), and respiratory depression (3.4%). Of the 176 unintentional pediatric poisonings, 73 children were observed at home and 103 were seen at a health care facility; 28 were hospitalized and 11 received naloxone. Of the 15 pediatric cases in the Adverse Events Reporting System data set, all were hospitalized, and 13 had ocular exposures only. All children < or =5 years of age with confirmed brimonidine ingestions should be medically evaluated and monitored for an extended period. Indications for the use of naloxone in brimonidine poisoning remain uncertain.

The outcome of North American pediatric unintentional mushroom ingestions with various decontamination treatments: An analysis of 14 years of TESS data

The optimum empiric decontamination therapy for unintentional pediatric mushroom ingestion is not known. We sought to determine case outcomes for unintentional mushroom ingestions in children by decontamination therapies utilized. The 1992–2005 American Association of Poison Control Centers Toxic Exposure Surveillance System was queried for cases of unintentional acute mushroom ingestions in children age <6 years. Cases were excluded if outcome was unknown, if exposure was coded as unrelated to the symptoms, or if there was co-ingestion of a non-mycoid substance. The treatment subgroups analyzed were ipecac, single-dose activated charcoal, and no gastric decontamination. 82,330 cases met the inclusion criteria with 22,454 cases excluded. There were 16 cases with major effects and no deaths. There were 57,531 cases in the three treatment subgroups. There was a significantly smaller percentage of cases with moderate or major outcomes in the ipecac subgroup compared to the no decontamination subgroup. There was a significantly greater percentage of cases with moderate or major outcomes in the activated charcoal compared to the no decontamination subgroup. If decontamination therapy is being performed, and this data suggests it may not be necessary, syrup of ipecac could still be considered an effective option.

Extracorporeal removal of toxins

Holubek et al. reviewed data on extracorporeal removal (ECR) of toxins from the Toxic Exposure Surveillance System (TESS) from 1985 to 2005. Hemodialysis use increased, but hemoperfusion nearly disappeared. Lithium, ethylene glycol, salicylate, and, increasingly, acetaminophen still often necessitate hemodialysis; ECR for theophylline has disappeared. TESS data do not separate continuous renal replacement therapy from hemodialysis, and not all poisonings were reported in this system. Nonetheless, these trends are useful to the nephrology community.

Enhanced clearance of highly protein-bound drugs by albumin-supplemented dialysate during modeled continuous hemodialysis

In 2006, there were 16 796 toxic exposures attributed to valproic acid (VPA), carbamazepine (CBZ) and phenytoin (PHT) reported to the US Toxic Exposure Surveillance System. Of these, 30% (5046) were treated in a health care facility with 12 cases resulting in death. These drugs are highly protein bound and poorly dialyzable; however, it has been suggested that albumin-supplemented dialysate may enhance dialytic clearance. We investigated whether the addition of albumin to dialysate affects dialytic clearance of VPA, CBZ and PHT. VPA, CBZ and PHT were added to a bovine blood-based in vitro continuous hemodialysis circuit, which included a polysulfone or an AN69 hemodialyzer. VPA, CBZ and PHT clearances were calculated from spent dialysate and pre-dialyzer plasma concentrations. VPA, CBZ and PHT clearances with control (albumin-free) dialysate were compared to clearances achieved with 2.5% or 5% human albumin-containing dialysate. The influences of blood flow (180 and 270 mL/min) and dialysate flow (1, 2 and 4 L/h) on dialysis clearance were also assessed. The addition of 2.5% albumin to dialysate significantly enhanced dialytic clearance of VPA and CBZ, but not PHT. Use of 5% albumin dialysate further increased VPA and CBZ clearance. Overall, drug clearance was related directly to dialysate flow but independent of blood flow. Continuous hemodialysis with albumin-supplemented dialysate significantly enhanced VPA and CBZ, but not PHT, clearance compared to control dialysate. Continuous hemodialysis with albumin-supplemented dialysate may be a promising therapy to enhance dialytic clearance of selected highly protein-bound drugs.

The state of dietary supplement adverse event reporting in the United States

The Dietary Supplements Information Expert Committee (DSI-EC; the Committee) of the United States Pharmacopeial Convention (USP) reviews safety profiles of dietary supplements before development of USP-National Formulary (USP-NF) quality monographs. Because the veracity of dietary supplement adverse event reports (DS AERs) directly affects DSI-EC safety reviews, the Committee reviewed the current status of DS AER reporting in the US. DSI-EC reviewed PubMed searches, information from the US Food and Drug Administration's (FDA) MedWatch program, the Toxic Exposure Surveillance System (TESS) of the American Association of Poison Control Centers (AAPCC), and reports from US and other agencies. DSI-EC analyzed this information to identify key factors that affect the quality of DS AERs. The overall incidence of DS AERs appears generally to be low. However, the primary reporting portal (FDA MedWatch) receives fewer AERs than do poison control centers (PCCs), and limited coordination exists among national and international surveillance programs for evaluating signals that may indicate potential public health risks. Both inadequate and poor-quality reporting of DS AERs are major limitations of DS safety monitoring in the US. Based on its assessments, the Committee advances recommendations to improve the quality of reporting, monitoring, and assessing DS AERs. These include (1) enhanced data collection approaches, (2) improved coordination of AER surveillance programs, (3) strengthening of educational programs for public and health care sectors, and (4) conduct of research concerning the safety of DS. If taken, these approaches are expected to improve the health and well-being of DS users.

Classification tree methods for development of decision rules for botulism and cyanide poisoning

Identification of predictors of potential mass poisonings may increase the speed and accuracy with which patients are recognized, potentially reducing the number ultimately exposed and the degree to which they are affected. This analysis used a decision-tree method to sort such potential predictors. Data from the Toxic Exposure Surveillance System were used to select cyanide and botulism cases from 1993 to 2005 for analysis. Cases of other poisonings from a single poison center were used as controls. After duplication was omitted and removal of cases from the control sample was completed, there remained 1,122 cyanide cases, 262 botulism cases, and 70,804 controls available for both analyses. Classification trees for each poisoning type were constructed, using 131 standardized clinical effects. These decision rules were compared with the current case surveillance definitions of one active poison center and the American Association of Poison Control Centers (AAPCC). The botulism analysis produced a 4-item decision rule with sensitivity (Se) of 68% and specificity (Sp) of 90%. Use of the single poison center and AAPCC definitions produced Se of 19.5% and 16.8%, and Sp of 99.5% and 83.2%, respectively. The cyanide analysis produced a 9-item decision rule with Se of 74% and Sp of 77%. The single poison center and AAPCC case definitions produced Se of 10.2% and 8.6%, and Sp of 99.8% and 99.8%, respectively. These results suggest the possibility of improved poisoning case surveillance sensitivity using classification trees. This method produced substantially higher sensitivities, but not specificities, for both cyanide and botulism. Despite limitations, these results show the potential of a classification-tree approach in the detection of poisoning events.

Evaluation of Centrally Acting Cholinesterase Inhibitor Exposures in Adults

There are 4 centrally acting cholinesterase inhibitors (CA-ChEI) available in the US: tacrine, galantamine, rivastigmine, and donepezil. Documented clinical experience involving exposure to these agents is limited. The lack of information makes decisions involving excessive or unintended CA-ChEI exposure difficult. To assess the effects, demographics, and outcomes of CA-ChEI exposures reported to US poison centers. A retrospective review of the Toxic Exposure Surveillance System of the American Association of Poison Control Centers data of acute and acute-onchronic exposures involving only a CA-ChEI in patients 19 years of age or older with documented medical outcomes from 2000-2005 was performed. There were 1026 records that met criteria for this study. Patients aged 70-89 years made up 73% of reports; 69% of the patients were female. Moderate (197) and major outcomes (20) accounted for 21% of exposures. There were no deaths. Clinical effects that occurred in 5% or more of patients included vomiting (34%), nausea (28%), diarrhea (12%), dizziness/vertigo (9.9%), drowsiness/lethargy (7.7%), diaphoresis (7.4%), tremor (5.2%), and bradycardia (5%). Patients were admitted to the hospital in 19% of all exposures. Of those patients, 42% were admitted to a critical care unit. The majority (65%) of exposures were attributed to unintentional therapeutic error. Patients received at least one form of therapy in 47% of exposures, including intravenous fluid (111), antiemetic (48), atropine (17), benzodiazepine (15), oxygen (14), antihypertensive (4), pralidoxime (4), intubation (3), antihistamine (2), antiarrhythmic (1), anticonvulsant (1), and pacemaker (1). The majority of patients evaluated in this retrospective study experienced no or mild effect; however, significant or life-threatening effects were observed in a small group of patients and an appreciable number of patients were admitted to a healthcare facility.

Child-Resistant Closures for Mouthwash

The Poison Prevention and Packaging Act of 1970 mandated that certain potentially hazardous drugs and other products be sold in child-resistant containers (CRCs). The Consumer Product Safety Commission estimates that CRCs for aspirin and oral prescription medicine saved the lives of about 700 children since the requirements went into effect in the 1970s. Under this Act, the Consumer Product Safety Commission issued a rule requiring child-resistant packaging for mouthwashes containing 3 g or more of ethanol per package. The effective date was July 24, 1995, and applied to all applicable products packaged on or after that date. To determine the effectiveness of this 1995 ruling, all American Association of Poison Control Center Toxic Exposure Surveillance System data involving children younger than 6 years who ingested ethanol-containing mouthwash 10 years before the implementation of this ruling, the transition year, and 10 years after were reviewed. Only single-substance exposures were included. Data reviewed included the total number of exposures per pre and post years and the outcome. A total of 61,185 cases met the criteria. There were 18,275 exposures from 1985 through 1994 prerequirement (0.12% of all exposures); 39,376 from 1996 to 2005 postrequirement years (AR) (0.17% of all exposures); and 3,534 cases reported in 1995 (0.17% of all exposures). Definitive outcomes were coded in 62.6% of the prerequirement group and 42.2% of the AR group. Numerous factors affect these results. However, in those cases where definitive outcomes were coded, the AR group has better outcomes.