Key considerations for developing an equitable faculty teaching workload.

PURPOSE: Faculty teaching workload has become a focus for many academic institutions given the increasing amount of faculty burnout and need for equitable distribution of effort. Many gaps exist in faculty workload guidance which contribute to decreased faculty productivity, lack of appropriate recognition, faculty burnout, and subsequently, retention of faculty. A task force was created to develop teaching workload guidance and to outline minimum teaching expectations at our school of pharmacy. DESCRIPTION: This manuscript highlights the need for clarity around the definition of roles of the contemporary educator and considerations when developing guidance around teaching workload expectations using the "What? So What? Now What?" reflection framework. ANALYSIS/INTERPRETATION: Teaching workload guidance first starts with establishing a definition of the contemporary roles of the educator. Challenges, considerations, and eight next steps are outlined that are critical to address before equitable teaching workload guidance is established. CONCLUSIONS: Teaching workload guidance should include transparency, clarity, credit, norms, context, and accountability. Additionally, solutions created to address the gaps in workload policies should be data driven. IMPLICATIONS: The current traditional system of evaluating faculty workload has many gaps due to forces driving change in pharmacy education. Roles of the pharmacy educator should be valued and recognized across all mission centric learning programs.

Defining contemporary roles of the pharmacy educator: The essential first step in developing equitable faculty teaching workload.

INTRODUCTION: Faculty workload policy has gained increased attention recently given the growing amount of faculty burnout leading to decreased productivity, worsened faculty morale, and impaired retention. Faculty are one of the most valuable resources of an academic institution; thus, it is essential that a clear picture of the "jobs to be done" are defined and valued. PERSPECTIVE: The approach of a task force charged with developing a teaching workload policy is described. Through this work, it was recognized that essential roles of the contemporary pharmacy educator have not been defined, resulting in workload policies that might only value and recognize "traditional" educator roles. This led the task force to evaluate the forces driving change in education and to identify the roles of faculty as educators. The stepwise approach used to define nine essential roles of contemporary pharmacy educators is described. IMPLICATIONS: Roles of the educator have become more complex, and traditional definitions of these roles do not recognize and value the multifaceted nature of the job to be done. Consideration of contemporary definitions of educator roles is a critical first step for developing workload policies. The new definition of educator roles will allow the academic institution to have more clarity around total teaching effort and recognize the value faculty provide the institution. We believe this is the essential first step for the Academy when developing teaching workload policies that are fair and equitable, while also understanding the overall faculty needs for executing their educational enterprise.

An Exploration of the Relationship Between Pharmacy School Admission Variables and PGY1 Pharmacy Residency Program Match.

OBJECTIVE: To explore the relationship between pharmacy school admission variables and matching to a postgraduate year 1 (PGY1) pharmacy residency program. METHODS: Demographic data, academic indicators, and application review scores were collected for the 2017-2020 Doctor of Pharmacy (PharmD) graduating classes. Multiple mini-interview (MMI) scores were collected for the 2018-2020 PharmD graduating classes. Postgraduate year 1 matching data were collected for all students. Bivariate analyses were performed comparing students who matched to a PGY1 residency versus those who did not match versus those who did not pursue a residency. Logistic regression modeling was performed to explore predictors of matching to a PGY1 residency program. RESULTS: A total of 616 students were included. Bivariate analyses revealed that students who matched to a PGY1 had a higher undergraduate grade point average, higher pharmacy college admissions test composite score, were younger in age, and were more likely to identify as female. Students who matched also scored higher on MMI stations with constructs related to integrity, adaptability, critical thinking, and why pursuing our school. Logistic regression modeling found that an increase in age was associated with lower odds of matching to a PGY1 (0.88 [0.78-0.99]) and an increase in composite MMI station score was associated with higher odds of matching (1.8 [1.31-2.47]). CONCLUSION: Several pharmacy school admission variables were found to be associated with successful matching to a PGY1 residency. These findings have the potential for impact at a programmatic level when evaluating the weight of certain criteria for admission decisions and at the individual student level when providing career services support.

Systematic review of community pharmacist administration of long-acting injectable antipsychotic medications.

BACKGROUND: Long-acting injectable antipsychotic (LAIA) medications offer an effective treatment option for patients with serious mental illness. Despite demonstrated clinical safety and efficacy as well as increased adherence and less frequent administration compared with daily oral regimens, LAIAs remain underutilized in clinical practice. With legislation allowing pharmacists to administer injectable medications in 48 U.S. states, community pharmacies are uniquely positioned to serve as an access point for patients with serious mental illnesses to receive LAIA injections. OBJECTIVE: This study aimed to conduct a systematic review of the health and economic benefits and costs of community pharmacist administration of LAIA medications. METHODS: A systematic search of the literature published from January 1996 to April 2022 was conducted across 3 databases (Embase, PubMed, and Scopus Plus). Publications describing pharmacist administration of LAIA medications in outpatient settings were included. Publications that examined the use of LAIAs but did not involve a pharmacist administering the medication were excluded. RESULTS: Of 2261 publications reviewed, we identified 8 publications (4 articles and 4 abstracts) that met our inclusion criteria, of which only 7 included results. Four studies reported high medication adherence achieved by patients receiving pharmacist-administered LAIAs. Two publications surveyed patient satisfaction with pharmacist administration of LAIAs in community pharmacy settings. One study found pharmacists' mixed attitudes regarding LAIA administration and time and safety barriers to offering the service. CONCLUSION: We found very little evidence on the impact of pharmacist administration of LAIAs on patient outcomes. This review highlights the need to generate greater evidence on the health and economic benefits as well as financial models for pharmacists to administer LAIA medications in outpatient and community pharmacy settings. Such evidence could support more community pharmacists to offer LAIA medications and contribute to the shift toward value-based care.

Systematic review on the use of activated charcoal for gastrointestinal decontamination following acute oral overdose.

INTRODUCTION: The use of activated charcoal in poisoning remains both a pillar of modern toxicology and a source of debate. Following the publication of the joint position statements on the use of single-dose and multiple-dose activated charcoal by the American Academy of Clinical Toxicology and the European Association of Poison Centres and Clinical Toxicologists, the routine use of activated charcoal declined. Over subsequent years, many new pharmaceuticals became available in modified or alternative-release formulations and additional data on gastric emptying time in poisoning was published, challenging previous assumptions about absorption kinetics. The American Academy of Clinical Toxicology, the European Association of Poison Centres and Clinical Toxicologists and the Asia Pacific Association of Medical Toxicology founded the Clinical Toxicology Recommendations Collaborative to create a framework for evidence-based recommendations for the management of poisoned patients. The activated charcoal workgroup of the Clinical Toxicology Recommendations Collaborative was tasked with reviewing systematically the evidence pertaining to the use of activated charcoal in poisoning in order to update the previous recommendations. OBJECTIVES: The main objective was: Does oral activated charcoal given to adults or children prevent toxicity or improve clinical outcome and survival of poisoned patients compared to those who do not receive charcoal?  Secondary objectives were to evaluate pharmacokinetic outcomes, the role of cathartics, and adverse events to charcoal administration. This systematic review summarizes the available evidence on the efficacy of activated charcoal. METHODS: A medical librarian created a systematic search strategy for Medline (Ovid), subsequently translated for Embase (via Ovid), CINAHL (via EBSCO), BIOSIS Previews (via Ovid), Web of Science, Scopus, and the Cochrane Library/DARE. All databases were searched from inception to December 31, 2019. There were no language limitations.  One author screened all citations identified in the search based on predefined inclusion/exclusion criteria. Excluded citations were confirmed by an additional author and remaining articles were obtained in full text and evaluated by at least two authors for inclusion. All authors cross-referenced full-text articles to identify articles missed in the searches. Data from included articles were extracted by the authors on a standardized spreadsheet and two authors used the GRADE methodology to independently assess the quality and risk of bias of each included study. RESULTS: From 22,950 titles originally identified, the final data set consisted of 296 human studies, 118 animal studies, and 145 in vitro studies. Also included were 71 human and two animal studies that reported adverse events. The quality was judged to have a Low or Very Low GRADE in 469 (83%) of the studies. Ninety studies were judged to be of Moderate or High GRADE. The higher GRADE studies reported on the following drugs: paracetamol (acetaminophen), phenobarbital, carbamazepine, cardiac glycosides (digoxin and oleander), ethanol, iron, salicylates, theophylline, tricyclic antidepressants, and valproate. Data on newer pharmaceuticals not reviewed in the previous American Academy of Clinical Toxicology/European Association of Poison Centres and Clinical Toxicologists statements such as quetiapine, olanzapine, citalopram, and Factor Xa inhibitors were included. No studies on the optimal dosing for either single-dose or multiple-dose activated charcoal were found. In the reviewed clinical data, the time of administration of the first dose of charcoal was beyond one hour in 97% (n = 1006 individuals), beyond two hours in 36% (n = 491 individuals), and beyond 12 h in 4% (n = 43 individuals) whereas the timing of the first dose in controlled studies was within one hour of ingestion in 48% (n = 2359 individuals) and beyond two hours in 36% (n = 484) of individuals. CONCLUSIONS: This systematic review found heterogenous data. The higher GRADE data was focused on a few select poisonings, while studies that addressed patients with unknown and or mixed ingestions were hampered by low rates of clinically meaningful toxicity or death.  Despite these limitations, they reported a benefit of activated charcoal beyond one hour in many clinical scenarios.

Extracorporeal treatment for poisoning to beta-adrenergic antagonists: systematic review and recommendations from the EXTRIP workgroup.

BACKGROUND: ß-adrenergic antagonists (BAAs) are used to treat cardiovascular disease such as ischemic heart disease, congestive heart failure, dysrhythmias, and hypertension. Poisoning from BAAs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in BAAs poisoning. METHODS: We conducted systematic reviews of the literature, screened studies, extracted data, and summarized findings following published EXTRIP methods. RESULTS: A total of 76 studies (4 in vitro and 2 animal experiments, 1 pharmacokinetic simulation study, 37 pharmacokinetic studies on patients with end-stage kidney disease, and 32 case reports or case series) met inclusion criteria. Toxicokinetic or pharmacokinetic data were available on 334 patients (including 73 for atenolol, 54 for propranolol, and 17 for sotalol). For intermittent hemodialysis, atenolol, nadolol, practolol, and sotalol were assessed as dialyzable; acebutolol, bisoprolol, and metipranolol were assessed as moderately dialyzable; metoprolol and talinolol were considered slightly dialyzable; and betaxolol, carvedilol, labetalol, mepindolol, propranolol, and timolol were considered not dialyzable. Data were available for clinical analysis on 37 BAA poisoned patients (including 9 patients for atenolol, 9 for propranolol, and 9 for sotalol), and no reliable comparison between the ECTR cohort and historical controls treated with standard care alone could be performed. The EXTRIP workgroup recommends against using ECTR for patients severely poisoned with propranolol (strong recommendation, very low quality evidence). The workgroup offered no recommendation for ECTR in patients severely poisoned with atenolol or sotalol because of apparent balance of risks and benefits, except for impaired kidney function in which ECTR is suggested (weak recommendation, very low quality of evidence). Indications for ECTR in patients with impaired kidney function include refractory bradycardia and hypotension for atenolol or sotalol poisoning, and recurrent torsade de pointes for sotalol. Although other BAAs were considered dialyzable, clinical data were too limited to develop recommendations. CONCLUSIONS: BAAs have different properties affecting their removal by ECTR. The EXTRIP workgroup assessed propranolol as non-dialyzable. Atenolol and sotalol were assessed as dialyzable in patients with kidney impairment, and the workgroup suggests ECTR in patients severely poisoned with these drugs when aforementioned indications are present.

Extracorporeal treatments for isoniazid poisoning: Systematic review and recommendations from the EXTRIP workgroup.

Isoniazid toxicity from self-poisoning or dosing errors remains common in regions of the world where tuberculosis is prevalent. Although the treatment of isoniazid poisoning is centered on supportive care and pyridoxine administration, extracorporeal treatments (ECTRs), such as hemodialysis, have been advocated to enhance elimination of isoniazid. No systematic reviews or evidence-based recommendations currently exist on the benefit of ECTRs for isoniazid poisoning. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup systematically collected and rated the available evidence on the effect of and indications for ECTRs in cases of isoniazid poisoning. We conducted a systematic review of the literature, screened studies, extracted data on study characteristics, outcomes, and measurement characteristics, summarized findings, and formulated recommendations following published EXTRIP methods. Forty-three studies (two animal studies, 34 patient reports or patient series, and seven pharmacokinetic studies) met inclusion criteria. Toxicokinetic or pharmacokinetic analysis was available for 60 patients, most treated with hemodialysis (n = 38). The workgroup assessed isoniazid as "Moderately Dialyzable" by hemodialysis for patients with normal kidney function (quality of evidence = C) and "Dialyzable" by hemodialysis for patients with impaired kidney function (quality of evidence = A). Clinical data for ECTR in isoniazid poisoning were available for 40 patients. Mortality of the cohort was 12.5%. Historical controls who received modern standard care including appropriately dosed pyridoxine generally had excellent outcomes. No benefit could be extrapolated from ECTR, although there was evidence of added costs and harms related to the double lumen catheter insertion, the extracorporeal procedure itself, and the extracorporeal removal of pyridoxine. The EXTRIP workgroup suggests against performing ECTR in addition to standard care (weak recommendation, very low quality of evidence) in patients with isoniazid poisoning. If standard dose pyridoxine cannot be administered, we suggest performing ECTR only in patients with seizures refractory to GABAA receptor agonists (weak recommendation, very low quality of evidence).

Extracorporeal Treatment for Chloroquine, Hydroxychloroquine, and Quinine Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup.

BACKGROUND: Although chloroquine, hydroxychloroquine, and quinine are used for a range of medical conditions, recent research suggested a potential role in treating COVID-19. The resultant increase in prescribing was accompanied by an increase in adverse events, including severe toxicity and death. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup sought to determine the effect of and indications for extracorporeal treatments in cases of poisoning with these drugs. METHODS: We conducted systematic reviews of the literature, screened studies, extracted data, and summarized findings following published EXTRIP methods. RESULTS: A total of 44 studies (three in vitro studies, two animal studies, 28 patient reports or patient series, and 11 pharmacokinetic studies) met inclusion criteria regarding the effect of extracorporeal treatments. Toxicokinetic or pharmacokinetic analysis was available for 61 patients (13 chloroquine, three hydroxychloroquine, and 45 quinine). Clinical data were available for analysis from 38 patients, including 12 with chloroquine toxicity, one with hydroxychloroquine toxicity, and 25 with quinine toxicity. All three drugs were classified as non-dialyzable (not amenable to clinically significant removal by extracorporeal treatments). The available data do not support using extracorporeal treatments in addition to standard care for patients severely poisoned with either chloroquine or quinine (strong recommendation, very low quality of evidence). Although hydroxychloroquine was assessed as being non-dialyzable, the clinical evidence was not sufficient to support a formal recommendation regarding the use of extracorporeal treatments for this drug. CONCLUSIONS: On the basis of our systematic review and analysis, the EXTRIP workgroup recommends against using extracorporeal methods to enhance elimination of these drugs in patients with severe chloroquine or quinine poisoning.

Comparing Empathy Levels in Doctor of Pharmacy Students and Exemplary Pharmacist Preceptors.

Objective. To determine how student pharmacists' empathy compares to that of exemplary pharmacist preceptors. Methods. First- through third-year Doctor of Pharmacy students and nominated preceptors demonstrating a model level of empathy in patient care were invited to take the Jefferson Scale of Empathy (JSE) and answer demographic questions. A comparison of total JSE scores was made between students and preceptors. Comparisons of total JSE scores were performed between male and female students, students with and without direct patient care experience, students with and without chronic care experience, and among students based on class year. A factor analysis was completed. Results. The response rate for students and preceptors was 70.3% (n=318) and 73.7% (n=14), respectively. No significant differences in median JSE scores were identified for any of the comparisons. Factor analysis revealed two factors as underlying constructs: "compassionate care" and "perspective taking." Seven of 20 items on the JSE had mean scores >6.0 (possible range 1-7). Conclusion. The majority of students had moderately high cognitive empathy not related to class year that was similar to that of exemplary pharmacist preceptors. A possible ceiling effect was found in several items on the JSE, potentially limiting its use for measuring changes in empathy longitudinally in students with baseline high empathy.

Factors associated with how often community pharmacists offer and dispense naloxone.

BACKGROUND: A recent Surgeon General's report encourages people to ask pharmacists about naloxone, but whether pharmacists are well-prepared to respond to these requests is unclear. OBJECTIVES: Determine factors that are associated with how often pharmacists offer and dispense naloxone. METHODS: A convenience sample of 457 community pharmacists in North Carolina completed a 5-min online survey. Linear regressions were conducted to identify factors that are associated with how often pharmacists offer and dispense naloxone. Pharmacists' self-reported barriers to teaching naloxone administration were identified. RESULTS: Most pharmacists (81.2%) worked in pharmacies that stocked naloxone, but many never offered (36.6%) or dispensed (19.4%) naloxone. Pharmacists offered (ß = 0.15, p < 0.01) and dispensed (ß = 0.15, p < 0.01) naloxone more often when their pharmacy stocked more naloxone formulations. Pharmacists who were more comfortable discussing naloxone offered it more often (ß = 0.26, p = 0.001). Pharmacists who worked in regional/local/grocery chain pharmacies dispensed and offered naloxone less often than other pharmacy types. Barriers to teaching naloxone administration included: time constraints, inadequate training, and perceived lack of patient comprehension. CONCLUSIONS: Many community pharmacists do not offer or dispense naloxone. Pharmacists who are uncomfortable discussing naloxone or work at smaller chain pharmacies may benefit from targeted naloxone training.

Experience with implementing pyramid examinations in an elective pharmacy course.

BACKGROUND AND PURPOSE: This article describes the implementation of pyramid tests, an assessment strategy that utilizes individual and cooperative testing for formal examinations in an elective course for third year pharmacy students. This strategy provides individual accountability and uses group collaboration to extend students depth of thinking through essay responses. Pyramid tests have been suggested as a way to improve grading efficiency compared to traditional tests that use essay questions. EDUCATIONAL ACTIVITY AND SETTING: A two-credit hour pharmacy elective taught by synchronous video conferencing on two campuses of a large public university utilized pyramid tests for both the midterm and final examinations. Each examination had individual and group components and utilized a simple metacognitive question. FINDINGS: The averages from the individual portions of the pyramid tests were similar to the prior year, while the combined group (2/3 weight) and individual (1/3 weight) pyramid test scores averages were slightly higher than the previous year's average (87% compared to 86%, respectively). Student feedback on this assessment technique was generally positive. SUMMARY: This assessment strategy was an efficient way to test students' knowledge. Although it had a collaborative component, it also provided individual accountability. Time spent on course administration and grading was similar to previous years that employed fixed choice assessments without collaborative work.

Care team perspectives on community pharmacy enhanced services.

OBJECTIVES: To determine the awareness, collaboration, and perceived values and barriers of enhanced pharmacy services from care managers and primary care practice responders. METHODS: An electronic questionnaire was sent to 1648 primary care practices and 600 care managers that work in 76 North Carolina counties containing an enhanced-service community pharmacy. Questionnaires were distributed in January 2017 and responses collected for 7 weeks. The questionnaire collected data on the awareness and perceived value of enhanced pharmacy services, preferred method and level of communication for referral, and barriers to using enhanced services. Data were gathered with the use of Likert-type, rank-order, dichotomous, and multiple-choice questions. Data were analyzed with the use of descriptive statistics, and group mean responses were compared by means of t tests. RESULTS: Data analysis was performed in March 2017. Response rates were 5.4% (n = 89) from practice responders and 45% (n = 270) from care managers. In the responses received, 35% of practice responders and 88% of care managers were familiar with enhanced services offered by community pharmacies. A majority of respondents thought that enhanced pharmacy services are valuable, with more than 85% of practice responders agreeing that partnering with an enhanced-service pharmacy can help to improve patient health outcomes. Lack of knowledge of enhanced-service pharmacies, services offered, and the referral process were identified as significant barriers for practice responders. CONCLUSION: Community-based pharmacies have an opportunity to collaborate with patient-centered medical home teams to provide enhanced pharmacy services, but provider outreach and education on enhanced services offered and the referral process are necessary to maximize this collaboration.

Relationship between Student Pharmacist Decision Making Preferences and Experiential Learning.

Objective. To determine if student pharmacists' preferences towards experiential and rational thinking are associated with performance on advanced pharmacy practice experiences (APPEs) and whether thinking style preference changes following APPEs. Methods. The Rational Experiential Inventory (REI), a validated survey of thinking style, was administered to student pharmacists before starting APPEs and re-administered after completing APPEs. APPE grades were compared to initial REI scores. Results. Rational Experiential Inventory scores remained consistent before and after APPEs. Overall, APPE grades were independent of REI scores. In a regression model, the REI experiential score was a significant negative predictor of hospital APPE grades. Conclusion. These findings suggest that overall APPE performance is independent of decision-making preference, and decision-making style does not change following immersion into APPEs. Instead of targeting teaching strategies towards a specific decision-making style, preceptors may use pedagogical approaches that promote sound clinical decision-making skills through critical thinking and reflection.

Professional Organizations for Pharmacy Students on Satellite Campuses.

Objective. To evaluate the structure and impact of student organizations on pharmacy school satellite campuses. Methods. Primary administrators from satellite campuses received a 20-question electronic survey. Quantitative data analysis was conducted on survey responses. Results. The most common student organizations on satellite campuses were the American Pharmacists Association (APhA) (93.1%), American Society of Health-System Pharmacists (ASHP) (89.7%), Christian Pharmacists Fellowship International (CPFI) (60.0%), state organizations (51.7%), and local organizations (58.6%). Perceived benefits of satellite campus organizations included opportunities for professional development, student engagement, and service. Barriers to success included small enrollment, communication between campuses, finances, and travel. Conclusion. Student organizations were an important component of the educational experience on pharmacy satellite campuses and allowed students to develop professionally and engage with communities. Challenges included campus size, distance between campuses, and communication.

A consensus-based gold standard for the evaluation of mass casualty triage systems.

INTRODUCTION: Accuracy and effectiveness analyses of mass casualty triage systems are limited because there are no gold standard definitions for each of the triage categories. Until there is agreement on which patients should be identified by each triage category, it will be impossible to calculate sensitivity and specificity or to compare accuracy between triage systems. OBJECTIVE: To develop a consensus-based, functional gold standard definition for each mass casualty triage category. METHODS: National experts were recruited through the lead investigators' contacts and their suggested contacts. Key informant interviews were conducted to develop a list of potential criteria for defining each triage category. Panelists were interviewed in order of their availability until redundancy of themes was achieved. Panelists were blinded to each other's responses during the interviews. A modified Delphi survey was developed with the potential criteria identified during the interview and delivered to all recruited experts. In the early rounds, panelists could add, remove, or modify criteria. In the final rounds edits were made to the criteria until at least 80% agreement was achieved. RESULTS: Thirteen national and local experts were recruited to participate in the project. Six interviews were conducted. Three rounds of voting were performed, with 12 panelists participating in the first round, 12 in the second round, and 13 in the third round. After the first two rounds, the criteria were modified according to respondent suggestions. In the final round, over 90% agreement was achieved for all but one criterion. A single e-mail vote was conducted on edits to the final criterion and consensus was achieved. CONCLUSION: A consensus-based, functional gold standard definition for each mass casualty triage category was developed. These gold standard definitions can be used to evaluate the accuracy of mass casualty triage systems after an actual incident, during training, or for research.

Rational and experiential decision-making preferences of third-year student pharmacists.

OBJECTIVE: To examine the rational (systematic and rule-based) and experiential (fast and intuitive) decision-making preferences of student pharmacists, and to compare these preferences to the preferences of other health professionals and student populations. METHODS: The Rational-Experiential Inventory (REI-40), a validated psychometric tool, was administered electronically to 114 third-year (P3) student pharmacists. Student demographics and preadmission data were collected. The REI-40 results were compared with student demographics and admissions data to identify possible correlations between these factors. RESULTS: Mean REI-40 rational scores were higher than experiential scores. Rational scores for younger students were significantly higher than students aged 30 years and older (p<0.05). No significant differences were found based on gender, race, or the presence of a prior degree. All correlations between REI-40 scores and incoming grade point average (GPA) and Pharmacy College Admission Test (PCAT) scores were weak. CONCLUSION: Student pharmacists favored rational decision making over experiential decision making, which was similar to results of studies done of other health professions.

Adverse drug reaction deaths reported in United States vital statistics, 1999-2006.

BACKGROUND: Adverse drug reactions (ADRs) are an important source of morbidity and mortality during medical care. OBJECTIVE: To examine the trends in mortality related to ADRs reported through the US vital statistics system since January 1999. METHODS: Demographic characteristics of people reported as dying as a result of ADRs from 1999 to 2006 were evaluated. The National Mortality Statistics database was queried for International Classification of Diseases, Tenth Revision, codes Y40-Y59, which are specific for deaths due to adverse effects of drugs in therapeutic use. The data were subgrouped based on demographic factors to identify important trends. Crude rates were calculated based on incidents per 100,000 population. Odds ratios and 95% confidence intervals for subgroups were calculated by logistical regression. RESULTS: During the 8-year study period 2,313,902,748 person years were evaluated and 2341 ADR-related deaths were identified. Annual rates ranged from 0.08/100,000 to 0.12/100,000, and rates increased significantly over time at a rate of 0.0058 per year. ADR deaths were significantly more likely in persons older than 55 years. The risk was greatest in those aged 75 years or older (OR 6.96, 95% CI 6.30 to 7.69). ADR deaths were higher among men than women. Rates varied by race and ethnicity and were highest among blacks (OR 1.38, 95% CI 1.23 to 1.54). Geographically, rates varied widely between states. Based on urbanization, rates were highest in extremely rural (non-core) areas (OR 2.05, 95% CI 1.76 to 2.38). The most common drug classes associated with death were anticoagulants, opioids, and immunosuppressants. CONCLUSIONS: ADR death rates have a clear association with age, race, and urbanization subgroups. Older individuals, males, blacks, and individuals residing in extremely rural areas experienced higher ADR death rates; these findings warrant further study to develop prevention strategies.

A pilot pharmacokinetic study of tricyclic antidepressant ovine Fab for TCA poisoning in children.

CONTEXT: A pilot study of tricyclic antidepressant (TCA)-specific antibody fragments (TCA Fab) in TCA-intoxicated adults showed a marked increase in serum total TCA concentrations following TCA Fab infusion with no worsening signs of TCA toxicity. TCA Fab pharmacokinetics (PK) was not described in this adult study. The objective of this study was to evaluate the PK of TCA Fab in children with TCA poisoning. METHODS: This was an open-label, single-center, dose escalation pilot trial of three patients. Inclusion criteria were documented TCA ingestion with at least one serious complication (QRS prolongation, dysrhythmia, hypotension, seizure, or coma). Patients were assigned to either a low-dose intravenous TCA Fab regimen (15, 30, and 60 mg/kg) or a high-dose regimen (30, 60, and 120 mg/kg) as needed to reverse TCA toxicity. Following the administration of TCA Fab, samples of blood and urine were obtained for PK evaluations. The outcomes of interest were serum and urine TCA concentrations (free and total), serum and urine Fab concentrations, improvement or worsening of TCA toxicity, and adverse effects. RESULTS: Three study patients were 11, 11, and 14 years of age. Two patients received 15 mg/kg of TCA Fab and one patient received a total of 90 mg/kg of TCA Fab (30 + 60 mg/kg). Serum-bound TCA increased significantly following TCA Fab administration with concomitant enhanced urinary elimination. Serum-free TCA concentrations were minimal to undetectable. Fab data were available for two patients. The serum TCA Fab area under the curve was 306.12 mg/L/h for the 15 mg/kg dose and 2,198.10 mg/L/h for the 90 mg/kg dose of TCA Fab. Maximum Fab concentrations correlated with maximum bound TCA in serum. The volume of distribution (V(D)) of TCA Fab was 0.2-0.3 L/kg. The clearance was 0.036-0.05 L/kg/h and the elimination half-life was 4 h. No adverse effects were observed. CONCLUSION: The limited PK data from this study are consistent with binding of TCA to TCA Fab and redistribution of TCA from the tissue to serum with subsequent enhanced urinary excretion of TCA. No toxic effects were observed with increased total TCA concentrations and no adverse effects were observed following TCA Fab administration. The small number of patients in this pilot study does not allow for safety or efficacy conclusions.