Informal Caregiving Among Faculty at a Large Academic Health Sciences University in the United States: an Opportunity for Policy Changes.

OBJECTIVE: This article aims to determine the prevalence of caregiving among faculty at a large academic health sciences institution, to examine the effect of gender and other demographic and professional covariates on caregiving status, and to explore caregiver-generated policy recommendations. METHOD: A cross-sectional, mixed-methods survey was collected from June through August 2018. Participants were faculty within one of the institution's health professional schools (dentistry, medicine, nursing, or pharmacy) receiving at least 50% salary from the institution. In addition to demographic information, we collected academic series and rank, and assessed association between covariates on caregiving status using logistic regression. We analyzed open-ended responses using thematic analysis to identify themes in caregiver barriers and policy suggestions. RESULTS: Among 657 eligible respondents, 11.4% were informal caregivers. Women were more likely to be caregivers than men (aOR 2.53, 95% CI: 1.40, 4.78), as were older faculty. Caregivers identified unsupportive climate or unrealistic work expectations, concern about career advancement, insufficient information about policies, and concern about colleague burden as barriers to support. Suggestions for workplace support included improved leave policies, increased flexibility, caregiver resource support, improved clarity and dissemination of policy information, and financial support. CONCLUSIONS: Women faculty are more likely to be informal caregivers, exacerbating disparities within academic medicine for promotion and retention among women faculty. Institutions might include caregiving status in annual burnout surveys to guide the development of structural support and policies for extension of family leave beyond childbearing (or catastrophic leave), flexibility in work hours, and subsidized eldercare services.

De novo mutations in epileptic encephalopathies.

Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown. Here we report a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms (n = 149) and Lennox-Gastaut syndrome (n = 115). We sequenced the exomes of 264 probands, and their parents, and confirmed 329 de novo mutations. A likelihood analysis showed a significant excess of de novo mutations in the ∼4,000 genes that are the most intolerant to functional genetic variation in the human population (P = 2.9 × 10(-3)). Among these are GABRB3, with de novo mutations in four patients, and ALG13, with the same de novo mutation in two patients; both genes show clear statistical evidence of association with epileptic encephalopathy. Given the relevant site-specific mutation rates, the probabilities of these outcomes occurring by chance are P = 4.1 × 10(-10) and P = 7.8 × 10(-12), respectively. Other genes with de novo mutations in this cohort include CACNA1A, CHD2, FLNA, GABRA1, GRIN1, GRIN2B, HNRNPU, IQSEC2, MTOR and NEDD4L. Finally, we show that the de novo mutations observed are enriched in specific gene sets including genes regulated by the fragile X protein (P < 10(-8)), as has been reported previously for autism spectrum disorders.

SOX11 identified by target gene evaluation of miRNAs differentially expressed in focal and non-focal brain tissue of therapy-resistant epilepsy patients.

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally control the expression of their target genes via RNA interference. There is increasing evidence that expression of miRNAs is dysregulated in neuronal disorders, including epilepsy, a chronic neurological disorder characterized by spontaneous recurrent seizures. Mesial temporal lobe epilepsy (MTLE) is a common type of focal epilepsy in which disease-induced abnormalities of hippocampal neurogenesis in the subgranular zone as well as gliosis and neuronal cell loss in the cornu ammonis area are reported. We hypothesized that in MTLE altered miRNA-mediated regulation of target genes could be involved in hippocampal cell remodeling. A miRNA screen was performed in hippocampal focal and non-focal brain tissue samples obtained from the temporal neocortex (both n=8) of MTLE patients. Out of 215 detected miRNAs, two were differentially expressed (hsa-miR-34c-5p: mean increase of 5.7 fold (p=0.014), hsa-miR-212-3p: mean decrease of 76.9% (p=0.0014)). After in-silico target gene analysis and filtering, reporter gene assays confirmed RNA interference for hsa-miR-34c-5p with 3'-UTR sequences of GABRA3, GRM7 and GABBR2 and for hsa-miR-212-3p with 3'-UTR sequences of SOX11, MECP2, ADCY1 and ABCG2. Reporter gene assays with mutated 3'-UTR sequences of the transcription factor SOX11 identified two different binding sites for hsa-miR-212-3p and its primary transcript partner hsa-miR-132-3p. Additionally, there was an inverse time-dependent expression of Sox11 and miR-212-3p as well as miR-132-3p in rat neonatal cortical neurons. Transfection of neurons with anti-miRs for miR-212-3p and miR-132-3p suggest that both miRNAs work synergistically to control Sox11 expression. Taken together, these results suggest that differential miRNA expression in neurons could contribute to an altered function of the transcription factor SOX11 and other genes in the setting of epilepsy, resulting not only in impaired neural differentiation, but also in imbalanced neuronal excitability and accelerated drug export.

The epilepsy phenome/genome project.

BACKGROUND: Epilepsy is a common neurological disorder that affects approximately 50 million people worldwide. Both risk of epilepsy and response to treatment partly depend on genetic factors, and gene identification is a promising approach to target new prediction, treatment, and prevention strategies. However, despite significant progress in the identification of genes causing epilepsy in families with a Mendelian inheritance pattern, there is relatively little known about the genetic factors responsible for common forms of epilepsy and so-called epileptic encephalopathies. Study design The Epilepsy Phenome/Genome Project (EPGP) is a multi-institutional, retrospective phenotype-genotype study designed to gather and analyze detailed phenotypic information and DNA samples on 5250 participants, including probands with specific forms of epilepsy and, in a subset, parents of probands who do not have epilepsy. RESULTS: EPGP is being executed in four phases: study initiation, pilot, study expansion/establishment, and close-out. This article discusses a number of key challenges and solutions encountered during the first three phases of the project, including those related to (1) study initiation and management, (2) recruitment and phenotyping, and (3) data validation. The study has now enrolled 4223 participants. CONCLUSIONS: EPGP has demonstrated the value of organizing a large network into cores with specific roles, managed by a strong Administrative Core that utilizes frequent communication and a collaborative model with tools such as study timelines and performance-payment models. The study also highlights the critical importance of an effective informatics system, highly structured recruitment methods, and expert data review.

Treatment of status epilepticus: an international survey of experts.

BACKGROUND: As part of the development of the Neurocritical Care Society (NCS) Status Epilepticus (SE) Guidelines, the NCS SE Writing Committee conducted an international survey of SE experts. METHODS: The survey consisted of three patient vignettes (case 1, an adult; case 2, an adolescent; case 3, a child) and questions regarding treatment. The questions for each case focused on initial and sequential therapy as well as when to use continuous intravenous (cIV) therapy and for what duration. Responses were obtained from 60/120 (50%) of those surveyed. RESULTS: This survey reveals that there is expert consensus for using intravenous lorazepam for the emergent (first-line) therapy of SE in children and adults. For urgent (second-line) therapy, the most common agents chosen were phenytoin/fosphenytoin, valproate sodium, and levetiracetam; these choices varied by the patient age in the case scenarios. Physicians who care for adult patients chose cIV therapy for RSE, especially midazolam and propofol, rather than a standard AED sooner than those who care for children; and in children, there is a reluctance to choose propofol. Pentobarbital was chosen later in the therapy for all ages. CONCLUSION: There is close agreement between the recently published NCS guideline for SE and this survey of experts in the treatment of SE.

Faculty knowledge, actions, and perceptions of sponsorship: an institutional survey study.

BACKGROUND: Women and underrepresented in medicine and the health sciences (URiM) faculty face inequities in advancement. Career sponsorship may be a remedy. Few studies have described sponsorship in academic medicine and none across an institution. OBJECTIVE: To examine faculty awareness, experiences, and perceptions of sponsorship at a large academic health center. DESIGN: Anonymous online survey. PARTICIPANTS: Faculty with a ≥50% appointment. MAIN MEASURES: The survey contained 31 Likert, multiple-choice, yes/no, and open-ended questions about familiarity with the concept of sponsorship; experience of having or being a sponsor; receipt of specific sponsorship activities; sponsorship impact and satisfaction; mentorship and sponsorship co-occurrence; and perception of inequities. Open-ended questions were analyzed using content analysis. KEY RESULTS: Thirty-one percent of the surveyed faculty (903/2900) responded of whom 53% (477/903) were women and 10% (95/903) were URiM. Familiarity with sponsorship was higher among assistant (91%, 269/894) and associate (182/894; 64%) professors versus full professors (38%, 329/894); women (67%, 319/488) versus men (62%, 169/488); and URiM (77%, 66/517) versus non-URiM faculty (55%, 451/517). A majority had a personal sponsor (528/691; 76%) during their career and were satisfied with their sponsorship (64%, 532/828). However, when responses from faculty of different professorial ranks were stratified by gender and URiM identity, we observed possible cohort effects. Furthermore, 55% (398/718) of respondents perceived that women received less sponsorship than men and 46% (312/672) that URiM faculty received less than their peers. We identified seven qualitative themes: sponsorship importance, growing awareness and change, institutional biases and deficiencies, groups getting less sponsorship, people with sponsorship power, conflation with mentorship, and potential for negative impact. CONCLUSIONS: A majority of respondents at a large academic health center reported sponsorship familiarity, receipt, and satisfaction. Yet many perceived persistent institutional biases and the need for systematic change to improve sponsorship transparency, equity, and impact.

Mood and Anxiety Disorders and Suicidality in Patients With Newly Diagnosed Focal Epilepsy: An Analysis of a Complex Comorbidity.

BACKGROUND AND OBJECTIVES: Mood, anxiety disorders, and suicidality are more frequent in people with epilepsy than in the general population. Yet, their prevalence and the types of mood and anxiety disorders associated with suicidality at the time of the epilepsy diagnosis are not established. We sought to answer these questions in patients with newly diagnosed focal epilepsy and to assess their association with suicidal ideation and attempts. METHODS: The data were derived from the Human Epilepsy Project study. A total of 347 consecutive adults aged 18-60 years with newly diagnosed focal epilepsy were enrolled within 4 months of starting treatment. The types of mood and anxiety disorders were identified with the Mini International Neuropsychiatric Interview, whereas suicidal ideation (lifetime, current, active, and passive) and suicidal attempts (lifetime and current) were established with the Columbia Suicidality Severity Rating Scale (CSSRS). Statistical analyses included the t test, χ2 statistics, and logistic regression analyses. RESULTS: A total of 151 (43.5%) patients had a psychiatric diagnosis; 134 (38.6%) met the criteria for a mood and/or anxiety disorder, and 75 (21.6%) reported suicidal ideation with or without attempts. Mood (23.6%) and anxiety (27.4%) disorders had comparable prevalence rates, whereas both disorders occurred together in 43 patients (12.4%). Major depressive disorders (MDDs) had a slightly higher prevalence than bipolar disorders (BPDs) (9.5% vs 6.9%, respectively). Explanatory variables of suicidality included MDD, BPD, panic disorders, and agoraphobia, with BPD and panic disorders being the strongest variables, particularly for active suicidal ideation and suicidal attempts. DISCUSSION: In patients with newly diagnosed focal epilepsy, the prevalence of mood, anxiety disorders, and suicidality is higher than in the general population and comparable to those of patients with established epilepsy. Their recognition at the time of the initial epilepsy evaluation is of the essence.

Guidelines for the evaluation and management of status epilepticus.

Status epilepticus (SE) treatment strategies vary substantially from one institution to another due to the lack of data to support one treatment over another. To provide guidance for the acute treatment of SE in critically ill patients, the Neurocritical Care Society organized a writing committee to evaluate the literature and develop an evidence-based and expert consensus practice guideline. Literature searches were conducted using PubMed and studies meeting the criteria established by the writing committee were evaluated. Recommendations were developed based on the literature using standardized assessment methods from the American Heart Association and Grading of Recommendations Assessment, Development, and Evaluation systems, as well as expert opinion when sufficient data were lacking.

Understanding herb and dietary supplement use in patients with epilepsy.

OBJECTIVE: To determine the prevalence of herb and dietary supplement use and to provide a comprehensive analysis of factors influencing the use of these products in patients with epilepsy. METHODS: We performed a cross-sectional study using self-administered questionnaires in a selected group of patients who were receiving care at a tertiary epilepsy center. Logistic regression was used to measure the association between the demographic variables and herb and dietary supplement use. In addition, we performed a MEDLINE search for each of the herb and dietary products used by our patients to determine the effect of these products on seizures and on their potential for interactions with other drugs metabolized by the liver. RESULTS: One hundred eighty-seven patients completed the survey. Fifty-six percent of this group of patients with epilepsy used herbs and dietary supplements at the time of the survey. A considerable portion (71%) of these patients reported the use of these products to their physician, and most of them relied on their physicians as the primary source of information. Most of the patients used dietary supplement for health promotion rather than to specifically benefit their epilepsy condition. Approximately one-third of patients used herb or dietary supplements that had the potential to increase seizures (16%) or to interact with hepatically metabolized drugs (19%). The most powerful independent predictors of herb and dietary supplement use were partial epilepsy [odds ratio (OR) 3.36; 95% confidence interval (CI) 1.27-8.88] and Caucasian race (OR 3.55; 95% CI 1.11-11.34). CONCLUSION: Patients with epilepsy commonly used dietary supplements along with their antiepileptic medications. The majority of these patients used herb and dietary supplements for health promotion rather than because of dissatisfaction with conventional treatment. It is important that physicians involved in the care of patients with epilepsy routinely inquire about the use of dietary supplements and that they make use of reliable resources to assess the safety of these products with regard to modification of seizure risk and the potential for interactions with antiepileptic drugs.

Developing faculty leadership from 'within': a 12-year reflection from an internal faculty leadership development program of an academic health sciences center.

Most academic health sciences centers offer faculty leadership development programs (LDPs); however, the outcomes of LDPs are largely unknown. This article describes perspectives from our 12-year experience cultivating a formal faculty LDP within an academic health center and longitudinal outcomes of our LDP. Responding to faculty concerns from University of California San Francisco's (UCSF) 2001 Faculty Climate Survey, UCSF established the UCSF-Coro Faculty Leadership Collaborative (FLC) in 2005. The FLC focused on building leadership skills using a cohort-based, experiential, interactive and collaborative learning approach. From 2005 to 2012, FLC has conducted training for 136 graduates over 7 cohorts with 97.6% completion rate. FLC faculty participants included 64% women and 13% underrepresented minority (URM). The proportions of graduates attaining leadership positions within UCSF such as deans or department chairs among all, URM, and women URM graduates were 9.6%, 33.3% and 45.5%, respectively. A 2013 online survey assessed 2005-2012 graduates' perceived impacts from 8 months to 8 years after program completion and showed 91.7% of survey respondents felt the program both increased their understanding of UCSF as an organization and demonstrated the University's commitment to foster faculty development. Qualitative results indicated that graduates perceived benefits at individual, interpersonal, and organizational levels. Though we did not directly assess impact on faculty recruitment and retention, the findings to date support cohort-based experiential learning in faculty leadership training development.

A multidisciplinary teamwork training program: the Triad for Optimal Patient Safety (TOPS) experience.

INTRODUCTION: Communication and teamwork failures are a common cause of adverse events. Residency programs, with a mandate to teach systems-based practice, are particularly challenged to address these important skills. AIM: To develop a multidisciplinary teamwork training program focused on teaching teamwork behaviors and communication skills. SETTING: Internal medicine residents, hospitalists, nurses, pharmacists, and all other staff on a designated inpatient medical unit at an academic medical center. PROGRAM DESCRIPTION: We developed a 4-h teamwork training program as part of the Triad for Optimal Patient Safety (TOPS) project. Teaching strategies combined didactic presentation, facilitated discussion using a safety trigger video, and small-group scenario-based exercises to practice effective communication skills and team behaviors. Development, planning, implementation, delivery, and evaluation of TOPS Training was conducted by a multidisciplinary team. PROGRAM EVALUATION: We received 203 evaluations with a mean overall rating for the training of 4.49 +/- 0.79 on a 1-5 scale. Participants rated the multidisciplinary educational setting highly at 4.59 +/- 0.68. DISCUSSION: We developed a multidisciplinary teamwork training program that was highly rated by all participating disciplines. The key was creating a shared forum to learn about and discuss interdisciplinary communication and teamwork.

Potential roles for pharmacists in pharmacogenetics.

OBJECTIVES: To highlight areas of pharmacogenetics in which pharmacists may play a role and to describe those roles in the context of specific examples from a major academic medical center. DATA SOURCES: Literature search (PubMed) and personal interviews for the University of California at San Francisco case examples. DATA SYNTHESIS: The field of pharmacogenetics presents a wide range of opportunities for pharmacists. Specific roles for pharmacists are likely to fall within three major domains: developing research methodologies and setting research directions, establishing the value of pharmacogenetic testing in clinical practice, and participating in education and infrastructure development that moves pharmacogenetic technologies toward implementation. CONCLUSION: As drug therapy experts, pharmacists are in a unique position to push the frontiers of pharmacogenetics in both the research and clinical practice environments.

Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society.

CONTEXT: The optimal pharmacologic treatment for early convulsive status epilepticus is unclear. OBJECTIVE: To analyze efficacy, tolerability and safety data for anticonvulsant treatment of children and adults with convulsive status epilepticus and use this analysis to develop an evidence-based treatment algorithm. DATA SOURCES: Structured literature review using MEDLINE, Embase, Current Contents, and Cochrane library supplemented with article reference lists. STUDY SELECTION: Randomized controlled trials of anticonvulsant treatment for seizures lasting longer than 5 minutes. DATA EXTRACTION: Individual studies were rated using predefined criteria and these results were used to form recommendations, conclusions, and an evidence-based treatment algorithm. RESULTS: A total of 38 randomized controlled trials were identified, rated and contributed to the assessment. Only four trials were considered to have class I evidence of efficacy. Two studies were rated as class II and the remaining 32 were judged to have class III evidence. In adults with convulsive status epilepticus, intramuscular midazolam, intravenous lorazepam, intravenous diazepam and intravenous phenobarbital are established as efficacious as initial therapy (Level A). Intramuscular midazolam has superior effectiveness compared to intravenous lorazepam in adults with convulsive status epilepticus without established intravenous access (Level A). In children, intravenous lorazepam and intravenous diazepam are established as efficacious at stopping seizures lasting at least 5 minutes (Level A) while rectal diazepam, intramuscular midazolam, intranasal midazolam, and buccal midazolam are probably effective (Level B). No significant difference in effectiveness has been demonstrated between intravenous lorazepam and intravenous diazepam in adults or children with convulsive status epilepticus (Level A). Respiratory and cardiac symptoms are the most commonly encountered treatment-emergent adverse events associated with intravenous anticonvulsant drug administration in adults with convulsive status epilepticus (Level A). The rate of respiratory depression in patients with convulsive status epilepticus treated with benzodiazepines is lower than in patients with convulsive status epilepticus treated with placebo indicating that respiratory problems are an important consequence of untreated convulsive status epilepticus (Level A). When both are available, fosphenytoin is preferred over phenytoin based on tolerability but phenytoin is an acceptable alternative (Level A). In adults, compared to the first therapy, the second therapy is less effective while the third therapy is substantially less effective (Level A). In children, the second therapy appears less effective and there are no data about third therapy efficacy (Level C). The evidence was synthesized into a treatment algorithm. CONCLUSIONS: Despite the paucity of well-designed randomized controlled trials, practical conclusions and an integrated treatment algorithm for the treatment of convulsive status epilepticus across the age spectrum (infants through adults) can be constructed. Multicenter, multinational efforts are needed to design, conduct and analyze additional randomized controlled trials that can answer the many outstanding clinically relevant questions identified in this guideline.

Prescription drug dispensing limits and patterns.

Dispensing limits, which ration prescriptions to 30-day supplies when filled at community pharmacies, is a strategy commonly used to control prescription drug costs. Yet, little is known about drug dispensing patterns. Prescription dispensing patterns may have important influences on adherence, therapeutic and preventive health outcomes, and costs. This study examined dispensing patterns for five drug classes commonly prescribed for chronic conditions.

Risk of seizures associated with psychotropic medications: emphasis on new drugs and new findings.

Psychotropic medications in the classes of antidepressants, antipsychotics and mood stabilisers have been recognised in the literature and clinical settings as having high epileptogenic potential. Among these three classes, clozapine, tricyclic antidepressants (TCAs) and lithium are agents that clinicians have historically recognised as precipitants of drug-induced seizures. There are few reports that review the epileptogenic risk of newer psychotropic agents; in this qualitative review, the authors provide an update on the most recently published reports on seizures associated with antidepressants, antipsychotics, mood stabilisers, anxiolytics and sedative-hypnotics. In general, the epileptogenic risks of the newer psychotropic agents appear to be quite low as long as dosing strategies are consistent with recommended guidelines. Whilst newer psychotropic medications appear to be safe in patients with epilepsy, few studies have specifically addressed this population. In addition, the potential for drug interactions between antiepileptic drugs and psychotropics may be substantial with certain agents. For example, many psychotropes are both substrates and inhibitors of cytochrome P450 (CYP450) isoenzymes, whilst many antiepileptic drugs are both substrates and inducers of CYP450 activity. Every attempt should be made to minimise potential interactions when these agents are concomitantly administered.

Effects of a multicentre teamwork and communication programme on patient outcomes: results from the Triad for Optimal Patient Safety (TOPS) project.

BACKGROUND: Improving communication between caregivers is an important approach to improving safety. OBJECTIVE: To implement teamwork and communication interventions and evaluate their impact on patient outcomes. DESIGN: A prospective, interrupted time series of a three-phase INTERVENTION: a run-in period (phase 1), during which a training programme was given to providers and staff on each unit; phase 2, which focused on unit-based safety teams to identify and address care problems using skills from phase 1; and phase 3, which focused on engaging patients in communication efforts. SETTING: General medical inpatient units at three northern California hospitals. PATIENTS: Administrative data were collected from all adults admitted to the target units, and a convenience sample of patients interviewed during and after hospitalisation. MEASUREMENTS: Readmission, length of stay and patient reports of teamwork, problems with care, and overall satisfaction. RESULTS: 10 977 patients were admitted; 581 patients (5.3% of total sample) were interviewed in hospital, and 313 (2.9% overall, 53.8% of interviewed patients) completed 1-month surveys. No phase of the study was associated with adjusted differences in readmission or length of stay. The phase 2 intervention appeared to be associated with improvement in reports of whether physicians treated them with respect, whether nurses treated them with respect or understood their needs (p<0.05 for all). Interestingly, patients were more likely to perceive that an error took place with their care and agreed less that their caregivers worked well together as a team. No phase had a consistent impact on patient reports of care processes or overall satisfaction. Limitations The study lacks direct measures of patient safety. CONCLUSIONS: Efforts to simultaneously improve caregivers' ability to troubleshoot care and enhance communication may improve patients' perception of team functions, but may also increase patients' perception of safety gaps.

AHRQ's hospital survey on patient safety culture: psychometric analyses.

OBJECTIVE: This project analyzed the psychometric properties of the Agency for Healthcare Research and Quality Hospital Survey on Patient Safety Culture (HSOPSC) including factor structure, interitem reliability and intraclass correlations, usefulness for assessment, predictive validity, and sensitivity. METHODS: The survey was administered to 454 health care staff in 3 hospitals before and after a series of multidisciplinary interventions designed to improve safety culture. Respondents (before, 434; after, 368) included nurses, physicians, pharmacists, and other hospital staff members. RESULTS: Factor analysis partially confirmed the validity of the HSOPSC subscales. Interitem consistency reliability was above 0.7 for 5 subscales; the staffing subscale had the lowest reliability coefficients. The intraclass correlation coefficients, agreement among the members of each unit, were within recommended ranges. The pattern of high and low scores across the subscales of the HSOPSC in the study hospitals were similar to the sample of Pacific region hospitals reported by the Agency for Healthcare Research and Quality and corresponded to the proportion of items in each subscale that are worded negatively (reverse scored). Most of the unit and hospital dimensions were correlated with the Safety Grade outcome measure in the tool. CONCLUSION: Overall, the tool was shown to have moderate-to-strong validity and reliability, with the exception of the staffing subscale. The usefulness in assessing areas of strength and weakness for hospitals or units among the culture subscales is questionable. The culture subscales were shown to correlate with the perceived outcomes, but further study is needed to determine true predictive validity.

Drug withdrawals in the United States: a systematic review of the evidence and analysis of trends.

There have been a number of highly publicized safety-based drug withdrawals in the United States in recent years. We conducted a review of drugs withdrawn since 1993 and examined trends in drug withdrawals. Our objective was to determine the frequency and characteristics of withdrawn drugs and trends since 1993, and to discuss the implications of the findings. We found that a mean of 1.5 drugs per year have been withdrawn since 1993, and that the number of withdrawals has not increased over time. However, some recent drug withdrawals have impacted large numbers of people. The rate of withdrawals alone is not an adequate measure of the status of drug safety in the US, and there is a serious dearth of data that can be used to examine the impact of drug withdrawals. Although drug withdrawals are an important issue to address, drug safety policies need to be developed within the broader context of drug safety and effectiveness. A comprehensive approach will be needed to address the improvement of drug safety. We propose improvements to the evidence base to increase drug safety and assess how new scientific evidence can be incorporated into drug safety efforts.